@article {pmid41443129,
year = {2025},
author = {Sukarni, S and Kunimitsu, M and Ogai, K and Liana, DF and Mahyarudin, M and Aminuddin, M and Mukai, K and Haryanto, H and Jais, S and Oe, M},
title = {Relationship between microbiota and healing status in diabetes-related foot ulcers treated with Trigona honey.},
journal = {Journal of tissue viability},
volume = {35},
number = {1},
pages = {100981},
doi = {10.1016/j.jtv.2025.100981},
pmid = {41443129},
issn = {0965-206X},
abstract = {AIMS: Diabetes-related foot ulcers (DFUs) are a major complication of diabetes, and treatment with honey, which has antimicrobial properties, has been utilized in patients. However, the effects have been shown to vary, with the causes of these differences remaining unclear. Recently, microbiota has been reported to be associated with wound healing. Therefore, we hypothesized that differences in microbiota might explain the variations observed in response to honey. The present study aimed to investigate the relationship between the microbiota and the healing status in DFUs treated with Trigona honey.

METHODS: A cohort study involving 12 DFUs categorized into healing and deteriorating groups was conducted. Wound and peri-wound microbiota observed at baseline and at 1 week later (after starting honey application) were investigated and then compared in the healing status.

RESULTS: Enterococcus was higher in the deteriorating group at baseline in the wound (p = 0.02), while Corynebacterium was higher in the healing group at 1 week later in the peri-wound skin (p = 0.02). Changes in the relative abundance of Prevotella and Brevundimonas in the peri-wound skin significantly differed based on the healing status.

CONCLUSION: The findings suggest that the honey's effects might differ based on the composition of the wound microbiota, and they highlight the bacterial interactions with the changes in the wound and peri-wound skin environment induced by the honey. These results also imply that honey therapy on its own may not be enough for treating DFUs. This study is limited by the small sample size and short follow-up period; further research will need to explore combined treatment strategies and long-term microbiota dynamics to improve DFU management.},
}

@article {pmid41443021,
year = {2025},
author = {Salamatullah, HK and AboAljadiel, L and Halabi, MH and Alqurashi, S and Aljohani, R and Aljafari, D and Alkhiri, A and Almaghrabi, AA and Makkawi, S},
title = {The association between antimicrobial exposure and subsequent multiple sclerosis risk: A systematic review and meta-analysis.},
journal = {Multiple sclerosis and related disorders},
volume = {107},
number = {},
pages = {106936},
doi = {10.1016/j.msard.2025.106936},
pmid = {41443021},
issn = {2211-0356},
abstract = {BACKGROUND: Multiple Sclerosis (MS) is a complex autoimmune inflammatory disease of the central nervous system with an incompletely understood etiology. Emerging evidence suggests a critical link between gut microbiome disruption and MS pathogenesis, with antibiotics potentially playing a significant role in microbiome alterations. We conducted a systematic review and meta-analysis to explore the relationship between antimicrobial exposure and the risk of developing MS.

METHODS: A comprehensive systematic review was conducted across four electronic databases, searching for studies until March 29, 2025. The meta-analysis included comparative studies examining antibiotic usage frequency prior to MS onset/diagnosis in MS patients versus control group. Adjusted odds ratios (OR) were pooled using the generic inverse variance method with corresponding 95% confidence intervals (CIs).

RESULTS: The analysis encompassed nine reports involving 109,784 participants (23,960 MS patients and 85,824 controls). A statistically significant association was observed between antibiotic exposure and MS odds (OR=1.18; 95% CI [1.03-1.36]; p = 0.02). Data source-based analysis showed that studies with high-quality registry data maintained the association (OR=1.36; 95% CI [1.17-1.58]; p < 0.0001). Time-trend analysis showed significant association when the exposure occurred ≥4 years prior MS onset/diagnosis (OR=1.26; 95% CI [1.19-1.33]). Stratified analysis revealed significant associations for multiple antimicrobial classes, including tetracyclines, macrolides, quinolones, nitrofurantoin, aminoglycosides, metronidazole, sulfonamides, and antimycotics.

CONCLUSION: This meta-analysis reveals a significant association between antimicrobial exposures, particularly those based on high-quality data and occurring at least four years prior to MS onset/diagnosis, and increased MS incidence. Longitudinal, prospective studies are required to conclusively determine whether antibiotic exposure is a true risk factor for MS.},
}

@article {pmid41442921,
year = {2025},
author = {Guo, H and Li, W and Peng, J and Fan, Y and Yang, S and Mao, H and Wang, Y and Lu, Z},
title = {Bacillus affects Taihe Silky Fowls growth performance, cecal microbiota, and metabolite during growing period.},
journal = {Poultry science},
volume = {105},
number = {2},
pages = {106251},
doi = {10.1016/j.psj.2025.106251},
pmid = {41442921},
issn = {1525-3171},
abstract = {Bacillus, a well-recognized probiotic genus, regulates intestinal microbiota to maintain gut homeostasis and enhance host immunity. Taihe Silky Fowl (Taihe SF)-a high-quality Chinese indigenous chicken breed-has poor disease resistance, limiting its commercial farming efficiency. This study evaluated the effects of four strains (Bacillus subtilis, Bacillus coagulans, Bacillus licheniformis, Clostridium butyricum) on growth performance, antioxidant capacity, intestinal barrier integrity, and cecal microbiota of 3-13-week-old Taihe SF, to identify the optimal strain for this stage. 1,200 3-week-old Taihe SF, with close body weights (45.2 ± 2.1 g, P > 0.05) and health status were randomly divided into 5 groups (6 replicates/group, 40 birds/replicate). Four experimental groups received diets supplemented with B. subtilis, B. coagulans, B. licheniformis, or C. butyricum (10[10] CFU/g, 1000 mg/kg). It was observed that four experimental groups remarkedly decreased (P < 0.05) the feed conversion ratio in Taihe SF from 3 to 13 weeks. The catalase, total antioxidant capacity, and total superoxide dismutase levels in serum experienced a significant rise (P < 0.05) in the BS and CB groups, compared with the CON group, while the content of malondialdehyde significantly decreased (P < 0.05). Compared with CON group, all four experimental groups significantly increased the villus length and reduced the crypt depth in the jejunum (P < 0.05). The level of diamine oxidase in the jejunum saw a notable decline (P < 0.05), and there was an increase in the relative mRNA expression of Occludin, Claudin-1, Claudin-2, and zonula occludens1 within the jejunum. Furthermore, the BS group exhibited a significant enhancement in the relative abundance of Firmicutes in the cecum, accompanied by a marked reduction in the relative abundances of Bacteroidota and Proteobacteria. B. subtilis also led to an elevation of indole-3-propionic acid concentrations in the intestines of Taihe SF. Based on these findings, B. subtilis is deemed the most advantageous among the tested strains for Taihe SF during the 3-13 week growth period.},
}

@article {pmid41442918,
year = {2025},
author = {Li, R and Quan, T and Chen, Y and Gao, T},
title = {Butyrate improves dextran sulfate sodium-induced imbalance of intestinal stem cell homeostasis in broilers.},
journal = {Poultry science},
volume = {105},
number = {2},
pages = {106307},
doi = {10.1016/j.psj.2025.106307},
pmid = {41442918},
issn = {1525-3171},
abstract = {BACKGROUOND: Intestinal homeostasis is maintained through the ongoing self-renewal and differentiation of intestinal stem cells (ISCs). Butyrate, a microbial metabolite, connects the gut microbiome with the epithelium. This research delves deeper into how butyrate influences ISC to enhance the intestinal mucosal barrier in broilers.

RESULTS: Our research results show that dextran sulfate sodium (DSS)-treated broilers exhibit damaged intestinal villi structure (including reduced villus length and increased crypt depth) and impaired intestinal mucosal barrier, including decreased numbers of goblet cells, mast cells and paneth cells, and MUC2 protein and tight junction protein expression. Importantly, DSS treatment not only reduces the number of ISCs but also hinders their differentiation and proliferation abilities. However, butyrate intervention can effectively improve intestinal mucosal barrier function by restoring the homeostasis of intestinal stem cells.

CONCLUSION: The findings imply that butyrate might promote ISC self-renewal and differentiation, improving the structure and function of the intestinal lining by triggering the Wnt/β-catenin and Notch signaling pathways. The study provides clinical value by highlighting the key role of immunometabolism in intestinal diseases and potential therapeutic targets, and it has broad application prospects in livestock and poultry farming for improving growth performance by enhancing gut health.},
}

@article {pmid41442770,
year = {2025},
author = {Liu, C and Zhang, L},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103718},
doi = {10.1002/alz70856_103718},
pmid = {41442770},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; *Gastrointestinal Microbiome/genetics ; *Apolipoprotein E4/genetics ; Aged ; *Biomarkers ; *Alzheimer Disease/genetics/microbiology ; Feces/microbiology ; Middle Aged ; },
abstract = {BACKGROUND: The gut-brain axis hypothesis proposes a bidirectional communication network between the gut microbiome and the central nervous system, shaping neuroinflammatory processes linked to Alzheimer's disease (AD). Although the APOE4 allele is the strongest genetic risk factor for AD-raising the likelihood of disease by two- to three-fold with even one copy-its association with the gut microbiome remains underexplored. This gap limits our full understanding of the pathways contributing to AD.

METHOD: We investigated the relationship between APOE4 status and gut microbiome composition in 114 healthy participants (average age: 77, 57% women). Stool samples underwent shotgun metagenomic sequencing. Rigorous quality control steps removed low-quality reads and human DNA contaminants. We performed taxonomic profiling and applied rarefaction to normalize sequencing depth. Alpha diversity (richness and evenness) and beta diversity (unweighted UniFrac-based principal coordinates analysis) were assessed. We then used permutational multivariate analysis of variance, adjusting for demographic and clinical variables, to identify group differences. Differential taxonomic analysis pinpointed bacterial taxa enriched in APOE4 carriers versus non-carriers.

RESULT: Alpha diversity metrics did not differ significantly between APOE4 carriers and non-carriers at the species level (p = 0.070). However, beta diversity analysis showed significant differences in overall community composition after adjusted by the covariates (p = 0.003), and APOE4 carrier status remained significant in PERMANOVA (p = 0.039). Furthermore, subgroup analysis of APOE4 genotypes (2/4, 3/4, 4/4) also revealed significant compositional differences (p = 0.030). Differential taxonomic analysis identified 21 species enriched in APOE4 carriers and 20 species enriched in non-carriers. Among non-carriers, Alistipes finegoldii (p = 0.035) and Odoribacter splanchnicus (p = 0.024) were more abundant. These species are involved in metabolic pathways related to short-chain fatty acid production, which can have anti-inflammatory effects. Their presence suggests a protective gut microbiome-mediated mechanism in individuals without the APOE4 allele.

CONCLUSION: Our findings suggest that APOE4 carriers have distinct gut microbiome patterns that may heighten the risk of neuroinflammation through the gut-brain axis, potentially contributing to AD onset or progression. These results highlight the interplay between genetic risk factors and gut microbial communities. They also underscore the potential for microbiome-targeted interventions to reduce AD risk in genetically susceptible individuals.},
}

Humans
Female
Male
*Gastrointestinal Microbiome/genetics
*Apolipoprotein E4/genetics
Aged
*Biomarkers
*Alzheimer Disease/genetics/microbiology
Feces/microbiology
Middle Aged

@article {pmid41442682,
year = {2025},
author = {Monzón, ÁRR and Ramos, JFO and Narvaez, YC and Rosales, MH},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e097688},
doi = {10.1002/alz70856_097688},
pmid = {41442682},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers/metabolism ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 2/metabolism/microbiology ; *Alzheimer Disease/metabolism/microbiology ; *Gastrointestinal Microbiome/physiology ; Male ; Female ; Metabolomics ; Middle Aged ; Adult ; Aged ; Young Adult ; },
abstract = {BACKGROUND: T2DM and AD are major public health concerns characterized by metabolic and cognitive impairments, respectively, with growing evidence suggesting that gut microbiota alterations contribute to their pathogenesis. Metagenomic and metabolomic analyses provide valuable insights into the microbiota's role in glucose regulation, inflammation, and dementia risk, offering potential for early diagnosis and targeted interventions. Understanding the interplay between gut microbiota and metabolic pathways could lead to novel therapeutic strategies to improve patient outcomes.

METHOD: A descriptive study with a quantitative approach, cross-sectional observational comparative, of relational scope will be conducted. The study population will be segmented into four groups and two subgroups: Control (CTRL) (n = 30), Type 2 Diabetes Mellitus (T2DM) (n = 30), Alzheimer's Disease (AD) without T2DM (n = 30), and AD with T2DM (n = 30). Subgroups include Control (Young adults) (n = 30) and T2DM (Young adults) (n = 30). All groups will undergo characterization, which includes blood chemistry, and clinical, mental, nutritional, and anthropometric evaluations. We obtained urine and stool samples for DNA extraction and library preparation. We used Magnetic Resonance Mass Spectrometry (MRMS) for metabolomic analysis, which uses eluents to detect metabolites. We will apply MetaHit bioinformatics tools to assess sample diversity and perform metabolomic analysis in RStudio.

RESULT: The study revealed distinct patterns of intestinal dysbiosis and metabolic changes in patients with T2DM and AD, categorized by age. A comprehensive taxonomic and functional representation of the gut microbiome highlighted condition-specific differences. Significant correlations were found between microbiological, metabolomic, and clinical biomarkers, particularly those related to cognitive decline. Key metabolic pathways and molecular processes underlying dysbiosis were identified. Fecal metabolite analysis uncovered distinctive compounds such as (+/-)-Ethylketocyclazocine, (-)-Quebrachamine, and (-)-jasmonoyl-L-isoleucine, while urinary metabolites like (Phenylthio) acetic acid and 2,3-Diketo-L-gulonate showed disease-associated variations. These findings support the development of personalized interventions to mitigate cognitive decline through microbiota and metabolomic profile modifications.

CONCLUSION: The study identifies distinct gut microbiota and metabolic patterns linked to cognitive decline in T2DM and AD, offering insights into disease mechanisms and supporting the development of personalized therapeutic strategies to improve patient outcomes.},
}

Humans
*Biomarkers/metabolism
Cross-Sectional Studies
*Diabetes Mellitus, Type 2/metabolism/microbiology
*Alzheimer Disease/metabolism/microbiology
*Gastrointestinal Microbiome/physiology
Male
Female
Metabolomics
Middle Aged
Adult
Aged
Young Adult

@article {pmid41442661,
year = {2025},
author = {Ivanich, K and Yackzan, A and Chang, YH and Aware, C and Govindarajan, M and Kramer, S and Yanckello, LM and Ericsson, A and Lin, AL},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e104646},
doi = {10.1002/alz70855_104646},
pmid = {41442661},
issn = {1552-5279},
mesh = {Animals ; *Gastrointestinal Microbiome ; Female ; Mice, Transgenic ; Male ; Apolipoprotein E4/genetics ; *Brain/metabolism ; Mice ; *Diet, Ketogenic ; *Alzheimer Disease/genetics/metabolism ; Apolipoprotein E3/genetics ; Metabolomics ; Disease Models, Animal ; },
abstract = {BACKGROUND: The apolipoprotein ε4 (APOE4) polymorphism is the primary genetic risk factor for Alzheimer's disease (AD). APOE4 carriers exhibit early deficits in brain metabolism and gut microbiome diversity, both elevating AD risk. This study investigated whether a ketogenic diet (KD) can restore brain metabolism and gut microbiome diversity in young, asymptomatic APOE4-positive mice, while also assessing sex-based differences, given the higher AD risk in females. Comparisons were also made with APOE3 mice, which carries a neutral AD risk, to determine genotype differences. Additionally, a correlative analysis explored relationships between microbes and brain metabolites, identifying potential therapeutic and screening targets for AD risk mitigation.

METHOD: Female and male APOE3 (n =  44) and APOE4 (n =  39) transgenic mice were randomly assigned to a control diet (5.1% fat) or a KD (75.1% fat). Mice ate ad libitum for 16 weeks, starting at 12 weeks of age. Brain tissue was collected for untargeted metabolomics (UPLC-MS/MS via Metabolon Inc.), and fecal samples were collected for 16s rRNA shotgun metagenomic sequencing (CosmosID). Gut microbiome species richness and evenness were measured using Shannon index (α-diversity). Bray-Curtis dissimilarity (β-diversity) measured intra-subject dissimilarity for pre- and post-diet gut microbiome composition, and Spearman's correlation heatmaps linked metabolites and microbes to correlations within amino acid, energy, and lipid metabolic pathways.

RESULT: The KD restored brain metabolism in APOE4 females by recovering levels of metabolites associated with mitochondrial function (Figure 1A) and glutamate metabolism (Figure 1B), while exerting variable effects on these metabolites in APOE3 mice and APOE4 males. The KD increased species' richness and evenness in APOE4 females (Figure 2A) and balanced microbiome composition in APOE4 mice, as indicated by limited changes pre- and post-dietary intervention (Figure 2B). Correlation analyses revealed that Bacteroides intestinalis, Clostridium sp. ASF502, Lachnospiraceae bacterium A4, Lactobacillus johnsonii, Lactobacillus reuteri had significant associations with metabolites involved in amino acids and energy (Figure 3A) and lipid (Figure 3B) pathways.

CONCLUSION: The KD effectively restored brain metabolism and gut microbiome diversity in APOE4 female mice. These effects were absent in APOE3 mice and APOE4 males. Correlations between microbes and metabolites provide potential targets for AD interventions and risk assessment.},
}

Animals
*Gastrointestinal Microbiome
Female
Mice, Transgenic
Male
Apolipoprotein E4/genetics
*Brain/metabolism
Mice
*Diet, Ketogenic
*Alzheimer Disease/genetics/metabolism
Apolipoprotein E3/genetics
Metabolomics
Disease Models, Animal

@article {pmid41442536,
year = {2025},
author = {Kazen, AB and Umfleet, LG and Aboulalazm, FA and Cohen, AD and Terhune, S and Mason, L and Obarski, S and Franczak, M and Kindel, T and Wang, Y and Kirby, J},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e097652},
doi = {10.1002/alz70856_097652},
pmid = {41442536},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; *Cognitive Dysfunction/microbiology/physiopathology ; *Gastrointestinal Microbiome/physiology ; Aged ; Biomarkers ; Magnetic Resonance Imaging ; Neuropsychological Tests/statistics & numerical data ; Feces/microbiology ; *Dysbiosis/microbiology ; *Cerebrovascular Circulation/physiology ; Middle Aged ; Cognition ; },
abstract = {BACKGROUND: Gut dysbiosis and cerebrovascular disease have both been implicated in Alzheimer's disease (AD) progression and pathophysiology. However, the interplay between them is unclear. The goal of this study was to identify relationships between gut microbiota (GMB), cerebrovascular functioning, and cognition in patients diagnosed with amnestic mild cognitive impairment (aMCI) compared to cognitively unimpaired older adult controls.

METHODS: Participants (N = 14 aMCI and 10 controls) provided fecal samples for 16S and shotgun metagenomics GMB sequencing, underwent an MRI, and completed neuropsychological tests. For MRI, cerebral vascular reactivity (CVR), cerebral blood flow (CBF) and arterial transit time (ATT) were assessed. Spearman rho correlational analysis was used to evaluate relationships between discriminatory microbial taxa, cerebrovascular metrics, and cognition.

RESULTS: Sequencing revealed differentially abundant bacterial and viral taxa distinguishing aMCI from controls. Spearman correlations revealed that bacteria known to induce inflammation were negatively associated with cognition and cerebrovascular function, whereas bacteria associated with a healthy gut microbiome had positive associations with cognitive and cerebrovascular function. For example, Alistipes indistinctus, which depletes intestinal urate levels was enriched in aMCI and had significant negative correlations with Trail Making Test-B (TMT-B; rs=-.587) and category fluency (CF) scores (rs=-.422), CVR (rs=-.437), and CBF (rs=-.546). Bilophila wadsworthia was negatively associated (trend-level) with CVR and CBF, and significantly correlated with TMT-B (rs = -.499) and category fluency (rs = -.503). The bile acid modifying bacterium, Turicibacter sp., had a significant positive correlation with CBF (rs=.423). Finally, we found that several bacteriophages had significant correlations with cognitive and cerebrovascular measures, such as a B. wadsworthia phage that was enriched in aMCI and had significant negative correlations with TMT-B (rs=-.491), delayed recall (rs=-.589), and CVR (rs=-.474). Further, this phage contained an acyl-coA synthetase capable of influencing central metabolism.

CONCLUSIONS: Consistent with previous research, we found that persons with aMCI have an altered gut microbiome relative to controls. Further, we demonstrate through metagenomics sequencing that both bacterial and viral taxa are associated with cognitive and neurovascular functioning in aMCI. Knowledge about the relationships between the microbiota, cognition, and cerebrovascular function paves the way for future studies cross-sectional and longitudinal studies.},
}

Humans
Male
Female
*Cognitive Dysfunction/microbiology/physiopathology
*Gastrointestinal Microbiome/physiology
Aged
Biomarkers
Magnetic Resonance Imaging
Neuropsychological Tests/statistics & numerical data
Feces/microbiology
*Dysbiosis/microbiology
*Cerebrovascular Circulation/physiology
Middle Aged
Cognition

@article {pmid41441924,
year = {2025},
author = {Dias, V and Vaigankar, D and Gaonkar, SK and Thakur, NL},
title = {Mudflat halophilic microbiome: research progress in biotechnology and eco-environmental sustainability.},
journal = {World journal of microbiology & biotechnology},
volume = {42},
number = {1},
pages = {3},
pmid = {41441924},
issn = {1573-0972},
}

@article {pmid41441899,
year = {2025},
author = {Lee, JT and Ngoi, S and Deng, B and Hill, M and He, K and Yang, Y and Liu, B},
title = {Commensal bacteria antigen-mediated immune response enhances anti-tumor immunity.},
journal = {Cancer immunology, immunotherapy : CII},
volume = {75},
number = {1},
pages = {28},
pmid = {41441899},
issn = {1432-0851},
support = {AI125859//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Animals ; Mice ; Mice, Inbred C57BL ; *Melanoma, Experimental/immunology/therapy/pathology ; Tumor Microenvironment/immunology ; *Antigens, Bacterial/immunology ; *Lung Neoplasms/immunology/secondary ; Cell Line, Tumor ; Immunotherapy/methods ; Female ; Gastrointestinal Microbiome/immunology ; Th17 Cells/immunology ; Humans ; },
abstract = {Immunotherapy has transformed cancer treatments, but the majority of cancer patients would inevitably develop resistance to immunotherapy. Th17 cells play complex but crucial roles in anti-cancer immune response, although their therapeutic potential remains underutilized. Segmented filamentous bacteria (SFB) function as prototypical commensal bacteria that can induce intestinal Th17 cells and impact host immune response. In this study, we investigated how SFB antigen-mediated immune responses modify the tumor microenvironment and enhance anti-tumor efficacy through a coordinated gut-lung immunological axis. We engineered B16F1 melanoma cells to express either the SFB3340 epitope (B16-3340, an I-A[b]-restricted epitope derived from SFBNYU_003340 and recognized by 7B8 TCR) or a control vector (B16-MEM) to evaluate SFB antigen effects on tumor immunogenicity. We found that expression of the SFB epitope in cancer cells decreased the number of lung tumor nodules, and SFB colonization further reduced tumor growth in a lung metastasis model. In addition, Th1, Th17, and CD8[+] Tc1 cells were all increased in the lungs of the B16-3340 tumor-bearing mice compared with B16-MEM control tumor-bearing mice without triggering a compensatory expansion of immunosuppressive Tregs. Interestingly, SFB triggers systemic metabolic changes and an increase metabolites from aromatic amino acid degradation pathways, providing biochemical evidence for a functional gut-lung conduit, which integrates innate microbial detection with adaptive tumor-specific immunity. Our research provides evidence to further investigate and develop novel cancer immunotherapies that utilize microbial antigens and microbiome modifications to improve patient outcomes.},
}

Animals
Mice
Mice, Inbred C57BL
*Melanoma, Experimental/immunology/therapy/pathology
Tumor Microenvironment/immunology
*Antigens, Bacterial/immunology
*Lung Neoplasms/immunology/secondary
Cell Line, Tumor
Immunotherapy/methods
Female
Gastrointestinal Microbiome/immunology
Th17 Cells/immunology
Humans

@article {pmid41441714,
year = {2025},
author = {Seong, H and Yoon, JG and Nham, E and Choi, YJ and Noh, JY and Cheong, HJ and Kim, WJ and Lim, S and Song, JY},
title = {Vaccine Platform-Dependent Differential Impact on Microbiome Diversity: Potential Advantages of Protein Subunit Vaccines.},
journal = {Vaccines},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/vaccines13121248},
pmid = {41441714},
issn = {2076-393X},
support = {Q2208691//Joon Young Song/ ; Q2208671//Sooyeon Lim/ ; Q2208341//Hye Seong/ ; },
abstract = {Background: The COVID-19 pandemic accelerated the development of diverse vaccine platforms, including mRNA, adenoviral vector, and protein subunit vaccines. Given the growing evidence that the gut microbiome modulates vaccine-induced immunity, this study compared the effects of a protein subunit vaccine (NVX-CoV2373), an mRNA vaccine (BNT162b2), and an adenoviral vector vaccine (ChAdOx1) on gut microbiome diversity following booster vaccination. Methods: We conducted a prospective cohort study involving 35 healthy adults who received an NVX-CoV2373 booster. Stool and blood samples were collected before vaccination and three weeks afterward. Gut microbiome profiles were analyzed using 16S rRNA gene sequencing, and the results were compared with our previous cohorts who received BNT162b2 or ChAdOx1 vaccines. Results: The NVX-CoV2373 booster was associated with a significant increase in the Shannon diversity index (p = 0.027), indicating enhanced alpha diversity. This finding contrasts with the decrease or absence of significant short-term change observed following repeated administrations of adenoviral vector and mRNA vaccines, respectively. Notably, NVX-CoV2373 vaccination was accompanied by an increased relative abundance of beneficial taxa such as Bacteroides fragilis and a decrease in Prevotella bivia. In comparison, repeated ChAdOx1 doses resulted in a sustained reduction in alpha diversity, whereas BNT162b2 showed a transient post-booster rise followed by a long-term decline in species richness. Conclusions: In the booster setting, the protein subunit vaccine NVX-CoV2373 exerted a distinct and favorable effect on gut microbiome diversity, increasing alpha diversity in contrast to the patterns observed with mRNA and adenoviral vector booster vaccines.},
}

@article {pmid41441257,
year = {2025},
author = {Sutton, SC and Hills, RD},
title = {Role of Nanoplastics in Decreasing the Intestinal Microbiome Ratio: A Review of the Scope of Polystyrene.},
journal = {Toxics},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/toxics13121036},
pmid = {41441257},
issn = {2305-6304},
abstract = {Micro- and nanoplastics (MNPs) are increasingly recognized as emerging intestinal toxicants. This scoping review maps and integrates evidence from 56 studies (47 primary and 11 review articles, 2000-mid-2025) on how nanoplastics, particularly ≤100 nm polystyrene, disrupt gut homeostasis. The evidence consistently supports a three-stage mechanistic cascade: 1. Oxidative-stress initiation-Nanoplastics generate reactive oxygen species (ROS) and suppress antioxidant defenses, producing redox imbalance in intestinal tissue and commensal bacteria. 2. Barrier dysfunction-Resulting oxidative injury reduces tight-junction proteins, depletes mucus-secreting goblet cells, and activates inflammatory signaling (NF-κB, TLR4). 3. Microbiome reconfiguration-The altered intestinal microenvironment favors Gram-negative expansion and depletion of Gram-positive commensals, observed as decreases in the Firmicutes/Bacteroidetes (F/B) and Gram+/Gram- ratios. High-dose nanoplastic exposures reproducibly induced these effects in mice and zebrafish, whereas environmentally realistic, low-dose PET fragments produced minimal dysbiosis. Functionally important taxa-short-chain-fatty-acid producers (Faecalibacterium, Roseburia) and mucin degraders (Akkermansia muciniphila)-were consistently reduced, linking microbial shifts to epithelial injury and inflammatory tone. Together, these findings define an oxidative-barrier-microbiome axis as the dominant pathway of nanoplastic-induced intestinal disruption. Future work should emphasize environmentally relevant exposures, multi-omics functional endpoints, and mechanistic models that integrate oxidative stress, epithelial pathology, and microbiome ecology to guide realistic human-health risk assessment.},
}

