@article {pmid40679396,
year = {2025},
author = {Searle, T and Al-Niaimi, F and Ali, FR},
title = {Modulation of the microbiome: a paradigm shift in the treatment of acne.},
journal = {Clinical and experimental dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1093/ced/llaf328},
pmid = {40679396},
issn = {1365-2230},
abstract = {The role of the gut-skin axis and the human microbiome has become increasingly explored in various studies and as a result, the therapeutic potential of microbiome-modulatory agents has piqued interest. Probiotics have been explored as both a monotherapy for acne but also as an adjunct to reduce the side-effects of traditional established prescriptions to improve compliance. We review the evidence to support the use of topical and oral probiotics, prebiotics and synbiotics in treating acne vulgaris. There is some evidence of a correlation between increased C. acnes colonisation and acne severity, supporting treatments targeting the skin microbiome. However, most studies rely on in vitro, animal models, or are of small sample sizes, with limited robust clinical trials currently available. Research often overlooks the interplay of endogenous and external factors affecting skin microbiota. Whilst many microbiome modulatory products are available, their multiple ingredients require further scrutiny to isolate any beneficial components and their potential adverse effects. Additionally, the role of other microbial species in acne pathogenesis needs further examination.},
}

@article {pmid40679335,
year = {2025},
author = {Parks, ST and Marchesani, A and Taylor, C},
title = {Scaffolding of assignments and grading to promote STEM literacy in a human microbiome course.},
journal = {Journal of microbiology & biology education},
volume = {},
number = {},
pages = {e0007625},
doi = {10.1128/jmbe.00076-25},
pmid = {40679335},
issn = {1935-7877},
abstract = {A special topics course investigating the human microbiome was developed such that there were three layers of feedback and grading available to students throughout the semester. An instructor of record, a teaching assistant, and a writing-across-the-curriculum consultant overlayed feedback and formative assessment to support student learning. Individual and group assignments were developed to build upon each other, with iterative feedback, to facilitate student STEM literacy. Rubrics were used at all levels of assessment to provide detailed feedback for students, with repetitive rubric components incorporated throughout the semester. Overall, scaffolding of assignments (both individual and group), along with scaffolded support and feedback, promoted student literacy and confidence.},
}

@article {pmid40676225,
year = {2025},
author = {Zhang, J and Dong, H and Liang, L and Hu, L and Chen, J and Li, W and Liu, J and Su, Y and Shi, M and Feng, Y and Naccasha, EZ and Lewis, C and Liu, H and Yang, X and Wen, C},
title = {Targeting gut microbiota and arginase boosts MEK inhibitors' enhancement of antitumour immunity via MHC-I upregulation in colorectal cancer.},
journal = {British journal of cancer},
volume = {},
number = {},
pages = {},
pmid = {40676225},
issn = {1532-1827},
support = {82172337//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {BACKGROUND: Elevating major histocompatibility complex class I (MHC-I) levels in tumour cells can boost antitumour immunity and enhance immunotherapy for colorectal cancer (CRC). Screening an FDA-approved drug library showed that MEK inhibitors (MEKis) significantly increase MHC-I expression in CRC cells, though the mechanisms and antitumour effects of MEKis, as well as their impact on gut microbiota, remain unclear.

METHODS: Dual-luciferase reporter system was employed to screen MHC-I inducers. MHC-I expression was analysed using qRT-PCR, flow cytometry, and western blot. OT-I TCR transgenic mice, subcutaneous mouse tumour models, RNA-seq, and ChIP-qPCR were used to identify the underlying mechanism. Gut microbiota was depleted using antibiotics cocktail and analysed via Shotgun sequencing, 16S rRNA sequencing and nontargeted metabolomic sequencing.

RESULTS: MEKis, particularly cobimetinib, increased MHC-I expression by inhibiting PRMT5-mediated repression of NLRC5, boosting CD8[+] T cell-mediated immunity and enhancing PD-L1 blockade efficacy. Cobimetinib also altered gut microbiota, reducing L-arginine via arginase production, which compromised antitumour immunity. Arginase inhibition or L-arginine supplementation restored immune responses.

CONCLUSIONS: This study uncovers a novel mechanism of MEKi-induced MHC-I expression and highlights the interplay between gut microbiota and antitumour immunity, providing insights for MEKi-based CRC immunotherapy.},
}

@article {pmid40675954,
year = {2025},
author = {Serna, C and Matamoros, BR and Pulido-Vadillo, M and Delgado-Blas, JF and Jansen, RR and Willems, RJL and Almeida, A and Harrison, EM and Dupuy, B and Coll, F and Gonzalez-Zorn, B},
title = {Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {6360},
pmid = {40675954},
issn = {2041-1723},
mesh = {DNA Transposable Elements/genetics ; *Methyltransferases/genetics/metabolism ; *Anti-Bacterial Agents/pharmacology ; *Enterococcus faecium/genetics/drug effects ; Humans ; *Aminoglycosides/pharmacology ; Clostridioides difficile/genetics/drug effects ; Genome, Bacterial/genetics ; *Interspersed Repetitive Sequences/genetics ; *Bacterial Proteins/genetics/metabolism ; *Gram-Positive Bacteria/genetics/drug effects ; *Drug Resistance, Bacterial/genetics ; Microbial Sensitivity Tests ; },
abstract = {The npmA gene, encoding a 16S rRNA methyltransferase, confers resistance to all clinically available aminoglycosides, posing a significant threat to effective antibiotic therapy. We analyze 1,932,812 bacterial genomes to investigate the distribution and mobilization of npmA variants. npmA is not found in Gram-negative bacteria, where it was originally described, but is identified among Gram-positive bacteria, predominantly as the npmA2 variant in the globally distributed Clostridioides difficile ST11 lineage. We also detect npmA2 in two vancomycin-resistant Enterococcus faecium isolates from a Dutch hospital. Upon sequencing and phenotypic analysis, we determine that E. faecium isolates are pan-resistant to aminoglycosides. Genomic characterization links npmA2 to a composite transposon, Tn7734, which is integrated within a previously uncharacterized Integrative and Conjugative Element (ICE) Tn7740, present in both npmA2-carrying C. difficile and E. faecium clinical isolates. Tn7740-like, but not npmA2, appears across diverse taxa, including human microbiome members. Here, we show that Tn7740 likely facilitates cross-species npmA2 mobilization between these Gram-positive bacteria and emphasize the risk of mobile genetic elements transferring pan-aminoglycoside resistance between clinically important bacterial pathogens.},
}

DNA Transposable Elements/genetics
*Methyltransferases/genetics/metabolism
*Anti-Bacterial Agents/pharmacology
*Enterococcus faecium/genetics/drug effects
Humans
*Aminoglycosides/pharmacology
Clostridioides difficile/genetics/drug effects
Genome, Bacterial/genetics
*Interspersed Repetitive Sequences/genetics
*Bacterial Proteins/genetics/metabolism
*Gram-Positive Bacteria/genetics/drug effects
*Drug Resistance, Bacterial/genetics
Microbial Sensitivity Tests

@article {pmid40674653,
year = {2025},
author = {Saarimäki, LA and Fratello, M and Del Giudice, G and Di Lieto, E and Afantitis, A and Alenius, H and Chiavazzo, E and Gulumian, M and Karisola, P and Lynch, I and Mancardi, G and Melagraki, G and Netti, P and Papadiamantis, AG and Peijnenburg, W and A Santos, H and Serchi, T and Shahbazi, MA and Stoeger, T and Valsami-Jones, E and Vivo, P and Vinković Vrček, I and Vogel, U and Wick, P and Winkler, DA and Serra, A and Greco, D},
title = {Wisdom of Crowds for Supporting the Safety Evaluation of Nanomaterials.},
journal = {Environmental science & technology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.est.5c00841},
pmid = {40674653},
issn = {1520-5851},
abstract = {The development of new approach methodologies (NAMs) to replace current in vivo testing for the safety assessment of engineered nanomaterials (ENMs) is hindered by the scarcity of validated experimental data for many ENMs. We introduce a framework to address this challenge by harnessing the collective expertise of professionals from multiple complementary and related fields ("wisdom of crowds" or WoC). By integrating expert insights, we aim to fill data gaps and generate consensus concern scores for diverse ENMs, thereby enhancing the predictive power of nanosafety computational models. Our investigation reveals an alignment between expert opinion and experimental data, providing robust estimations of concern levels. Building upon these findings, we employ predictive machine learning models trained on the newly defined concern scores, ENM descriptors, and gene expression profiles, to quantify potential harm across various toxicity end points. These models further reveal key genes potentially involved in underlying toxicity mechanisms. Notably, genes associated with metal ion homeostasis, inflammation, and oxidative stress emerge as predictors of ENM toxicity across diverse end points. This study showcases the value of integrating expert knowledge and computational modeling to support more efficient, mechanism-informed, and scalable safety assessment of nanomaterials in the rapidly evolving landscape of nanotechnology.},
}