@article {pmid41441238,
year = {2025},
author = {Qin, J and Jiang, S and Zhang, Z and Wang, J and Li, Y and Li, Y and Zhang, H and Li, C and Ma, H and Wang, J},
title = {Involvement of the Gut-Lung Axis in LMW-PAHs-Induced Pulmonary Inflammation.},
journal = {Toxics},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/toxics13121017},
pmid = {41441238},
issn = {2305-6304},
support = {81828011//National Natural Science Foundation of China/ ; 72064002//National Natural Science Foundation of China/ ; 25JRRA1273//Gansu Joint Reasearch Fund/ ; lzuyxcx-2022-122//Medical Innovation and Deveopment Project of Lanzhou University/ ; lzujbky-2024-14//Fundamental Research Funds for the Central Universities/ ; lzujbky-2024-it21//Fundamental Research Funds for the Central Universities/ ; },
abstract = {Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants recognized for their toxicological significance. Increasing evidence suggests that chronic exposure to low-molecular-weight PAHs (LMW-PAHs) contributes to heightened disease vulnerability and immune dysregulation, particularly among rural female populations. Recent studies have further linked a significant association between PAH exposure and gut microbiome (GM) modifications. Considering the common embryonic origin of the intestinal and respiratory systems, cross-organ communication under conditions of PAH exposure warrants deeper exploration. Although current gut-lung axis research largely emphasizes microbial metabolites such as short-chain fatty acids and bile acids, the contribution of arachidonic acid (AA) metabolites in LMW-PAH-induced pulmonary inflammation via this axis remains poorly defined. To address this knowledge gap, we developed an animal model employing integrated 16S rRNA sequencing and metabolomics approaches to systematically examine phenanthrene (Phe) and fluorene (Flu) induced GM compositional shifts and associated metabolic reprogramming. Through comprehensive profiling, we identified candidate microorganisms and metabolites potentially involved in dysbiosis-mediated pulmonary inflammation, thereby elucidating the mechanistic basis of Phe and Flu-associated health risks.},
}

@article {pmid41441197,
year = {2025},
author = {Logan, AC and Berryessa, CM and Greeson, JM and Mishra, P and Prescott, SL},
title = {The Metabolic Mind: Revisiting Glucose Metabolism and Justice Involvement in Neurolaw.},
journal = {NeuroSci},
volume = {6},
number = {4},
pages = {},
doi = {10.3390/neurosci6040120},
pmid = {41441197},
issn = {2673-4087},
abstract = {Neuropsychiatric interest in the relationship between glucose metabolism and criminal behavior dates back nearly a century. In particular, hypoglycemia was thought to play a causative role in some criminal acts, especially non-planned incidents involving impulsivity and in-the-moment risk-taking or aggression. While interest in carbohydrate metabolism in forensic populations faded in the 1990s, recent years have witnessed a renewed interest in metabolic dysfunction, mental health, and cognition. This area of research has grown increasingly robust, bolstered by mechanistic discoveries, epidemiological work, and intervention trials. Advances in microbiome (legalome) sciences, aided by omics technologies, have allowed researchers to match objective markers (i.e., from genomics, epigenomics, transcriptomics, and metabolomics) with facets of cognition and behavior, including aggression. These advances, especially the concentrated integration of microbiome and omics, have permitted novel approaches to the subject of glucose metabolism, and cast new light on older studies related to justice involvement. With current technologies and contemporary knowledge, there are numerous opportunities for revisiting the subject of glucose metabolism in the context of neurolaw. Here in this viewpoint article, we reflect on the historical research and emergent findings, providing ideation for future directions.},
}

@article {pmid41441091,
year = {2025},
author = {Hu, J and Bao, G and Hu, W and Wu, J and Du, J and Zhou, H and Zhao, Y and Xing, N and Liu, W and Fu, Z},
title = {Molecular Trojan Effect of Microplastic Diethyl Phthalate Drives Multiscale Stress Vortex through Interfacial Engineering in Cold Agroecosystems during Freeze-Thaw Cycles.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.5c16751},
pmid = {41441091},
issn = {1936-086X},
abstract = {Global climate change exacerbates the synergistic effects of freeze-thaw (FT) cycles and emerging pollutants in cold-region ecosystems. To elucidate their multidimensional stress mechanisms, this study integrated a "seed-to-seed" full-life-cycle soil cultivation experiment (120 days), physio-ecological assays, molecular dynamics (MD) simulations, and multiomics technologies to systematically analyze the cascading damage mechanisms in rye induced by the combined stress of FT, microplastics (MPs), and diethyl phthalate (DEP). Long-term experiments demonstrated that MPs + DEP copollution led to approximately 27.5% reduction in spike length, over 36% decrease in 1000-grain weight, and an 18-23 d delay in flowering time; these indicators worsened further with the superposition of FT, indicating significant inhibition of reproductive growth. At the physiological mechanism level, DEP competitively inhibited ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activity, impeding carbon assimilation; MPs induced thylakoid membrane lipid peroxidation, disrupting the electron transport chain; and FT exacerbated chloroplast ultrastructural damage, collectively causing a 41.1% decrease in the photosynthetic rate (Pn), a 65.8% reduction in stomatal conductance (Gs), and a 140% increase in the malondialdehyde (MDA) content. MD simulations revealed that FT enhanced the binding stability of nonspecific lipid-transfer protein (nsLTP) with DEP, promoting the upward translocation of pollutants, with the highest DEP residue in grains reaching 0.306 ± 0.038 mg/kg, posing a potential food safety risk. Metabolomic analysis indicated that MPs activated genes promoting cell wall fibrosis defense, whereas DEP inhibited lipoxygenase, leading to lipid accumulation, with Mg[2+] loss and S accumulation exacerbating the oxidative damage cascade. The endophytic microbiome facilitated cooperative pollutant degradation via the Pseudomonas acidovorax module, achieving partial ecological compensation. This study reveals a "stress compensation-metabolic imbalance-oxidative damage" vicious cycle mechanism, which advances our understanding of composite pollution risks in high-latitude farmland and the synergistic effects of climate change and pollutants.},
}

@article {pmid41441029,
year = {2025},
author = {Carbonell-Garzón, E and Ibanco-Cañete, R and Sanchez-Jerez, P and Egea, FCM},
title = {Osmolytes vs. Anabolic Reserves: Contrasting Gonadal Metabolomes in Two Sympatric Mediterranean Sea Urchins.},
journal = {Metabolites},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/metabo15120787},
pmid = {41441029},
issn = {2218-1989},
support = {GASTERRA 2024//CONVOCATORIA DEL PROGRAMA PROPIO DEL CENTRO DE GASTRONOMÍA DEL MEDITERRÁNEO (Gasterra 2023-24) UA_DENIA PARA EL FOMENTO DE LA I+D+i EN El ÁMBITO DE LA GASTRONOMÍA (GASTERRA 2024)/ ; },
abstract = {Background an Objectives: The Mediterranean sea urchins Paracentrotus lividus and Arbacia lixula co-occur on shallow rocky reefs but display contrasting ecological and physiological traits. We compared their gonadal metabolomes to identify species-specific metabolic strategies. Methods: High-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy to intact gonadal tissues, combining multivariate chemometric modelling with targeted integration, boxplot-based univariate analysis and pathway analysis. Results:A. lixula showed an osmolyte- and redox-oriented phenotype with elevated betaine, taurine, sarcosine, trimethylamine (TMA), trimethylamine N-oxide (TMAO), carnitine, creatine, malonate, methylmalonate, uridine and xanthine. In contrast, P. lividus exhibited an amino-acid-enriched anabolic profile dominated by lysine, glycine and glutamine, together with higher levels of formaldehyde, methanol and 3-carboxypropyl-trimethylammonium. Pathway analysis indicated that A. lixula metabolites mapped onto glycine/serine-threonine metabolism and the folate-linked one-carbon pool, whereas P. lividus metabolites were enriched in glyoxylate/dicarboxylate, nitrogen and amino-acid pathways. These contrasting osmolyte-C1 versus nitrogen-amino-acid strategies are compatible with species-specific host-microbiota metabolic interactions inferred from published microbiome data. Conclusions: Overall, our results support a framework in which A. lixula adopts a resilience-oriented osmolyte strategy and P. lividus an efficiency-oriented anabolic strategy, highlighting HR-MAS NMR metabolomics as a powerful approach to investigate adaptive biochemical diversity in marine invertebrates.},
}

@article {pmid41441026,
year = {2025},
author = {Godsey, TJ and Eden, T and Emerson, SR},
title = {Ultra-Processed Foods and Metabolic Dysfunction: A Narrative Review of Dietary Processing, Behavioral Drivers and Chronic Disease Risk.},
journal = {Metabolites},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/metabo15120784},
pmid = {41441026},
issn = {2218-1989},
abstract = {Background/Objectives: Ultra-processed foods (UPFs) have become a dominant component of the modern diet, paralleling the rise in obesity and chronic disease prevalence worldwide. This narrative review aims to synthesize evidence on how dietary processing and UPF consumption interacts with dietary quality, energy balance, and biological pathways to influence metabolic health. Methods: We performed a targeted literature search of peer-reviewed articles and authoritative reports examining UPF definition (via the NOVA classification), global consumption patterns, behavioral drivers of overconsumption, nutrient composition, and mechanistic links to metabolic dysfunction. Emphasis was placed on recent human and animal research relating UPFs to obesity, cardiometabolic outcomes, inflammation and gut microbiome alterations. Results: High UPF intake is consistently associated with reduced diet quality (higher saturated fat, sugar, sodium; lower fiber and micronutrients), increased energy density, faster eating rates and activation of reward pathways. These factors facilitate excessive energy intake and adiposity, promoting metabolic dysregulation, chronic low-grade inflammation, hormonal disturbances and gut microbiome shifts. While cross-sectional and cohort evidence is extensive, causal intervention trials and mechanistic human work remain limited. Conclusions: The accumulated evidence suggests that UPFs may influence chronic disease risk through their unbalanced nutrient profiles and through additional effects introduced by industrial processing. To translate these insights into public health strategies, future work should prioritize real-world intervention studies to reduce UPF consumption and examine resulting effects on energy balance, inflammation and gut health.},
}

@article {pmid41441004,
year = {2025},
author = {Alabi, JO and Kholif, AE and Ike, KA and Okedoyin, DO and Adelusi, OO and Wuaku, M and Anotaenwere, CC and Enikuomehin, JM and Oderinwale, OA and Adebayo, JO and Gentry-Apple, AR and Anele, UY},
title = {Rumen Fluid Metabolomics and Microbiome Profiling of Dairy Cows Fed Combinations of Prebiotics, Essential Oil Blend, and Onion Peel Using the RUSITEC System.},
journal = {Metabolites},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/metabo15120762},
pmid = {41441004},
issn = {2218-1989},
support = {NC.X338-5-21-120-1//United States Department of Agriculture/ ; },
abstract = {BACKGROUND AND OBJECTIVES: Dairy products provide vital energy, high-quality protein, and micronutrients for over six billion people worldwide, with dairy cows contributing nearly 81% of global milk production. Sustainable strategies to enhance productivity are therefore critical. Feed additives such as essential oil blends (EOB), onion peel (OPE), and prebiotics including mannan oligosaccharides (MOS) and galacto-oligosaccharides (GOS) have been proposed to improve rumen fermentation, modulate microbial ecology, and mitigate greenhouse gas emissions. This study evaluated the combined effects of EOB, OPE, MOS, and GOS on rumen metabolism using the rumen simulation technique (RUSITEC).

MATERIALS AND METHODS: Rumen inoculum from three cannulated Holstein Friesian cows was incubated across 16 vessels (four treatments × four replicates) for nine days. Treatments included a control (CON; TMR only), GEO (TMR + GOS + EOB + OPE), MEO (TMR + MOS + EOB + OPE), and OLEO (TMR + a 1:1 mixture of GOS and MOS + EOB + OPE). Additives were included at 3 µL/g TMR for EOB and 30 mg/g TMR (3% w/w) for OPE, GOS, MOS, or OLG. Rumen effluents were collected for untargeted metabolomic profiling by liquid chromatography-mass spectrometry, identifying 661 metabolites.

RESULTS: Partial least squares-discriminant analysis revealed clear separation between CON and additive groups, confirming distinct metabolic shifts. GEO primarily enhanced tryptophan, tyrosine, and purine metabolism; MEO stimulated phosphonate and pyrimidine pathways and bile acid biosynthesis; OLEO promoted phosphonate, nicotinamide, and taurine metabolism. Microbial analysis showed enrichment of taxa such as Lachnospira, Succinivibrionaceae, Macellibacteroides, Lysinibacillus, and Christensenellaceae, indicating complementary effects on fermentation and microbial stability.

CONCLUSIONS: These results demonstrate that dietary supplementation with GEO, MEO, or OLEO modulates rumen metabolism and microbial ecology without impairing fermentation, supporting improved nutrient utilization, antioxidant defenses, and metabolic resilience in dairy cows, with potential benefits for productivity and sustainability.},
}

@article {pmid41440958,
year = {2025},
author = {Rahmani, AR and Madani, SA and Aminov, E and Gogokhia, L and Bench, T and Kalogeropoulos, A},
title = {Heart Failure and Cognitive Impairment Through the Lens of the Gut Microbiome: A Narrative Review.},
journal = {Journal of personalized medicine},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/jpm15120595},
pmid = {41440958},
issn = {2075-4426},
abstract = {Heart failure (HF) affects over 55 million individuals globally, with prevalence projected to exceed 11 million in the United States by 2050 and is increasingly recognized as a systemic disorder extending beyond hemodynamic dysfunction to encompass profound alterations in neural and gut physiology. Cognitive impairment affects nearly half of HF patients and represents a major determinant of morbidity, self-care capacity, and mortality. Recent advances suggest that the gut microbiome serves as a pivotal intermediary in the heart-brain crosstalk, influencing neurocognitive outcomes through inflammatory, metabolic, and neurohumoral pathways. Dysbiosis in HF disrupts intestinal barrier integrity, facilitating translocation of endotoxins and microbial metabolites such as trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acids, which in turn modulate neuroinflammation, cerebral perfusion, and neuronal signaling. The gut-heart-brain axis provides an integrative framework linking HF and cognitive impairment pathophysiology through dysbiosis-driven systemic inflammation and metabolite dysregulation. Gut-derived biomarkers and microbiome-targeted interventions represent promising strategies for detection of early alterations and precision treatment, highlighting the urge for prospective, multi-omics studies to establish causality and therapeutic efficacy. This review synthesizes current evidence connecting gut microbiome dysbiosis and metabolite alterations to both HF and cognitive impairment pathophysiology and proposes translational strategies for integrating microbiome-targeted therapies in HF patients with cognitive dysfunction.},
}

@article {pmid41440831,
year = {2025},
author = {Kuehn, JF and Zhang, Q and Heston, MB and Kang, JW and Harding, S and Davenport-Sis, NJ and Kerby, RL and Schiffmann, EC and Wheeler, JL and Clements, E and Shankar, S and Mickol, A and Zemberi, J and Chow, H and Zhang, E and Harpt, J and Mushtaque, A and Yoo, M and Cook, A and Carlsson, CM and Johnson, SC and Asthana, S and Zetterberg, H and Blennow, K and Ulland, TK and Bendlin, BB and Rey, FE},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e098071},
doi = {10.1002/alz70856_098071},
pmid = {41440831},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers/cerebrospinal fluid ; Male ; *Alzheimer Disease/metabolism/diagnosis ; Female ; *Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome ; Feces/chemistry/microbiology ; Aged ; Middle Aged ; Cohort Studies ; Metagenome ; },
abstract = {BACKGROUND: Short-chain fatty acids (SCFA), including acetate, propionate, and butyrate, are abundant gut bacterial metabolites produced via the fermentation of dietary fibers and resistant starch. Several lines of evidence, particularly in preclinical mouse models, suggest a protective role of SCFA against Alzheimer's Disease (AD) pathology. In one study, supplementation of mice with tributyrin, a butyrate prodrug, significantly attenuated AD pathology. However, the relationships between SCFA, the bacterial taxa that produce them, and AD biomarkers require further elucidation in humans.

METHOD: We assessed gut metagenomes and SCFA levels in fecal samples from 213 cognitively unimpaired Microbiome Alzheimer's Risk Study (MARS) participants (Table 1). The cohort was co-enrolled in the Wisconsin Alzheimer's Disease Research Center and Wisconsin Registry for Alzheimer's Prevention, which track preclinical disease progression in middle-aged and older adults at risk for AD. We sequenced DNA extracted from 213 fecal samples (one sample per participant, 30 million reads per sample), created metagenome-assembled genomes (MAGs), and annotated their functions. We measured levels of the major SCFA in fecal samples using headspace gas chromatography. We performed multiple linear regressions between levels of cerebrospinal fluid (CSF) AD biomarkers and each SCFA or MAG, controlling for age, sex, body mass index, and APOE genotype.

RESULT: We found an inverse association between amyloid positive status (CSF Aꞵ42/Aꞵ40 <0.046) and MAGs encoding propionate or butyrate production pathways. Fecal acetate, propionate, and butyrate levels were reduced in females and in participants with amyloid-positive status. Mediation analysis detected a trend indicating that butyrate may mediate the inverse relationship between MAGs with butyrate production pathways and amyloid positive status.

CONCLUSION: Relative abundances of MAGs encoding enzymes for propionate and butyrate production were reduced in amyloid-positive participants in a cognitively unimpaired human cohort enriched for AD risk. These results, combined with the extensive literature in preclinical AD mouse models, suggest that SCFA may play a causal role in AD progression.},
}

Humans
*Biomarkers/cerebrospinal fluid
Male
*Alzheimer Disease/metabolism/diagnosis
Female
*Fatty Acids, Volatile/metabolism
*Gastrointestinal Microbiome
Feces/chemistry/microbiology
Aged
Middle Aged
Cohort Studies
Metagenome

@article {pmid41440729,
year = {2025},
author = {Hirji, I and John, D and Jith, J and Khoshnaw, H and Ganeshananthan, M},
title = {Challenges and Strategies in Managing Recurrent Clostridioides difficile Infection in Older Adults.},
journal = {Geriatrics (Basel, Switzerland)},
volume = {10},
number = {6},
pages = {},
doi = {10.3390/geriatrics10060158},
pmid = {41440729},
issn = {2308-3417},
abstract = {BACKGROUND: Clostridioides difficile infections (CDIs) are caused by a Gram-positive, spore-forming bacillus and are defined by more than three episodes of watery diarrhoea per day. CDI is a major cause of morbidity and mortality in older adults, particularly over 65 years. Recurrent CDI leads to higher mortality and prolonged, debilitating illness.

CASE PRESENTATIONS: This article presents two patients, aged over 80 years old, who developed recurrent CDI causing complicated and prolonged treatment courses. Patient 1 required an extended course of antibiotics for treatment of discitis and a congruent psoas abscess. Patient 2 developed CDI after multiple short courses of antibiotics for urinary tract infections (UTIs) in the context of multiple comorbidities. Both patients experienced three distinct episodes of CDI and were treated in collaboration with microbiology specialists. Following the third episode, both were successfully treated with oral capsule faecal microbiome transplants (FMTs). Their cases highlight the challenge of balancing systemic antibiotic use against CDI risk.

DISCUSSIONS: These cases underscore known risk factors for recurrent CDI, including advanced age and prolonged antibiotic exposure. Recurrence rates in patients over 65 can reach 58%. The British Society of Gastroenterology and Healthcare Infection Society support the use of FMTs in recurrent cases. Environmental decontamination, including terminal cleaning with sporicidal agents, is critical in reducing reinfection in hospital settings.

CONCLUSIONS: Recurrent CDI in elderly patients reflects a complex interplay between infection control and managing comorbidities. New guidelines suggest that FMTs can significantly reduce morbidity and mortality. These cases emphasise the need for individualised, multidisciplinary care, adherence to guidelines, and further research to improve safe, effective CDI management in older adults.},
}

@article {pmid41440663,
year = {2025},
author = {Gong, W and Chen, M and Lai, Y and Yang, D and Soares, MA and Gond, SK and Li, H},
title = {Deciphering the Role of Reshaped Fungal Microbiome in Cadmium Accumulation in Rice Grains.},
journal = {Journal of fungi (Basel, Switzerland)},
volume = {11},
number = {12},
pages = {},
doi = {10.3390/jof11120837},
pmid = {41440663},
issn = {2309-608X},
support = {202403AP140035//Yunnan International Joint Laboratory of Research and Development of Crop Safety Produc-tion on Heavy Metal Pollution Areas/ ; 202501AS070148//Yunnan Fundamental Research Projects/ ; 42267059//Natural Science Foundation of China/ ; KUST-AN2023006Y//Medical Joint Special Project of Kunming University of Science and Technology-The First People's Hospital of Anning/ ; },
abstract = {Rice cadmium (Cd) contamination is a serious threat to global food security and human health. Plant-associated microbiomes are known to affect Cd accumulation in plants. However, the response of the rice microbiome to Cd contamination and its role in modulating grain Cd accumulation remain poorly understood. In the present study, the responses of the rhizospheric fungi (RF) community and seed endophytic fungi (SEF) community to the soil physiochemical properties of rice from moderately (MC) and severely (SC1 and SC2) Cd-contaminated paddies were investigated. Moreover, the effects of soil physiochemical properties, RF community and SEF community on grain Cd accumulation were analyzed through correlation analysis. The results showed that the Cd concentration in rice grains from SC2 exceeded the food safety standard of China and was higher than that of SC1 and MC. The Cd concentration in rice grains was positively correlated with the soil-available Cd concentration, while being negatively correlated with the available nutrient elements and pH value of soil. In addition, it was found that the diversity of RF increased with the soil-available Cd concentration, while the diversity and richness of SEF decreased with the soil-available Cd concentration. Moreover, the RF community was influenced by soil physiochemical properties. The Spearman correlation analysis showed that the soil-available Cd was positively correlated with RF Sebacina, Clonostachys, Acremonium, Talaromyces and Fusarium, and most of them were related to grain Cd concentration, while unclassified SEF Pleosporales and Xylariales were associated with grain Cd concentration. These results suggested that Cd stress triggered a niche-specific response of the rice fungal microbiome. The fungi related to soil Cd availability and rice grain Cd accumulation may have a great potential application in food safety production in Cd-contaminated soil.},
}

@article {pmid41440534,
year = {2025},
author = {Orjichukwu, CK and Orjichukwu, RO and Akpunonu, PK and Ugwu, PC and Nnabuife, SG},
title = {Microbiome and Heart Failure: A Comprehensive Review of Gut Health and Microbiota-Derived Metabolites in Heart Failure Progression.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {13},
number = {4},
pages = {},
doi = {10.3390/medsci13040302},
pmid = {41440534},
issn = {2076-3271},
mesh = {Humans ; *Heart Failure/microbiology/metabolism/physiopathology ; *Gastrointestinal Microbiome/physiology ; Disease Progression ; Dysbiosis/microbiology ; Probiotics ; Methylamines/metabolism ; Animals ; },
abstract = {A multifaceted clinical disease, heart failure (HF) is typified by decreased cardiac function and systemic symptoms caused by anatomical or functional abnormalities in the heart. Although traditional studies have concentrated on hemodynamic and neurohormonal processes, new data highlight the vital role that the gut microbiota and its byproducts play in the pathogenesis of HF. An imbalance in the microbial structure known as gut dysbiosis is common in HF patients and is linked to increased gut permeability, systemic inflammation, and changed bioactive metabolite synthesis. Prominent metabolites generated by the microbiota, including phenylacetylglutamine, short-chain fatty acids (SCFAs), secondary bile acids, and trimethylamine N-oxide (TMAO), have a major impact on endothelial function, cardiac remodeling, and inflammation. Together with gut-derived lipopolysaccharides, these metabolites interact with host systems to exacerbate the course of HF. Further impacting HF outcomes are comorbidities such as diabetes, obesity, and chronic renal disease, which intensify gut dysbiosis. The importance of metabolites originating from the microbiota in the progression of HF is highlighted in this review, which summarizes recent findings regarding the gut-heart axis. Additionally, it investigates how dietary changes, probiotics, prebiotics, and multi-omics techniques can all be used to improve the management of HF. This thorough analysis emphasizes the necessity of integrative therapy approaches and longitudinal research to better address the complex link between HF and the gut microbiota.},
}

Humans
*Heart Failure/microbiology/metabolism/physiopathology
*Gastrointestinal Microbiome/physiology
Disease Progression
Dysbiosis/microbiology
Probiotics
Methylamines/metabolism
Animals

@article {pmid41440484,
year = {2025},
author = {Ramos-Nino, ME},
title = {Operationalizing Chronic Inflammation: An Endotype-to-Care Framework for Precision and Equity.},
journal = {Clinics and practice},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/clinpract15120233},
pmid = {41440484},
issn = {2039-7275},
abstract = {Background/Objectives: Chronic inflammation arises from self-reinforcing immune-metabolic circuits encompassing pattern-recognition signaling, inflammasome activation, cytokine networks, immunometabolic reprogramming, barrier-microbiome disruption, cellular senescence, and neuro-immune-endocrine crosstalk. This review synthesizes these mechanistic axes across diseases and introduces an operational endotype-to-care framework designed to translate mechanistic insights into precision-based, scalable, and equitable interventions. Methods: A narrative, mechanism-focused review was performed, integrating recent literature on immune-metabolic circuits, including pattern-recognition receptors, inflammasome pathways, cytokine modules, metabolic reprogramming, barrier-microbiome dynamics, senescence, and neuro-immune-endocrine signaling. Validated, low-cost screening biomarkers (hs-CRP, NLR, fibrinogen) were mapped to phenotype-guided endotyping panels and corresponding therapeutic modules, with explicit monitoring targets. Results: We present a stepwise, pragmatic pathway progressing from broad inflammatory screening to phenotype-specific endotyping (e.g., IL-6/TNF for metaflammation; ISG/IFN for autoimmunity; IL-23/17 for neutrophilic disease; IL-1β/NLRP3 or urate for crystal-driven inflammation; permeability markers for barrier-dysbiosis). Each module is paired with targeted interventions and prespecified treat-to-target outcomes: for example, achieving a reduction in hs-CRP (e.g., ~40%) within 8-12 weeks is used here as a pragmatic operational benchmark rather than a validated clinical threshold. Where feasible, cytokine and multi-omic panels further refine classification and prognostication. A tiered implementation model (essential, expanded, comprehensive) ensures adaptability and equity across clinical resource levels. Conclusions: Distinct from prior narrative reviews, this framework defines numeric triage thresholds, minimal endotype panels, and objective monitoring criteria that make chronic inflammation management operationalizable in real-world settings. It embeds principles of precision, equity, and stewardship, supporting iterative, evidence-driven implementation across diverse healthcare environments.},
}

@article {pmid41440381,
year = {2025},
author = {Otálora-Otálora, BA and Payán-Gómez, C and López-Rivera, JJ and Patiño-Unibio, LF and Arboleda-Mojica, SL and Aristizábal-Guzmán, C and Isaza-Ruget, MA and Álvarez-Moreno, CA},
title = {The Exosome-Mediated Epigenome: Non-Coding RNA and mRNA-Coding Networks in Microbiome-Cellular Communication, Inflammation, and Tumorigenesis Along the Oral-Gut-Lung Axis.},
journal = {Epigenomes},
volume = {9},
number = {4},
pages = {},
doi = {10.3390/epigenomes9040052},
pmid = {41440381},
issn = {2075-4655},
abstract = {Background/Objectives: The oral-gut-lung axis represents a dynamic system where exosomes carrying mRNAs and non-coding RNAs might help to regulate microbiota and human cell crosstalk to establish transcriptional regulatory networks controlling cellular biological processes and signaling pathways. Methods: We conducted a comprehensive transcriptomic analysis to characterize the molecular cargo of extracellular exosomes in the context of gut and lung cancer. Results: By analyzing gut and lung exosomes cargo with our previous transcriptomic studies from tumoral and inflammatory tissues, we found that exosomes can transport key RNAs that codify specific receptors that facilitate pathogenic interaction with microorganisms and RNAs that are part of interacting gene and transcriptional regulatory networks that control the function of differentially expresses genes, all involved in biological processes like cell cycle, plasticity and growth regulation, invasion, metastasis, microenvironmental remodeling, epigenetic, and microbial and immunological modulation, during the unlocking of phenotypic plasticity for the acquisition of the hallmarks of cancer in the oral-gut-lung axis. Conclusions: Exosomal RNA regulation of transcriptional networks represents a pivotal axis in the interplay between inflammation and cancer, offering opportunities for innovative diagnostic and therapeutic approaches.},
}

@article {pmid41440353,
year = {2025},
author = {Chauca-Bajaña, L and Ordoñez Balladares, A and Lorenzo-Pouso, AI and Caicedo-Quiroz, R and Erazo Vaca, RX and Dau Villafuerte, RF and Avila-Granizo, YV and Salazar Minda, CH and Salavarria Vélez, MA and Velásquez Ron, B},
title = {Periodontitis and Oral Pathogens in Colorectal Cancer: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.},
journal = {Dentistry journal},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/dj13120595},
pmid = {41440353},
issn = {2304-6767},
abstract = {Background: Periodontitis and oral dysbiosis have been linked to systemic inflammation and carcinogenesis. Among oral pathogens, Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) are biologically plausible contributors to colorectal cancer (CRC) via inflammatory and immunomodulatory pathways. However, the magnitude and consistency of these associations remain uncertain. Objective: To evaluate whether periodontitis and key oral pathogens are associated with CRC risk and prognosis through a systematic review, meta-analysis, and trial sequential analysis (TSA). Methods: We searched PubMed, Scopus, and Web of Science from inception to December 2024 following PRISMA 2020. Eligible observational studies assessed periodontitis exposure or detection of oral bacteria in relation to CRC incidence or survival. Effect estimates (RRs/HRs) were log-transformed and pooled using random-effects models; heterogeneity was quantified with I[2]. TSA was conducted to appraise information size and the stability of the primary association. Risk of bias was evaluated with ROBINS-I/QUIPS as appropriate. PROSPERO: CRD420251168522. Results: Five studies evaluating periodontitis/oral-pathogen exposure and CRC incidence yielded a 70% higher risk (HR = 1.70; 95% CI: 1.33-2.19; I[2] = 0%). Detection of Fn was associated with approximately threefold higher risk of CRC (RR = 3.20; 95% CI: 1.76-5.82; p < 0.001). Pg presence was linked to worse overall survival (HR ≈ 2.4; p < 0.01). TSA suggested that the accrued evidence for the primary incidence association is likely sufficient to reduce random errors; nevertheless, interpretability is constrained by the small number of observational studies and between-study differences in exposure and outcome ascertainment. Conclusions: Current evidence indicates that periodontitis and oral pathogens-particularly Fn and Pg-are significantly associated with CRC development and progression. These findings support the clinical relevance of the oral-gut axis and underscore oral health as a potentially modifiable factor in cancer prevention. Further large, well-designed prospective cohorts and mechanistic studies are warranted to strengthen causal inference.},
}

@article {pmid41440348,
year = {2025},
author = {Sonets, IV and Galeeva, IS and Krivonos, DV and Pavlenko, AV and Vvedenskiy, AV and Ahmetzyanova, AA and Mikaelyan, KA and Ilina, EN and Yanushevich, OO and Revazova, ZE and Vibornaya, EI and Runova, GS and Aliamovskii, VV and Bobr, IS and Tsargasova, MO and Kalinnikova, EI and Govorun, VM},
title = {In-Depth Multi-Approach Analysis of WGS Metagenomics Data Reveals Signatures Potentially Explaining Features in Periodontitis Stage Severity.},
journal = {Dentistry journal},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/dj13120590},
pmid = {41440348},
issn = {2304-6767},
abstract = {Background: Periodontitis is a chronic inflammatory disease mostly associated with Porphyromonas gingivalis infection and characterized by progressive destruction of the supporting structures of the tooth, including the gingiva, periodontal ligament and alveolar bone. However, the impact of other members of the periodontal microbiome on stage of the severity of the periodontitis remains largely uncharacterized. Methods: This exploratory study employs whole-genome shotgun (WGS) metagenomics to characterize the periodontal microbiome in patients suffering from mild and severe periodontitis, aiming to identify microbial signatures linked to disease severity via analysis of taxonomic composition, predicted metabolic pathways and metagenome-assembled genomes (MAGs). After initial selection, 28 adult patients with a computer tomography (CT)-confirmed diagnosis of mild and severe stage of periodontitis from 2 clinics were included in the research project. Results: Taxonomic analysis confirms the presence of various commensal and pathogenic bacteria detectable at the species level, especially belonging to so-called "red, orange and green periodontal complexes"-P. gingivalis, T. forsythia, C. rectus, and Capnocytophaga spp. that may contribute to disease heterogeneity. The conducted investigation suggests that non-microbial factors such as cardiovascular diseases and antibiotic usage in the last 6 months prior to the hospital admission could explain variance of disease progression and impact on severity. Analysis of microbial functional composition revealed metabolic traits showing positive correlations with severe stage of periodontitis. Robust network analysis suggested interactions between pathogenic bacteria of the red complex and other members of the periodontal microbiome. Conclusions: These findings underscore the multifactorial nature of periodontitis pathogenesis, highlighting the need for integrated approaches combining microbial, host, and environmental data to unravel drivers of disease progression. The study provides a foundation for future large-scale investigations into personalized diagnostic or therapeutic strategies.},
}

@article {pmid41440336,
year = {2025},
author = {Burlea, ȘL and Buzea, CG and Nedeff, F and Mirilă, D and Nedeff, V and Agop, M and Ochiuz, L and Armencia, AO},
title = {Deep Learning Analysis of CBCT Images for Periodontal Disease: Phenotype-Level Concordance with Independent Transcriptomic and Microbiome Datasets.},
journal = {Dentistry journal},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/dj13120578},
pmid = {41440336},
issn = {2304-6767},
abstract = {BACKGROUND: Periodontitis is a common inflammatory disease characterized by progressive loss of alveolar bone. Cone-beam computed tomography (CBCT) can visualize 3D periodontal bone defects, but its interpretation is time-consuming and examiner-dependent. Deep learning may support standardized CBCT assessment if performance and biological relevance are adequately characterized.

METHODS: We used the publicly available MMDental dataset (403 CBCT volumes from 403 patients) to train a 3D ResNet-18 classifier for binary discrimination between periodontitis and healthy status based on volumetric CBCT scans. Volumes were split by subject into training (n = 282), validation (n = 60), and test (n = 61) sets. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and calibration metrics with 95% bootstrap confidence intervals. Grad-CAM saliency maps were used to visualize the anatomical regions driving predictions. To explore phenotype-level biological concordance, we analyzed an independent gingival transcriptomic cohort (GSE10334, n ≈ 220 arrays after quality control) and an independent oral microbiome cohort based on 16S rRNA amplicon sequencing, using unsupervised clustering, differential expression/abundance testing, and pathway-level summaries.

RESULTS: On the held-out CBCT test set, the model achieved an AUROC of 0.729 (95% CI: 0.599-0.850) and an AUPRC of 0.551 (95% CI: 0.404-0.727). At a high-sensitivity operating point (sensitivity 0.95), specificity was 0.48, yielding an overall accuracy of 0.62. Grad-CAM maps consistently highlighted the alveolar crest and furcation regions in periodontitis cases, in line with expected patterns of bone loss. In the transcriptomic cohort, inferred periodontitis samples showed up-regulation of inflammatory and osteoclast-differentiation pathways and down-regulation of extracellular-matrix and mitochondrial programs. In the microbiome cohort, disease-associated samples displayed a dysbiotic shift with enrichment of classic periodontal pathogens and depletion of health-associated commensals. These omics patterns are consistent with an inflammatory-osteolytic phenotype that conceptually aligns with the CBCT-defined disease class.

CONCLUSIONS: This study presents a proof-of-concept 3D deep learning model for CBCT-based periodontal disease classification that achieves moderate discriminative performance and anatomically plausible saliency patterns. Independent transcriptomic and microbiome analyses support phenotype-level biological concordance with the imaging-defined disease class, but do not constitute subject-level multimodal validation. Given the modest specificity, single-center imaging source, and inferred labels in the omics cohorts, our findings should be interpreted as exploratory and hypothesis-generating. Larger, multi-center CBCT datasets and prospectively collected paired imaging-omics cohorts are needed before clinical implementation can be considered.},
}

@article {pmid41440201,
year = {2025},
author = {Ye, G and Zhang, H and Feng, Q and Xiao, J and Wang, J and Liu, J},
title = {Important Role of Bacterial Metabolites in Development and Adjuvant Therapy for Hepatocellular Carcinoma.},
journal = {Current oncology (Toronto, Ont.)},
volume = {32},
number = {12},
pages = {},
doi = {10.3390/curroncol32120673},
pmid = {41440201},
issn = {1718-7729},
support = {2021ZQNZD009//Major Scientiffc Research Program for Young and Middle-aged Health Professionals of Fujian Province, China/ ; 2023Y9416//Fujian Science and Technology Innovation Joint Fund Project/ ; },
mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/microbiology/immunology/metabolism ; *Liver Neoplasms/therapy/microbiology/immunology/metabolism ; *Bacteria/metabolism ; Tumor Microenvironment/immunology ; Animals ; },
abstract = {Bacterial metabolites play a dual role in hepatocellular carcinoma (HCC), exhibiting both tumor-promoting and tumor-suppressing activities dictated by their structural diversity. This review synthesizes recent advances in understanding how key microbial metabolites-such as bile acids, short-chain fatty acids, and polyamines-remodel the tumor immune microenvironment through mechanisms including immunometabolic reprogramming, epigenetic modification, and regulation of signaling pathways (e.g., FXR, TLR, and mTOR). We highlight their roles in modulating the function of T cells, NK cells, and tumor-associated macrophages and discuss emerging strategies that target these metabolites-including probiotic interventions, fecal microbiota transplantation, and metabolite-based adjuvants-to enhance immunotherapy efficacy and overcome resistance. By integrating mechanistic insight into translational potential, this work outlines a metabolite-immunometabolism-hepatocarcinogenesis framework and proposes novel combinatorial approaches for HCC treatment.},
}

Humans
*Carcinoma, Hepatocellular/therapy/microbiology/immunology/metabolism
*Liver Neoplasms/therapy/microbiology/immunology/metabolism
*Bacteria/metabolism
Tumor Microenvironment/immunology
Animals

@article {pmid41439783,
year = {2025},
author = {de Lima, AMDL and Bastiani, M and Borelli, WV and Senger, JE and Werle, BM and Zanella, L and Netson, LV and Detogni, A and Bruscato, NM and Schumacher-Schuh, AF and Senger, J and Moriguchi, EH and Perquim, L and de Souza, IC and Barth, RA and Ebert, ELK and Guerra, RR and Barboza, JVC and Gaio, EJ and Martins, AF and da Rocha, JBT and Souza, DO and Zimmer, ER},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e106628},
doi = {10.1002/alz70855_106628},
pmid = {41439783},
issn = {1552-5279},
mesh = {Humans ; Male ; Aged ; Female ; *Alzheimer Disease/microbiology ; *Cognitive Dysfunction/microbiology ; *Gastrointestinal Microbiome ; *Saliva/microbiology ; Feces/microbiology ; Brazil ; RNA, Ribosomal, 16S/genetics ; Aged, 80 and over ; Pilot Projects ; },
abstract = {BACKGROUND: Longevity is influenced by a combination of genetic factors, lifestyle choices, and environmental conditions. These factors can alter microbiota composition, potentially influencing susceptibility to Alzheimer's disease (AD) and cognitive decline. We hypothesize that the microbiome in elderly individuals may be associated with different clinical stages of AD. This study aims to investigate the relationship between oral and gut microbiota composition in a Brazilian long-lived population and cognitive impairment within the AD continuum.

METHOD: We conducted a pilot characterization of the oral and gut microbiota of 12 elderly individuals (>65 years) recruited by the Moriguchi Institute in Veranópolis, a longevity hotspot in southern Brazil. Participants underwent clinical-cognitive assessment, including the Clinical Dementia Rating (CDR), and were classified as cognitively unimpaired (CU), mild cognitive impairment (MCI), or Alzheimer's disease (AD). Saliva and fecal samples were sequenced using Illumina MiSeq™, targeting the V3-V4 regions of the 16S rRNA gene, and processed in R using DADA2. Amplicon sequence variants (ASVs) were inferred, and taxonomic assignments were performed with SILVA. Abundance data were used for alpha and beta diversity, and relative abundance analyses.

RESULT: Alpha diversity was similar across groups, except for reduced salivary richness in MCI (Chao1, p = 0.002; Figure 1). Rarefaction curves indicated higher richness in the feces compared to saliva. PCoA analysis showed distinct group separations in feces, with MCI and AD being more similar, while saliva samples were more uniform. Relative abundance demonstrated alterations in phylum Bacillota, Bacteroidota, and Pseudomonadota in MCI and AD compared to the CU group (Figure 2). Changes were particularly evident in fecal families Lachnospiraceae, Bacteroidaceae, and Ruminococcaceae, and genus such as Bacteroides, Blautia, and Faecalibacterium. Notably, Streptococcus was almost exclusively elevated in fecal samples of the AD group. Saliva samples were more homogeneous across groups, though changes were observed in families Prevotellaceae and Streptococcaceae, and genus Prevotella, Streptococcus, Haemophilus, and Neisseria in MCI and AD compared to CU.

CONCLUSION: Fecal microbiota exhibited clinical-stage-specific changes, while salivary microbiota displayed more stability, underscoring microbial adaptations to the distinct. These findings highlight microbiome changes along the AD continuum, emphasizing the potential microbiome's role in healthy aging and resilience against neurodegeneration.},
}

Humans
Male
Aged
Female
*Alzheimer Disease/microbiology
*Cognitive Dysfunction/microbiology
*Gastrointestinal Microbiome
*Saliva/microbiology
Feces/microbiology
Brazil
RNA, Ribosomal, 16S/genetics
Aged, 80 and over
Pilot Projects

@article {pmid41439715,
year = {2025},
author = {Bae, M and Dong, X and Avila-Pacheco, J and Nguyen, QD and Inyama, F and Hill-Maini, V and Clish, CB and Balskus, EP},
title = {Distinct classes of gut bacterial molybdenum-dependent enzymes produce urolithins.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {52},
pages = {e2501312122},
doi = {10.1073/pnas.2501312122},
pmid = {41439715},
issn = {1091-6490},
support = {CHE-20380529//NSF (NSF)/ ; N/A//Biocodex Microbiota Foundation (BMF)/ ; N/A//HHMI (HHMI)/ ; N/A//Kwanjeong Educational Foundation (KEF)/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome ; *Coumarins/metabolism ; *Molybdenum/metabolism ; Inflammatory Bowel Diseases/microbiology/metabolism ; *Bacteria/enzymology/metabolism/genetics ; *Bacterial Proteins/metabolism/genetics ; Xanthine Oxidase/metabolism/genetics ; },
abstract = {Urolithin A is an anti-aging and anti-inflammatory gut bacterial metabolite derived from ellagic acid (EA), a polyphenol abundant in berries and nuts. The conversion of EA to urolithin A involves multiple chemically challenging phenol dehydroxylation steps that produce urolithins with varying bioactivities. Despite their biological and chemical significance, the bacterial enzymes responsible for urolithin production remain largely unidentified. Here, we use differential gene expression analysis, anaerobic protein production, and enzyme assays to identify members of two distinct molybdenum enzyme families (the DMSO reductase family and the xanthine oxidase family) capable of regioselective dehydroxylation and urolithin generation. These two enzyme families have distinct substrate requirements, suggesting they employ different catalytic mechanisms for phenol dehydroxylation. Multiomics analysis of a human cohort uncovers decreased levels of urolithin A and genes encoding urolithin A-producing enzymes in patients with inflammatory bowel disease (IBD), implying reduced health effects of EA consumption in this setting. Together, this study elucidates the molecular basis of urolithin production, expands the known enzymatic repertoire of the human gut microbiome, and suggests a potential link between gut bacterial urolithin production and reduced host inflammation.},
}

Humans
*Gastrointestinal Microbiome
*Coumarins/metabolism
*Molybdenum/metabolism
Inflammatory Bowel Diseases/microbiology/metabolism
*Bacteria/enzymology/metabolism/genetics
*Bacterial Proteins/metabolism/genetics
Xanthine Oxidase/metabolism/genetics

@article {pmid41439692,
year = {2025},
author = {González-García, S and Bustos-Hamdan, A and Hamdan-Partida, A and Bustos-Martínez, J},
title = {Staphylococcus aureus colonization in the pharynx and nasal cavity: why are some people more susceptible?.},
journal = {Future microbiology},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/17460913.2025.2605944},
pmid = {41439692},
issn = {1746-0921},
abstract = {Staphylococcus aureus is one of the most important pathogenic bacteria in humans. The nose and pharynx constitute two fundamental ecological niches for this bacterium, supporting the asymptomatic carrier state and acting as sources of infection in susceptible organisms. Colonization dynamics depend on the balance between the bacteria's virulence factors, the host's immune response, and the environment. Colonization is favored by attenuated immune responses, with evidence of partial tolerance and low protective antibody titers. Colonization also appears to depend on the microbiome of the colonized site. Genetic, metabolic, lifestyle, and age factors of the host may also contribute to colonization. Global prevalence rates vary widely depending on the geographic, social, and economic context. Recently, emerging strategies such as the use of phages, microbiome modulation, nanoparticles, gene editing technologies, and vaccines have been developed as promising alternatives to prevent colonization and infection by this bacterium. This review summarizes the current evidence on the factors that allow nasal and pharyngeal colonization of S. aureus, as well as therapeutic perspectives to prevent colonization by this bacterium.},
}

@article {pmid41439635,
year = {2025},
author = {Sioutas, GS and Reavey-Cantwell, J and Rivet, DJ},
title = {The gut-brain axis: a nationwide propensity score-matched analysis of gastrointestinal syndromes preceding ischemic stroke.},
journal = {Brain injury},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/02699052.2025.2604022},
pmid = {41439635},
issn = {1362-301X},
abstract = {BACKGROUND: It has been hypothesized that the gut microbiome affects ischemic stroke occurrence. However, the relationship between stroke and gastrointestinal (GI) disorders is not well understood. We aimed to determine whether GI syndromes are associated with an increased risk of ischemic stroke.

METHODS: We conducted case-control and cohort studies using the TriNetX US Collaborative Network database (2018-2022). In the case-control study, patients with ischemic stroke were compared to propensity-score-matched controls with at least 3 years of prior data. The cohort study assessed the risk of stroke in patients with specific GI syndromes over 5 years compared to matched controls.

RESULTS: For the case-control study, 551,738 patients with ischemic stroke were matched with 19,419,979 negative controls, resulting in 548,179 pairs after matching. Compared to matched negative controls, all GI syndromes, appendectomy, and GI medications were significantly associated with ischemic stroke (all p < 0.001). In the cohort study, all GI syndromes were significantly associated with ischemic stroke (all risk ratio (RR) > 1, p < 0.001), but appendectomy was not [RR 1.28, 95% Confidence Interval (CI): 0.89-1.82].

CONCLUSION: Several GI disorders were associated with an increased risk of future ischemic stroke, providing more evidence on the gut-brain axis. Further research is warranted to confirm these findings and investigate underlying mechanisms.},
}

@article {pmid41439619,
year = {2026},
author = {Haykal, D},
title = {Translating Geroscience Into Clinical Longevity Dermatology: From Mechanisms of Aging to Skin-Centered Interventions.},
journal = {Journal of cosmetic dermatology},
volume = {25},
number = {1},
pages = {e70616},
doi = {10.1111/jocd.70616},
pmid = {41439619},
issn = {1473-2165},
mesh = {Humans ; *Longevity/physiology ; *Skin Aging/physiology ; Artificial Intelligence ; *Dermatology/methods/trends ; *Geroscience/methods ; Biomarkers/metabolism ; Skin/microbiology ; Translational Research, Biomedical ; *Aging/physiology ; Microbiota ; },
abstract = {BACKGROUND: Longevity medicine is an emerging clinical framework aimed at extending healthspan by targeting the biological mechanisms of aging rather than treating disease in isolation. Geroscience, which investigates the molecular and cellular pathways linking aging to chronic pathology, provides the scientific foundation for this approach. Dermatology is uniquely positioned within this paradigm, as the skin represents both a visible marker of biological aging and an accessible source of biomarkers.

OBJECTIVE: To explore how principles of geroscience can be translated into clinical dermatology and cosmetic practice, with a focus on skin-centered biomarkers, artificial intelligence (AI), and preventive longevity-oriented interventions.

METHODS: This piece integrates current evidence from geroscience, dermatologic aging research, microbiome science, and AI-driven analytics to examine emerging models of longevity-focused dermatologic care. Conceptual frameworks, clinical readiness of interventions, and ethical considerations are critically discussed.

RESULTS: Advances in biological aging biomarkers, including epigenetic clocks, inflammatory signatures, mitochondrial and metabolic markers, and skin microbiome profiling, offer promising tools for assessing cutaneous and systemic aging. AI-enabled platforms facilitate the integration of multidimensional data, enabling refined biological age assessment and potential prediction of treatment responses. However, most longevity-oriented diagnostics and interventions remain in early or experimental stages, requiring rigorous validation before routine clinical adoption.

CONCLUSION: Dermatology can serve as a translational bridge between geroscience and clinical longevity medicine by integrating validated skin biomarkers, aesthetic procedures, and preventive strategies within an evidence-based framework. Careful attention to scientific limitations, ethical considerations, and health equity is essential to ensure responsible implementation. Dermatologists would play a key role in shaping clinically sound, prevention-focused longevity care centered on long-term skin health and resilience.},
}

Humans
*Longevity/physiology
*Skin Aging/physiology
Artificial Intelligence
*Dermatology/methods/trends
*Geroscience/methods
Biomarkers/metabolism
Skin/microbiology
Translational Research, Biomedical
*Aging/physiology
Microbiota

@article {pmid41439545,
year = {2025},
author = {Ding, J and Yu, C and Gao, J and Luo, W and Yang, Y and Li, H and Wu, QL},
title = {Stratification-driven divergence between taxonomic and functional diversity in a deep lake microbiome.},
journal = {FEMS microbiology ecology},
volume = {},
number = {},
pages = {},
doi = {10.1093/femsec/fiaf129},
pmid = {41439545},
issn = {1574-6941},
abstract = {Thermal stratification drivers of microbial community organization and functional potential in deep lakes, yet comparative analyses of epilimnetic and hypolimnetic microbiome dynamics remain limited. In this study, we combined 16S rRNA gene sequencing with functional microarray (GeoChip 5.0) to investigate stratification-induced shifts in microbial community composition and functional structure in Lake Fuxian, a deep monomictic plateau lake in Yunnan Province, Southwest China. Our analyses revealed a partial decoupling between taxonomic and functional diversity across water layers: the oxygen-depleted hypolimnion harbored higher bacterial taxonomic richness and distinct taxa (Nitrospirae, Parcubacteria, Thaumarchaeota), whereas the epilimnion exhibited greater functional gene richness with lower beta diversity, indicating enhanced metabolic flexibility. Molecular ecological network analysis uncovered contrasting interaction patterns, with hypolimnetic communities exhibiting greater complexity and modularity. Notably, the Chloroflexi-associated amyA gene emerged as a module hub in hypolimnetic functional molecular ecological networks while distinct connector taxa characterized both epilimnetic and hypolimnetic species molecular ecological networks. Multivariate analyses identified dissolved oxygen and nutrient availability as key environmental drivers of vertical microbial stratification. These findings elucidate microbial adaptation to stratified conditions and underscore the distinct roles of epilimnetic and hypolimnetic communities in biogeochemical cycling in deep lakes experiencing climate-mediated thermal regime shifts.},
}

@article {pmid41439395,
year = {2025},
author = {Chakkarai, S and Tabar, MS and Jian, X and Satizabal, CL and Casale, FP and Gutiérrez, JB and Habes, M and Blangero, J and Seshadri, S and Sargurupremraj, M},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e103860},
doi = {10.1002/alz70855_103860},
pmid = {41439395},
issn = {1552-5279},
mesh = {Humans ; Male ; *Gene-Environment Interaction ; Female ; Quantitative Trait Loci ; Magnetic Resonance Imaging ; *Alzheimer Disease/genetics/pathology/diagnostic imaging ; Aged ; *Brain/pathology/diagnostic imaging ; Risk Factors ; Genome-Wide Association Study ; Hippocampus/pathology/diagnostic imaging ; },
abstract = {BACKGROUND: Epidemiological studies highlight the relation between environmental exposures and the risk of Alzheimer's disease (AD) and related disorders (ADRD). However, due to the prolonged preclinical phase of ADRD, the underlying molecular mechanisms disrupted by environmental factors and their impact on brain structure remain poorly understood. Additionally, investigating gene-environment interactions has been challenging, primarily due to difficulties in accurately defining environmental variables and the substantial inter-study heterogeneity.

METHOD: Since gene-environment interaction effects influence phenotypic variability across genotypes, we leveraged deviations in phenotypic variance to identify variance quantitative trait loci (vQTLs) with heightened environmental sensitivity. Utilizing UK Biobank data (N = 45,275) with comprehensive genomic, brain imaging, and risk factor profiles, we mapped vQTLs for key MRI markers: hippocampal volume (HV) for atrophy, white matter hyperintensity (WMH) for vascular injury, and diffusion MRI metrics (fractional anisotropy [FA] and mean diffusivity [MD]) for microstructural changes. Sentinel vQTLs were further examined using linear mixed models to pinpoint environmental exposures, such as air pollution, physical activity, and lifestyle factors, that mediate these associations.

RESULT: The genome-wide vQTL analysis identified five novel, genome-wide significant loci associated with WMH burden (2q12.3, 3q27.3-q28, 5p13.2, 10p11.22, and 17p11.2) along with four suggestive loci for HV and FA. Notably, associations at 2q12.3 (ST6GAL2), 10p11.22 (ZEB1), and 17p11.2 (EPN2) with WMH burden were significantly mediated by sedentary behavior and lifestyle factors (smoking, alcohol consumption). Functional insights suggest that ZEB1 regulates gut microbiome species involved in inflammatory bowel diseases, while ST6GAL2 has been implicated as an inflammatory biomarker associated with alcohol consumption. Additionally, differential gene expression analysis revealed significant downregulation of these risk loci in the spleen, with further enrichment observed in kidney cell-type specific signatures.

CONCLUSION: Our study identifies novel genome-wide loci that interact with environmental factors and are associated with preclinical MRI markers of AD. These findings underscore the impact of modifiable lifestyle factors on genetic risk, offering potential avenues for preventive and therapeutic strategies. Ongoing efforts aim to replicate these findings in well-characterized cohorts, including the Framingham Heart Study and the San Antonio Family Heart Study of predominantly Mexican-Americans.},
}

Humans
Male
*Gene-Environment Interaction
Female
Quantitative Trait Loci
Magnetic Resonance Imaging
*Alzheimer Disease/genetics/pathology/diagnostic imaging
Aged
*Brain/pathology/diagnostic imaging
Risk Factors
Genome-Wide Association Study
Hippocampus/pathology/diagnostic imaging

@article {pmid41439274,
year = {2026},
author = {Li, Y and Xu, C and Park, H and Omstead, AN and Anees, M and Sherry, C and Khan, AF and Grayhack, E and Weksler, B and Wagner, P and Bartlett, DL and Meltzer, SJ and Zaidi, AH and Goel, A},
title = {A machine-learning informed circulating microbial DNA signature for early diagnosis of esophageal adenocarcinoma.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2604334},
doi = {10.1080/19490976.2025.2604334},
pmid = {41439274},
issn = {1949-0984},
mesh = {Humans ; *Esophageal Neoplasms/diagnosis/microbiology/blood ; *Adenocarcinoma/diagnosis/microbiology/blood ; *Machine Learning ; *Early Detection of Cancer/methods ; Barrett Esophagus/diagnosis/microbiology ; Male ; Female ; Middle Aged ; Aged ; Gastroesophageal Reflux/diagnosis/microbiology ; Bacteria/genetics/classification/isolation & purification ; *DNA, Bacterial/blood/genetics ; Liquid Biopsy/methods ; *Cell-Free Nucleic Acids/blood/genetics ; Metagenomics ; Biomarkers, Tumor/blood ; },
abstract = {Esophageal adenocarcinoma (EAC) has seen a dramatic rise in incidence in developed countries over the past three decades. Early detection of its precursors-gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and high-grade dysplasia (HGD) is critical for cancer prevention. This study presents the development and validation of a novel liquid biopsy assay based on circulating microbial DNA (cmDNA) for the early detection of EAC and HGD. Using metagenomic sequencing, we identified significant differences in microbial diversity and composition between EAC and HGD patients, as well as between BE and GERD patients. A total of 46 microbial candidates in tissue and 419 in serum were upregulated in EAC & HGD, with 11 consistently elevated in both sample types. Following qRT-PCR validation and LASSO regression, a 6-marker cmDNA panel was selected. This signature was incorporated into a diagnostic model trained with the XGBoost algorithm, achieving an AUC of 0.93 in the training cohort (52 HGD & EAC cases vs. 54 BE & GERD controls). Importantly, the model demonstrated robust performance in an independent testing cohort (23 HGD & EAC cases vs. 22 BE & GERD controls), yielding AUCs of 0.91 for EAC and 0.88 for HGD. These findings highlight the diagnostic potential of cmDNA-based profiling and support its utility as a minimally invasive, accurate, and generalizable tool for early detection of esophageal adenocarcinoma.},
}

Humans
*Esophageal Neoplasms/diagnosis/microbiology/blood
*Adenocarcinoma/diagnosis/microbiology/blood
*Machine Learning
*Early Detection of Cancer/methods
Barrett Esophagus/diagnosis/microbiology
Male
Female
Middle Aged
Aged
Gastroesophageal Reflux/diagnosis/microbiology
Bacteria/genetics/classification/isolation & purification
*DNA, Bacterial/blood/genetics
Liquid Biopsy/methods
*Cell-Free Nucleic Acids/blood/genetics
Metagenomics
Biomarkers, Tumor/blood

@article {pmid41439255,
year = {2025},
author = {Dodani, D and Talhouk, A},
title = {Multi-cohort ensemble learning framework for vaginal microbiome-based endometrial cancer detection.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1641413},
pmid = {41439255},
issn = {2235-2988},
mesh = {Humans ; Female ; *Endometrial Neoplasms/diagnosis/microbiology ; *Vagina/microbiology ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Machine Learning ; Cohort Studies ; Early Detection of Cancer/methods ; ROC Curve ; Bacteria/classification/genetics/isolation & purification ; Middle Aged ; Sensitivity and Specificity ; Ensemble Learning ; },
abstract = {INTRODUCTION: Endometrial cancer is the most common gynecological malignancy in high-income countries and lacks an established strategy for early detection. Prior studies suggest that the vaginal microbiome may hold diagnostic potential, but inconsistent findings have limited clinical translation.