@article {pmid40674481,
year = {2025},
author = {Whitaker, WR and Russ, ZN and Stanley Shepherd, E and Popov, LM and Louie, A and Lam, K and Zong, DM and Gill, CCC and Gehrig, JL and Rishi, HS and Tan, JA and Buness, A and Godoy, J and Banta, D and Jaidka, S and Wilson, K and Flood, J and Bukshpun, P and Yocum, R and Cook, DN and Warsi, T and McLean, L and Sonnenburg, JL and DeLoache, WC},
title = {Controlled colonization of the human gut with a genetically engineered microbial therapeutic.},
journal = {Science (New York, N.Y.)},
volume = {389},
number = {6757},
pages = {303-308},
doi = {10.1126/science.adu8000},
pmid = {40674481},
issn = {1095-9203},
mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Animals ; Mice ; Oxalates/urine/metabolism ; Genetic Engineering ; Colon/microbiology ; *Clostridiales/genetics ; Promoter Regions, Genetic ; Prebiotics ; Kidney Calculi/therapy/prevention & control ; },
abstract = {Precision microbiome programming for therapeutic applications is limited by challenges in achieving reproducible colonic colonization. Previously, we created an exclusive niche that we used to engraft engineered bacteria into diverse microbiota in mice by using a porphyran prebiotic. Building on this approach, we have now engineered conditional attenuation into a porphyran-utilizing strain of Phocaeicola vulgatus by replacing native essential gene regulation with a porphyran-inducible promoter to allow reversible engraftment. Engineering a five-gene oxalate degradation pathway into the reversibly engrafting strain resulted in a therapeutic candidate that reduced hyperoxaluria, a cause of kidney stones, in preclinical models. Our phase 1/2a clinical trial demonstrated porphyran dose-dependent abundance and reversible engraftment in humans, reduction of oxalate in the urine, and characterized genetic stability challenges to achievinglong-term treatment.},
}

Humans
*Gastrointestinal Microbiome/genetics
Animals
Mice
Oxalates/urine/metabolism
Genetic Engineering
Colon/microbiology
*Clostridiales/genetics
Promoter Regions, Genetic
Prebiotics
Kidney Calculi/therapy/prevention & control

@article {pmid40672279,
year = {2025},
author = {Dallon, E and Moran, HM and Chidambaran, SR and Kian, A and Huang, BYH and Fried, SD and DiRuggiero, J},
title = {Investigation of the global translational response to oxidative stress in the model archaeon Haloferax volcanii reveals untranslated small RNAs with ribosome occupancy.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.04.08.647799},
pmid = {40672279},
issn = {2692-8205},
abstract = {UNLABELLED: Oxidative stress induces a wide range of cellular damage, often causing disease and cell death. While many organisms are susceptible to the effects of oxidative stress, haloarchaea have adapted to be highly resistant. Several aspects of the haloarchaeal oxidative stress response have been characterized, however little is known about the impacts of oxidative stress at the translation level. Using the model archaeon Haloferax volcanii , we performed RNA-seq and ribosome profiling (Ribo-seq) to characterize the global translation landscape during oxidative stress. We identified 281 genes with differential translation efficiency (TE). Downregulated genes were enriched in ribosomal and translation proteins, in addition to peroxidases and genes involved in the TCA cycle. We also identified 42 small noncoding RNAs (sRNAs) with ribosome occupancy. Size distributions of ribosome footprints revealed distinct patterns for coding and noncoding genes, with 12 sRNAs matching the pattern of coding genes, and mass spectrometry confirming the presence of seven small proteins encoded in these sRNAs. However, the majority of sRNAs with ribosome occupancy had no evidence of coding potential. Of these ribosome-associated sRNAs, 12 had differential ribosome occupancy or TE during oxidative stress, suggesting that they may play a regulatory role during the oxidative stress response. Our findings on ribosomal regulation during oxidative stress, coupled with potential roles for ribosome-associated noncoding sRNAs and sRNA-derived small proteins in H. volcanii , revealed additional regulatory layers and underscore the multifaceted architecture of stress-responsive regulatory networks.

IMPORTANCE: Archaea are found in diverse environments, including as members of the human microbiome, and are known to play essential ecological roles in major geochemical cycles. The study of archaeal biology has expanded our understanding of the evolution of eukaryotes, uncovered novel biological systems, and revealed new opportunities for applications in biotechnology and bioremediation. Many archaeal systems, however, remain poorly characterized. Using Haloferax volcanii as a model, we investigated the global translation landscape during oxidative stress. Our findings expand current knowledge of translational regulation in archaea and further illustrate the complexity of stress-responsive gene regulation.},
}

@article {pmid40669445,
year = {2025},
author = {Omary, L and Canfora, EE and Puhlmann, ML and Gavriilidou, A and Rijnaarts, I and Holst, JJ and Op den Kamp-Bruls, YMH and de Vos, WM and Blaak, EE},
title = {Intrinsic chicory root fibers modulate colonic microbial butyrate-producing pathways and improve insulin sensitivity in individuals with obesity.},
journal = {Cell reports. Medicine},
volume = {6},
number = {7},
pages = {102237},
doi = {10.1016/j.xcrm.2025.102237},
pmid = {40669445},
issn = {2666-3791},
mesh = {Humans ; *Insulin Resistance ; *Butyrates/metabolism ; *Obesity/microbiology/metabolism/diet therapy ; Male ; *Dietary Fiber ; *Gastrointestinal Microbiome/drug effects ; *Plant Roots/chemistry/metabolism ; Middle Aged ; *Cichorium intybus/chemistry ; Female ; *Colon/microbiology/metabolism ; Adult ; Diabetes Mellitus, Type 2 ; Triglycerides/blood ; },
abstract = {Type 2 diabetes and obesity have become major public health concerns. Growing evidence suggests that increased dietary fiber intake, through its interaction with the gut microbiota, may help prevent these diseases. Here, we demonstrate in a 12-week randomized, placebo-controlled trial in individuals at risk for type 2 diabetes that intake of an intrinsic fiber product, consisting of entire plant cells, tended to improve peripheral insulin sensitivity (p = 0.085), increased whole-body insulin sensitivity (p = 0.032), reduced circulating triglycerides (p = 0.049), and tended to reduce intrahepatic lipid content (p = 0.063), along with an increased proportion of small adipocytes (p = 0.008). Phylogenetic and metagenomic analysis revealed that these outcomes coincided with increased levels of fiber-degrading Bifidobacterium spp. and butyrate-producing Anaerostipes spp. and a functional shift toward a distal butyrogenic trophic chain while the best responding individuals had increased levels of pectin degraders that may produce propionate. Our findings demonstrate the pivotal role of slowly fermented, intrinsic plant cell fibers in improving cardiometabolic health. This study was registered at ClinicalTrials.gov (NCT04714944).},
}

Humans
*Insulin Resistance
*Butyrates/metabolism
*Obesity/microbiology/metabolism/diet therapy
Male
*Dietary Fiber
*Gastrointestinal Microbiome/drug effects
*Plant Roots/chemistry/metabolism
Middle Aged
*Cichorium intybus/chemistry
Female
*Colon/microbiology/metabolism
Adult
Diabetes Mellitus, Type 2
Triglycerides/blood

@article {pmid40666679,
year = {2025},
author = {Lei, S and Wang, J and Zhang, M and Huang, J and Liu, Y and Long, Y and Xing, Y and Yu, Z},
title = {The Succession of Cervical Canal Microbiota in Endometrial Cancer and Cervical Cancer: A Clinical Metagenomics Study.},
journal = {International journal of women's health},
volume = {17},
number = {},
pages = {2039-2050},
pmid = {40666679},
issn = {1179-1411},
abstract = {OBJECTIVE: To define stage-specific cervical canal microbiota signatures across the continuum of gynecologic malignancies from benign endometrial cancer (BE)/cervical cancer precancerous lesions (CIN) to endometrial cancer (EC)/cervical cancers (CC), and to evaluate their potential as diagnostic biomarkers and therapeutic targets.

METHODS: In the observational study, metagenomic sequencing was employed to investigate the cervical canal microbiota of 45 patients, including BE, EC, CIN, and CC. Specimen collection was performed by an experienced physician. All samples were sequenced utilizing the shotgun approach. The microbial statistical analyses were conducted using R.

RESULTS: Compared to the non-cancerous group (BE and CIN), the index related to microbial community stability decreases significantly and the incidence of cervical canal dysbiosis increases in the cancerous group (EC and CC). Microbial diversity exhibited significant differences between BE and EC, CIN and CC, as well as cancerous and non-cancerous groups. At the species level, some species were significantly decreased (eg, Lactobacillus iners) and increased (eg, Staphylococcus haemolyticus, Pasteurella multocida, Pseudomonas putida, and other opportunistic pathogen) in the cancerous group.

CONCLUSION: The cervical canal represents a distinct microbial niche, with its dysbiotic progression reflecting the trajectory of oncogenic transformation. The progression from non-cancerous to cancerous states is characterized by the replacement of the vaginal microbial community, which is dominated by Lactobacillus iners, with a gradual shift towards opportunistic pathogen. Disease diagnosis and complementary therapies focused on lactobacilli and hallmark opportunistic pathogen may offer new insights for precision oncology.},
}

@article {pmid40660385,
year = {2025},
author = {Ji, X and Zhi, M and Gu, X and Han, Y and Lan, X and Song, L and Sun, P and Li, J and Qi, X and Feng, Q},
title = {DnaK of Parvimonas micra extracellular vesicles interacts with the host fibroblasts BAG3-IKK-γ axis to accelerate TNF-α secretion in oral lichen planus.},
journal = {Microbiome},
volume = {13},
number = {1},
pages = {164},
pmid = {40660385},
issn = {2049-2618},
support = {ZR2023MH045//Shandong Natural Science Foundation/ ; YJRC2021002//the start-up fund for introduction of talents to Jinan Central Hospital/ ; 2022-2-7//Science and Technology Development Program of Jinan Municipal Health Commission/ ; 82270980//National Natural Science Foundation of China/ ; 2019//he National Young Scientist Support Foundation/ ; ZR2021JQ29//Excellent Young Scientist Foundation of Shandong Province/ ; 2021SFGC0502//Major Innovation Projects in Shandong Province/ ; 2021GXRC021//the Periodontitis innovation team of Jinan City/ ; 2019//Taishan Young Scientist Project of Shandong Province/ ; 2020KJK001//Oral Microbiome Innovation Team of Shandong Province/ ; 2021ZDSYS18//Shandong Province Key Research and Development Program/ ; },
mesh = {Humans ; *Fibroblasts/metabolism/microbiology ; *Extracellular Vesicles/metabolism ; *Tumor Necrosis Factor-alpha/metabolism ; *Lichen Planus, Oral/microbiology/metabolism/pathology ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Mouth Mucosa/microbiology ; *I-kappa B Kinase/metabolism/genetics ; Male ; Signal Transduction ; Female ; NF-kappa B/metabolism ; Middle Aged ; *Bacterial Proteins/metabolism/genetics ; *HSP70 Heat-Shock Proteins/metabolism/genetics ; Apoptosis Regulatory Proteins ; },
abstract = {BACKGROUND: Oral lichen planus (OLP) is one of the most frequent oral mucosal diseases associated with chronic inflammation, despite a profoundly limited understanding of its underlying pathogenic mechanisms.