METHODS: We conducted a systematic review to collect and analyze vaginal 16S rRNA sequencing data from five independent cohorts (n = 265). These studies included women with histologically confirmed endometrial cancer and controls with benign gynecologic conditions. We used these datasets to identify microbial signatures associated with endometrial cancer and to develop a predictive machine learning model.

RESULTS: Microbial diversity was significantly higher in endometrial cancer samples, and host characteristics influenced community composition. Peptoniphilus was reproducibly enriched in cancer samples across cohorts. An ensemble classifier accurately identified endometrial cancer in a held-out test set, achieving an area under the receiver operating characteristic curve of 0.93 (95% CI: 0.71-0.93), sensitivity of 1.0 (95% CI: 0.74-1.0), and a negative predictive value of 1.0 (95% CI: 0.59-1.0).

DISCUSSION: These findings support the potential of vaginal microbiome profiling as a minimally invasive approach for early detection of endometrial cancer.},
}

Humans
Female
*Endometrial Neoplasms/diagnosis/microbiology
*Vagina/microbiology
*Microbiota/genetics
RNA, Ribosomal, 16S/genetics
Machine Learning
Cohort Studies
Early Detection of Cancer/methods
ROC Curve
Bacteria/classification/genetics/isolation & purification
Middle Aged
Sensitivity and Specificity
Ensemble Learning

@article {pmid41439252,
year = {2025},
author = {Tu, Y and Zhou, Z and Lu, Y and Wei, B and Ge, Y and Ding, G and Dong, X and Sheng, J and Zhang, Y and Jin, L and Huang, H},
title = {The composition of lower genital tract microbiota correlates with in vitro fertilization and frozen embryo transfer outcomes in women with polycystic ovarian syndrome.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1617187},
pmid = {41439252},
issn = {2235-2988},
mesh = {Humans ; Female ; *Polycystic Ovary Syndrome/microbiology ; *Fertilization in Vitro ; *Embryo Transfer ; Adult ; *Microbiota/genetics ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; Pregnancy ; Lactobacillus/isolation & purification/genetics ; *Genitalia, Female/microbiology ; },
abstract = {Adverse reproductive outcomes remain a significant concern for women of reproductive age with polycystic ovary syndrome (PCOS), yet the role of the lower genital tract (LGT) microenvironment has been largely overlooked. This study aimed to investigate the association between the LGT microbiome and the outcomes of in vitro fertilization and frozen embryo transfer (IVF-FET) in women with PCOS. A total of 191 reproductive-aged women undergoing assisted reproductive technology (ART) treatment between December 2018 and October 2021 were recruited. The LGT microbiota was profiled using 16S rRNA sequencing and analyzed in relation to ART outcomes and clinical parameters. Furthermore, cervical transcriptome sequencing was performed in a subset of PCOS patients to investigate whether LGT microbiota alterations were associated with functional changes in mucosal epithelial cells. The results demonstrate significant dysbiosis of the LGT microbiome in patients with PCOS, characterized by a reduction in Lactobacillus abundance. Among 72 PCOS patients undergoing IVF-FET, those with a relative Lactobacillus abundance of ≥50% (n = 57) exhibited significantly improved reproductive outcomes compared to those with Lactobacillus abundance <50% (n = 15). Elevated testosterone levels were identified as the most significant factor associated with a reduced abundance of Lactobacillus in PCOS patients. Transcriptomic analysis further revealed that the LGT microbiota was associated with maintaining mucosal epithelial barrier integrity and immune homeostasis in PCOS. In conclusion, the findings highlight that dysbiosis of the LGT microbiota may significantly influence reproductive outcomes in PCOS patients, emphasizing the importance of targeting the LGT microenvironment to improve ART success rates.},
}

Humans
Female
*Polycystic Ovary Syndrome/microbiology
*Fertilization in Vitro
*Embryo Transfer
Adult
*Microbiota/genetics
Dysbiosis/microbiology
RNA, Ribosomal, 16S/genetics
Pregnancy
Lactobacillus/isolation & purification/genetics
*Genitalia, Female/microbiology

@article {pmid41439238,
year = {2026},
author = {Kumar, A and Solanki, MK and Kumar, M and Kaushik, A and Arya, A and Saikia, M and Gaur, VK and Singh, RP and Singh, SK and Singh, VK and Dufossé, L},
title = {The microbial strategies for the management of chemical pesticides: A comprehensive review.},
journal = {Current research in microbial sciences},
volume = {10},
number = {},
pages = {100519},
pmid = {41439238},
issn = {2666-5174},
abstract = {Chemical pesticides considered as one of the emerging environmental contaminants that severally affect the human health and soil and water ecosystem. Despite their well-documented adverse effects on fruit quality, soil structure, the emergence of pesticide-resistant pests, and human well-being, chemical pesticides are still widely used for crop protection, particularly in developing countries. Although to manage the chemical pesticides, various traditional approaches have been employed, however the higher cost, and the generation of toxic residues have shifted research attention toward eco-friendly and sustainable bioremediation strategies. Microorganisms including the bacteria, fungi, and algae play a crucial role in pesticide degradation by transforming toxic compounds into less toxic forms. However, to optimize microbial bioremediation, a comprehensive understanding of microbial metabolism and physiology is essential. In this context, omics technologies such as genomics, metagenomics, transcriptomics, proteomics, and metabolomics, offer powerful tools for elucidating the molecular mechanisms involved in pesticide degradation. These approaches facilitate the identification of microorganism, key genes, enzymes, and metabolic pathways responsible for the breakdown of pesticide compounds and their by-products. Furthermore, advanced technology like the gene editing can enhance the efficacy of pesticides biodegradation by knocking out undesirable genes or introducing beneficial ones in the microorganisms. The Artificial intelligence also plays a significant role in analysing big data, understanding microbial communities' structure, identifying nature of pesticides and selecting or predicting the microbial species with enhanced pesticides degrading efficacy.},
}

@article {pmid41439235,
year = {2026},
author = {Zou, B and Huo, Q and Zhou, X and Lv, Y and Li, G and Fu, G and Shen, H and Shu, S},
title = {Characteristics and longitudinal stability of Gut Microbiota in healthy individuals across different age groups.},
journal = {Current research in microbial sciences},
volume = {10},
number = {},
pages = {100512},
pmid = {41439235},
issn = {2666-5174},
abstract = {Fecal microbiota transplantation (FMT) efficacy relies on donor microbiome composition and temporal stability, yet the influence of donor age remains inadequately investigated. This longitudinal analysis addressed this gap by examining 81 healthy individuals (3-30 years), stratified into four age groups, who provided monthly fecal samples over 12 months (n = 972 samples). Gut microbiota composition (16S rDNA sequencing) and temporal stability were assessed using Bray-Curtis dissimilarity, intraclass correlation coefficient (ICC), and genus-level co-occurrence network analysis. Results demonstrated a strong age-dependency in microbiota stability. The teenage cohort (13-17 years) exhibited the highest stability, characterized by minimal fluctuations in α- and β-diversity and significantly stronger network centrality. Furthermore, specific genera, notably Faecalibacterium and Bifidobacterium, displayed exceptionally high ICC values (>0.90), identifying them as core taxa associated with temporal consistency. These findings underscore the critical role of donor age in microbial stability and highlight teenagers as possessing optimal microbiota characteristics for FMT. They strongly support the development of an ICC-based screening framework to enhance donor selection protocols.},
}

@article {pmid41439197,
year = {2025},
author = {Liang, J and Qiu, Y and Fu, T and Li, J and Yang, J and Tong, Y},
title = {The Gut-Kidney Axis in Uric Acid Nephropathy: Microbiota, Metabolic Crosstalk, and Translational Prospects.},
journal = {Journal of multidisciplinary healthcare},
volume = {18},
number = {},
pages = {8111-8132},
pmid = {41439197},
issn = {1178-2390},
abstract = {Uric acid nephropathy (UAN) represents a critical and multifactorial renal disorder closely linked to hyperuricemia, inflammation, and gut microbiota dysregulation. Recent advances have revealed the pivotal role of the gut-kidney axis in modulating urate metabolism, immune activation, and oxidative stress. This review synthesizes emerging preclinical and clinical evidence to construct an integrative framework for understanding UAN, highlighting both crystal-dependent and crystal-independent mechanisms that drive tubular injury and fibrosis. Accumulating data underscore the reciprocal crosstalk between renal dysfunction and gut dysbiosis, mediated by microbial metabolites such as short-chain fatty acids (SCFAs), indoxyl sulfate, and p-cresol sulfate. We further evaluate therapeutic interventions targeting the gut-kidney axis-including probiotics, synbiotics, postbiotics, fecal microbiota transplantation (FMT), and engineered microbial therapies-which have shown promise in restoring microbial balance and improving urate handling. By integrating multi-omics profiling with systems biology, this review proposes a precision-medicine roadmap that leverages microbiome signatures and metabolic phenotyping for risk stratification and personalized intervention. Moreover, we emphasize the need for supportive regulatory frameworks and interdisciplinary collaboration to enable the clinical translation of microbiota-based strategies. Collectively, this work provides a strengthened conceptual foundation for microbiome-informed prevention and treatment of uric acid-related kidney disease.},
}

@article {pmid41439190,
year = {2025},
author = {Tronel, A and Roger-Margueritat, M and Plazy, C and Biennier, S and Craspay, A and Mohanty, I and Portier, SC and Laiola, M and Roeselers, G and Mathieu, N and Hupe, M and Dorrestein, PC and Alcaraz, JP and Martin, D and Cinquin, P and Silvent, AS and Giai, J and Proust, M and Soranzo, T and Buelow, E and Le Gouellec, A},
title = {Exploring the human small intestinal luminal microbiome via a newly developed ingestible sampling device.},
journal = {ISME communications},
volume = {5},
number = {1},
pages = {ycaf224},
pmid = {41439190},
issn = {2730-6151},
abstract = {Because accessing the small intestine is technically challenging, studies of the small intestinal microbiome are predominantly conducted in patients rather than in healthy individuals. Invasive clinical procedures, such as endoscopy or surgery, usually performed for therapeutic purposes, are typically required for sample collection. Although stomas offer a less invasive means for repeated sampling, their use remains restricted to patient populations. As a result, the small intestinal microbiome of healthy individuals remains largely understudied. This study evaluated a novel ingestible medical device for collecting luminal samples from the small intestine. A monocentric interventional trial (NCT05477069) was conducted on 15 healthy subjects. Metagenomics, metabolomics, and culturomics were used to assess the effectiveness of the medical device in characterizing the healthy small intestinal microbiome and identifying potential biomarkers. The small intestinal microbiota differed significantly from the fecal microbiota, displaying high inter-individual variability, lower species richness and reduced alpha diversity. A combined untargeted and semi-targeted LC-MS/MS metabolomics approach identified a distinct small intestinal metabolic footprint, with bile acids and amino acids being the most abundant metabolite classes. Host- and host/microbe-derived bile acids were particularly abundant in small intestinal samples. Using a fast culturomics approach on two small intestinal samples, we achieved species-level characterization and identified 90 bacterial species, including five potentially novel ones. This study demonstrates the efficacy of our novel sampling device in enabling comprehensive small intestinal microbiome analysis through an integrative, multi-omics approach. This approach allows distinct microbiome signatures to be identified between small intestinal and fecal samples.},
}

@article {pmid41439181,
year = {2025},
author = {Yang, M and He, T and Moukarzel, R and Li, M and Li, M and Zhang, Z and He, Y and Liu, Y and Yu, L and Zhu, S and Du, F},
title = {Phyllosphere microbiome responses to nano-berberine and chemical fungicides in powdery mildew infected strawberry.},
journal = {Frontiers in plant science},
volume = {16},
number = {},
pages = {1712123},
pmid = {41439181},
issn = {1664-462X},
abstract = {Strawberry powdery mildew, caused by the obligate biotroph Podosphaera aphanis, is a major threat to commercial strawberry production, reducing both yield parameters and fruit quality. While chemical fungicides remain a standard control method, their non-target effects on phyllosphere microbial communities have raised important ecological and environmental concerns. Nano-pesticides are increasingly applied in plant disease management, however, their influence on the composition and functional potential of phyllosphere microbial communities remains poorly understood. The nano-berberine formulation (BBR-M) used in this study was provided by a collaborative group, with synthesis and physicochemical characteristics consistent with those previously reported for this material. In this study, we compared the field-level effects of a nano-berberine formulation (BBR-M) and conventional chemical fungicides (e.g., bupirimate) on the strawberry phyllosphere microbiota using high-throughput sequencing, bioinformatics analysis, and microbial isolation techniques. The results showed that nano-fungicide application significantly reduced the disease index of powdery mildew and markedly decreased its incidence in field-grown strawberries, ultimately lowering leaf disease incidence to 5.06% with a control efficacy of 96.81%. Furthermore, nano-fungicides and conventional chemical fungicides treatments were associated with distinct impacts on the phyllosphere microenvironment of strawberry. Application of BBR-M was associated with a more structured and potentially stable microbial community, characterized by increased fungal diversity and higher modularity in co-occurrence networks. In contrast, bupirimate treatment increased microbial complexity but coincided with reduced network stability. A strain of Bacillus siamensis-a genus identified as a core taxon within the BBR-M phyllosphere network-was subsequently isolated from nano-berberine-treated leaves and exhibited strong antagonistic activity against Colletotrichum nymphaeae. Field assays showed that this strain effectively suppressed strawberry powdery mildew with 98.18% control efficacy. Collectively, these findings provide important insights into the ecological safety and functional implications of novel pesticide technologies, underscoring the potential of nano-fungicides and native biocontrol agents for sustainable strawberry disease management.},
}

@article {pmid41438919,
year = {2025},
author = {Eissenberg, JC},
title = {Autism Spectrum Disorder: Nature vs. Nurture.},
journal = {Missouri medicine},
volume = {122},
number = {6},
pages = {501-507},
pmid = {41438919},
issn = {0026-6620},
mesh = {Humans ; *Autism Spectrum Disorder/genetics/etiology/epidemiology ; Genetic Predisposition to Disease ; Environmental Exposure/adverse effects ; },
abstract = {Autism Spectrum Disorder (ASD) is associated with a variety of inherited disorders, but most diagnoses have no identifiable genetic etiology. There has been a significant increase in the incidence of ASD diagnoses in the past three decades. The now-discredited vaccine theory of ASD causation has driven concerns over environmental exposures that may or may not lead to ASD. Here, I discuss the evidence for an underlying genetic basis for ASD, the evidence that environmental inputs could play a significant role ASD and potential treatments for associated symptoms.},
}

Humans
*Autism Spectrum Disorder/genetics/etiology/epidemiology
Genetic Predisposition to Disease
Environmental Exposure/adverse effects

@article {pmid41438742,
year = {2025},
author = {Chen, PJ and Devkota, S and Shiao, S and Hendifar, A and Yang, JD},
title = {Gut microbiome, a novel precision medicine biomarker for hepatocellular carcinoma.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1568962},
pmid = {41438742},
issn = {1664-3224},
mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/immunology/microbiology/metabolism ; *Liver Neoplasms/therapy/immunology/microbiology/metabolism ; *Gastrointestinal Microbiome/immunology ; Precision Medicine/methods ; Biomarkers, Tumor ; Animals ; Immune Checkpoint Inhibitors/therapeutic use ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Immunotherapy/methods ; },
abstract = {Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have transformed systemic therapy, durable responses are achieved in only a subset of patients, highlighting the need for reliable predictive biomarkers. The gut-liver axis, a bidirectional network linking intestinal microbiota, microbial metabolites, and hepatic immune pathways, has emerged as a key regulator of liver immunity and tumor progression. Growing evidence indicates that the gut microbiome modulates ICI efficacy by shaping immune activation, cytokine signaling, and drug metabolism. This review summarizes current insights into how gut microbial composition and metabolites influence immunotherapy outcomes in HCC and discusses microbiome-targeted strategies, including fecal microbiota transplantation (FMT), prebiotics, probiotics, and dietary interventions. Further research and clinical validation are needed before these insights can be effectively integrated into HCC management.},
}

Humans
*Carcinoma, Hepatocellular/therapy/immunology/microbiology/metabolism
*Liver Neoplasms/therapy/immunology/microbiology/metabolism
*Gastrointestinal Microbiome/immunology
Precision Medicine/methods
Biomarkers, Tumor
Animals
Immune Checkpoint Inhibitors/therapeutic use
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Immunotherapy/methods

@article {pmid41438680,
year = {2025},
author = {Li, Z and Zhang, J and Zhang, Y and Chen, H and Bao, Y},
title = {Skin Microbiome in Health and Disease: Mechanisms and Emerging Therapeutic Strategies.},
journal = {Clinical, cosmetic and investigational dermatology},
volume = {18},
number = {},
pages = {3443-3455},
pmid = {41438680},
issn = {1178-7015},
abstract = {The skin microbiome plays a vital role in maintaining skin homeostasis by regulating immune responses, preserving barrier integrity, and inhibiting pathogen colonization. This review systematically explores the mechanisms underlying its dysregulation in conditions such as acne, atopic dermatitis, psoriasis, and impaired wound healing, with a focus on key factors including microbial over colonization, diminished diversity, and host immune dysregulation. The influence of microbial metabolites, such as short-chain fatty acids and porphyrins, is also examined. We further evaluate emerging microbial-targeted therapeutic strategies, including live biotherapeutic products, skin microbiota transplantation, epigenetic and metabolic interventions, and precision antimicrobial polymers. These approaches aim to restore microbial balance rather than achieve broad-spectrum sterilization, representing a significant shift in the treatment paradigm for cutaneous diseases. In contrast to previous reviews, this article places special emphasis on the mechanisms of multi-organ interactions within the gut-skin axis and discusses the potential of integrating multi-omics technologies and artificial intelligence to advance the clinical translation of personalized microbial therapies, thereby providing a forward-looking perspective on the field.},
}

@article {pmid41438381,
year = {2025},
author = {Chen, X and Zhang, Y and Zhang, G and Wang, D and Dou, L and Wang, Y and Huang, Z and Liu, X},
title = {Spatial microbiome-metabolic crosstalk drives CD8[+] T-cell exhaustion through the butyrate-HDAC axis in colorectal cancer.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1704491},
pmid = {41438381},
issn = {1664-302X},
abstract = {BACKGROUND: The spatial organization of intratumoral microbiota and its metabolic impact on immunotherapy response in colorectal cancer (CRC) is unclear, limiting targeted interventions.

METHODS: We integrated single-cell RNA-seq, spatial transcriptomics, and microbial multi-omics from a discovery cohort of 23 treatment-naïve CRC patients. Findings were validated in an independent validation cohort from The Cancer Genome Atlas (TCGA-CRC, n = 159).

RESULTS: Spatial depletion of Streptococcus and Acetivibrio in tumor niches disrupts butyrate-histone deacetylase (HDAC) signaling, leading to programmed cell death 1 (PDCD1) hyperacetylation and CD8[+] T-cell exhaustion. The Colorectal Cancer Microbiome Score (CMS) may serve as a predictive biomarker for immunotherapy response and HDAC inhibitor-based combination therapy. We developed the CMS, a spatial biomarker that stratifies patients by microbial-metabolic dysfunction, predicting immunotherapy resistance (e.g., higher tumor immune dysfunction and exclusion (TIDE) scores; p < 0.01) and guiding combinatorial HDAC inhibition for CMS-defined subgroups. In silico fecal microbiota transplantation (FMT) validated CMS as an actionable target for microbiota modulation. Butyrate supplementation in vitro restored HDAC activity and reduced PD-1 expression on CD8[+] T cells, validating the proposed mechanism.

CONCLUSION: Our study unveils a spatially defined, microbiome-driven metabolic niche that epigenetically programs CD8[+] T-cell exhaustion via the butyrate-HDAC axis, revealing a targetable mechanism to overcome immunotherapy resistance in CRC.},
}

@article {pmid41438378,
year = {2025},
author = {Yang, W and Liu, H and Xu, R and Peng, Y and Xu, T and Yang, Y and Li, Y and Xiang, H},
title = {Integrated genomics, metagenomics and metatranscriptomics to reveal the biocontrol mechanism of Bacillus velezensis JY10 against tobacco target spot disease.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1707097},
pmid = {41438378},
issn = {1664-302X},
abstract = {Tobacco target spot (TTS) disease, a prevalent fungal disease caused by Rhizoctonia solani, severely reduces tobacco yield and quality, imposing substantial economic losses on the tobacco industry. In this study, we employed a biological control approach against TTS using a Bacillus velezensis JY10 isolated from healthy tobacco stems. We further elucidated the mechanism of JY10 in controlling TTS through genomics, metagenomics and metatranscriptomics. The results showed that JY10 exhibited robust inhibitory effects against R. solani, with an inhibition rate exceeding 95%, and achieved a TTS control efficacy of 68.63% in pot experiments. Whole-genome sequencing demonstrated that the JY10 genome spans 3,929,772 bp, contains 4,026 protein-coding genes, and has a GC content of 46.5%. AntiSMASH analysis predicted 12 secondary metabolite biosynthetic gene clusters, encoding antimicrobial compounds such as surfactin, fengycin, difficidin, bacillaene, bacillibactin, macrolactin H, and bacilysin. Metagenomic profiling showed that JY10 treatment had no significant influence on tobacco phyllosphere and rhizosphere microbiome structure, however, it significantly increased the relative abundance of beneficial microbes, including Bacillus, Pseudonocardia, and Pseudomonas. Metatranscriptomic analysis revealed that JY10 might enhance tobacco TTS resistance by modulating oxidative phosphorylation pathway and upregulating several antibiotics biosynthesis. Taken together, JY10 may employ a dual control strategy against TTS, involving the direct production of antifungal compounds, as well as indirectly increasing the abundance of beneficial microbes and modulating their oxidative phosphorylation and antibiotic synthesis pathways in the phyllosphere and rhizosphere of tobacco. These findings provide a theoretical foundation for understanding biocontrol mechanisms of JY10 and introduce a promising bacterial resource for the development of sustainable TTS management strategies.},
}

@article {pmid41438377,
year = {2025},
author = {Shang, X and He, Z and Chen, W and Jin, X},
title = {Soil bacterial community diversity, composition, and species specificity across different geographical landscapes in the Mu Us Sandy Land.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1714794},
pmid = {41438377},
issn = {1664-302X},
abstract = {The Mu Us Sandy Land represents a typical region for ecological restoration in China, characterized by the development of diverse landscapes including desert, meadow patches, arbor forests, and mixed arbor-shrub forests. This study aimed to investigate the diversity, composition, and differential taxa of soil bacterial communities across these distinct geographical landscapes, thereby elucidating the driving mechanisms of vegetation restoration on the sandy land soil microbiome. Soil samples were collected from four typical landscapes in the Mu Us Sandy Land: desert (B), meadow patch (D), arbor forest (T), and mixed arbor-shrub forest (C). High-throughput sequencing of the 16S rRNA gene was performed using the Illumina NextSeq 2000 platform. Our results revealed distinct patterns of bacterial community composition: Actinobacteria dominated the desert (37.42%), while Proteobacteria were more abundant in meadow patches and mixed arbor-shrub forests, and Bacillota were significantly enriched in arbor forests (20.32%). Beta diversity analysis combined with the ANOSIM test (R = 0.7168, P = 0.001) revealed significant divergence in bacterial community structure among the different landscapes. LEfSe analysis further identified specific biomarkers for each landscape, such as Rubrobacter and Streptomyces in the desert, and taxa associated with Acidobacteria and Proteobacteria in the mixed arbor-shrub forests. The research demonstrates that the different geographical landscapes in the Mu Us Sandy Land shape distinct soil bacterial communities. The mixed arbor-shrub forest exhibited a more complex community structure compared to the pure arbor forest, indicating its potential as a more sustainable and resilient ecological restoration model. These findings provide a baseline understanding of microbial community shifts associated with vegetation restoration, which may inform future studies integrating soil physicochemical drivers.},
}

@article {pmid41438373,
year = {2025},
author = {Burgio, M and Pellegrini, F and Frattina, L and Carbonari, A and Bramante, G and Andriulo, OM and Camero, M and Lanave, G and Parisi, A and Martella, V and Rizzo, A and Cicirelli, V},
title = {Oral microbiota in cesarean-delivered puppies.},
journal = {Frontiers in veterinary science},
volume = {12},
number = {},
pages = {1711728},
pmid = {41438373},
issn = {2297-1769},
abstract = {INTRODUCTION: The microbiota plays a fundamental role in host health, and alterations in its composition have been associated with numerous pathological conditions. The neonatal period is a critical window for establishing a stable microbiota that shapes long-term health. The aim of this study was to characterize the oral microbiota of cesarean-delivered puppies at birth and 15 days postpartum, using 16S rRNA gene sequencing. This microbiota was compared with the maternal oral and colostrum microbiota.

METHODS: The study included 15 puppies delivered by cesarean section from four French Bulldogs. Oral swabs were collected from puppies at birth (T0) and day 15 (T15), and from dams together with colostrum before anesthesia. DNA was extracted and the full-length 16S rRNA gene amplified with universal primers. Libraries were prepared, purified, and sequenced on a MinION Mk1C for 24 h. FastQ files were analyzed with EPI2ME (Fastq 16S), and taxonomic assignment was performed using the NCBI_16S database via BLAST.

RESULTS: Microbial DNA was detected in neonatal samples at birth, indicating that colonization had already begun. Diversity analyses showed significant differences between the puppies' oral microbiota at T0 and T15 (p = 0.006), as well as between neonates at T0 and their mothers (p = 0.018). By contrast, no significant differences in alpha diversity were observed between puppies at T15 and their mothers, suggesting convergence toward an adult-like microbial profile. Colostrum did not show significant differences compared with the puppies' oral microbiota at both time points, suggesting it may act as a possible, though not exclusive, source of microbial transfer.

CONCLUSION: The oral microbiota of cesarean-delivered puppies undergoes rapid compositional changes within the first 15 days of life, marked by increased alpha diversity and a shift toward a microbial profile resembling that of the mother. Initial colonization likely derives from non-oral maternal or environmental sources, with convergence by day 15 due to maternal contact. Maternal colostrum did not significantly influence oral diversity, though it may act as a vector of microbial transfer. These findings underscore the dynamic nature of early-life colonization and contribute to our understanding of host-microbiota interactions in a One Health context.},
}

@article {pmid41438339,
year = {2026},
author = {Van Espen, L and Brol, MJ and Close, L and Schierwagen, R and Gu, W and Keller, MI and Balogh, B and Fullam, A and De Coninck, L and Nakamura, T and Kuhn, M and Bork, P and Laleman, W and Bajaj, JS and Papp, M and Schnabl, B and Trebicka, J and Matthijnssens, J and , },
title = {L actococcus A phages predict ACLF while Enterococcus B phages predict bacterial infection in decompensated cirrhosis.},
journal = {JHEP reports : innovation in hepatology},
volume = {8},
number = {1},
pages = {101622},
pmid = {41438339},
issn = {2589-5559},
abstract = {BACKGROUND & AIMS: As portal hypertension progresses in cirrhosis, bacterial translocation across a compromised gut barrier leads to endotoxemia, systemic inflammation and immune dysfunction. Gut phages play a key role in these processes by influencing bacteria-host interactions. This study explores the role of the human gut virome in acute decompensation of cirrhosis and acute-on-chronic liver failure (ACLF).

METHODS: The fecal virome was longitudinally assessed by metagenomic sequencing in two independent cohorts: 93 patients (292 samples) with acute decompensation or ACLF from the PREDICT study, and 94 patients (94 samples) with decompensated cirrhosis undergoing TIPS (transjugular intrahepatic portosystemic shunt) surgery collected in a tertiary care setting. Besides descriptive analysis, phages were grouped according to their predicted bacterial host and lifestyle, and associated with clinical parameters.

RESULTS: Phage alpha-diversity was higher in patients with ACLF and correlated with ACLF severity. In the absence of ACLF, the phageome was dominated by virulent phages, but in ACLF, temperate phages became more prevalent. Genus-level analysis showed that phageomes were highly patient-specific. Lactococcus A phages were the only phage-host group predicting ACLF development (odds ratio [OR] = 14; Fisher test p = 0.0129). Enterococcus B phages (OR = 14.7; p = 0.0015; adj. p = 0.037) and their bacterial hosts (OR = 2.8; p = 0.020) were significantly more prevalent in cases of proven systemic bacterial infection. The presence of both phage families was linked to increased 90-day mortality rates.

CONCLUSION: ACLF is characterized by increased fecal virome diversity and a shift from virulent toward temperate phages at disease onset. Our study links Lactococcus A phages to ACLF development, and Enterococcus B phages to bacterial infection, while both are associated with increased 90-day mortality.

CLINICAL TRIAL NUMBER: NCT03056612.

IMPACT AND IMPLICATIONS: The human gut virome is a poorly investigated part of the human gut microbiome, especially in the context of decompensated cirrhosis and acute-on-chronic liver failure. This study identified two phage groups (Lactococcus A phages and Enterococcus B phages) with particular prognostic value. In the future, virome analysis of fecal samples could be useful for patient stratification in clinical practice.},
}

@article {pmid41438083,
year = {2025},
author = {Spiess, K},
title = {Sensing the good vibes: Audience vocal engagement with the oral microbiota.},
journal = {iScience},
volume = {28},
number = {12},
pages = {114071},
pmid = {41438083},
issn = {2589-0042},
abstract = {This immersive performance explores speech as a biological environment for oral microbiota, merging art and science to promote ecological awareness. Using scientific data, recursive echo, and tactile feedback, it encourages visitors to engage directly with microbial processes through vocalizations and vibrations, blurring boundaries between human and non-human elements. Here an art-science collaboration turns laboratory research into a public, sensory experience that supports reflection on our shared biological environments, fostering sensory, evocative, and scientific engagement with microbiome ecology.},
}

@article {pmid41438065,
year = {2025},
author = {Xia, W and Gao, C and Cui, X and Li, H and Wang, X and Wang, F and Zhu, L and Li, D},
title = {Evidence for the effects on the wildlife gut microbiome by grazing: The potential gut microbiota transmission between Yunnan snub-nosed monkeys (Rhinopithecus bieti) and sympatric livestock.},
journal = {iScience},
volume = {28},
number = {12},
pages = {114147},
pmid = {41438065},
issn = {2589-0042},
abstract = {Grazing can impact wildlife by resource competition, habitat degradation, and pathogen transmission. The Yunnan snub-nosed monkeys (Rhinopithecus bieti) are endemic and endangered primates, facing the negative effects of grazing. In the study, we conducted 16S rRNA sequencing to investigate the gut microbiota of Yunnan snub-nosed monkeys and sympatric livestock. Our results revealed that cattle exhibited relatively higher microbial similarity with monkeys compared to pigs. The SourceTracker analysis further indicated a potential cattle-origin gut microbiome in monkeys (mean ± standard deviation (SD): 11.24% ± 0.43%), while no pig-derived microbiome was detected. We speculated that shared environment and partial dietary similarities may drive the microbial similarity and transmission. Furthermore, our findings suggested potential microbial transmission between the gut microbiome of livestock and the environment, revealing probable environmental influence caused by grazing. Overall, our study showed the impacts of grazing on the wildlife microbiome and the environment and provided insights for conservation management.},
}

@article {pmid41438044,
year = {2025},
author = {Dennis, N and Vazquez-Prada, M and Freeman, LM and Xue, F and White, LJ and Karamalegos, AA and Sullivan, WG and Kudzminkaite, B and Brown, I and Hiscock, JR and Ezcurra, M},
title = {A microbial community that alters mitochondrial morphology and age-related motor function in C. elegans.},
journal = {iScience},
volume = {28},
number = {12},
pages = {114128},
pmid = {41438044},
issn = {2589-0042},
abstract = {Across diverse taxa, the composition of the microbiota is associated with host fitness. A mechanistic understanding of how microbial communities influence host physiology could lead to microbiota-based interventions for lifelong health. Here, we have developed a host-microbiota model system consisting of the model organism C. elegans combined with a defined natural microbiota (DefNatMta) consisting of 11 bacterial strains isolated from wild C. elegans to study natural host-microbiota interactions in the laboratory. We show that DefNatMta persists in the C. elegans gut, forming a stable and distinct gut microbiota. Utilizing this host-microbiota system, we find that DefNatMta affects age-related motility and protects against age-related decline in motor function. DefNatMta acts by altering metabolism and mitochondrial network dynamics in muscle and requires dynamin-related protein 1 (DRP-1), a regulator of mitochondrial fission to protect against age-related motility decline. Our findings are consistent with microbe-mitochondria communication affecting age-related muscle function.},
}

@article {pmid41438041,
year = {2025},
author = {Zhou, J and Li, Y and Zhu, T and Yang, K and Zhang, C and Zhang, R and Zhang, X and Zhou, D and Ding, X and Qiao, Y and Han, C and Zhu, Z},
title = {Single-cell analysis of testicular bacterial microbiome changes during aging and effect on reproductive capacity in mice.},
journal = {iScience},
volume = {28},
number = {12},
pages = {114174},
pmid = {41438041},
issn = {2589-0042},
abstract = {The testis supports spermatogenesis through a tightly regulated microenvironment, and the bacterial microbiome (BM) may influence host cells through immune and metabolic pathways, thereby impacting reproductive capacity. Here, we applied invasion-adhesion-directed expression sequencing (INVADE-seq), a single-cell RNA sequencing approach that simultaneously captures host and bacterial transcripts, to examine how bacterial signals shape testicular cell states. We detected a sparse but widespread bacterial presence across multiple cell types, with somatic and early germ cells outside the blood-testis barrier (BTB) showing relatively higher bacterial abundance. Bacterial load increased with age, coinciding with transcriptional signatures of reduced BTB function. At the cellular level, bacterial-positive Leydig cells exhibited activation of steroidogenic genes, whereas macrophages upregulated pathways related to autophagy and immune modulation. These findings not only deepen our understanding of testicular microbiome biology but also hold promise for the discovery of novel diagnostic biomarkers and therapeutic targets for BM-related and age-associated male subfertility.},
}

@article {pmid41438035,
year = {2025},
author = {Thon, T and Kopelentova, E and Srutkova, D and Coufal, S and Kreisinger, J and Rob, F and Reiss, Z and Kverka, M and Capkova, S and Cadova, J and Bulantova, L and Bystry, V and Sediva, A and Tlaskalova-Hogenova, H and Jiraskova Zakostelska, Z and Polouckova, A},
title = {Skin and gut microbiota composition and immune regulatory response differentiate IgE and non-IgE cow's milk allergy patients with atopic dermatitis.},
journal = {iScience},
volume = {28},
number = {12},
pages = {113943},
pmid = {41438035},
issn = {2589-0042},
abstract = {Precise identification of food allergy and atopic dermatitis (AD) endotypes in infants is needed to target treatments effectively. Therefore, we investigated markers associated with changes in the microbiota and immune responses within the gut-skin axis of immunoglobulin E (IgE) and non-IgE-mediated cow's milk allergy (CMA) patients with AD. We report that the skin microbiota of patients with IgE CMA differs significantly from healthy controls (HCs) and from patients with non-IgE CMA, despite similar AD severity. Regarding the immune response to bacteria, we found a significant increase in soluble CD14 in patients with non-IgE CMA compared to patients with IgE CMA. Patients with a non-IgE CMA have more regulatory T cells in their blood that migrate into the intestine than patients with IgE CMA. These findings provide insights into the complex interplay between the damaged epithelial barrier, microbiome, and immune responses in CMA patients with AD.},
}

@article {pmid41438002,
year = {2025},
author = {Guantai, LM and Bavinton, CE and Shazzad, JB and Mahajan, S and Thompson, S and Pereira, FC},
title = {Taxonomic and mechanistic insights into gut microbiota bioaccumulation of entacapone using bioorthogonal drug labelling.},
journal = {Microbiome research reports},
volume = {4},
number = {4},
pages = {41},
pmid = {41438002},
issn = {2771-5965},
abstract = {Aim: The gut microbiota plays a key role in shaping individual responses to drugs, but current tools have limited potential to probe drug-microbe interactions within the complex, individualised gut environment. This study employed bioorthogonal labelling to track and identify gut microbial taxa and molecular mechanisms involved in the bioaccumulation of entacapone, a Parkinson's disease drug. Methods: We synthesised alkyne-tagged derivatives of entacapone and evaluated their suitability as molecular probes in ex vivo incubations with faecal communities or different Escherichia coli (E. coli) strains. Following incubation, tagged drugs were conjugated to a fluorescently labelled azide via click chemistry. Labelled cells were visualised, quantified, sorted via fluorescence-activated cell sorting (FACS), and identified via 16S ribosomal RNA (rRNA) gene amplicon sequencing. Results: Entacapone alkyne derivatives retained the biological activity and effects of the original drug on the microbiota, significantly reducing microbial loads and shifting community composition across the three donors tested. Conjugation of alkyne-entacapone with a labelled azide revealed that between 80% to 96% of all microbial cells in a donor's faecal sample accumulate entacapone. Nearly all taxa detected in incubations were recovered in labelled FACS fractions, confirming widespread uptake of the drug. Finally, we demonstrate that different E. coli strains exhibit varying levels of entacapone accumulation and identify a siderophore transporter that plays a role in this process. Conclusion: Our findings reveal that entacapone is widely bioaccumulated by the gut microbiota across three donors and identify a key molecular mediator of this accumulation. This study expands the toolkit for investigating drug-microbiome interactions and holds significant potential to advance our understanding of drug-microbiome dynamics and therapeutic outcomes.},
}

@article {pmid41437936,
year = {2025},
author = {Guan, C and Li, X and Zeng, X and Du, Z and Zhou, Z and Zhao, J and Song, L and Yu, L},
title = {Unraveling the alterations and biomarkers in the tumor microenvironment in lung adenocarcinoma metastases and their indications for therapeutic response and prognosis.},
journal = {Therapeutic advances in medical oncology},
volume = {17},
number = {},
pages = {17588359251403904},
pmid = {41437936},
issn = {1758-8340},
abstract = {Lymph nodes, brain, bone, and liver are recognized as the four most common metastatic sites for lung adenocarcinoma (LUAD). Metastasis to these locations exhibits some common features, such as immune suppression, and distinct tumor microenvironment (TME) heterogeneity involving differentiation of immune cells, impacting treatment efficacy and prognosis. Lymph node metastases are characterized by immune suppression with exhausted CD8+ T cells, expanded regulated T cell (Tregs), M2-polarized macrophages, and high programmed death ligand-1 (PD-L1) expression. Brain metastases display an "immune desert" phenotype due to blood-brain barrier constraints, reduced T-cell infiltration, and microglia-mediated immunosuppression. Bone metastases involve osteoclast activation, RANKL/OPG pathway dysregulation, and metabolic reprogramming, while liver metastases show Kupffer cell-driven PD-L1/ programmed death 1(PD-1) axis suppression and elevated Treg infiltration. Key biomarkers across all types of metastases include PD-L1, cytokine profiles, immune cell ratios, and metabolic markers. Therapeutic strategies focus on combination therapies such as immune checkpoint inhibitors (ICIs) with metabolic modulators, localized drug delivery, and biomarker-guided approaches. Challenges in this field encompass spatial heterogeneity, dynamic TME evolution, and clinical translation barriers. Future research directions highlight spatial transcriptomics, microbiome interactions, and organoid models to optimize personalized immunotherapy. This article aims to provide a comprehensive review of regarding TME alterations across these four main metastatic locations of LUAD. It will also discuss relevant TME biomarkers and their clinical significance on therapeutic response and prognosis. We expect this article to serve as a source of evidence and inspiration for the future development of treatment strategies based on LUAD TME.},
}

@article {pmid41437842,
year = {2026},
author = {Siewert, LK and Berve, K and Pössnecker, E and Dyckow, J and Zulji, A and Baumann, R and Munoz-Blazquez, A and Krishnamoorthy, G and Schreiner, D and Sagan, S and Nelson, C and Sabatino, JJ and Nagashima, K and Diard, M and J Macpherson, A and Ganal-Vonarburg, SC and Fischbach, MA and Zamvil, SS and Schirmer, L and Baranzini, SE and Pröbstel, AK},
title = {Antigen-specific activation of gut immune cells drives autoimmune neuroinflammation.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2601430},
doi = {10.1080/19490976.2025.2601430},
pmid = {41437842},
issn = {1949-0984},
mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; Mice ; *Encephalomyelitis, Autoimmune, Experimental/immunology/microbiology ; Mice, Inbred C57BL ; T-Lymphocytes/immunology ; B-Lymphocytes/immunology ; Disease Models, Animal ; *Neuroinflammatory Diseases/immunology/microbiology ; Multiple Sclerosis/immunology/microbiology ; Autoimmunity ; Bacteria/genetics/immunology ; Female ; Antigens/immunology ; },
abstract = {Microbiome-based therapies are promising new treatment avenues. While global alterations in microbiota composition have been shown in multiple sclerosis, whether and how gut microbiota influence autoimmune responses in an antigen-specific manner is unclear. Here, we genetically engineered gut bacteria to express a brain antigen and dissect their pathogenic potential in a murine model of autoimmune neuroinflammation. Colonization with bacteria expressing myelin - but not ovalbumin-peptide exacerbates an encephalitogenic immune response in the gut by activating antigen-specific T cells as well as B cells leading to accelerated neuroinflammatory disease. These results demonstrate how antigen-specific microbial modulation can influence autoimmunity, providing insight for development of therapeutic strategies targeting specific bacterial taxa for treatment of MS and other autoimmune diseases.},
}

Animals
*Gastrointestinal Microbiome/immunology
Mice
*Encephalomyelitis, Autoimmune, Experimental/immunology/microbiology
Mice, Inbred C57BL
T-Lymphocytes/immunology
B-Lymphocytes/immunology
Disease Models, Animal
*Neuroinflammatory Diseases/immunology/microbiology
Multiple Sclerosis/immunology/microbiology
Autoimmunity
Bacteria/genetics/immunology
Female
Antigens/immunology

@article {pmid41437750,
year = {2025},
author = {Marano, G and Bardi, F and De Chiara, E and Lisci, FM and Brisi, C and Caroppo, E and Sani, G and Gasbarrini, A and Pola, R and Gaetani, E and Mazza, M},
title = {Neuroimmune Crossroads: Pathophysiological Links Between Bipolar Disorder and Inflammatory Bowel Disease.},
journal = {Actas espanolas de psiquiatria},
volume = {53},
number = {6},
pages = {1432-1447},
doi = {10.62641/aep.v53i6.2001},
pmid = {41437750},
issn = {1578-2735},
mesh = {Humans ; *Bipolar Disorder/physiopathology/immunology/epidemiology/complications ; *Inflammatory Bowel Diseases/physiopathology/immunology/complications/epidemiology ; *Neuroimmunomodulation/physiology ; },
abstract = {BACKGROUND: Bipolar disorder (BD) and inflammatory bowel disease (IBD) frequently co-occur, posing unique treatment challenges and implicating shared inflammatory mechanisms. Although each condition has been extensively studied in isolation, the clinical and pathophysiological interplay between BD and IBD remains poorly characterized.

METHODS: We conducted a narrative review of peer-reviewed literature from January 2000 through May 2025, retrieved from PubMed, Web of Science, and PsycINFO. Search terms included "bipolar disorder", "inflammatory bowel disease", "comorbidity", and related inflammatory markers. Titles/abstracts were screened by two reviewers, and eligible studies reporting clinical, epidemiological, or mechanistic data on BD-IBD overlap were included.

RESULTS: Prevalence estimates suggest that BD affects approximately 3-7% of IBD patients, compared with 1-2% in the general population. Comorbid BD-IBD is associated with increased hospitalization rates, more severe gastrointestinal and psychiatric symptoms, and reduced quality of life. Treatment interactions are complex: mood stabilizers and antipsychotics may exacerbate gastrointestinal inflammation, while corticosteroids and biologics can destabilize mood. Mechanistic studies highlight dysregulated cytokine profiles (e.g., elevated Interleukin-6, Tumor Necrosis Factor-alpha I), gut-microbiome alterations, and genetic pleiotropy as convergent pathways.

CONCLUSIONS: The intersection of BD and IBD underscores a bidirectional gut-brain neuroimmune axis, with systemic inflammation as a central mediator. Recognizing and managing this comorbidity requires integrated multidisciplinary care. Future research should focus on longitudinal studies and targeted anti-inflammatory interventions to improve outcomes in this high-risk population.},
}

Humans
*Bipolar Disorder/physiopathology/immunology/epidemiology/complications
*Inflammatory Bowel Diseases/physiopathology/immunology/complications/epidemiology
*Neuroimmunomodulation/physiology

@article {pmid41437718,
year = {2025},
author = {Wee, CL},
title = {You are what you eat, and more.},
journal = {Essays in biochemistry},
volume = {69},
number = {6},
pages = {},
doi = {10.1042/EBC20254001},
pmid = {41437718},
issn = {1744-1358},
}

@article {pmid41437389,
year = {2025},
author = {Morales, MFG and Hogue, SR and Pitcher, S and Jeong, D and Radosavljevic, I and Stefanou, A and Felder, SI and Burns, JR and Dowd, SE and Vogtmann, E and Sinha, R and Wang, L and Wang, X and Permuth, JB and Sears, CL and Andersen, SW and Greathouse, KL and Kresovich, JK and Friedman, MS and Siegel, EM and Byrd, DA},
title = {Survival implications of the age-associated tumor and normal adjacent tissue microbiome among colorectal cancer patients.},
journal = {Gut pathogens},
volume = {17},
number = {1},
pages = {109},
pmid = {41437389},
issn = {1757-4749},
support = {IRG-21-145-25//American Cancer Society and Tampa Merit Society/ ; },
abstract = {BACKGROUND: CRC incidence is rising among individuals younger than 50 years of age, with significant gaps in our understanding of the composition of the tissue microbiome across the age spectrum. The microbiome of tumors and normal adjacent tissue among colorectal cancer (CRC) patients may provide critical insights into the tumor microenvironment and CRC prognosis.

METHODS: We characterized the tumor and normal adjacent tissue microbiome of early-onset (EoCRC, n = 46) and frequency-matched later-onset (LoCRC, N = 101) CRC patients who underwent surgery at Moffitt Cancer Center. We extracted DNA from archival tissue from 147 patients and sequenced the 16 S rRNA gene. We estimated the relative abundance of a priori and exploratory bacteria and alpha and beta diversity. We used multivariable linear regression models to estimate the association of age with the tumor and normal adjacent tissue microbiome. Then, we estimated associations of primarily age-associated microbiome metrics with overall survival using multivariable Cox proportional hazard models.

RESULTS: In normal adjacent tissue, for every 10-year increase in age, there was a 1-SD higher relative abundance of a priori-selected Porphyromonas (Beta = 0.14, P = 0.03), Peptostreptococcus (Beta = 0.14, P = 0.03), and Prevotella (Beta = 0.13, P = 0.04). Fusobacterium and Bacillus were more abundant among EoCRC cases than LoCRC cases. In turn, Prevotella was associated with a 47% higher risk of mortality per 1-SD increase (95% CI = 1.19, 1.81; P < 0.001). Fusobacterium was not associated with mortality, but Bacillus was inversely associated with mortality.

CONCLUSION: We found that age at diagnosis was associated with the relative abundance of several bacteria, including oral-origin genera that were previously CRC-associated, in CRC normal adjacent tissue. In turn, some of these bacteria were associated with survival, suggesting potential age-related mechanisms underlying associations of the microbiome with survival.

Emerging evidence has highlighted the important role of the microbiome in colorectal cancer (CRC). Since the 1990s, there has been an increase in cases of early-onset colorectal cancer. However, there is still a limited understanding of the risk factors contributing to this rise. Investigating the associations between the microbiome of tumors and normal adjacent tissue in relation to aging offers a unique perspective on potential modifiable factors. Notably, our study has shown that age-related changes in the abundance of bacteria originating from the oral cavity, such as Porphyromonas, Peptostreptococcus, and Prevotella, are linked to CRC prognosis. These findings suggest that changes in the tissue microbiome with age may serve as prognostic markers for CRC and could help inform future prevention strategies that consider dietary and oral health interventions.},
}

@article {pmid41437386,
year = {2025},
author = {Aminu, S and Ascandari, A and Mokhtar, MM and Allali, AE and Benhida, R and Daoud, R},
title = {Genome-resolved surveillance and predictive ecological risk modeling of urban microbiomes.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-025-02315-3},
pmid = {41437386},
issn = {2049-2618},
abstract = {BACKGROUND: Human-built environment microbiomes mediate pathogen persistence and antimicrobial resistance (AMR) circulation, yet their ecological organization and resilience remain poorly quantified. Hospitals, sewage systems, ambulances, and public transport form interconnected microbial networks where contamination potential and compositional stability define biosurveillance risk. Understanding these dynamics requires genome-resolved frameworks capable of linking community composition to ecological behavior.

METHODS: We analyzed 767 publicly available Illumina metagenomes from four urban environments using the GRUMB workflow. Quality-filtered reads were assembled into 10,834 metagenome-assembled genomes (MAGs) and dereplicated into 1542 species-level representatives. Functional annotation with CARD and VFDB identified ARG- and VF-carrying species, producing a genome-resolved abundance matrix used for ecological and predictive modeling. Alpha and beta diversity, indicator taxa, and prevalence were assessed in R, while machine learning (Random Forest, scikit-learn) achieved a nested cross-validation balanced accuracy of 0.97 ± 0.01. Synthetic donor-recipient simulations (α = 0-1) implemented in Python modeled compositional blending, entropy-based uncertainty, and Minimal Detectable Contamination (MDC) thresholds.

RESULTS: Microbial communities exhibited strong environment-specific structure (PERMANOVA R[2] = 0.12, p < 0.001). Hospital sewage contained the highest richness and compositional heterogeneity, whereas ambulances and hospital environments showed low-diversity, surface-filtered microbiomes. Machine learning identified consistent ecological predictors (Pseudomonas_E fragi, Sphingomonas sp000797515, Acinetobacter variabilis, Roseomonas mucosa) that delineated environmental identity. Synthetic blending revealed a directional source-sink hierarchy with hospital sewage acting as the primary donor (MDC = 0.2-0.3), while hospital environments displayed the greatest compositional resilience (MDC ≥ 0.8). Entropy-based uncertainty analysis identified tipping zones (α = 0.3-0.5), and dominance mapping highlighted hospital environments as stabilizing ecological nodes. WHO-priority pathogens (Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli) occupied central positions in the network, bridging environmental and clinical compartments.

CONCLUSIONS: This genome-resolved and simulation-driven framework reveals a directional microbial continuum across urban infrastructures governed by dominance, resilience, and clinical connectivity. Hospital sewage functions as a microbial donor, while hospital environments act as ecological stabilizers anchoring built-environment microbiomes. These findings advance biosurveillance from descriptive profiling to predictive ecological modeling, offering quantitative metrics for risk-informed infrastructure design. Video Abstract.},
}

@article {pmid41437366,
year = {2025},
author = {Park, Y and Yang, J and Son, H and Park, MJ and Moon, SJ and Kim, KJ and Kwok, SK},
title = {Distinct gut microbiome profiles in Korean systemic lupus erythematosus patients.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-025-07438-7},
pmid = {41437366},
issn = {1479-5876},
abstract = {BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease associated with systemic inflammation and multi-organ involvement. Emerging evidence suggests that gut microbiota dysbiosis may contribute to its immunopathogenesis.

OBJECTIVE: This study aimed to characterize gut microbial composition and diversity in Korean SLE patients and evaluate associations with clinical features.

METHODS: Fecal samples from 157 SLE patients and 50 healthy controls (HC) were analyzed using 16S rRNA gene sequencing. Alpha and beta diversity metrics were assessed, and taxonomic differences were analyzed. Subgroup comparisons were conducted based on lupus nephritis (LN) status and disease activity. Functional predictions were inferred using PICRUSt2.

RESULTS: SLE patients exhibited significantly reduced microbial richness (Chao1, ACE, Fisher indices), while evenness (Shannon, Simpson) was preserved. Beta diversity analysis revealed distinct clustering between SLE and HC groups. SLE was characterized by enrichment of Bacteroides, Streptococcus, and Veillonella, and depletion of Collinsella, Ruminococcus, and Bifidobacterium. LEfSe identified several discriminatory taxa. However, no significant microbial differences were observed between LN-positive and LN-negative groups or between high and low disease activity groups. Functional prediction revealed minimal differences in microbial pathways between groups.

CONCLUSION: These findings highlight distinct gut microbial alterations in Korean SLE patients and support the potential utility of microbiome profiles as diagnostic biomarkers or therapeutics.},
}

@article {pmid41437272,
year = {2025},
author = {Zhu, W and Li, F and Lin, D and Cai, L and Dai, C and Liu, H and Lin, Y},
title = {The airway mycobiome in chronic respiratory diseases: current advances and future frontiers.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1411},
pmid = {41437272},
issn = {1479-5876},
}

@article {pmid41437205,
year = {2026},
author = {Dinesh, D and Morgan, XC and Kim, H and Scott, TM and Garelnabi, M and Lee, JS and Mangano, KM and Nguyen, LH and Huttenhower, C and Tucker, KL and Palacios, N},
title = {Gut Microbial Variations Associated With Proton Pump Inhibitor Use in the Boston Puerto Rican Health Study.},
journal = {Pharmacology research & perspectives},
volume = {14},
number = {1},
pages = {e70205},
doi = {10.1002/prp2.70205},
pmid = {41437205},
issn = {2052-1707},
support = {RF1AG075922/AG/NIA NIH HHS/United States ; P01 AG023394/NH/NIH HHS/United States ; P50 HL105185/NH/NIH HHS/United States ; R01 AG055948/NH/NIH HHS/United States ; R01 NS09772/NH/NIH HHS/United States ; //University of Massachusetts/ ; },
mesh = {Humans ; *Proton Pump Inhibitors/adverse effects/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Female ; Male ; Aged ; Middle Aged ; Prospective Studies ; Boston ; Cross-Sectional Studies ; Puerto Rico/ethnology ; Hispanic or Latino ; Feces/microbiology ; White ; },
abstract = {Proton pump inhibitors (PPI), used to treat gastrointestinal disorders, are associated with alterations in the gut microbiome. However, this is understudied in Puerto Ricans who have unique lifestyle characteristics. Puerto Ricans, including participants of the Boston-Puerto Rican Health Study (BPRHS), report high PPI use. Therefore, we examined gut microbial variations associated with PPI use in the BPRHS. BPRHS is a prospective cohort. 309 BPRHS participants self-reported PPI use and self-collected, metagenomically profiled, stool samples. PPI use was classified as any use in the past 30 days. Cross-sectional associations between gut microbial taxa, functional pathways, and PPI use were examined using omnibus analyses, multivariate linear modeling in MaAsLin2, and random forest classifier in feature-wise analyses. We further compared our results with the non-Hispanic Health Professionals Follow-Up Study (HPFS) to validate key findings and examine ethnicity-related differences. Among 309 participants (mean age 68.8 years; female 74.6%), 112 (36%) self-reported PPI use. After adjusting for relevant covariates, we observed an enrichment of Streptococcus parasanguinis (β = 3.16, FDR p = 0.01), S. anginosus (β = 2.89, FDR p < 0.01), S. salivarius (β = 2.56, FDR p = 0.01), S. gordonii (β = 1.98, FDR p = 0.15), and Rothia mucilaginosa (β = 1.54, FDR p = 0.06), among PPI users compared to non-users. Streptococci, Lactobacilli, and Enterococci predominantly contributed to the functional pathways associated with PPI use. The observed enrichment of oral-typical taxa, such as Streptococci, among PPI users in the BPRHS suggests the potential of PPIs to alter gut microbial composition. More studies are needed to understand the impact of PPI use on the gut microbiome in different ethnicities. Trial Registration: Parent study (BPRHS) NCT01231958.},
}

Humans
*Proton Pump Inhibitors/adverse effects/pharmacology
*Gastrointestinal Microbiome/drug effects
Female
Male
Aged
Middle Aged
Prospective Studies
Boston
Cross-Sectional Studies
Puerto Rico/ethnology
Hispanic or Latino
Feces/microbiology
White

@article {pmid41437183,
year = {2025},
author = {Cai, X and Sun, T and Feng, M and Chen, G and Zhou, J and Zhuang, H and Wang, D and Chen, Y and Cheng, Z and Xu, Z and Zheng, X and Zhang, X and Yuan, Y},
title = {Taurocholic Acid Is Associated With Disturbed Functional Connectivity in the Hippocampus of Patients With Depression.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e08693},
doi = {10.1002/advs.202508693},
pmid = {41437183},
issn = {2198-3844},
support = {2024YFA1308200//National Key Research and Development Program of China/ ; 82571747//National Natural Science Foundation of China/ ; 82271570//National Natural Science Foundation of China/ ; BK20240095//Outstanding Youth Talent funding of Jiangsu Province/ ; GSP-LCYJFH12//Jiangsu Province High-Level Hospital Construction Funds to Zhongda Hospital Affiliated to Southeast University/ ; },
abstract = {Major Depressive Disorder (MDD) is characterized by abnormal metabolic profiles along the microbiome-gut-brain axis. Bile acids (BAs), a class of steroid compounds regulated by the host and microbes, are increasingly shown to become dysregulated in models of depression. However, the identity of key regulatory BA metabolite in patients with MDD and associated mechanism remain to be clarified. Here, a prospective observational study in patients with depression (n = 235) and control subjects (n = 232) for identifying functional BA metabolites regulating depressive behavior and brain functional connectivity is performed. Using comparative metabolomics assay, an increased level of taurocholic acid (TCA) in the serum of patients with MDD is observed, which is reversed by anti-depressant treatments. Transferring fecal microbiome from patients with MDD induced TCA accumulation to the hippocampus of recipient mice exhibiting depression-like behavior. TCA supplementation suppressed hippocampal neurogenesis, triggered microglial activation, and elicited depression-like behavior in mice, which are alleviated by a sphingosine-1-phosphate receptor 2 (S1PR2) antagonist. In patients with MDD, functional neuroimaging and spearman correlation analysis revealed that circulating TCA is strongly correlated with functional connectivity in the subregions of hippocampus. The results highlight the potential of harnessing TCA as a prognostic marker and therapeutic target for depression.},
}

@article {pmid41437143,
year = {2025},
author = {Yang, C and Yue, H and Sun, A and Feng, Z and Feng, H and Zhang, Y and Zhao, L and Zhou, J and Zhu, H and Wei, F},
title = {Intercropping-mediated enrichment of core microbiome enhances suppression of Verticillium wilt in cotton.},
journal = {Environmental microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40793-025-00840-0},
pmid = {41437143},
issn = {2524-6372},
support = {2024D14007//Tianshan Innovation Team Project/ ; TCYC2023TP02//Xinjiang Tianchi Talents Program/ ; 2022YFD1400300//National Key R&D Program of China/ ; },
abstract = {BACKGROUND: Verticillium wilt, caused by Verticillium dahliae Kleb., is a devastating soilborne disease threatening global cotton production. Intercropping is a sustainable agricultural practice known to suppress soilborne diseases, yet the microbiome-mediated mechanisms underlying its efficacy against Verticillium wilt remain poorly understood.