RESULTS: The microbiome analysis was conducted on buccal and lip mucosae, tongue dorsum, and saliva in nonerosive/erosive OLP patients and healthy individuals. Significant variations were observed in the oral microbiome of OLP patients, particularly in the buccal mucosa. Network, random forest, and NetShift analysis collectively indicated that Parvimonas micra (P. micra) emerged as a crucial bacterium in OLP. In vivo analysis further demonstrated that P. micra was abundant at the junction of epithelial and connective tissue layers in OLP lesions. Single-cell RNA sequencing data implicated fibroblasts as potential targets, characterized by upregulation of the NF-κB pathway linked to TNF-α. Co-culturing of P. micra or its extracellular vesicles (EVs) with fibroblasts showed that P. micra and EVs could activate the NF-κB signaling pathway and suppress autophagy in buccal mucosal fibroblasts. Among the pathogenic effectors, DnaK from P. micra EVs was identified to interact with BAG3 in fibroblasts. The interaction of DnaK with BAG3 subsequently activated the NF-κB pathway and decreased autophagy flux. Additionally, we identified that IKK-γ was the key downstream protein that could bind with DnaK-BAG3, thereby inhibiting autophagy and promoting TNF-α secretion.

CONCLUSIONS: We initially revealed that P. micra was a crucial pathogen in the development of OLP and demonstrated that P. micra's EVs induce the inhibition of autophagy and enhanced TNF-α secretion in OLP fibroblasts via the DnaK-BAG3-IKK-γ axis. This study offers novel insights into the pathogenic mechanisms underlying OLP. Video Abstract.},
}

Humans
*Fibroblasts/metabolism/microbiology
*Extracellular Vesicles/metabolism
*Tumor Necrosis Factor-alpha/metabolism
*Lichen Planus, Oral/microbiology/metabolism/pathology
*Adaptor Proteins, Signal Transducing/metabolism/genetics
Mouth Mucosa/microbiology
*I-kappa B Kinase/metabolism/genetics
Male
Signal Transduction
Female
NF-kappa B/metabolism
Middle Aged
*Bacterial Proteins/metabolism/genetics
*HSP70 Heat-Shock Proteins/metabolism/genetics
Apoptosis Regulatory Proteins

@article {pmid40657927,
year = {2025},
author = {Robinson, JM and Crino, OL and Camargo, A and Breed, MF},
title = {Does a microbial-endocrine interplay shape love-associated emotions in humans? A hypothesis.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0041525},
doi = {10.1128/msystems.00415-25},
pmid = {40657927},
issn = {2379-5077},
abstract = {Emerging evidence suggests that the human gut microbiome plays a regulatory role in the endocrine system, influencing hormone activity and potentially shaping the emotional and physiological dimensions of behaviors such as aggression and emotional states, including love. Here, we review the hypothesis that microbial-endocrine interactions shape love-associated emotions by modulating hormone levels and activity. While the division of love into discrete components such as lust, attraction, and attachment is somewhat artificial and may not fully capture the complexity of human experience, the associated emotions nevertheless correspond to well-characterized neuroendocrine processes. Psycho-endocrinological theory proposes that the complex and nonlinear interplay between testosterone, estradiol, and other hormones drives emotions associated with lust; serotonin and dopamine play a role in emotions linked to attraction; and oxytocin and vasopressin influence the modulation of attachment and social bonds. Microbial communities may influence emotions and relationship dynamics through effects on the hormonal pathways linked to love-associated emotions. While non-human animal studies suggest microbiota can impact social bonding, sexual preferences, and stress-related behaviors, direct evidence in humans remains limited. Investigating the evolutionary underpinnings of microbial-endocrine interactions could provide insights into how microbes influence emotions beyond love, including hate and aggression-with important societal implications. Indeed, understanding these mechanisms could have profound implications for human relationships, mental health, and even therapeutic interventions targeting the microbiota-gut-brain axis. Future research is needed to unravel the extent to which microbiomes contribute to the neurobiology of love (and other emotions) and whether manipulating microbial communities could modulate emotional and social behaviors.IMPORTANCELove is often considered an abstract emotion, but emerging science suggests that it may be shaped by the microscopic inhabitants of our bodies: microbes. This paper explores the intriguing hypothesis that microbes can influence the hormonal and neural systems linked to love-associated emotions-via the microbiota-gut-brain axis. Drawing on animal studies and early human microbiome and endocrine research, we highlight how microbes modulate neurohormones like oxytocin, dopamine, and testosterone, which play key roles in social bonding. By regulating these systems, microbes may also shape emotional and behavioral responses. This research opens new avenues for understanding not just the (micro)biology of love but also the potential for microbiome-targeted therapies to support relational well-being. By linking microbiome and emotion science, the article raises the important question of whether love is a phenomenon influenced by our resident symbionts, adding an intriguing and potentially impactful dimension to our understanding of human connection and behavior.},
}

@article {pmid40655157,
year = {2025},
author = {Pena-Amelunxen, G and Asghari, M and Khatri, K and Glesner, J and Versteeg, SA and van Ree, R and Chapman, MD and Smith, SA and Chruszcz, M and Pomés, A and Aglas, L},
title = {Pre-clinical allergenicity assessment of IgE epitope-targeted Der p 2 mutants demonstrate potential as hypoallergenic AIT candidates.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1623920},
pmid = {40655157},
issn = {1664-3224},
mesh = {*Immunoglobulin E/immunology ; *Antigens, Dermatophagoides/immunology/genetics ; Animals ; Humans ; *Epitopes/immunology/genetics ; *Arthropod Proteins/immunology/genetics ; Rats ; Mutation ; Antibodies, Monoclonal/immunology ; *Desensitization, Immunologic/methods ; *Allergens/immunology/genetics ; Epitope Mapping ; *Hypersensitivity/immunology ; *Cysteine Endopeptidases/immunology/genetics ; Cell Line, Tumor ; },
abstract = {BACKGROUND: Advancements in hybridoma technology have enabled the production of human IgE monoclonal antibodies (hIgE mAb) for successful IgE epitope mapping of major allergens. Here, we assessed the hypoallergenicity of three IgE-epitope mutants (single 4C8 or 2F10, and double 4C8 + 2F10 epitope mutants) of house dust mite allergen (HDM) Der p 2.

METHODS: Humanized rat basophilic leukemia (huRBL) cells, passively sensitized overnight with either pairs of Der p 2 specific hIgE mAb (2F10, 4C8 or 2G1) or HDM-allergic serum (n=8), were stimulated with either wildtype (WT) Der p 2 or an epitope mutant and mediator release was measured.

RESULTS: No degranulation was induced upon stimulation with all mutants, when cells were sensitized with pairs of hIgE mAb specific for at least one mutated epitope. HIgE mAb specific for non-mutated epitopes led to mediator release comparable to WT Der p 2, indicating that epitopes recognized by the three different hIgE mAb are not overlapping and that the 3D-structure of the mutants is conserved. The double 4C8 + 2F10 epitope mutant had a significantly reduced maximal mediator release (48.3%) compared to the WT, in cells sensitized with allergic donor serum. Overall, the area-under-the-curve of mediator release curves induced by the mutants was significantly lower (31-65%) compared to WT. When comparing the EC20, the double 4C8 + 2F10 epitope mutant required a 158-fold higher antigen concentration to induce the same extent of mediator release as WT Der p 2.

CONCLUSION: Der p 2 epitope mutants display significantly reduced allergenicity. Particularly, the double 4C8 + 2F10 epitope mutant demonstrated a strong potential as a novel AIT vaccine candidate.},
}

*Immunoglobulin E/immunology
*Antigens, Dermatophagoides/immunology/genetics
Animals
Humans
*Epitopes/immunology/genetics
*Arthropod Proteins/immunology/genetics
Rats
Mutation
Antibodies, Monoclonal/immunology
*Desensitization, Immunologic/methods
*Allergens/immunology/genetics
Epitope Mapping
*Hypersensitivity/immunology
*Cysteine Endopeptidases/immunology/genetics
Cell Line, Tumor

@article {pmid40653356,
year = {2025},
author = {Sarath Krishnan, MP and Goyal, B and Nampui, L and Gupta, SC},
title = {The role of microbiome in gastrointestinal cancer.},
journal = {International review of cell and molecular biology},
volume = {395},
number = {},
pages = {67-98},
doi = {10.1016/bs.ircmb.2024.12.009},
pmid = {40653356},
issn = {1937-6448},
mesh = {Humans ; *Gastrointestinal Neoplasms/microbiology/pathology/therapy ; *Gastrointestinal Microbiome ; Animals ; },
abstract = {The human microbiome consists of the diverse microorganisms with their equally diverse functional abilities that have evolved over millions of years with humans. This microbiome creates a mutually beneficial symbiotic relationship with their host. Through their varied functions, the human gut microbiota is crucial for preserving health and homeostasis. Any imbalance in this microbial population can lead to an array of diseased states, including cancer especially of the gastrointestinal system. The focus of this chapter is to discuss the mechanisms through which the gut microbiome creates a conducive environment for initiation and progression of cancer. In addition, the effect of microbial products such as short chain fatty acids, bile acids and Trimethylamine N-oxide on the formation of gastrointestinal cancer is also discussed. The various experimental methods and new molecular techniques that have facilitated the characterization and study of microorganisms is also discussed. The developments in microbiome research have shed light on the potential role of gut microbiota for novel biomarker discovery and therapeutic interventions in gastrointestinal cancer, like fecal microbiota transplantation. The prospects of these areas for further exploration are discussed.},
}

Humans
*Gastrointestinal Neoplasms/microbiology/pathology/therapy
*Gastrointestinal Microbiome
Animals

@article {pmid40653354,
year = {2025},
author = {Gupta, R and Gaur, S},
title = {Effect of diet and lifestyle on microbiome composition.},
journal = {International review of cell and molecular biology},
volume = {395},
number = {},
pages = {157-174},
doi = {10.1016/bs.ircmb.2024.12.008},
pmid = {40653354},
issn = {1937-6448},
mesh = {Humans ; *Life Style ; *Diet ; *Microbiota ; Animals ; },
abstract = {Microbes are major drivers of many important physiological pathways in the human body. A well-adapted and established microbial community at key body sites performs a wide range of functions, including digestive and immunological roles. However, the structure of these microbial communities depends on numerous factors, both genetic and external. Diet and lifestyle are the most common external factors influencing microbiome composition. A healthy diet and lifestyle promote the growth of beneficial microbes, while disturbances in these factors can alter the entire microbial dynamics, potentially leading to pathogenesis. These perturbations can occur at any stage of life, from birth to old age, and may result in serious clinical conditions such as obesity, diabetes, cancers, metabolic syndromes, and many others. Therefore, it is essential to identify the dietary and lifestyle factors that support a healthy microbiome and prevent dysbiosis. This chapter aims to discuss the role of various component of diet and life style that can ultimately shape the human microbiome.},
}

Humans
*Life Style
*Diet
*Microbiota
Animals

@article {pmid40647535,
year = {2025},
author = {Palkovsky, M and Modrackova, N and Neuzil-Bunesova, V and Liberko, M and Hlodakova, A and Soumarova, R},
title = {Role of Human Microbiome in Development and Management of Head and Neck Squamous Cell Carcinoma.},
journal = {Cancers},
volume = {17},
number = {13},
pages = {},
doi = {10.3390/cancers17132238},
pmid = {40647535},
issn = {2072-6694},
abstract = {Despite decades of research, cancer remains a major global health problem [...].},
}

@article {pmid40643244,
year = {2025},
author = {Seekatz, AM},
title = {Straining to define a healthy microbiome.},
journal = {mSphere},
volume = {},
number = {},
pages = {e0079724},
doi = {10.1128/msphere.00797-24},
pmid = {40643244},
issn = {2379-5042},
abstract = {In 2020, I wrote an mSphere of Influence commentary on two studies that shaped my research perspective on the human gut microbiome (McNulty et al., Sci Transl Med 3:106ra106, 2011, https://doi.org/10.1126/scitranslmed.3002701; Hamilton et al., Gut Microbes 4:125, 2013, https://doi.org/10.4161/gmic.23571). The microbiome field has continued to progress since the publication of these studies over 10 years ago, emerging as a considerable factor in almost all areas focused on disease development. My previous commentary highlighted two areas that piqued my interest early on in my career: (i) that the extant microbial community should be considered when proposing to manipulate the microbiota, such as via probiotics or fecal microbiota transplantation, and (ii) that realized (i.e., transcribed) functional changes of the microbiota may occur independent of changes in its composition. Since writing that commentary, two microbiota-based therapeutics for the treatment of Clostridioides difficile infection have been approved, highlighting the potential success of using the microbiota to treat or prevent disease. Despite these wins and ever-growing evidence of the importance of the microbiome in managing our health, translating mechanistic studies into therapeutic value has been slower. In this minireview, I expand upon two large questions that would increase our ability to translate the microbiome into therapies, highlighting both historical and recent progress.},
}

@article {pmid40642982,
year = {2025},
author = {Qi, X and Zhang, M and Wei, T and Lin, J and Zhao, X and Yao, Y and Hu, Y and Zheng, Y},
title = {LorDist: a novel method for calculating the distance based on functional data analysis with application to longitudinal microbial data.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0154225},
doi = {10.1128/spectrum.01542-25},
pmid = {40642982},
issn = {2165-0497},
abstract = {Longitudinal human microbial data offer insights into microbiome dynamics over time. Traditional methods usually overlook temporal relationships among samples from the same subject. Here, we presented the Longitudinal Microbial Data Distance (LorDist) method, which uses functional data fitting to construct a distance matrix integrating information from the same subject at different time points. Simulation data showed that LorDist handled well up to 60% sparseness and worked robustly with various sequencing depths and time points. Empirical data analysis demonstrated that LorDist excels in capturing differences across subjects with longitudinal microbiome data. LorDist presented the potential of longitudinal microbial data in addressing temporal autocorrelation and distinguishing phenotypes.IMPORTANCELongitudinal analysis of the human microbiome is critical for understanding its dynamic role in health and disease. However, current analytical approaches struggle to address key challenges, such as data sparsity and irregular sampling, inherent to time-series microbiome studies. Here, we developed longitudinal microbial data distance (LorDist), an innovative method leveraging functional data analysis to model temporal microbial dynamics with enhanced precision. Compared to existing methods, LorDist consistently outperforms in discerning biologically meaningful group differences, even in highly sparse data sets or under fluctuating sequencing depths. Our findings demonstrate LorDist's robust performance on real-world data sets involving inflammatory bowel disease and infant gut development. By explicitly preserving the temporal structure inherent in microbiome data, LorDist enables robust detection of subtle yet critical biological shifts, paving the way for improved diagnostics and personalized therapeutic strategies in microbiome science.},
}

@article {pmid40642105,
year = {2025},
author = {Jasemi, SK and Faridafshar, H and Amin, MN and Babamohamadi, M and Falahati, M and Amirian, R and Izadi, Z},
title = {NO: a key player in microbiome dynamics and cancer pathogenesis.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1532255},
pmid = {40642105},
issn = {2235-2988},
mesh = {Humans ; *Neoplasms/pathology/metabolism/microbiology/etiology ; *Nitric Oxide/metabolism ; *Microbiota/physiology ; Mouth/microbiology ; Nitrates/metabolism ; Animals ; Bacteria/metabolism ; },
abstract = {The human microbiome refers to the genomic content of microorganisms inhabiting the human body, including the lungs, oral cavity, intestinal tract, esophagus, and other areas. The human oral microbiota is a diverse and complex ecosystem that includes bacteria, microeukaryotes, archaea, and viruses. These communities have a highly structured biogeography resulting from the various microenvironments in the oral cavity, shaping local metabolic exchange. Dietary nitrate (NO3 [-]) is an ion naturally present in vegetables, especially leafy greens. When consumed, it leads to the production of nitric oxide (NO). This bioactive molecule benefits bodily functions like host defense and neuronal communication and improves vascular and metabolic health. Dietary NO3 [-] is reduced to NO via the nitrate-nitrite-NO pathway, facilitated by nitrate-reducing bacteria inside the oral cavity. NO has a leading role in different types of diseases, including cancer, cardiovascular disease, and diabetes. The bioavailability of NO is greatly enhanced by the activity of bacteria residing in the mouth, which reduces NO3 [-]to NO2 [-] and increases the concentration of circulating NO2 [-]. NO is the key to causing different malignancies, including gastrointestinal cancers. NO can cause cell death by inducing DNA damage and anti-apoptotic signaling pathways. Low to moderate levels of NO derived from tumors can activate angiogenesis and promote an invasive phenotype, while high levels of NO may have an anti-tumor effect in protecting against cancer. In this review, we intend to discuss the human microbiome, dietary NO3 [-]consumption, the vital role of NO in the human body, types of cancers, and treatments based on it.},
}

Humans
*Neoplasms/pathology/metabolism/microbiology/etiology
*Nitric Oxide/metabolism
*Microbiota/physiology
Mouth/microbiology
Nitrates/metabolism
Animals
Bacteria/metabolism