RESULTS: A three-year field trial (2019-2021) showed that intercropping cotton with mustard significantly reduced Verticillium wilt severity (32.11-39.2%), increased yield (13.88-23.22%), and lowered soil microsclerotia density. Intercropping reshaped soil microbial communities and enriched a core set of beneficial taxa compared to monocropping, generating more complex and cooperative rhizosphere networks during flowering and boll stage. We then constructed an intercropping-enriched synthetic community (IC-SynCom) from the enriched core microbiotas with multiple beneficial traits; this consortium, comprising Bacillus altitudinis strain CRB-021, Lysobacter firmicutimachus strain CRB-253, Rhizobium soli strain CRB-314, Enterobacter hormaechei strain CRB-070, and Pantoea sp. strain CRB-006, achieved the highest control efficacy at 72.83 ± 1.31%, promoted cotton growth, and outperformed single-strain inoculants. qRT-PCR further showed that IC-SynCom activated systemic plant defenses by the upregulation of key defense-related genes, including phenylalanine ammonia-lyase (GhPAL), cinnamate 4-hydroxylase (GhC4H1), pathogenesis-related protein 10 (GhPR10), peroxidase (GhPOD), and β-1,3-glucanase (Ghβ-1,3-glucanase), which are involved in salicylic acid signaling and lignin biosynthesis.

CONCLUSIONS: Our findings demonstrate that intercropping enhances soil's capacity to suppress Verticillium wilt by reshaping root-associated microbiomes. A core consortium of intercropping-enriched beneficial microbes (IC-SynCom) effectively suppresses Verticillium wilt through direct antagonism and activation of plant immunity. These results highlight the potential of microbiome-based strategies for sustainable management of soilborne diseases.},
}

@article {pmid41437131,
year = {2025},
author = {Orel, N and Fadeev, E and Celussi, M and Turk, V and Klun, K and Afjehi-Sadat, L and Herndl, GJ and Tinta, T},
title = {Down the drain: exploring wastewater's role in coastal microbiome transformations.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-025-02298-1},
pmid = {41437131},
issn = {2049-2618},
support = {P1-0237//The Slovenian Research and Innovation Agency/ ; P4-0432//The Slovenian Research and Innovation Agency/ ; I 4978-B//Austrian Science Fund/ ; 10046144//INTERREG Italy - Croatia/ ; },
abstract = {BACKGROUND: Many coastal ecosystems worldwide are impacted by wastewater discharges, which introduce nutrients, pollutants, and allochthonous microbes that can alter microbiome composition and function. Although the severity and distribution of these impacts vary across regions, their potential consequences for key ecological processes remain a concern. The resilience and functional adaptability of native coastal microbiomes are still poorly understood. To study the immediate ecological impact of wastewater discharge on a coastal seawater microbiome, we conducted short-term microcosm experiments, exposing a coastal microbiome to two types of treated wastewater: (i) unfiltered wastewater containing nutrients, pollutants, and allochthonous microbes; and (ii) filtered wastewater containing only nutrients and pollutants.

RESULTS: By integrating multi-omics and metabolic assays, we show that wastewater-derived organic matter and nutrients (mostly ammonia and phosphate) did not alter the taxonomic composition of the coastal microbiota, but triggered reorganization of metabolic pathways in them. We observed enhanced metabolism of proteins, amino acids, lipids, and carbohydrates, particularly of the lineages Alteromonadales, Rhodobacterales, and Flavobacteriales. Glaciecola (Alteromonadales), a copiotroph with antagonistic traits, significantly contributed to these shifts. Conversely, allochthonous taxa like Legionellales and Pseudomonadales had minimal impact. Elevated phosphorus concentrations resulting from wastewater input reduced the synthesis of proteins linked to scavenging phosphorus from organic phosphorus compounds, including alkaline phosphatase activity in native Rhodobacterales and Flavobacteriales, with important ecological implications for phosphorus-depleted coastal ecosystems. Furthermore, the presence of wastewater caused a decline in relative abundance and metabolic activity of Synechococcus, potentially affecting carbon cycling. Yet, the coastal microbiome rapidly respired wastewater-derived dissolved organic carbon, resulting in bacterial growth efficiencies consistent with global coastal averages.

CONCLUSIONS: Our findings highlight the capacity of coastal microbiomes to withstand wastewater discharge, with critical implications for assessment of anthropogenic perturbations in coastal ecosystems. However, wastewater-driven changes in metabolic functions and niche utilization within the autochthonous microbial community, impacting phosphorus cycling and potentially affecting carbon cycling, may have long-term consequences for ecosystem functioning. Video Abstract.},
}

@article {pmid41437105,
year = {2025},
author = {Son, Y and He, P and Craft, EJ and Piñeros, MA and Baldwin, M and Wang, Z and Gu, AZ and Kao-Kniffin, J},
title = {Synergistic enhancement of Sorghum bicolor nutrient uptake and growth by microbiomes in enhanced biological phosphorus removal system and arbuscular mycorrhizal fungi.},
journal = {Environmental microbiome},
volume = {20},
number = {1},
pages = {155},
pmid = {41437105},
issn = {2524-6372},
support = {PS00298891//Fulbright Program/ ; 2019-67013-29364//National Institute of Food and Agriculture/ ; },
abstract = {BACKGROUND: Understanding soil microbial interactions is essential for developing biofertilizers in regenerative agriculture. Polyphosphate-accumulating organisms (PAOs) play a pivotal role in enhanced biological phosphorus removal (EBPR) systems by sequestering phosphorus from wastewater and storing it as intracellular polyphosphate. However, their role in terrestrial phosphorus cycling remains poorly characterized, despite their potential to serve as a reservoir of plant-available phosphorus. This study investigates PAO-enriched microbiomes in the sorghum rhizosphere, focusing on their novel interactions with arbuscular mycorrhizal fungi (AMF). By integrating PAOs derived from EBPR biosolids and compost with AMF, we assessed their synergistic effects on plant growth and nutrient uptake in Sorghum bicolor (sorghum), as well as their broader influence on rhizosphere microbial traits and functional dynamics.

RESULTS: We employed plant biometry analysis, nutrient assays, [31]P NMR spectroscopy, single-cell Raman microspectroscopy (SCRS), and microbiome profiling to comprehensively evaluate rhizosphere microbial interactions and their effects on plant physiology and nutrient dynamics. [31]P NMR confirmed polyphosphate accumulation by PAOs derived from both compost and EBPR biosolids, demonstrating the soil adaptability of EBPR-derived PAOs. AMF showed enhanced synergy with EBPR-derived microbiomes, significantly enhancing sorghum growth, nutrient acquisition, and microbial diversity. Key PAOs, Thauera, Rhodanobacter, and Paracoccus, were successfully incorporated into the rhizosphere and positively correlated with improved phosphorus uptake. PICRUSt2 analysis indicated enrichment of microbial functions linked to motility and xenobiotic metabolism in EBPR-treated rhizospheres. SCRS revealed AMF-induced phenotypic shifts in EBPR-derived microbiomes, while network analysis showed that AMF reorganized community connectivity, fostering novel microbial interactions in EBPR-amended environments.

CONCLUSIONS: This study explored the interactions between AMF and microbiomes derived from EBPR biosolids, in comparison with those from compost, uncovering novel microbial synergies that enhance phosphorus uptake in Sorghum bicolor and promote plant productivity. The findings underscore the potential of targeted microbial co-inoculation such as integrating EBPR microbiomes with AMF as an innovative strategy for improving soil fertility and advancing biofertilizer development through microbial-driven nutrient recycling. By harnessing wastewater-derived phosphorus via PAOs, this approach offers a sustainable alternative to conventional fertilization, supporting regenerative agriculture, nutrient circularity, and the broader application of microbial biofertilizers in crop production.},
}

@article {pmid41437084,
year = {2025},
author = {Jiang, W and Chen, R and Song, L and Qin, L and Xu, X and Li, X and Zhao, L and Lyu, J and Wang, X and Wang, G and Chen, X and Liu, Y and Wang, M and Yin, C and Wang, Y and Mao, Z},
title = {From metabolic fingerprints to field solutions: engineering the apple rhizosphere microbiome via host-directed Bacillus recruitment for sustainable apple replant disease control.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-025-02301-9},
pmid = {41437084},
issn = {2049-2618},
support = {CARS-27//China Agriculture Research System of MOF and MARA/ ; 2022TZXD0037//Key R&D program of Shandong Province/ ; 2023YFD2301003//National Key Research and Development Program/ ; },
abstract = {BACKGROUND: The rhizosphere microbiome, as the second genome of plant immunity, forms a critical ecological barrier in plant-pathogen interactions. However, its functional mechanism in resisting the replanting disease pathogenic Fusarium proliferatum MR5 in apples has not been systematically elucidated. This study employed an integrated multi-omics approach to investigate the rhizosphere mechanisms of resistant (CG935) and sensitive (M9T337) apple rootstocks, aiming to uncover the metabolic and microbial interactions underlying apple replant disease resistance.

RESULTS: Multiple omics joint analysis found that the infection of Fusarium proliferatum MR5 triggered the activation of a specific lysine biosynthesis pathway in resistant rootstocks, and the expression levels of key rate limiting enzymes aspartate kinase and dihydrodipicolinate synthase were significantly upregulated by 2.79 ~ 6.81 times compared to M9T337. Along with the metabolic reprogramming process, the efflux of lysine from the rhizosphere increased, and Bacillus with broad-spectrum antibacterial activity were specifically recruited, increasing its relative abundance by 40.73%. In vitro assays demonstrated that the recruited Bacillus suppressed Fusarium spore germination and disrupted mycelial growth through the production of antifungal compounds, including 2,4-di-tert-butylphenol and bacillomycin. Potted experiments have confirmed that the synergistic treatment of Bacillus and lysine significantly reduces the number of pathogenic Fusarium in the rhizosphere, increases soil enzyme activity, and reshapes a more stable rhizosphere bacterial community structure by enhancing the modularity (the degree of modularity in microbial network structure) of the microbial network. This collaborative strategy effectively alleviates the physiological damage of apple seedlings under replanting stress, resulting in a 31.18% increase in plant fresh weight. Field validation experiments further demonstrate that this strategy can promote the growth of replanted apple saplings and reduce the occurrence of apple replant disease.

CONCLUSIONS: Our findings elucidate an apple replant disease resistance mechanism in apple rootstocks involving lysine-mediated recruitment of protective Bacillus, which enhances rhizosphere microbiome stability and suppresses soil pathogenic Fusarium. Developed a technology for synergistic control of apple replant disease using Bacillus-lysine. The research results provide theoretical basis and practical solutions for green control of apple replant disease based on precise regulation of rhizosphere microbiome. Video Abstract.},
}

@article {pmid41436928,
year = {2025},
author = {Nath, S and Mittinty, M and Zilm, P and Santiago, PHR and Ketagoda, DKH and Jamieson, L and Weyrich, L},
title = {Super donor assessment tool for oral microbiome transplantation.},
journal = {BMC microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12866-025-04630-z},
pmid = {41436928},
issn = {1471-2180},
support = {2019/GNT1187737//National Health and Medical Research Council/ ; },
abstract = {AIMS: Oral microbiome transplantation (OMT) involves transferring microbiota from donor to recipient. However, selecting suitable donors remains challenging due to a lack of standardised guidelines. This study developed a novel super donor assessment tool (SDAT) combining a multi-criteria decision-making (MCDM) process and an analytical hierarchical process (AHP) to identify OMT "super donors" for dental caries prevention.

METHODS: This cross-sectional study used four sequential screening phases with data from 93 healthy participants, capturing socio-demographics, lifestyle, dietary and oral health behaviours. The SDAT employed MCDM, AHP, combining criteria with normalised and weighted ranks to establish the top 10 donors for three models: "Optimal donor" (Model 1), "Ideal donor" (Model 2), and "Sub-optimal donor" (Model 3). Donor plaque samples underwent 16S ribosomal RNA amplicon sequencing for microbial profiling, examining alpha and betadiversity, differential abundance, and network analysis.

RESULTS: Alpha diversity analysis showed significant differences among groups (Kruskal-Wallis p < 0.001), with Model 1 showing the lowest diversity and Model 3 the highest. Beta diversity analysis using Permutational Multivariate Analysis of Variance revealed significant differences in microbial community composition (R² = 0.19, p = 0.001). Differential abundance analysis (False Discovery Rate < 0.05, controlling for age and sex) identified health-associated genera (Neisseria, Lautropia, Streptococcus, Veillonella) in Model 1, whereas Model 3 showed higher levels of disease-associated taxa (Treponema, Capnocytophaga). Network analysis revealed that Model 1 was organised around Actinomyces and Prevotella, Model 2 around Rothia and Haemophilus, and Model 3 was dominated by pathogenic taxa.

CONCLUSION: SDAT provides a systematic, transparent framework for super-donor selection, ensuring precision and reproducibility in donor rankings. The scoring system standardises the donor selection process, the effectiveness of donor screening, and reduces the risk of adverse events for OMT.},
}

@article {pmid41436743,
year = {2025},
author = {Prajapati, SK and Shukla, R and Kumar, V and Yadav, D and Lekkala, L and Szekeres, C and Ma, Y and Jain, S and Yadav, H},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e102998},
doi = {10.1002/alz70855_102998},
pmid = {41436743},
issn = {1552-5279},
mesh = {Humans ; Male ; *Gastrointestinal Microbiome/immunology ; Aged ; Female ; *Cognitive Dysfunction/immunology/microbiology ; Middle Aged ; *Alzheimer Disease/immunology/microbiology ; Aged, 80 and over ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) pathogenesis has been linked to the microbiota-immune-brain axis; however, the relationship between gut microbiota, immune activity, and cognitive impairment remains unclear. Thus, this study examines the connection between intestinal microbial composition, immune cell phenotype, and cognitive function in older adults.

METHOD: Data and biological samples were obtained from participants aged ≥60 years (Control, n = 30; mild cognitive impairment (MCI), n = 30) from the MiaGB (Microbiome in Aging Gut and Brain) consortium, a multi-site, clinical study. Cognitive function was assessed using Montreal Cognitive Assessment (MoCA) scores, immunophenotyping through flow cytometry, stool microbiome analysis using whole-genome metagenomics, and bulk transcriptomics analysis was carried out.

RESULTS: The abundance of immune cells such as granulocytes, lymphocytes, T-cells, and NK cells was significantly decreased in MCI group. Interestingly, the levels of CD4+ were reduced while CD8+ cells increased in MCI participants compared to controls. Microbial profiling revealed distinct bacterial signatures, with MCI participants showing higher relative abundances of Eubacterium hallii, Parabacteroides distasonis, Eggerthella_sp_CAG_298, Dorea formicigenerans and Alistipes finegldii. Differential expression analysis of transcriptomics data identified 1632 upregulated and 240 downregulated genes. Gene ontology and pathway analysis revealed that upregulated genes are involved in several immune functions such as response to stimulus, adaptive immune response, lymphocyte, and T cell activation, while downregulated genes are linked to nervous system functions and signaling processes such as neuron projection. Transcriptomics analysis further highlighted that several downregulated genes are involved in the key pathways that participate in the neural functions.

CONCLUSION: These distinct bacteria, immune cells, and gene expression profiles suggest that alterations in immune cell populations, gene expression, and gut microbiota are associated with cognitive function in aging, highlighting potential interactions between the microbiota-immune-brain axis and cognitive impairment.},
}

Humans
Male
*Gastrointestinal Microbiome/immunology
Aged
Female
*Cognitive Dysfunction/immunology/microbiology
Middle Aged
*Alzheimer Disease/immunology/microbiology
Aged, 80 and over

@article {pmid41436619,
year = {2025},
author = {Do Nascimento, S and Theodosiou, AA and Sergaki, C},
title = {Microbiotoxicity: an under-recognised player in drug efficacy, toxicity, and health outcomes.},
journal = {npj antimicrobials and resistance},
volume = {3},
number = {1},
pages = {102},
pmid = {41436619},
issn = {2731-8745},
abstract = {The gut microbiome regulates immunity, inflammation, and metabolism. Disruption by antibiotic and non-antibiotic drugs, termed microbiotoxicity, may impair efficacy of treatments, including cancer immunotherapy and vaccination, and contribute to antimicrobial resistance (AMR). This review explores microbiotoxicity's clinical impacts, highlighting non-antibiotic drug effects. Further research into drug-microbiome interactions in future may help inform prescribing practices and drug development as a way to improve health outcomes, reduce toxicity, and support AMR stewardship.},
}

@article {pmid41436524,
year = {2025},
author = {Frey, DL and Helm, B and Guerra, M and Hagner, M and Lu, J and Dittrich, AS and Wege, S and Eberhardt, R and Herth, FJF and Sommerburg, O and Schultz, C and Dalpke, AH and Klingmüller, U and Mall, MA and Boutin, S},
title = {SputOMICs identifies common and distinct markers in cystic fibrosis and chronic obstructive pulmonary disease.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {44418},
pmid = {41436524},
issn = {2045-2322},
abstract = {Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are muco-obstructive lung diseases. Knowledge of molecular processes has much improved therapeutic options in CF, whereas much less is known for COPD, a disease affecting an increasing number of patients. Here, we report a multilayer workflow integrating microbiome, inflammation and proteome profiling with clinical data to identify disease specific characteristics in sputum. Our proof-of-concept study shows that CF sputum is dominated by Pseudomonas and Staphylococcus, exhibits heightened neutrophilic inflammation, and a severe protease-antiprotease imbalance. In contrast, COPD displays heterogeneous microbiome composition, eosinophilic inflammation, and altered extracellular matrix remodeling. Proteome-based cellular deconvolution identifies disease-specific immune cell signatures, underscoring the complexity, especially in COPD. Multi-omics factor analysis suggests that matrisome and nucleotide metabolism changes may act as disease discriminators, though future confirmation in larger cohorts is needed. These findings highlight the potential of our integrated approach to uncover sputum biomarkers as tools for patient stratification and personalized therapeutic strategies in CF and COPD.},
}

@article {pmid41436448,
year = {2025},
author = {Manghi, P and Antonello, G and Schiffer, L and Golzato, D and Wokaty, A and Beghini, F and Mirzayi, C and Long, K and Gravel-Pucillo, K and Piccinno, G and Gamboa-Tuz, SD and Bonetti, A and D'Amato, G and Azhar, R and Eckenrode, K and Zohra, F and Giunchiglia, V and Keller, M and Pedrotti, A and Likhotkin, I and Elsafoury, S and Geistlinger, L and Blanco-Miguez, A and Thomas, AM and Zolfo, M and Ramos, M and Valles-Colomer, M and Tamburini, S and Asnicar, F and Jones, HE and Huttenhower, C and Carey, V and Davis, S and Pasolli, E and Oh, S and Segata, N and Waldron, L},
title = {Meta-analysis of 22,710 human microbiome metagenomes defines an oral-to-gut microbial enrichment score and associations with host health and disease.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-66888-1},
pmid = {41436448},
issn = {2041-1723},
support = {5R01CA230551//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; 5R01CA230551//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {Large public datasets of the human microbiome now exist but combining them for large-scale analysis is difficult due to a lack of standardization. We developed curatedMetagenomicData (cMD) 3, a uniformly processed collection of over 22,000 human microbiome samples with manually curated metadata from 94 studies and 42 countries. This large and diverse resource allows for meta-analysis of the links between microbes and human health. Through meta-analysis, we identified hundreds of microbial species and thousands of microbial functions significantly associated with a person's sex, age, body mass index, and disease status, and catalog these as references. We developed an "oral enrichment score" (OES) based on the relative abundance of bacteria typically found in the oral cavity and not in the gut. Higher OES in the gut is a consistent feature in individuals with disease, suggesting that the relative abundance of oral bacteria in the gut is a simple and quantifiable signal of altered microbiome health. These analyses identify modest but widely shared patterns in human microbiomes, serving as a reproducible and readily updatable reference.},
}

@article {pmid41436256,
year = {2025},
author = {Viganò, P and Abodi, M and Benaglia, L and Bolis, I and Casalechi, M and Ferraro, C and Li Piani, L and Reschini, M and Ruggiero, F and Salmeri, N and Somigliana, E and Horne, AW and Nap, AW and Dolmans, MM and , },
title = {Effectiveness of an anti-inflammatory diet before in vitro fertilisation in women with endometriosis: protocol for a randomised controlled trial.},
journal = {BMJ open},
volume = {15},
number = {12},
pages = {e108596},
doi = {10.1136/bmjopen-2025-108596},
pmid = {41436256},
issn = {2044-6055},
mesh = {Humans ; Female ; *Fertilization in Vitro ; *Endometriosis/complications/diet therapy ; *Infertility, Female/etiology/therapy/diet therapy ; Adult ; Randomized Controlled Trials as Topic ; Quality of Life ; Ovulation Induction/methods ; },
abstract = {INTRODUCTION: Endometriosis is a common, benign, chronic inflammatory disease with multiple consequences, from chronic pain to systemic comorbidities and poor quality of life. As it usually affects people of reproductive age, one of the most distressing consequences is infertility, which can be only partly overcome by medically assisted reproduction. Poor outcomes are, in fact, frequent adverse events. As no definitive therapy exists for endometriosis-related infertility, affected women often tend to try either complementary and alternative medicine or self-management strategies to improve their quality of life, with the hope of also enhancing their fertility. Among available options, dietary interventions are commonly explored, even if no robust evidence is available on the optimal type of diet and its effects on reproductive outcomes. This trial will investigate whether an anti-inflammatory dietary intervention can improve fertility outcomes in women affected by endometriosis undergoing in vitro fertilisation (IVF).

METHODS AND ANALYSIS: The DietAry interveNtion in ameliorating fertiliTy parameters in women with Endometriosis undergoing IVF (DANTE) study is a single-centre, randomised, controlled, non-pharmacological interventional trial in patients living with endometriosis who are infertile and require IVF. Participants will be allocated to either a 12-week intervention based on an anti-inflammatory diet or no diet before the beginning of controlled ovarian stimulation. Following baseline assessment, 438 participants aged <40 years with a diagnosis of infertility according to WHO criteria (ie, not conceiving after 12 months or more of regular unprotected intercourse) and a normal ovarian reserve will be randomly allocated to one of the two groups (1:1 ratio). In both groups, the dietary habits of participants will be assessed at baseline, and adherence to the intervention will be monitored throughout the study period via 24-hour recalls and food diaries. Participants will provide biological samples (peripheral blood, vaginal swabs and faeces) before and after the intervention to evaluate potential differences in inflammatory markers and microbiome composition between the two groups and across timepoints (before and after diet in the intervention group). Follicular fluid will be collected at the time of oocyte retrieval to describe potential difference in sex steroid levels. Patients will also complete questionnaires on quality of life, sexual function and symptom severity before and after the intervention to assess differences between the two groups and across time points. The primary outcome will be the rate of inadequate ovarian response (defined as the retrieval of ≤3 oocytes according to the Poseidon 2016 criteria) at the time of oocyte retrieval in the treatment versus the no-treatment groups. Secondary outcomes will include clinical pregnancy and live birth rates, IVF-related embryological outcomes, inflammatory marker levels in peripheral blood, vaginal and bowel microbiota features, steroid composition of follicular fluid, life quality and pain symptoms variation.

ETHICS AND DISSEMINATION: The study has received ethics approval from Comitato Etico Territoriale Lombardia 3 (#5587_18.12.2024). Results will be presented in peer-reviewed journals and at international conferences.

TRIAL REGISTRATION NUMBER: NCT06885125.},
}

Humans
Female
*Fertilization in Vitro
*Endometriosis/complications/diet therapy
*Infertility, Female/etiology/therapy/diet therapy
Adult
Randomized Controlled Trials as Topic
Quality of Life
Ovulation Induction/methods

@article {pmid41436068,
year = {2025},
author = {Yang, CY and Jalsrai, A and Hsieh, HM},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e101570},
doi = {10.1002/alz70855_101570},
pmid = {41436068},
issn = {1552-5279},
mesh = {Animals ; Mice ; *Alzheimer Disease/drug therapy/pathology ; Mice, Inbred C57BL ; *Neuroprotective Agents/pharmacology ; Disease Models, Animal ; Mice, Transgenic ; *Polysaccharides/pharmacology ; Male ; Maze Learning/drug effects ; *Plant Extracts/pharmacology ; RAW 264.7 Cells ; *Anti-Inflammatory Agents/pharmacology ; },
abstract = {BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by a progressive decline in cognitive functions. Key pathological features of AD include the accumulation of Aβ plaques, the formation of neurofibrillary tangles (NFTs) composed of hyperphosphorylated Tau, and significant neuronal loss. Neuroinflammation is critical to the pathogenesis of AD, closely linked to the development of these pathological hallmarks and the progression of neuronal damage. Hedysarum, a traditional herbal medicine and dietary supplement with a long history of clinical application, is widely recognized for its health-promoting and disease-managing properties.

METHODS: In this study, we investigated the neuroprotective and anti-inflammatory potential of Hedysarum alpinum L. polysaccharide extracts (HAP) using two models, in vivo 5xFAD mice and in vitro LPS-induced RAW264.7 macrophages. The 4-month-old 5xFAD and wild-type (C57BL/6J) mice were orally administered with HAP (20 mg/kg) or saline vehicle daily for six weeks, respectively. Behavioral tests were conducted during the last two-week treatment to evaluate cognitive functions.

RESULTS: In the Barnes maze, the TG+HAP group exhibited a significantly shorter latency to locate the escape hole during the training phase compared to the TG+saline group. During the probe phase, the HAP-treated group also spent considerably more time in the target quadrant, indicating improved spatial learning and memory. Moreover, in the Y-maze test, 5xFAD mice showed a significantly reduced spontaneous alternation rate compared to wild-type mice, reflecting impaired short-term memory. However, HAP administration significantly improved the spontaneous alternation rate in 5xFAD mice. Furthermore, HAP effectively attenuated LPS-induced activation of the NLRP3 inflammasome in RAW264.7 macrophages by inhibiting the NFκB signaling pathway. HAP significantly reduced LDH release and gene expression levels of pro-inflammatory mediators, including IL-1β, IL-6, TNF-α, and iNOS.