@article {pmid40638549,
year = {2025},
author = {Dasgupta, S},
title = {Unraveling the Microbiome-Asthma Axis: Metagenomic Insights from Airway and Gut Microbial Communities.},
journal = {Omics : a journal of integrative biology},
volume = {},
number = {},
pages = {},
doi = {10.1177/15578100251358958},
pmid = {40638549},
issn = {1557-8100},
abstract = {Asthma is a heterogeneous respiratory disease with complex pathogenesis involving immune dysregulation, environmental triggers, and increasingly recognized to have contributions from the human microbiome. Emerging evidence from longitudinal birth cohorts and multi-omics studies reveals that early-life microbial colonization patterns in both the gastrointestinal and respiratory tracts play a crucial role in shaping immune trajectories and influencing asthma susceptibility. This expert review highlights the findings from pivotal studies that associate dysbiosis in the gut and airway microbiota with asthma development and its diverse phenotypic manifestations. Reduced abundance of immunomodulatory genera such as Bifidobacterium, Faecalibacterium, and Lachnospira in the gut has been consistently associated with increased asthma risk. In the airways, increased colonization by potentially pathogenic taxa, including Moraxella, Haemophilus, and Streptococcus, correlates with viral respiratory infections and persistent wheezing. Microbiome diversity patterns also differ between asthma phenotypes: eosinophilic asthma typically features a community profile closer to healthy individuals, while neutrophilic asthma is marked by enrichment of pro-inflammatory bacterial species. Moreover, protective genera such as Dolosigranulum and Corynebacterium in the upper airways are associated with lower risk of asthma and reduced respiratory infections. Elucidating these microbiome-mediated mechanisms holds promise for the development of targeted microbiota-based strategies for asthma prevention and phenotype-specific therapeutic interventions. The present review unpacks these localized microbial patterns and their mechanistic implications for asthma development, severity, and endotypic variation. Finally, unraveling the microbiome-asthma axis from airway and gut microbial communities also has implications for new ways of thinking personalized medicine in the future.},
}

@article {pmid40638496,
year = {2025},
author = {Hyvönen, S and Solasaari, T and Pokka, T and Korpela, K and de Vos, WM and Salonen, A and Ruuska-Loewald, T and Kolho, KL},
title = {Maternal Prenatal and Postnatal Stress and Infections in Infancy.},
journal = {Acta paediatrica (Oslo, Norway : 1992)},
volume = {},
number = {},
pages = {},
doi = {10.1111/apa.70228},
pmid = {40638496},
issn = {1651-2227},
support = {5044//Signe and Ane Gyllenberg Foundation/ ; 200141/WT_/Wellcome Trust/United Kingdom ; 210168//Lastentautien Tutkimussäätiö/ ; 5851//Finnish Medical Foundation/ ; //Juho Vainio Foundation/ ; 329/31/2015//Tekes/Business Finland/ ; },
abstract = {AIM: To study maternal stress as a possible risk factor for early infections in infants in a well-characterised, prospective infant HELMi cohort.

METHODS: We measured maternal stress during the last trimester with questionnaires (4 items, scales 0-100) and breastmilk cortisol levels at 3 months. We compared maternal stress between infants with several infections (n = 125) and infants with no infections (n = 122) during the first 6 months of life. The episodes and days with symptoms were recorded using an online diary. Control subjects were matched for sex, year of birth, mode of delivery, and timing of breastmilk sample. The analysis was adjusted for season of birth and number of siblings.

RESULTS: The median maternal prenatal stress, related to household during the last trimester, was higher in the infection group than in controls (37 [IQR 19.5-61] vs. 19 [7.8-42.3]; p = 0.02). There was no difference in prenatal stress related to pregnancy or the relationship between the groups. The breastmilk cortisol levels did not differ between the groups (medians of 6.8 nmol/L [IQR 4.8-8.8] and 6.2 nmol/L [4.5-8.4], respectively; p = 0.12).

CONCLUSION: Prenatal stress was linked to the occurrence of infections in infancy. Whether support for stress reduction may reduce the risk for infections warrants further study.},
}

@article {pmid40626521,
year = {2025},
author = {Wan, H and Weng, J and Cai, J and Chen, Z and Li, P and Han, J and Li, Z and Wan, Z and Yuan, Z and Gan, Y and Huang, M and Li, X and Li, T and Liu, X and Wang, X and Yu, H and Liu, B and Lin, J and Luo, Y},
title = {Nodal Downstaging in Rectal Cancer Patients: Survival is Promising if YpN0 is Achieved.},
journal = {Diseases of the colon and rectum},
volume = {},
number = {},
pages = {},
doi = {10.1097/DCR.0000000000003846},
pmid = {40626521},
issn = {1530-0358},
abstract = {BACKGROUND: Locally advanced rectal cancer is a critical health concern, with neoadjuvant therapy emerging as a pivotal strategy to enhance survival rates.

OBJECTIVE: This study aims to evaluate the prognostic value of achieving ypN0 status following neoadjuvant therapy patients with locally advanced rectal cancer, comparing survival outcomes among natural N0, downstaged N0, and ypN + groups.

DESIGN: We conducted a post hoc analysis of the FOWARC trial, employing Kaplan-Meier survival analysis and Cox regression models to assess overall survival, disease-free survival, and locoregional recurrence-free survival.

SETTINGS: The multicenter, randomized phase III FOWARC trial was conducted across 15 hospitals in China, adhering to ethical standards.

PATIENTS: Our cohort included 449 patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision.

INTERVENTIONS: Neoadjuvant chemoradiotherapy followed by total mesorectal excision.

MAIN OUTCOME MEASURES: The primary endpoint was 5-year overall survival, with secondary endpoints being 3-year disease-free survival and 3-year locoregional recurrence-free survival.

RESULTS: The 5-year overall survival for natural N0 and downstaged N0 groups were 88% and 89%, respectively, significantly higher than the 73% observed in the ypN+ group (p = 0.0034). The complete pathological response rate was markedly lower in the ypN+ group. Multivariable analysis showed the ypN stage as an independent prognostic factor for overall survival.

LIMITATIONS: The study's retrospective design may introduce potential biases in patient selection and preoperative staging.

CONCLUSIONS: Achieving ypN0 status via neoadjuvant chemoradiotherapy significantly improves survival in patients with locally advanced rectal cancer, regardless of ypT or cN status. This status not only serves as an independent prognostic factor, but may also help to guide hypothesis-driven, individualized postoperative-treatment strategies. See Video Abstract.ClinicalTrials.gov identifier: NCT01211210.},
}

@article {pmid40626364,
year = {2025},
author = {Sequoia, JA and Haddock, NL and Gay, PM and Barkal, LJ and Narasimhan, P and Martinez, N and Winn, VD and Bollyky, PL},
title = {Identification of bacteriophage DNA in human umbilical cord blood.},
journal = {JCI insight},
volume = {10},
number = {13},
pages = {},
doi = {10.1172/jci.insight.183123},
pmid = {40626364},
issn = {2379-3708},
mesh = {Humans ; *Fetal Blood/virology ; Female ; Pregnancy ; *DNA, Viral/blood/genetics/isolation & purification ; *Bacteriophages/genetics/isolation & purification ; Adult ; Infant, Newborn ; Pre-Eclampsia/virology/blood ; Cell-Free Nucleic Acids/blood ; Chorioamnionitis/virology/blood ; Premature Birth/virology/blood ; },
abstract = {Bacteriophages, viruses that parasitize bacteria, are abundant in the human microbiome and may influence human health, in part, through their interactions with bacterial hosts. Whether endogenous bacteriophages or their products are vertically transmitted from mother to fetus during human pregnancy is not known. Here, we searched for bacteriophage sequences from five bacteriophage databases (474,031 total sequences) in cell-free DNA (cfDNA) of paired maternal and umbilical cord blood samples from two independent cohorts. First, we sequenced cfDNA from 10 pairs of maternal and cord blood samples, including four pairs affected by preeclampsia. We validated our findings in a previously published dataset of 62 paired maternal and cord blood samples, including 43 pairs from preterm or chorioamnionitis-affected deliveries. We identified 94 and 596 bacteriophage sequences in maternal and cord blood cfDNA samples from the first and second cohort, respectively. We identified 58 phage sequences across maternal-infant dyads and 581 phage sequences that were unique to a single sample. We did not identify any phage sequences consistently associated with preeclampsia, preterm, or chorioamnionitis-affected samples. This study demonstrated the presence of bacteriophage DNA in human cord blood at birth, providing evidence that the human fetus is exposed to bacteriophage DNA in utero.},
}

Humans
*Fetal Blood/virology
Female
Pregnancy
*DNA, Viral/blood/genetics/isolation & purification
*Bacteriophages/genetics/isolation & purification
Adult
Infant, Newborn
Pre-Eclampsia/virology/blood
Cell-Free Nucleic Acids/blood
Chorioamnionitis/virology/blood
Premature Birth/virology/blood

@article {pmid40623769,
year = {2025},
author = {Basoya, R and Singh, B and Basi, A and Aggarwal, S},
title = {Role of microbiome in cancer progression.},
journal = {International review of cell and molecular biology},
volume = {394},
number = {},
pages = {79-106},
doi = {10.1016/bs.ircmb.2024.12.013},
pmid = {40623769},
issn = {1937-6448},
mesh = {Humans ; *Neoplasms/microbiology/pathology/therapy ; *Disease Progression ; *Microbiota ; Animals ; },
abstract = {The human microbiome plays a crucial role in maintaining health and preventing disease. Dysbiosis, or imbalance, in the microbiome, has been linked to various diseases, including cancer. This chapter explores the influence of microbiomes on different organs, immune system modulation, and cancer development. Specific microorganisms, such as Helicobacter pylori, Escherichia coli, and human papillomavirus (HPV), contribute to gastric, colorectal, and cervical cancer through mechanisms like immunomodulation and proliferative signaling pathways. Dysbiosis-induced cancer progression involves NF-κB, Wnt/β-catenin, and JAK/STAT signaling. Recent studies highlight the microbiome's potential in cancer diagnosis and immunotherapy. Fecal Microbiota Transplantation (FMT) and predictive biomarkers, such as Porphyromonas gingivalis and Escherichia-Shigella, show promise in treating colorectal cancer. The microbiome influences tumor biology and immune response, affecting immunotherapeutic efficacy. Understanding microbiome-cancer interactions offers new opportunities for improved diagnosis and personalized therapy. This chapter provides comprehensive insights into the role of microbiome in cancer progression, emphasizing the importance of microbiome research in developing effective cancer treatments.},
}

Humans
*Neoplasms/microbiology/pathology/therapy
*Disease Progression
*Microbiota
Animals

@article {pmid40623763,
year = {2025},
author = {Agrawal, P and Mendhey, P and Kumar, R and Patel, S and Kaushik, PK and Dadsena, A and Kumar, S},
title = {Introduction to microbiomes in health and diseases.},
journal = {International review of cell and molecular biology},
volume = {394},
number = {},
pages = {1-42},
doi = {10.1016/bs.ircmb.2024.12.010},
pmid = {40623763},
issn = {1937-6448},
mesh = {Humans ; *Microbiota ; *Health ; *Disease ; Animals ; },
abstract = {The human microbiome is a complex ecological system of commensal, symbiotic, and pathogenic microorganisms that plays a crucial role in human health and disease. The microbiome includes both the living microorganisms also called microbiota and their synthesized metabolites and structural components. It is distributed to the gastrointestinal tract, skin, respiratory system, and oral cavity, each with a distinct microbial composition. Dysbiosis, or imbalance in the microbiome is linked to numerous diseases such as eczema, gastric ulcers, cardiovascular diseases, and cancer. The axes of microbial activity and their connections to disease, including the gut-skin, gut-lung, gut-brain, and gut-kidney play a crucial role in health and disease conditions. Also, the role of the microbiome in cancer development and response to therapy is examined. This book chapter underscores the importance of maintaining a balanced microbiome for overall health and the potential for microbiome-based interventions in disease prevention and treatment.},
}

Humans
*Microbiota
*Health
*Disease
Animals

@article {pmid40621920,
year = {2025},
author = {Ventin-Holmberg, R and Eriksson, J and Eberl, A and Sipponen, T and Nissilä, E and Saavalainen, P},
title = {The total gut mucosal and fecal bacterial load increases in successful treatment of inflammatory bowel disease with infliximab.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0189424},
doi = {10.1128/spectrum.01894-24},
pmid = {40621920},
issn = {2165-0497},
abstract = {Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory gastrointestinal disorders linked to genetic predisposition and environmental factors. The gut microbiota, composed of various microorganisms, plays a crucial role in IBD, as reduced anaerobic bacteria and short-chain fatty acid (SCFA) producers are associated with predisposition to IBD. There is no cure for IBD, but the treatment aims for mucosal healing including conventional treatment and biological therapies such as infliximab (IFX). IFX, a tumor necrosis factor alpha (TNF-α) blocker, effectively reduces inflammation, but around 50% of patients do not achieve long-term remission. Fecal samples were collected from 70 patients with IBD (24 CD, 44 UC, and 2 IBDU), and mucosal samples were collected from both ileum and colon from 63 patients before, during, and after IFX treatment. The bacterial microbiota composition was investigated by targeting the conserved 16S region in MiSeq sequencing. Additionally, the relative sequencing data were quantified by qPCR. Responders to IFX had an increase in the total bacterial load in ileum and fecal samples during treatment, primarily driven by butyrate-producing bacteria in the Firmicutes phylum. Interestingly, this was only observed in the fecal samples in responders, but not non-responders to IFX. These results indicate that the gut bacterial microbiota of responders to IFX is changing toward a more favorable composition during successful IFX treatment.IMPORTANCEThe research described in this paper enhances our understanding of how infliximab (IFX) treatment affects the gut mucosal and fecal microbiota in patients with inflammatory bowel disease (IBD). Using 16S sequencing technique and quantification by qPCR, the study revealed that successful treatment with IFX led to an increase in the total bacterial load in both ileal and fecal samples, as well as a shift in bacterial composition toward a more favorable profile with an increase in butyrate-producing bacteria in the fecal samples in responders but not in non-responders to infliximab. This study emphasizes that the gut microbiota plays an important role in the healing process during infliximab treatment in IBD.},
}

@article {pmid40618318,
year = {2025},
author = {Wu, K and Zhu, E and Chen, J and Kuang, Q and Lin, J and Zhao, S and Xu, X and Li, S and Sui, Y and Huang, M and Zhang, Y},
title = {Overexpression of GPX4 in diabetic rat kidney alleviates renal injury induced by ferroptosis.},
journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine},
volume = {},
number = {},
pages = {},
pmid = {40618318},
issn = {1572-8773},
abstract = {Ferroptosis-mediated injury in diabetic kidney (DKD) is receiving increasing attention. Glutathione Peroxidase 4 (GPX4) has long been considered a key protein to prevent ferroptosis, but its exact role in the progression of DKD, where this protein down-regulated, remains unclear. Thus, to clarify GPX4 in DKD progression, we have used adeno-associated viruses (AAVs) to overexpress it in kidneys of DKD rats. Streptozotocin (STZ)-induced DKD rats were injected once with GPX4-AAVs via tail vein. Renal function and kidney pathology were measured. Before and after treatment with GPX4-AAV, variations in kidney of ferroptosis-related indicators, such as GPX4, dihydroorotate dehydrogenase (DHODH), iron content, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), transferrin receptor 1 (TFR1), ferritin heavy chain (FTH), were monitored. The kidneys of STZ-treated rats showed reduced expression of GPX4, DHODH, GSH and SOD, increased expression of TFR1 and FTH, and higher levels of iron and MDA. Histopathology was consistent with renal fibrosis and thickened renal tubules. Changes were partly reversed after overexpression of GPX4, with decreased expression of FTH, together with reduced iron and MDA levels, although expression of TFR1, GSH and SOD showed no significant change. Renal function showed a lower urine protein-creatinine ratio, whereas the effect on renal fibrosis and thickened renal tubules was alleviated. Our study demonstrates that GPX4 is downregulated in DKD, and its AAV-mediated overexpression in kidney of DKD rats partly alleviates the diabetic kidney injury induced by ferroptosis.},
}

@article {pmid40616741,
year = {2025},
author = {Renton, N and Pillinger, MH and Toprover, M},
title = {Gout, Hyperuricemia, and the Intestinal Microbiome.},
journal = {Inflammation},
volume = {},
number = {},
pages = {},
pmid = {40616741},
issn = {1573-2576},
abstract = {Gout is a disease of hyperuricemia (HU) leading to monosodium urate crystal deposition in the joint, resulting in inflammation and joint damage. Recently, efforts have been made to characterize the intestinal microbiome of patients who suffer from HU and gout, and pre-clinical studies have evaluated the utility of prebiotics and probiotics in alleviating gout. Herein we review recent notable studies addressing these topics. In brief, the "gouty" microbiome is characterized by reduced diversity, an elevated Bacteroides: Firmicutes ratio, and reduced presence of Akkermansia and Bifidobacterium. In anserine models, supplementation with Lactobacillus probiotic strains appears to reduce serum urate (SU) and HU-induced inflammation. Murine models suggest that the chicory-derived prebiotic inulin may reduce SU, and oral supplementation with the anti-inflammatory short-chain fatty acid butyrate may lower SU by enhancing urate excretion and alleviate HU-induced tissue inflammation. Many of these studies are limited by modest numbers of participants and/or incompletely documented experimental controls, and, in the case of animal models, questionable reproducibility in humans. Many studies have been geographically limited. There remains a need for more information regarding the features of the "gouty" microbiome in wider populations, as well as for additional well-controlled probiotic and prebiotic studies in more physiologically relevant animal models prior to clinical trials.},
}

@article {pmid40615170,
year = {2025},
author = {Chowdhury, R and Maddheshiya, A and Taneja, S and Bhandari, N and Majumder, PP and Strand, TA and Pandey, RM and Kurpad, AV and Mukherjee, S},
title = {Impact of an Integrated Intervention Package During Preconception, Pregnancy, and Early Childhood on the Gut Microbiome at Six Months of Age: Findings from the Women and Infants Integrated Growth Study (WINGS) Randomized Controlled Trial.},
journal = {The Journal of nutrition},
volume = {155},
number = {7},
pages = {2355-2366},
doi = {10.1016/j.tjnut.2025.04.016},
pmid = {40615170},
issn = {1541-6100},
mesh = {Humans ; Female ; *Gastrointestinal Microbiome ; Pregnancy ; Infant ; Adult ; Young Adult ; Adolescent ; Male ; Feces/microbiology ; *Preconception Care ; },
abstract = {BACKGROUND: The infant gut microbiome is essential for healthy growth and development. However, limited research has explored how interventions targeting maternal and infant health, nutrition, and psychosocial conditions during preconception, pregnancy, and early childhood impact microbiome development. To address this research gap and better understand the potential impact of such interventions, this study was designed to evaluate their effects on the infant gut microbiome.

OBJECTIVE: The aim was to evaluate the effects of an integrated intervention package on infant gut microbiome at 6 mo of age compared with routine care.