CONCLUSIONS: Our findings demonstrate that HAP significantly reduces inflammation and improves cognitive function in 5xFAD mice. These beneficial effects could be mediated through the modulation of the microbiota-gut-brain axis, which will be further elucidate through analyzing of the gut microbiome composition.},
}

Animals
Mice
*Alzheimer Disease/drug therapy/pathology
Mice, Inbred C57BL
*Neuroprotective Agents/pharmacology
Disease Models, Animal
Mice, Transgenic
*Polysaccharides/pharmacology
Male
Maze Learning/drug effects
*Plant Extracts/pharmacology
RAW 264.7 Cells
*Anti-Inflammatory Agents/pharmacology

@article {pmid41436038,
year = {2025},
author = {Zhang, T and Peng, G},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e101496},
doi = {10.1002/alz70855_101496},
pmid = {41436038},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; *Alzheimer Disease/pathology/metabolism ; *Cognitive Dysfunction/pathology/metabolism ; Aged ; *Gastrointestinal Microbiome/physiology ; *Bile Acids and Salts/blood ; *Basal Forebrain/pathology/diagnostic imaging ; Cognition/physiology ; Magnetic Resonance Imaging ; Aged, 80 and over ; },
abstract = {BACKGROUND: Emerging research highlights the role of the gut microbiome in the progress of Alzheimer's disease (AD). Alterations in serum bile acid (BA) profiles, reflecting gut microbial activity, have been observed in AD patients; however, the connection to cognitive decline is still poorly understood. This research aims to deepen our understanding of the complex mechanisms through which the gut microbiome and its metabolites influence cognitive function in AD patients.

METHOD: We analyzed data from 1,414 participants enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 389 cognitively unimpaired controls, 754 mild cognitive impairment (MCI) individuals, and 271 AD patients. We examined 15 BA metabolites and 8 BA ratios to explore their correlations with volumes of the basal forebrain cholinergic system (BFCS) and cognitive performance. We also conducted mediation analyses to assess the role of BFCS in the impact of BA profiles on cognitive function, as well as the role of AD pathology in the effect of BA profiles on BFCS.

RESULT: Associations were observed between serum BA profiles, BFCS volumes, and cognitive performance, even after adjusting for demographic factors. The mediation analysis suggested the mediating role of the BFCS in the relationship between gut microbiota metabolism-related secondary-to-primary BA ratios and cognitive function. Furthermore, the influence of secondary-to-primary BA ratios on BFCS was modulated by tau pathology.

CONCLUSION: Our findings suggest that BFCS may modulate the relationship between BAs and cognitive function, with tau pathology potentially mediating the influence of BAs on BFCS. These results enhance our understanding of the intricate mechanisms through which the brain-gut axis modulates cognitive function in AD.},
}

Humans
Male
Female
*Alzheimer Disease/pathology/metabolism
*Cognitive Dysfunction/pathology/metabolism
Aged
*Gastrointestinal Microbiome/physiology
*Bile Acids and Salts/blood
*Basal Forebrain/pathology/diagnostic imaging
Cognition/physiology
Magnetic Resonance Imaging
Aged, 80 and over

@article {pmid41436029,
year = {2025},
author = {Huang, Z and Sekhon, VK and Guo, O and Newman, M and Sadeghian, R and Vaida, ML and Jo, C and Ward, D and Bucci, V and Haran, JP},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e100530},
doi = {10.1002/alz70855_100530},
pmid = {41436029},
issn = {1552-5279},
mesh = {Humans ; *Alzheimer Disease/diagnosis ; *Gastrointestinal Microbiome ; Female ; Male ; Aged ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a complicated neurodegenerative disorder influenced by dynamic interactions among clinical, microbial, and other complex underlying mechanisms. The Alzheimer's Disease Analysis Model Generation 1 (ADAM-1) is an innovative multi-agent large language model (LLM) framework proposed to deal with the complications of analyzing diverse and multi-modal datasets. ADAM-1 integrates clinical datasets, microbiome profiles, and existing Alzheimer's publications using retrieval-augmented generation (RAG) techniques supporting AI agents to enhance diagnostic and analytical capabilities offering unified and comprehensive insights into Alzheimer's disease prognosis.

METHOD: The study incorporates a multi-modal dataset with paired clinical and gut microbiome data from 102 nursing home residents, including 64 healthy controls (HC) and 38 individuals with AD, collected across four facilities in central Massachusetts as part of one of our previous studies. ADAM-1, built on the GPT-4o-mini-2024-07-18 model, integrates three AI agents designed for Alzheimer's binary classification: a computational agent for generating descriptive statistics, a summarization agent for synthesizing insights from the data and knowledge database, and a classification agent for performing binary predictions based on prior outputs. The knowledge database comprises 80,909 Alzheimer's-focused publications from PubMed. Classification performance was assessed using F1 scores across 15 randomized seeds, with comparisons to XGBoost as the baseline model. The study was conducted using Python 3.10.14 on an Ubuntu 24.04.1 LTS workstation with four 3090 GPUs.

RESULT: For Alzheimer's classification, ADAM-1 achieved a mean F1 score comparable to that of XGBoost (p = 0.0967, t-test) while demonstrating significantly reduced F1 score variance (p = 0.0083, F-test), indicating more stable performance across evaluations using 15 randomized seeds. The reduced variance in F1 scores emphasizes the reliability of ADAM-1 in handling relatively small sample data, a common scenario in clinical translational research.

CONCLUSION: ADAM-1 offers a robust and consistent platform for multi-modal data analysis in Alzheimer's research. The system's human-machine interaction through natural language queries enhances data interpretability, expanding and broadening researchers' insights in analyzing such complex datasets. Future versions of ADAM will include blood biomarkers and neuroimaging thus enabling more comprehensive and precise diagnostics, advancing the understanding of the complicated and dynamic underlying mechanisms of Alzheimer's disease progression.},
}

Humans
*Alzheimer Disease/diagnosis
*Gastrointestinal Microbiome
Female
Male
Aged

@article {pmid41435933,
year = {2025},
author = {Ganamurali, N and Sabarathinam, S},
title = {Digoxin-Induced Gut Dysbiosis: Mechanistic Links to Prostaglandin Dysregulation and Lipid Metabolic Imbalance.},
journal = {Prostaglandins & other lipid mediators},
volume = {},
number = {},
pages = {107055},
doi = {10.1016/j.prostaglandins.2025.107055},
pmid = {41435933},
issn = {1098-8823},
abstract = {Digoxin, a cardiac glycoside with established roles in heart failure and arrhythmia, increasingly exemplifies drug-microbiome-host interactions. Its bioavailability and efficacy are profoundly influenced by Eggerthella lenta-mediated reduction, producing inactive metabolites that reshape systemic physiology. Emerging evidence demonstrates that digoxin-induced gut dysbiosis perturbs arachidonic acid metabolism, altering cyclooxygenase-driven prostaglandin production and disrupting vascular tone and inflammatory homeostasis. These changes extend to lipid regulation, where reduced short-chain fatty acid production and bile acid derangements impair hepatic lipid utilization, promoting steatosis and metabolic dysfunction. This review integrates mechanistic insights into digoxin-microbiota interactions, prostaglandin pathway perturbation, and lipid imbalance, emphasizing their clinical significance and therapeutic implications for precision medicine in cardiovascular care.},
}

@article {pmid41435858,
year = {2025},
author = {Asadullin, A and Kashchenko, G and Klochev, A and Taldaev, A and Adonin, L and Smutin, D},
title = {Meta-analysis of sources and transmission pathways of Apis mellifera (Hymenoptera: Apidae) microbiota based on 16S sequencing data.},
journal = {Journal of insect science (Online)},
volume = {25},
number = {6},
pages = {},
doi = {10.1093/jisesa/ieaf093},
pmid = {41435858},
issn = {1536-2442},
support = {25-26-00381//Russian Science Foundation/ ; },
mesh = {Animals ; Bees/microbiology ; RNA, Ribosomal, 16S/analysis/genetics ; *Microbiota ; *Gastrointestinal Microbiome ; Bacteria/classification/genetics/isolation & purification ; Honey/microbiology ; },
abstract = {This study investigates the mechanisms governing the formation and transfer of microbial communities associated with the honey bee (Apis mellifera L.) superorganism, focusing on the interplay between plant, in-hive, and bee environments. By analyzing 16S rRNA sequencing data from multiple public datasets through bioinformatics and statistical modeling, we characterized the structure and transmission pathways of these microbiota. Our analysis reveals that each environment hosts a distinct and specialized microbial community, with significant barriers to free microbial exchange. Alpha and beta-diversity analyses confirmed the uniqueness of the bee gut microbiota and the mixed, intermediate nature of the honey microbiome. Structural equation modeling identified that direct microbial transfer from plants to bees is negligible. Instead, honey serves as an obligate intermediary and selective filter, with microorganisms transitioning from plants to honey before a lower-probability transfer to bees occurs. Furthermore, we identified key bacterial taxa, including Apilactobacillus kunkeei, Acinetobacter, and Pseudomonas, that potentially act as generalists capable of persisting across multiple environments. These findings underscore the possibility of the selective bacterial transfer between hives, which may play roles in both pathogens transfer and maintaining hive microbiome stability.},
}

Animals
Bees/microbiology
RNA, Ribosomal, 16S/analysis/genetics
*Microbiota
*Gastrointestinal Microbiome
Bacteria/classification/genetics/isolation & purification
Honey/microbiology

@article {pmid41435750,
year = {2025},
author = {Maruyama, T and Ogawa, M and Nagai, R and Hirose, K and Iwata, S and Tanaka, G and Ito, T and Kamikawa, M and Kitazawa, H and Uemoto, Y},
title = {Impact of heritable and non-heritable gut microbiota on microbiability estimation and phenotype prediction of production traits in Duroc pigs.},
journal = {Animal : an international journal of animal bioscience},
volume = {20},
number = {1},
pages = {101727},
doi = {10.1016/j.animal.2025.101727},
pmid = {41435750},
issn = {1751-732X},
abstract = {Pig phenotypes are influenced by host genetics and the gut microbiota. However, the impacts of classification methods and the heritability of the gut microbiota on production traits in pigs remain unclear. Here, we evaluated the impacts of the gut microbiota with different classifications and heritabilities on the estimation of microbiability (i.e., the proportion of host phenotypic variance explained by the gut microbiota) and prediction of production traits in Duroc pigs. We identified the most effective microbial classification based on heritability and microbiability; determined the relationship between heritability of the microbiota and host phenotypic values; and investigated the impact of components of the gut microbiota with different heritabilities on microbiability estimation and phenotype prediction. In total, 961 Duroc pigs with both phenotypic and pedigree data were evaluated through bacterial 16S rRNA gene sequencing of the gut microbiotas from faecal samples. Microbiability for all traits was higher when estimated using amplicon sequence variants (ASVs) than when using other microbial classifications. Therefore, the ASV classification was used in subsequent analyses. The microbiability estimates of daily gain (DG) and backfat thickness (BF) (0.21 and 0.15, respectively) were higher than those of other traits, such as body measurement traits (range of 0.00-0.06). In total, 154 of 368 ASVs with high prevalence were significantly heritable in this population. Furthermore, 17 and 27 ASVs exhibited significant heritability and were associated with DG and BF, respectively. Microbiability estimates were high using heritable ASVs in DG (0.08) and using non-heritable ASVs in BF (0.09). Phenotype prediction using a model that included the sum of breeding values and heritable ASV effects had the highest prediction accuracy in DG (i.e., 0.45, compared with 0.20 for a model including breeding values alone). No difference was observed between heritable and non-heritable ASV effects in BF. Our results indicate that the gut microbiota explains a substantial portion of phenotypic variance, and microbial effects can be used to predict DG and BF. Our results indicate that it is important to differentiate between heritable and non-heritable ASVs when evaluating the impact of host genetics and the gut microbiota on host phenotypes in pigs.},
}

@article {pmid41435605,
year = {2025},
author = {Xu, Y and Yang, W and Yang, Z and Pan, Y and Zhu, Y and Shen, B and Chen, J},
title = {Differential and complementary effects of Baizhu and Fuling on spleen deficiency syndrome by regulating microbiota-gut-metabolite axis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {150},
number = {},
pages = {157690},
doi = {10.1016/j.phymed.2025.157690},
pmid = {41435605},
issn = {1618-095X},
abstract = {BACKGROUND: Atractylodes macrocephala Koidz. (commonly known as Baizhu, BZ) and Poria cocos (Schwan.) Wolf. (referred to as Fuling, FL) are frequently employed in the treatment of spleen deficiency syndrome (SDS) owing to their spleen-tonifying and dampness-eliminating properties. The combination of the two herbs, referred to as the BZ-FL herb pair, exhibited complementary and enhancing effects. Nevertheless, the distinct and complementary mechanisms and effects of BZ and FL individually remain inadequately understood.

PURPOSE: This study aimed to investigate the differential and complementary effects and underlying mechanisms of BZ and FL on SDS.

METHODS: The chemical components in BZ, FL, and the BZ-FL herb pair were qualitatively and quantitatively analyed using UHPLC-Q Exactive HF-X and UPLC-MS technique. SDS model rats were established by a combination of dietary and fatigue-inducing methods and then treated with BZ, FL, and the BZ-FL herb pair. In order to elucidate the effects on gastrointestinal motility, immune function, and water metabolism, the concentrations of gastrointestinal hormones, low-density lipoprotein, high-density lipoprotein, total cholesterol, serum protein levels, and albumin were measured. Additionally, the levels of IL-2, IgA, IL-4, IgG, and IFN-γ in colon tissue were quantified utilizing enzyme-linked immunosorbent assay (ELISA) and biochemical assays. Pathological changes were examined using hematoxylin and eosin staining, while immunofluorescence was used to measure the levels of the intestinal barrier proteins and aquaporins (Aqps) in colonic tissues. The levels of Aqps and cAMP/PKA/CREB signaling pathway were detected in colon and kidney tissues using western blot analysis. Untargeted metabolomics was used to analyze the serum and feces metabolic profile. The 16S rRNA gene high-throughput sequencing was performed to detect the gut microbiota composition in fecal samples.

RESULTS: The quantification of chemical components revealed that BZ significantly enhanced the dissolution of triterpene acids from FL. BZ, FL, and the BZ-FL herb pair effectively mitigated SDS by modulating gastrointestinal hormones, kidney and colon Aqps, and protein expression within the cAMP/PKA/CREB signaling pathway, while also enhancing intestinal barrier integrity. Serum metabolomics analysis demonstrated that BZ influenced bile acid biosynthesis, FL affected the citrate cycle and glycerophospholipid metabolism, and the BZ-FL herb pair impacted all these pathways. Gut microbiota analysis indicated that the efficacy of the BZ-FL herb pair in ameliorating SDS was associated with a preserved gut microbiome, characterized by the relative abundance of microbial taxa such as Escherichia-Shigella, Kurthia, and UCG-005. Fecal metabolomics analysis indicated that the BZ-FL herb pair synergistically enhances and complements each other by influencing metabolites in butanoate, arginine and proline, starch and sucrose, cysteine and methionine, purine, and propanoate metabolism. Moreover, correlation and comprehensive analyses identified a robust association among SDS phenotypes, serum metabolites, fecal metabolites, and microbial genera. In addition, the BZ-FL herb pair and BZ alone exhibited significantly greater regulatory effects on gastrointestinal function-related indicators compared to FL.

CONCLUSIONS: This study presents initial evidence of the differential and complementary effects of BZ and FL, analyzing their chemical compositions and their influence on water-fluid metabolism and the microbiota-gut-metabolites axis in SDS. These findings reflect the rationality and scientific basis of the compatibility theory. The study identified potential mechanisms of the BZ-FL herb pair in treating SDS, providing a reference for future research and clinical applications.},
}

@article {pmid41435506,
year = {2025},
author = {Souto-Silva, MV and Bispo, ECI and de Oliveira, NN and Pogue, R and Zonari, A and Saldanha-Araujo, F and Carvalho, JL},
title = {The cytokine-skin barrier axis in health and disease.},
journal = {Cytokine & growth factor reviews},
volume = {87},
number = {},
pages = {113-123},
doi = {10.1016/j.cytogfr.2025.12.009},
pmid = {41435506},
issn = {1879-0305},
abstract = {The skin barrier functions as both a structural defense and an immunological interface that integrates environmental, microbial, and systemic signals. Its disruption predisposes to cutaneous inflammation and contributes to systemic immune dysregulation. In this review, we provide an integrated analysis of how cytokine signaling regulates skin barrier integrity, highlighting both mechanistic insights and clinical implications across health and disease. We first revisit the architecture of the skin barrier and describe common insults that compromise its function, and the mechanisms by which these activate canonical signalling pathways-NF-κB, MAPK, JAK-STAT, and PI3K/Akt/mTOR-leading to the release of cytokines from keratinocytes and immune cells. Particular attention is given to cytokine families with direct relevance for epidermal physiology: IL-1 and IL-17 in antimicrobial defense and hyperinflammation; IL-20, IL-31, and type 2 cytokines in keratinocyte proliferation, differentiation, and barrier protein suppression; and TNF and interferons in amplifying inflammation and tissue injury. We also discuss how these cytokine networks drive systemic manifestations, linking skin barrier dysfunction to atopic dermatitis (AD), psoriasis, inflammaging, and metabolic disorders. Finally, we review therapeutic approaches that target cytokine signaling or restore barrier integrity, ranging from emollients and microbiome-based strategies to biologics and JAK inhibitors. By systematically reviewing the cytokine-barrier axis, this work highlights how modulation of cytokine signaling represents a promising avenue for clinical and preventive interventions in dermatology and systemic health.},
}

@article {pmid41435214,
year = {2025},
author = {Yoshida-Court, K and Teka, B and Cisneros Napravnik, T and Karpinets, T and El Alam, MB and Firdawoke, E and Chanyalew, Z and Mihret, A and Addissie, A and Gizaw, M and Lan, J and Haymaker, C and Duose, DY and Luthra, R and Colbert, LE and Jhingran, A and Kantelhardt, EJ and Kaufmann, AM and Abebe, T and Klopp, AH},
title = {Linking Microbiome Diversity and Immune Profiles in Ethiopian Patients With Cervical Cancer.},
journal = {JCO global oncology},
volume = {11},
number = {},
pages = {e2500060},
doi = {10.1200/GO-25-00060},
pmid = {41435214},
issn = {2687-8941},
mesh = {Humans ; *Uterine Cervical Neoplasms/immunology/microbiology ; Female ; Ethiopia ; *Microbiota/immunology ; Adult ; Middle Aged ; *Receptors, Antigen, T-Cell/immunology/genetics ; },
abstract = {PURPOSE: This study investigates the interplay between T-cell receptor (TCR) immune characteristics and microbiome profiles to explore the relationship between immune diversity and microbial composition in cervical samples from Ethiopia.

METHODS: Cervical specimens were collected from patients at Tikur Anbessa Specialized Hospital in Addis Ababa, and rural Butajira, south-central Ethiopia. Patient data, including age, human papillomavirus status, pathology, and TCR immune characteristics, were analyzed with a focus on the interactions between TCR profiles and microbiome compositions in malignant samples.

RESULTS: Three distinct TCR profiles were identified: Group 1 (TCR active) exhibited features of active immune engagement, including high diversity, clonal expansion, and repertoire richness. Group 2 (TCR restricted) showed reduced TCR diversity and expansion, suggesting a restricted repertoire. Group 3 (TCR balanced) had moderate diversity and clonal activity. TCR repertoire groups were linked with microbial diversity, with Group 1 (TCR active) showing the highest number of microbes (high operational taxonomic units and microbial diversity). Maximum TCR clonal expansion positivity associated with microbial richness, while Group 3 (TCR balanced) was linked to reduced microbial alpha diversity. Taxonomic analysis revealed specific organisms enriched in TCR repertoire group.

CONCLUSION: Variations in TCR profiles are linked to distinct microbial environments in cervical cancer with greater microbial richness in patients with greater maximum productive frequency. These findings underscore the interplay between TCR diversity, microbiome composition, and malignancy, offering insights into the potential implications for microbiome-targeted therapies and prognostic biomarkers in cervical cancer.},
}

Humans
*Uterine Cervical Neoplasms/immunology/microbiology
Female
Ethiopia
*Microbiota/immunology
Adult
Middle Aged
*Receptors, Antigen, T-Cell/immunology/genetics

@article {pmid41435148,
year = {2025},
author = {Katuwawala, KS and Fernando, WMADB and Bharadwaj, P and Martins, RN},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e098838},
doi = {10.1002/alz70855_098838},
pmid = {41435148},
issn = {1552-5279},
mesh = {Humans ; *MicroRNAs/metabolism ; *Alzheimer Disease/diagnosis/metabolism/genetics ; *Gastrointestinal Microbiome/physiology ; Biomarkers/metabolism ; Feces/chemistry ; Brain/metabolism ; },
abstract = {BACKGROUND: Alzheimer's Disease (AD) is a complex neurodegenerative disorder characterized by cognitive decline and memory loss. Emerging research suggests that gut microbiota play a significant role in AD progression through mechanisms like neuroinflammation and neurotransmitter dysregulation. Fecal microRNAs (miRNAs) have gained attention as non-invasive biomarkers reflecting gut-brain communication, offering potential insights into disease pathogenesis and therapeutic targets. This review examines the significance of fecal miRNA profiles in AD, focusing on their role in early diagnosis, disease monitoring, and potential therapeutic intervention.

METHOD: A systematic literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar for studies published from 2010 to 2023. Inclusion criteria were based on research articles investigating fecal miRNA expression in AD, miRNAs involved in gut-brain communication, and studies highlighting miRNAs as diagnostic or prognostic biomarkers. Search terms such as "Alzheimer's Disease," "fecal microRNA," "gut microbiome," "biomarkers," and "gut-brain axis" were used. A total of 40 studies, including both clinical and preclinical research, met the inclusion criteria and were reviewed.

RESULT: Key miRNAs such as miR-146a, miR-155, and miR-34a were consistently dysregulated, indicating their involvement in neuroinflammatory pathways and synaptic dysfunction. These miRNAs also influenced amyloid precursor protein (APP) processing and tau phosphorylation, critical factors in AD pathogenesis. Additionally, miR-132 and miR-181c were associated with cognitive decline and AD severity, suggesting their potential as non-invasive biomarkers for disease progression. Preclinical studies also demonstrated that dietary interventions and probiotics could modulate fecal miRNA expression, indicating potential therapeutic strategies targeting the gut microbiome.

CONCLUSION: Fecal miRNA profiles offer valuable insights into the gut-brain axis in Alzheimer's Disease and serve as promising non-invasive biomarkers for early diagnosis and disease monitoring. Altered miRNA expression reflects gut dysbiosis and neuroinflammatory responses, making them potential targets for therapeutic interventions. Future research should focus on validating these findings through large-scale clinical trials and exploring how dietary and probiotic treatments can modify miRNA expression to benefit AD patients. This review emphasizes the need for a multidisciplinary approach to better understand the role of the gut microbiome in neurodegenerative diseases and develop novel strategies for AD management.},
}

Humans
*MicroRNAs/metabolism
*Alzheimer Disease/diagnosis/metabolism/genetics
*Gastrointestinal Microbiome/physiology
Biomarkers/metabolism
Feces/chemistry
Brain/metabolism

@article {pmid41435039,
year = {2025},
author = {Elorriaga, IT and Imatz, E and Ibarlucea, B and Cano, A and Sanmartín, E and Tueros, I and Ayala, U and de Heredia, AG and Zaldua, C and Zugaza, JL and Aleman, IT and Garcia-Sebastian, M and Martínez-Lage, P and Erramuzpe, A},
title = {Public Health.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 6},
number = {},
pages = {e099250},
doi = {10.1002/alz70860_099250},
pmid = {41435039},
issn = {1552-5279},
mesh = {Humans ; Aged ; *Public Health ; Female ; Male ; Aged, 80 and over ; Biomarkers ; Middle Aged ; *Aging ; *Healthy Aging ; },
abstract = {BACKGROUND: The ITTHACA project is a collaborative initiative involving six research institutions from the Basque Country including Universities, Health, Technology and Basic Research Institutions. It builds upon the ongoing CITA GO-ON) CITA Go-On study, ClinicalTrials.gov, NCT04840030) cohort study, which adapts the Finnish FINGER [Ngandu, T., et al. 2015] model to the local context. ITTHACA focuses on enhancing healthy aging by identifying markers, prediction models and sensors for in vivo monitoring that allow the establishment and implementation of combined intervention strategies in the population.

METHOD: This one-year randomized-controlled trial (total n = 250; 125 control and 125 intervention), focused on 60-85-year-old males and females at risk of dementia, adopts a multimodal approach. Biomarker identification includes proteomics and metabolomics in biological fluids (blood) and 16S metagenomics and lipidomics in the gut microbiome (stool), as well as employing a FINGER-like mice model. Biosensor technology under development includes multi-channel bioimpedance spectroscopy for tissue analysis and electrochemical sensors for real-time detection of aging markers in biofluids. Predictive modeling integrates data from these analyses and multiple domains-cognition, cardiovascular health, voice, food texture perception and habits-to generate diagnostic tools that monitor biological aging and inform early interventions. A proof-of-concept study in an older population sample, with special attention to user experience, will evaluate the potential benefits of these findings in improving the quality of life for older adults.

RESULT: Not applicable. The ITTHACA project is ongoing, with outcomes expected to include validated biomarkers, novel biosensors, and predictive models that facilitate early interventions.

CONCLUSION: ITTHACA demonstrates the power of interdisciplinary collaboration in tackling the complex multidomain challenge of aging. By leveraging the expertise of complementary Basque Country Research Centers, this initiative is poised to produce innovative resources for prolonging healthy and autonomous living. The project's outcomes are expected to support new therapeutic strategies and socio-healthcare interventions that address the rising prevalence of aging-related conditions, including cognitive decline.},
}

Humans
Aged
*Public Health
Female
Male
Aged, 80 and over
Biomarkers
Middle Aged
*Aging
*Healthy Aging

@article {pmid41434948,
year = {2025},
author = {Kaiyrlykyzy, A and Zholdasbekova, G and Alzhanova, D and Kozhakhmetov, S and Kushugulova, A and Askarova, S},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e097791},
doi = {10.1002/alz70855_097791},
pmid = {41434948},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; *Alzheimer Disease/genetics/epidemiology ; Aged ; Kazakhstan/epidemiology ; Polymorphism, Single Nucleotide/genetics ; Gastrointestinal Microbiome ; Cytokines/blood ; Risk Factors ; Cohort Studies ; Middle Aged ; Apolipoproteins E/genetics ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia and a critical social issue. Its multifactorial nature necessitates evaluating risk factors in diverse populations.

METHODS: This study analyzed 181 AD patients and 244 controls in Kazakhstan, comparing clinical, genetic, and microbial traits.

RESULTS: In our cohort, significant dementia-associated variables included smoking, depression, dyslipidemia, insulin resistance, and liver dysfunction. AD patients had higher HDL, bilirubin, AST/ALT ratios, and lower ALT. Genetic analysis identified 13 SNPs linked to AD, notably in APOE, TOMM40, and MED12L genes involved in lipid metabolism, mitochondrial function, and gene transcription. APOE4 increased AD risk 1.9x, with higher prevalence in northern Kazakhstan (Astana). We also found specific alterations in the gut microbiome, specifically, a decreased Firmicutes/Bacteroidetes ratio, a reduced Bifidobacterium, and increased proteobacteria and inflammatory bacteria. The investigation of cytokine profiles demonstrated that pro-inflammatory cytokines such as IFN-γ, IL-6, TNF-β, MCP-1, and IL-17A were significantly elevated in AD patients, along with anti-inflammatory cytokines IL-4 and IL-1RA, suggesting a dysregulated inflammatory response in AD. Additionally, elevated serum adiponectin levels, observed at three times higher than in controls, were strongly correlated with multiple cytokines and specific microbial taxa, such as Actinobacteria and Acidomicrobiia, indicating a potential interplay between gut microbiota, adipose tissue, and neuroinflammation in AD.