METHODS: The study was embedded in a randomized factorial trial involving women aged 18-30 y. Participants were randomly assigned to receive either a preconception intervention package or routine care until pregnancy. Pregnant women were then randomly assigned to receive a pregnancy and early childhood intervention package or routine care. The intervention included health care for growth-related conditions, nutrition, water, sanitation, and hygiene (WASH), and psychosocial care. Stool samples from 392 infants (185 from the preconception, pregnancy, and early childhood intervention group and 207 from the routine care group) were collected at 6 mo, followed by microbiome DNA isolation and high-throughput sequencing of the V3-V4 region of 16S rRNA gene. Generalized linear models were used to estimate the mean relative abundance of core gut microbiome phyla, genera, and species between the intervention and routine care groups.

RESULTS: Infants in the group who received preconception, pregnancy, and early childhood intervention had a significantly lower mean relative abundance of Klebsiella genus under the Pseudomonadota phylum (45% lower; 95% confidence interval [CI]: 18, 63) and Klebsiella pneumoniae species (38% lower; 95% CI: 8, 59) compared with routine care group. In contrast, the relative abundance of Megasphaera (72% higher; 95% CI: 7, 175), Prevotella (72% higher; 95% CI: 3, 187), and Bifidobacterium breve (34% higher; 95% CI: 2, 79) was significantly higher in the group received preconception, pregnancy and early childhood intervention compared with routine care.

CONCLUSIONS: The findings indicate that improving maternal and infant health, nutrition, and psychosocial conditions enhances the relative abundance of beneficial gut bacteria at 6 mo of age, supporting healthy growth and development. This trial was registered at Clinical Trials Registry-India as CTRI/2020/10/028770; https://ctri.nic.in/Clinicaltrials/advsearch2.php.},
}

Humans
Female
*Gastrointestinal Microbiome
Pregnancy
Infant
Adult
Young Adult
Adolescent
Male
Feces/microbiology
*Preconception Care

@article {pmid40613581,
year = {2025},
author = {Dang, T and Lysenko, A and Boroevich, KA and Tsunoda, T},
title = {VBayesMM: variational Bayesian neural network to prioritize important relationships of high-dimensional microbiome multiomics data.},
journal = {Briefings in bioinformatics},
volume = {26},
number = {4},
pages = {},
doi = {10.1093/bib/bbaf300},
pmid = {40613581},
issn = {1477-4054},
support = {JP20H03240//JSPS KAKENHI/ ; JP24K15175//JSPS KAKENHI/ ; JPMJCR2231//JST CREST/ ; },
mesh = {Bayes Theorem ; *Microbiota ; *Neural Networks, Computer ; *Metagenomics/methods ; Humans ; *Computational Biology/methods ; Algorithms ; Multiomics ; },
abstract = {The analysis of high-dimensional microbiome multiomics datasets is crucial for understanding the complex interactions between microbial communities and host physiological states across health and disease conditions. Despite their importance, current methods, such as the microbe-metabolite vectors approach, often face challenges in predicting metabolite abundances from microbial data and identifying keystone species. This arises from the vast dimensionality of metagenomics data, which complicates the inference of significant relationships, particularly the estimation of co-occurrence probabilities between microbes and metabolites. Here we propose the variational Bayesian microbiome multiomics (VBayesMM) approach, which aims to improve the prediction of metabolite abundances from microbial metagenomics data by incorporating a spike-and-slab prior within a Bayesian neural network. This allows VBayesMM to rapidly and precisely identify crucial microbial species, leading to more accurate estimations of co-occurrence probabilities between microbes and metabolites, while also robustly managing the uncertainty inherent in high-dimensional data. Moreover, we have implemented variational inference to address computational bottlenecks, enabling scalable analysis across extensive multiomics datasets. Our large-scale comparative evaluations demonstrate that VBayesMM not only outperforms existing methods in predicting metabolite abundances but also provides a scalable solution for analyzing massive datasets. VBayesMM enhances the interpretability of the Bayesian neural network by identifying a core set of influential microbial species, thus facilitating a deeper understanding of their probabilistic relationships with the host.},
}

Bayes Theorem
*Microbiota
*Neural Networks, Computer
*Metagenomics/methods
Humans
*Computational Biology/methods
Algorithms
Multiomics

@article {pmid40611411,
year = {2025},
author = {Islam, A},
title = {Advances in Microbiome Research: Implications for Infectious Disease Management and Treatment.},
journal = {Recent advances in anti-infective drug discovery},
volume = {},
number = {},
pages = {},
doi = {10.2174/0127724344384934250624040634},
pmid = {40611411},
issn = {2772-4352},
abstract = {INTRODUCTION: The human microbiome plays a pivotal role in health and disease, with microbial imbalances (dysbiosis) increasingly linked to heightened susceptibility to infections and exacerbated disease severity. This review explores how the microbiome confers protection through mechanisms, such as colonization resistance, immune modulation, and antimicrobial metabolite production, while also examining its potential as a predictive tool for infection risk and outcomes, as exemplified in COVID-19.

METHODS: This article synthesizes current literature on microbiome dynamics, leveraging advances in high-throughput sequencing, bioinformatics, and machine learning to analyze microbial profiles and identify biomarkers. It evaluates microbiome-based therapeutic strategies, including probiotics, prebiotics, and engineered microbes, and assesses challenges in translating these approaches into clinical practice.

RESULTS: Microbiome profiles demonstrate prognostic value in predicting infection risk and severity, supported by enhanced analytical tools that enable precise biomarker discovery for diagnostics and personalized medicine. Therapeutic interventions show promise in restoring microbial balance and combating infections, though clinical adoption is hindered by variability, regulatory hurdles, and the need for standardized methodologies.

CONCLUSION: Integrating microbiome insights into clinical practice requires rigorous clinical trials, standardized protocols, and resolution of ethical and regulatory challenges. Future research should focus on elucidating microbiome-host-pathogen interactions and developing targeted interventions, and advanced computational models are critical to unlocking the full potential of microbiome-based diagnostics and therapeutics for infectious disease management.},
}

@article {pmid40607434,
year = {2025},
author = {Kim, SI and Rha, MS and Kim, J and Ahn, SH and Ryu, JH and Cho, HJ and Kim, CH},
title = {Inflammation-driven periostin in ECRS has contrasting effects on tissue structural integrity and osteitis.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1596746},
pmid = {40607434},
issn = {1664-3224},
mesh = {Animals ; *Cell Adhesion Molecules/metabolism/genetics ; Humans ; Mice ; *Sinusitis/metabolism/immunology/pathology ; Mice, Knockout ; *Osteitis/metabolism/immunology/pathology/etiology ; *Rhinitis/metabolism/immunology/pathology ; Inflammation/immunology/metabolism ; Disease Models, Animal ; Male ; Chronic Disease ; Female ; Osteogenesis ; Nasal Mucosa/metabolism/pathology/immunology ; Fibroblasts/metabolism/immunology ; *Eosinophilia/immunology/metabolism/pathology ; Periostin ; },
abstract = {INTRODUCTION: Eosinophilic chronic rhinosinusitis (ECRS) is a severe form of chronic rhinosinusitis characterized by type 2 inflammation, tissue remodeling, and bone thickening, known as osteitis. Periostin, a matricellular protein involved in extracellular matrix (ECM) regulation and T helper 2 (Th2)-mediated inflammation, is markedly elevated in patients with ECRS; however, its pathophysiological role remains unclear.

METHODS: We investigated the role of periostin in inflammation and tissue remodeling in ECRS using samples from ECRS patients, human nasal epithelial cells and fibroblasts, as well as an ECRS mouse model including periostin knockout mice.

RESULTS: Periostin levels were elevated in ECRS tissues and modestly correlated with osteitis scores. Th2 cytokines increased periostin expression, particularly in nasal fibroblasts. Conditioned medium containing periostin promoted osteogenic differentiation in vitro, whereas neutralizing antibodies reduced the expression of osteogenic markers. In an ECRS mouse model, periostin deficiency led to reduced bone thickening and lower expression of osteogenic markers despite similar eosinophil infiltration. Furthermore, periostin-deficient mice exhibited greater epithelial collapse and reduced fibronectin levels, indicating compromised ECM integrity.

DISCUSSION: These findings demonstrate that periostin contributes to osteogenesis and maintenance of structural stability in the inflamed sinonasal mucosa. Periostin may be a potential therapeutic target for controlling chronic inflammation and tissue remodeling in ECRS.},
}

Animals
*Cell Adhesion Molecules/metabolism/genetics
Humans
Mice
*Sinusitis/metabolism/immunology/pathology
Mice, Knockout
*Osteitis/metabolism/immunology/pathology/etiology
*Rhinitis/metabolism/immunology/pathology
Inflammation/immunology/metabolism
Disease Models, Animal
Male
Chronic Disease
Female
Osteogenesis
Nasal Mucosa/metabolism/pathology/immunology
Fibroblasts/metabolism/immunology
*Eosinophilia/immunology/metabolism/pathology
Periostin

@article {pmid40607343,
year = {2025},
author = {Xu, H and Zhang, F and Che, Y and Cui, Y and Yao, Q and Guan, Y and Chen, H and Huang, Y},
title = {Integrative multi-omics and bioinformatics analysis of the effects of BaiRui YuPingFeng Powder on intestinal health in broilers.},
journal = {Frontiers in veterinary science},
volume = {12},
number = {},
pages = {1606531},
pmid = {40607343},
issn = {2297-1769},
abstract = {INTRODUCTION: In recent years, global poultry consumption has increased rapidly, making chicken the most widely consumed meat worldwide by 2019. To increase livestock development, antibiotics are often added to animal feed as growth promoters. But overuse of antibiotics may alter the gut microbiota, make people more resistant to them, and raise the possibility that they will spread antibiotic resistance genes to the human microbiome. Therefore, identifying safe and effective alternatives to antibiotics in livestock production is crucial for maintaining and improving gut microbial balance, ultimately promoting poultry health. The aim of this study was to investigate the mechanisms behind the impacts of BaiRui YuPingFeng Powder (TCYP) on intestinal health in broilers using combined metabolomics, bioinformatics analysis, and 16S rRNA sequencing.