CONCLUSION: These findings underscore the importance of considering bio-geographic and environmental factors in AD research. The study's outcomes may aid in further research and the development of personalized approaches for managing and treating AD in distinct geographical regions. Research support: Nazarbayev University Collaborative Research Program Grant [Funder Project Reference: 20122022CRP1602] and the Ministry of Higher Education and Science of the Republic of Kazakhstan Grant [Funder Project Reference: AP14871338].},
}

Humans
Male
Female
*Alzheimer Disease/genetics/epidemiology
Aged
Kazakhstan/epidemiology
Polymorphism, Single Nucleotide/genetics
Gastrointestinal Microbiome
Cytokines/blood
Risk Factors
Cohort Studies
Middle Aged
Apolipoproteins E/genetics

@article {pmid41434766,
year = {2025},
author = {Lwere, K},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e097665},
doi = {10.1002/alz70855_097665},
pmid = {41434766},
issn = {1552-5279},
mesh = {Humans ; *Alzheimer Disease/microbiology ; Cross-Sectional Studies ; *Gastrointestinal Microbiome/genetics ; Male ; *Cognitive Dysfunction/microbiology ; Female ; Aged ; *Dysbiosis/microbiology ; Uganda ; RNA, Ribosomal, 16S/genetics ; Middle Aged ; Feces/microbiology ; Phylogeny ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is the leading cause of global cognitive decline. However, its mechanisms remain poorly understood in sub-Saharan Africa (SSA), where genetic, dietary, and environmental factors differ significantly. Emerging evidence links the gut microbiota to AD through neuroinflammation and gut-brain axis dysfunction. This study investigated phylogenetic and compositional microbiome shifts in AD, Mild Cognitive Impairment (MCI), and healthy controls in Uganda, providing novel insights into microbial dysbiosis and its role in cognitive decline in low-resource settings.

METHOD: In this cross-sectional study, stool samples from 104 participants (AD: 77; MCI: 14; controls: 13) were analyzed using 16S rRNA sequencing (V3-V4 region), with DADA2 generating amplicon sequence variants (ASVs). Beta diversity was assessed using Weighted UniFrac (phylogenetic differences) and Bray-Curtis (compositional differences) metrics. Principal Coordinate Analysis (PCoA) was used to visualize clustering patterns, whereas group differences were assessed using Permutational Multivariate Analysis of Variance (PERMANOVA) at p < 0.05.

RESULT: Beta diversity analysis revealed distinct microbial shifts that were linked to cognitive decline. Weighted UniFrac PCoA showed clear clustering, with Axis 1 (39.46% variation) separating AD patients from controls and Axis 2 (16.28%) capturing within-group variability, particularly in AD. The MCI group occupied an intermediate position, reflecting the microbial gradient associated with cognitive decline. Confidence ellipses highlighted minimal overlap between AD and controls, whereas MCI partially overlapped with both groups, suggesting a transitional profile. Bray-Curtis PCoA confirmed compositional differences, with PC1 (28.66%) separating AD from controls and PC2 (14.44%) capturing MCI dispersion. PERMANOVA confirmed significant group-level differences (Weighted UniFrac: R² = 0.18, p = 0.001; Bray-Curtis: R² = 0.21, p = 0.001), with the strongest divergence between AD and controls (p = 0.001), and significant differences between AD and MCI (p = 0.005).

CONCLUSION: Distinct microbial shifts across AD, MCI, and control groups highlight the role of the gut microbiome in neurodegeneration. The transitional profile of MCI underscores its potential as an early marker of dysbiosis, supporting the development of microbiome-targeted strategies for the early detection and intervention of Alzheimer's disease.},
}

Humans
*Alzheimer Disease/microbiology
Cross-Sectional Studies
*Gastrointestinal Microbiome/genetics
Male
*Cognitive Dysfunction/microbiology
Female
Aged
*Dysbiosis/microbiology
Uganda
RNA, Ribosomal, 16S/genetics
Middle Aged
Feces/microbiology
Phylogeny

@article {pmid41434746,
year = {2025},
author = {Williams, C and Golden, A and Yadav, H and Masternak, MM and , },
title = {Public Health.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 6},
number = {},
pages = {e100453},
doi = {10.1002/alz70860_100453},
pmid = {41434746},
issn = {1552-5279},
mesh = {Humans ; *Public Health ; *Gastrointestinal Microbiome ; *Patient Selection ; },
abstract = {BACKGROUND: Gut microbiota is crucial in nutrient extraction, metabolism, cognition, and immune function. Consequently, the increasing number of microbiome studies aims to link specific bacteria, fungi, and viruses with various cognitive disease outcomes. Unfortunately, clinical studies often exclude many older adults with Alzheimer's Disease and Related Dementia who are homebound or from racially/ethnically diverse populations. The homebound older adult population is estimated to be three times larger than the equally impaired and chronically ill nursing home population. People of color often hesitate to participate in clinical trials due to mistrust, logistical barriers, and lack of awareness. Recruiting a diverse group of patients has been challenging.

METHOD: We review the literature using CINAL, PubMed, Medline, PsycINFO, and Embase to highlight evidence-based strategies for promoting inclusivity among homebound and minority communities in microbiome studies. Additionally, we discussed the inclusion and exclusion criteria necessary for clinical trials.

RESULTS: We identified strategies such as community engagement, culturally appropriate assistance, mobile health units, and strategic partnerships with feedback mechanisms to improve recruitment and retention of underserved populations. We also discussed inclusion and exclusion criteria while highlighting factors that can confound results. While these criteria may complicate trials involving vulnerable populations, they are essential for optimizing outcomes. We must recognize and adequately support these populations while keeping these criteria in mind.

CONCLUSION: This review emphasized recruitment strategies for underrepresented groups in microbiome studies and underscores the importance of inclusion and exclusion criteria to ensure robust study results. Without inclusivity in microbiota clinical trials, we cannot effectively address health inequities or ensure the generalizability of findings. The complexity and long-term nature of these trials suggest that additional support for patients and caregivers may be necessary for participants with cognitive decline. Diverse participation helps uncover variations in disease prevalence, progression, and treatment responses among different populations, leading to more personalized and effective healthcare solutions. It also enhances the overall quality of research by incorporating a wide range of perspectives and experiences.},
}

Humans
*Public Health
*Gastrointestinal Microbiome
*Patient Selection

@article {pmid41434707,
year = {2025},
author = {Dempsey, DA and Agarwal, P and Fernandez, S and Brosch, JR and Quirke, M and Graham-Dotson, Y and Gao, S and Clark, D and Apostolova, LG and Clark, DG and Farlow, MR and Mathew, S and Unverzagt, F and Wang, S and Diaz, E and Schimmel, L and French, R and Blach, C and Kaddurah-Daouk, RF and Saykin, AJ and Risacher, SL and , },
title = {Public Health.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 6},
number = {},
pages = {e105690},
doi = {10.1002/alz70860_105690},
pmid = {41434707},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; Aged ; *Cognitive Dysfunction/diet therapy ; *Public Health ; Surveys and Questionnaires ; *Diet, Mediterranean ; Middle Aged ; Indiana ; Alzheimer Disease ; Self Report ; Reproducibility of Results ; Aged, 80 and over ; },
abstract = {BACKGROUND: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has been associated with cognitive benefits and reduced risk of Alzheimer's disease. Adherence is typically assessed using comprehensive but time-consuming food frequency questionnaires (FFQs). We examined concurrent validity between a brief MIND diet screener and a more extensive FFQ.

METHODS: 94 participants (51 cognitively normal (CN), 31 subjective cognitive decline (SCD), 12 mild cognitive impairment (MCI)) from the Indiana Alzheimer's Disease Research Center (IADRC) who participated in the Alzheimer's Gut Microbiome Project (AGMP) completed both the self-reported 15-item MIND screener and computerized Vioscreen FFQ. For both measures, we used the same cutoff criteria to assign values of 0, 0.5, or 1 corresponding to low, medium, and high intake for the 'healthy' food groups and reverse correspondence for the 'unhealthy' food groups, which were then summed to generate a total MIND diet score (0-15) with higher scores indicating greater adherence. Agreement between the two methods was assessed using Pearson correlation, intraclass correlation coefficient (ICC) for absolute agreement and consistency, and a tertile-based cross-classification. ANOVA was used to test differences in MIND scores between diagnostic groups, adjusting for age, sex, and education.

RESULTS: The mean MIND diet score from the FFQ was 7.49 (range: 2.5-11), and from the screener was 10.05 (range: 5-13.5), with a mean 2.56-point difference showing consistently higher scores on the screener (Figure 1). The screener demonstrated moderate correlation with the FFQ score (r = 0.63, p <0.001, R2=0.40). Absolute agreement was low (ICC=0.34), while consistency was moderate (ICC=0.64) (Figure 2). In cross-classification, 19.15% of individuals were classified into disparate tertiles. A significant difference was observed between CN and MCI groups using both methods, but only the screener-derived score remained marginally significant after adjustments (p = 0.05) (Figure 3).

CONCLUSIONS: The MIND screener shows moderate correlation and consistency with the FFQ, with participants systematically reporting higher scores on the screener, indicating overestimation of their MIND diet score. While the screener does not capture detailed or food item specific dietary variations assessed by the FFQ, it is a valid tool for rapid estimation of MIND diet score and may be useful in research and clinical practice.},
}

Humans
Male
Female
Aged
*Cognitive Dysfunction/diet therapy
*Public Health
Surveys and Questionnaires
*Diet, Mediterranean
Middle Aged
Indiana
Alzheimer Disease
Self Report
Reproducibility of Results
Aged, 80 and over

@article {pmid41434687,
year = {2025},
author = {Hisham, HIH and Lim, SM and Ramasamy, K and Majeed, ABA and Shahar, S},
title = {Public Health.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 6},
number = {},
pages = {e106306},
doi = {10.1002/alz70860_106306},
pmid = {41434687},
issn = {1552-5279},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Male ; Female ; *Public Health ; Aged ; *Cognitive Dysfunction/microbiology/therapy ; *Frailty/microbiology/psychology ; *Dysbiosis/microbiology ; Exercise ; Feces/microbiology ; },
abstract = {BACKGROUND: Cognitive frailty (CF), a condition characterised by the co-occurrence of physical frailty and cognitive impairment, has been linked to dysregulated gut microbiota (i.e., dysbiosis) and increased intestinal permeability. Emerging evidence suggests that the gut microbiome plays a crucial role in maintenance of gut-brain barrier integrity, suppression of neuroinflammation, regulation of neurotransmitter production, and ultimately promotion of psychological health. This study aimed at examining the effects of a 6-month multidomain intervention (i.e., physical exercise, cognitive training, psychosocial training and nutritional guidance) on gut microbiota composition.

METHOD: A total of 27 CF participants (12 control; 15 intervention) were recruited and stool samples were collected for 16S rRNA sequencing. The stool samples were homogenised, and DNA was extracted, followed by PCR amplification, DNA library preparation, and sequencing. Statistical analysis was performed using GraphPad Prism. Normality was assessed using the Shapiro-Wilk Test, and differences between groups were analysed using the Ordinary One-way ANOVA Test. Correlations between genus abundance and psychosocial parameters were evaluated using Pearson's correlation analysis.

RESULT: Microbiota profiling revealed a significant increase of the Blautia genus in the intervention group (IV6, intervention after 6 months) when compared to the control group (C6, control after 6 months) (p = 0.0132), suggesting a positive shift in gut microbial balance following lifestyle modifications. The Blautia genus abundance was negatively correlated with depression (r = -0.4120, p = 0.0022) and loneliness scores (r = -0.3328, p = 0.0184), indicating its potential protective role against psychosocial factors. On the contrary, the Prevotella genera exhibited a positive correlation with depression scores (r = 0.2820, p = 0.04), reinforcing its association with neuroinflammation which disrupts neurotransmitter balance.

CONCLUSION: The present results highlight the positive impact of lifestyle interventions on gut microbial composition and their possible implications for psychosocial health in older adults with CF. The Blautia genus enrichment may serve as a biomarker or therapeutic target for improving psychosocial well-being in CF individuals. This warrants further investigation of the mechanistic pathways linking gut microbiota modifications with psychosocial outcomes.

FUNDING: This study is part of the Transforming Cognitive Frailty to Later-Life Self-sufficiency (AGELESS) project funded by the Ministry of Higher Education, Malaysia under the Long-Term Research Grant Scheme (LRGS/1/2019/UM/01/1/3).},
}

Humans
*Gastrointestinal Microbiome/physiology
Male
Female
*Public Health
Aged
*Cognitive Dysfunction/microbiology/therapy
*Frailty/microbiology/psychology
*Dysbiosis/microbiology
Exercise
Feces/microbiology

@article {pmid41434599,
year = {2025},
author = {Dinesh, D and Morgan, X and Scott, TM and Garelnabi, M and Mangano, KM and Noel, SE and Huttenhower, C and Tucker, KL and Palacios, N},
title = {Public Health.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 6},
number = {},
pages = {e098660},
doi = {10.1002/alz70860_098660},
pmid = {41434599},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; *Gastrointestinal Microbiome ; Aged ; *Public Health ; Puerto Rico/ethnology ; Prospective Studies ; Feces/microbiology/virology ; *Cognition/physiology ; Hispanic or Latino ; Boston ; Cross-Sectional Studies ; Dysbiosis ; *Virome ; Aged, 80 and over ; Middle Aged ; Alzheimer Disease ; White ; },
abstract = {BACKGROUND: Gut bacterial variations and dysbiosis may influence cognitive function via the microbiome-gut-brain-axis. Gut viruses may also, directly or indirectly, impact cognitive function by modulating the gut bacteria. Hispanics/Latinos, who may have unique microbiome characteristics, are at a higher risk of Alzheimer's disease and related dementia. There is a lack of research on the gut microbiome and, especially, the virome in Hispanics/Latinos. Here, we examined variations in the gut bacteriome and virome associated with cognitive function in the Boston Puerto Rican Health Study (BPRHS), a prospective cohort of older Puerto Rican adults residing in the Boston area.

METHOD: This study was conducted in 316 BPRHS participants with fecal metagenomic sequencing and cognitive assessments, summarized as a composite global cognitive score (GCS). Taxonomic profiling of the gut bacteriome was performed using MetaPhlAN 4.0. Gut virome profiles from shotgun sequencing were generated using BAQLaVa 1.0. Cross-sectional associations between bacterial and viral composition and GCS were assessed using alpha (Shannon) and beta (Bray-Curtis) diversity indices. Feature-wise testing was performed using multivariate linear regression (MaAsLin2) to identify bacterial and viral taxa associated with the GCS.

RESULT: Among 316 participants (mean age 68.7 years, 70.9% female), there were no differences in overall bacterial or viral composition, measured by alpha and beta diversity, based on GCS. In feature-wise analyses, adjusted for age, sex, and BMI, among participants with higher GCS (better cognitive function), we observed an enrichment of Faecalibacterium prausnitzii bacterium (β = 0.78, p = 0.01, FDR p = 0.22), and depletion of the phage Carjivirus communis (β = -1.07, p < 0.01, FDR p = 0.09).

CONCLUSION: The observed results suggest an enrichment of F. prausnitzii, a beneficial butyrate producing taxa, among participants with better cognitive function, and enrichment of Carjivirus communis, a Crassvirales dsDNA Bacteroidetes phage, among participants with worse cognitive function. A recent study reported an association between Bacteroidetes phages and amyloid β and Alzheimer's disease pathology. Gut viral variations may modulate gut bacteria, impacting cognitive function. Future work will test interactions of the gut bacteriome, virome and their functional pathways, as related to cognitive function in Puerto Rican adults.},
}

Humans
Female
Male
*Gastrointestinal Microbiome
Aged
*Public Health
Puerto Rico/ethnology
Prospective Studies
Feces/microbiology/virology
*Cognition/physiology
Hispanic or Latino
Boston
Cross-Sectional Studies
Dysbiosis
*Virome
Aged, 80 and over
Middle Aged
Alzheimer Disease
White

@article {pmid41434434,
year = {2025},
author = {de Souza, IC and de Lima, AMDL and Bastiani, M and Borelli, WD and Ebert, ELK and Barth, RA and Senger, JE and Schumacher-Schuh, AF and Moriguchi, EH and Senger, J and Bruscato, NM and Werle, BM and Zanella, L and Netson, LV and Detogni, A and Guerra, RR and Martins, AF and Barboza, JVC and Gaio, EJ and Zimmer, ER},
title = {Developing Topics.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 7},
number = {},
pages = {e108925},
doi = {10.1002/alz70861_108925},
pmid = {41434434},
issn = {1552-5279},
mesh = {Humans ; *Cognitive Dysfunction/microbiology ; Aged ; Male ; *Alzheimer Disease/microbiology ; Female ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Saliva/microbiology ; Aged, 80 and over ; *Dysbiosis/microbiology ; *Mouth/microbiology ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that ultimately leads to dementia. Emerging evidence suggests that oral dysbiosis may contribute to AD. The oral microbiota plays a crucial role in maintaining systemic health, and its imbalance has been associated with neurodegeneration. However, beyond the identification of individual taxa, the structure and dynamics of microbial communities-particularly their ecological interactions-remain poorly understood in AD. Here, we investigated abundance association networks of the oral microbiota across the AD continuum.

METHOD: Saliva samples collected from 12 elderly individuals classified as cognitively unimpaired (CU), having mild cognitive impairment (MCI), or having Alzheimer's disease (AD) were sequenced on the Illumina MiSeq™ platform, targeting the V3-V4 regions of the 16S rRNA gene. FASTQ files were processed using the DADA2 pipeline. Amplicon sequence variants (ASVs) were inferred, and taxonomic assignments were performed using the eHOMD 16S rRNA database. ASVs were normalized by rarefaction without replacement. Finally, normalized, centered log-ratio transformed abundance data were used to construct genus-level correlation networks for the CU, MCI, and AD groups.

RESULT: In CU individuals, Eikenella maintained exclusively positive associations with other microbial taxa (Figure 1). However, these interactions were significantly reduced or shifted toward negative relationships in individuals with AD. Notably, one of the most pronounced changes was the weakened association between Eikenella and Lachnospiraceae_G_3 in individuals with AD. Additionally, a positive relationship between Eikenella and Peptostreptococcaceae_XIG_1 observed in CU shifted to a negative relationship in the AD group. These specific microbial associations were not observed in the MCI group.

CONCLUSION: In summary, our results suggest a disruption in microbial synergy, which may reflect or potentially contribute to the underlying pathological mechanisms of AD. Network analysis may provide valuable insights into the dynamic changes within the oral microbiome across different stages of AD, thereby enhancing our understanding of the oral microbiome's role in neurodegenerative processes.},
}

Humans
*Cognitive Dysfunction/microbiology
Aged
Male
*Alzheimer Disease/microbiology
Female
RNA, Ribosomal, 16S/genetics
*Microbiota/genetics
*Saliva/microbiology
Aged, 80 and over
*Dysbiosis/microbiology
*Mouth/microbiology

@article {pmid41434376,
year = {2025},
author = {Blanco, EJ and Gonzalez, R and Perez, G and Piñero, J and Morales, H and Olivieri-Henry, G and Gonzalez, C and Godoy-Vitorino, F and Sepulveda, V},
title = {Developing Topics.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 7},
number = {},
pages = {e108947},
doi = {10.1002/alz70861_108947},
pmid = {41434376},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Aged ; *Alzheimer Disease/epidemiology/genetics/complications ; *Periodontitis/epidemiology ; Puerto Rico/epidemiology ; Hispanic or Latino ; *Periodontal Diseases/epidemiology ; Aged, 80 and over ; Severity of Illness Index ; White ; },
abstract = {BACKGROUND: Periodontal inflammation has been implicated in Alzheimer's Disease (AD) through systemic inflammatory and neurodegenerative pathways, including microbial dysbiosis and cytokine signaling and microbial infiltration. While the oral microbiome's role in cognitive decline has gained momentumrecently, there is limited research on these associations in Hispanic population, underrepresented in Alzheimer's research and facing disproportionately high burden of both dementia and oral disease.

OBJECTIVE: To evaluate the association between periodontal disease severity and clinical, cognitive, metabolic, and genetic factors in a cohort of Puerto Rican older adults with and without Alzheimer's Disease.

METHODS: We conducted a cross-sectional analysis of 43 community-dwelling participants enrolled in the Association-Gut-Microbiome-AD (IRB: 2290033626) study. Each underwent a full-mouth periodontal examination, including clinical attachment loss (CAL), probing depth (PD), and bleeding on probing (BOP) at six sites per tooth. Periodontal disease severity was classified using CDC-AAP 2012 case definitions: mild, moderate, or severe periodontitis based on interproximal CAL and PDthresholds. Predictor variables included age, BMI, insulin resistance (HOMA-IR), APOE-ε4 status, AD, and cognitive scores (MoCA and CDR). Bivariate analyses and Multinomial logistic regression were used to assess associations.

RESULTS: Eighty-one percent of participants met criteria for periodontitis, including 28% with severe and 49% with moderate disease. Age was the most consistent predictor of worsening periodontal inflammation (p < 0.01). CDR scores were significantly associated with greater severity in both bivariate (p < 0.01) and unadjusted models (CDR mild vs none: OR = 0.13; 95% CI, 0.02-0.86; p = 0.03). Severe periodontitis was more commonly observed in Alzheimer's, showing a higher odds ratio when compared to controls (OR = 2.75; p = 0.44) though not statistically significant. MoCA scores, APOE-ε4 status, BMI, and HOMA-IR were not significantly associated with periodontal severity.

CONCLUSION: Aging and dementia severity (CDR) were the strongest predictors of periodontal inflammation. These findings align with emerging literature linking oral microbial dysbiosis and neuroinflammatory mechanisms in AD. The use of standardized CDC-AAP definitions provided clinical rigor, and the elevated periodontitis prevalence observed in this cohort underscores the need for integrated oral-systemic care strategies in dementia prevention and management, particularly in underrepresented populations such as Puerto Rico.},
}

Humans
Male
Female
Cross-Sectional Studies
Aged
*Alzheimer Disease/epidemiology/genetics/complications
*Periodontitis/epidemiology
Puerto Rico/epidemiology
Hispanic or Latino
*Periodontal Diseases/epidemiology
Aged, 80 and over
Severity of Illness Index
White

@article {pmid41434102,
year = {2025},
author = {Ngouongo, YJW and Muhammad, JA and Bernal, R and Satizabal, CL and Beiser, AS and Ramachandran, VS and Kautz, TF and Seshadri, S and Himali, JJ and Fongang, B},
title = {Public Health.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 6},
number = {},
pages = {e103169},
doi = {10.1002/alz70860_103169},
pmid = {41434102},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; *Gastrointestinal Microbiome/physiology ; Middle Aged ; *Public Health ; *Cognition/physiology ; Feces/microbiology ; },
abstract = {BACKGROUND: Emerging evidence indicates a complex interplay between cardiovascular health, gut microbiome composition, and cognitive function. Life's Essential 8 (LE8), created by the American Heart Association, encompasses crucial cardiovascular health metrics. This study aimed to explore the relationship between LE8 adherence, gut microbiota, and cognition.

METHOD: We used stool samples, LE8 metrics, and cognitive assessment measures from a sample of 781 participants (mean age 54.9 years, 57.1% Female) from the Framingham Heart Study (generation3, New Offspring Spouses, and the Omni2 cohorts) at the 3[rd] examination (2016-2019). Associations between LE8 adherence, gut microbiome diversity, and cognitive performance were evaluated using multivariable linear regression models, adjusting for potential confounders. Mediation analysis was conducted to explore whether specific bacterial taxa mediated the relationship between LE8 adherence and cognitive performance.

RESULT: Participants with greater adherence to LE8 demonstrated significantly increased gut microbial diversity (α-diversity: Chao1, p = 0.0014; Shannon, p = 0.0071) and distinct microbial compositions (β-diversity: PERMANOVA p = 1e-4). Higher adherence to LE8 was related to an increased abundance of genera Barnesiella and Ruminococcus, while reduced abundance of Clostridium was associated with higher LE8 adherence. Greater gut microbial diversity (α-diversity: Chao1, p = 0.0012; Shannon, p = 0.0066), and beneficial genera like Oscillospira correlated with better global cognitive scores (GCS). Taxonomic overlap analyses revealed microbial taxa that simultaneously influence LE8 adherence and cognitive outcomes. Mediation analyses indicated that specific taxa, including Barnesiella and Lentisphaerae, mediated the link between higher LE8 adherence and better cognitive performance. These taxa could be key modulators in the gut-brain axis, connecting cardiovascular and brain health. Conversely, higher Clostridium abundance was associated with poorer cognitive performance.

CONCLUSION: This study highlights the interconnected relationship between cardiovascular health, gut microbiome diversity, and cognitive function. Higher adherence to LE8 was associated with favorable microbial profiles and better cognitive performance, with the gut microbiome serving as a critical mediator. These findings emphasize the importance of integrated lifestyle interventions that address cardiovascular and cognitive health simultaneously. To validate these results and refine therapeutic strategies, future research should prioritize longitudinal studies and randomized controlled trials that explore the causal pathways and clinical applications of these findings.},
}

Humans
Male
Female
*Gastrointestinal Microbiome/physiology
Middle Aged
*Public Health
*Cognition/physiology
Feces/microbiology

@article {pmid41433829,
year = {2025},
author = {Nyame, I and Ngouongo, YJW and Ayele, BA and Djotsa, AN and Jian, X and Fonteh, AN and Seshadri, S and Himali, JJ and Fongang, B and , },
title = {Public Health.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 6},
number = {},
pages = {e096594},
doi = {10.1002/alz70860_096594},
pmid = {41433829},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; *Gastrointestinal Microbiome/physiology ; Middle Aged ; *Sleep/physiology ; *Public Health ; Feces/microbiology ; *Cognition/physiology ; Aged ; RNA, Ribosomal, 16S/genetics ; },
abstract = {BACKGROUND: The American Heart Association has identified eight metrics for improving heart and brain health, including sleep health. Recent studies highlight the strong link between sleep health, gut microbiome, and diseases like Alzheimer's. While sleep deprivation is known to affect gut microbiome and brain health, the specific impact of sleep health on gut microbiome and cognitive disorders remains largely unexplored.

METHOD: We analyzed stool samples and sleep metrics from 781 participants (mean age 54.9, 57.1% female) in the Framingham Heart Study to examine the effect of sleep on gut microbiome composition and cognitive performance. Using the V4 region of the 16S rRNA and Lefse analysis, we identified microbiome profiles related to sleep health. ANOVA assessed the sleep-cognitive performance relationship, while multivariable and differential abundance analyses explored the microbiome's link to cognitive function, controlling for age, sex, and education.

RESULT: Differences in bacterial diversity were observed between low, moderate, and high groups. Lefse analysis showed higher levels of aldenense, bolteae, symbiosium, and lavalense in the low group, while Butyrivibrio, putredinis, and Dorea were less abundant. ANOVA indicated a significant correlation between global cognitive scores and sleep metrics (p = 0.0024). Positive correlations were found between cognitive scores and Pseudobutyrivibrio and Ruminococcus, while negative correlations were observed with Barnesiella and Clostridium. At the species level, xylanivorans and lactaris were positively correlated, whereas boltea, callidus, and intestinihominis were negatively correlated with cognitive scores.

CONCLUSION: Our findings showed that individuals with good sleep scores had higher cognitive performance, while those with lower sleep scores had lower cognitive performance. The results also indicated an association between gut microbiome and sleep metric as well as between gut microbiome and cognitive performance. Finally, our work revealed that the taxa Clostridium and bolteae exhibited association with both sleep metric and cognitive performance. Further studies should be conducted to understand the effects of sleep metric on the relationship between gut microbiome and the risk of developing Alzheimer's Disease and Related Dementias (ADRD).},
}

Humans
Female
Male
*Gastrointestinal Microbiome/physiology
Middle Aged
*Sleep/physiology
*Public Health
Feces/microbiology
*Cognition/physiology
Aged
RNA, Ribosomal, 16S/genetics

@article {pmid41432929,
year = {2025},
author = {Garcia, M and Sadler, NC and Stohel, I and Zhao, S and Krishnamoorthy, S and Farris, Y and Reichart, NJ and Bagwell, CE and Zambare, N and McClure, R},
title = {Community Dynamics Drive Calcium Carbonate Production in an Enriched Consortium of Soil Microbes.},
journal = {Microbial ecology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s00248-025-02632-y},
pmid = {41432929},
issn = {1432-184X},
abstract = {Recently, there has been a focus on using soil microbes as a means to store carbon in the soil in the form of calcium carbonate, outcomes of which include soil stabilization and biocementation. The molecular processes involved in microbially induced calcium carbonate formation are known, but there is still a significant knowledge gap regarding how community interactions, emergent processes that are distinct from the roles of individual members, may drive the formation of carbonate. To answer these questions, we describe the development and application of a consortium of soil microbes consisting of one species each of the Rhodococcus, Microbacterium, and Curtobacterium genera and two species from the Bacillus genus. We term these five species cultivated together carbon storing consortium A (CSC-A). Growth assays show that only a subset of CSC-A members produces CaCO3 with Rhodococcus producing the most CaCO3 but the complete CSC-A produces significantly higher amounts of CaCO3 compared to the sum total carbonate produced by all member species. The development of CSC-A shows that CaCO3 production may be as much a community process as it is the contribution of individual species, requiring us to move beyond single species analysis to fully understand carbonate formation by microbial communities in nature. CSC-A will allow the scientific community to ask and answer key questions about the molecular interactions surrounding inorganic carbon formation in soil, an important knowledge gap that must be filled if we wish to stabilize soils and harness microbial processes for materials production.},
}