METHODS: In a 42-day feeding trial, 300 one-day-old broilers were randomly divided into five groups (six replicates per group; 10 broilers per replicate) fed a basal diet with or without supplements: control (CON), antibiotic (ATB), and TCYP at 500, 1000, and 1500 mg/kg. Growth performance, serum biochemical parameters, intestinal morphology, cecal microbiota composition, and metabolomic profiles were analyzed. Bioinformatics analysis was used to identify potential targets and pathways, followed by qPCR validation of key genes.

RESULTS: Compared with the CON group, TCYP administration dose-dependently reduced the feed-to-gain ratio (F/G) and average daily feed intake (ADFI) while increasing average daily gain (ADG), with the high-dose TCYP showing more pronounced effects (p < 0.05). Serum biochemical analysis revealed that TCYP treatment significantly decreased serum levels of total cholesterol (T-CHO), triglycerides (TG), lactate dehydrogenase (LDH), and alanine aminotransferase (ALT) in a dose-dependent manner, while elevating albumin (ALB) content. These beneficial effects were particularly marked in the high-dose TCYP group (p < 0.05). Histopathological examination indicated that high-dose TCYP significantly enhanced villus height and the villus-to-crypt ratio (V/C) in the duodenum, jejunum, and ileum compared to the CON group (p < 0.05). 16S rRNA sequencing analysis revealed that TCYP treatment significantly modified the β-diversity of cecal microbiota (p < 0.01). Compared to the CON group, ATB treatment increased the abundance of Faecalibacterium and Lachnospiraceae_unclassified but reduced Ruminococcaceae_unclassified and Firmicutes_unclassified. Notably, dietary TCYP supplementation maintained gut microbiota profiles similar to the CON group, demonstrating its stabilizing effect on microbial community structure in broilers. Metabolomic analysis identified differential metabolites primarily involved in lipid and lipid-like molecules, organic heterocyclic compounds, and organic acids and derivatives. Spearman correlation analysis revealed significant associations between Lachnospiraceae_unclassified and metabolites such as Gly-Leu, fumarate, and phenylpyruvic acid (|r| > 0.5, p < 0.05). Bioinformatics analysis suggested that TCYP may improve intestinal health by regulating key targets, including MMP9, TGFB1, and PPARG, as well as the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Quantitative PCR (qPCR) results showed that, compared to the CON group, TCYP dose-dependently significantly upregulated the mRNA expression of PPARG, PDPK1, and Bcl2 in jejunal tissues (p < 0.05), while significantly downregulating the expression of MMP1 and Bax (p < 0.05).

CONCLUSION: TCYP enhances growth performance and intestinal health in broilers through multiple mechanisms, including maintaining cecal microbial homeostasis, modulating lipid and amino acid metabolism, with potential involvement of the PPAR signaling pathway based on bioinformatics and gene expression analysis.},
}

@article {pmid40606566,
year = {2025},
author = {Wang, L and Wang, L and Chen, L},
title = {NetNiche: Microbe-Metabolite Network Reconstruction and Microbial Niche Analysis.},
journal = {Phenomics (Cham, Switzerland)},
volume = {5},
number = {2},
pages = {208-211},
pmid = {40606566},
issn = {2730-5848},
abstract = {UNLABELLED: Metagenomics and metabolomics technologies have been widely used to investigate the microbe-metabolite interactions in vivo. However, the computational methods that accurately infer the microbe-metabolite interactions are lacking. We present a context-aware framework for graph representation learning, NetNiche, which predicts microbe-metabolite and microbe-microbe interactions in an accurate manner, by integrating their abundance data with prior knowledge. We applied NetNiche to datasets on gut and soil microbiome, and demonstrated that NetNiche can outperform the state-of-the-art methods, such as SParse InversE Covariance Estimation for Ecological Association Inference (SPIEC-EASI), Sparse Correlations for Compositional data (SparCC) and microbe-metabolite vectors (mmvec). NetNiche is an effective tool with wide applicability for the multi-omics study of human microbiome.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-024-00168-8.},
}

@article {pmid40604393,
year = {2025},
author = {Yao, S and Yan, X and Chen, H and Lei, S and Huang, J and Guo, K and Yu, Z},
title = {Dynamic changes of gut and skin microbiota in pancreatic cancer-induced skin injury.},
journal = {BMC microbiology},
volume = {25},
number = {1},
pages = {392},
pmid = {40604393},
issn = {1471-2180},
support = {32170071//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Skin lesions can occur during the progression of pancreatic cancer. With growing attention on the gut-skin axis, these lesions may be linked to the microbiota. Microbiota play a crucial role in skin-related conditions, including hair loss and overall skin health. However, few studies have investigated the dynamic changes in gut and skin microbiota associated with skin lesions during cancer progression. In this study, 16S rRNA gene sequencing was used to investigate the dynamic changes of the gut microbiota in mice without non-depilation (Unepi) and depilation (Epi) after PAN02 cell injection. We also revealed the changes in skin microbiota of Unepi mice (Unepi_D) and Epi mice (Epi_D) after depilation.

RESULTS: Our study found that the alpha diversity significantly increased in Unepi_D, indicating an imbalance in gut microbiota homeostasis. In the skin microbiota, certain genera such as Staphylococcus and Devosia were up-regulated, while others like Lactobacillus were down-regulated. Similarly, in the gut microbiota, Parasutterella was enriched, whereas Blautia showed reduced abundance. In the Epi group, the trend of increasing pathogenic bacteria and decreasing probiotics suggests a disrupted microbial environment that may contribute to skin injury through the gut–skin axis. These findings highlight potential microbial targets for diagnosis and therapeutic intervention in pancreatic cancer-associated skin complications.

CONCLUSION: Therefore, our findings provide new insights and references for the prevention and treatment of skin-related diseases in clinical practice. Specific gut and skin microbiota alterations may serve as potential biomarkers or therapeutic targets for managing skin complications in pancreatic cancer patients.

CLINICAL TRIAL NUMBER: Not applicable.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-025-04068-3.},
}

@article {pmid40604155,
year = {2025},
author = {Wen, W and Yang, C and Zuo, T},
title = {Viewing MASLD through an integrative gut microbiome lens.},
journal = {Nature metabolism},
volume = {},
number = {},
pages = {},
pmid = {40604155},
issn = {2522-5812},
}

@article {pmid40601380,
year = {2025},
author = {Bağcı, U and Ulusan Bağcı, Ö},
title = {The bibliometric analysis of documents concerning the relationship between the microbiota and urological malignancies.},
journal = {Journal of medical microbiology},
volume = {74},
number = {7},
pages = {},
doi = {10.1099/jmm.0.002041},
pmid = {40601380},
issn = {1473-5644},
mesh = {Humans ; *Bibliometrics ; *Microbiota ; *Urologic Neoplasms/microbiology ; Male ; Prostatic Neoplasms/microbiology ; Urinary Bladder Neoplasms/microbiology ; Kidney Neoplasms/microbiology ; },
abstract = {Introduction. The microbiota, which has a major impact on both health and illness, has recently become one of the most popular research topics.Hypothesis/Gap statement. To the best of our knowledge, no research has undertaken a bibliometric analysis of publications examining the connection between microbiome and urological cancer to date. In this respect, it is thought that our study will contribute to the literature.Aim. The purpose of this study is to raise awareness of the topic by performing a bibliometric analysis of the publications examining the connection between the microbiota and the most common urological cancers, including bladder, prostate, and kidney cancers.Methodology. All publications about prostate, renal and bladder cancers and microbiota indexed in Web of Science between 2000 and 2024 were included in the study.Results. A total of 310 publications were obtained. Before 2018, there were only three or fewer publications annually; however, following 2018, the number of publications increased rapidly, reaching a peak of 77 in 2024. The USA led with 98 (31.61%) documents, followed by China (60, 19.35%) and Italy (31, 10%). With 19 publications, Hirotsugu Uemura is the most contributing author, followed by Norio Nonomura with 17. Prostate cancer accounted for 45.48% of the publications, bladder cancer for 36.77% and kidney malignancies for 17.64%.Conclusion. Despite the fact that microbiota has been known for 80 years, research on the connection between microbiota and cancer accelerated after the completion of the Human Microbiome Project. The number of studies examining the connection between urological cancer and microbiota peaked in 2024 and is probably going to rise. More research is required on this topic, since the correlation between microbiota and especially prostate and bladder malignancies raises the possibility that variations in microbiota may be utilized in diagnosis, treatment and prognosis.},
}

Humans
*Bibliometrics
*Microbiota
*Urologic Neoplasms/microbiology
Male
Prostatic Neoplasms/microbiology
Urinary Bladder Neoplasms/microbiology
Kidney Neoplasms/microbiology

@article {pmid40593076,
year = {2025},
author = {Krawczyk, K and Rybaczek, D and Locht, C and Pyrzanowska-Banasiak, A and Ciołek, M and Sicinska, P and Rachubik, M and Kowalewicz-Kulbat, M},
title = {Uptake of environmental halophilic archaea by human dendritic cells.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {21912},
pmid = {40593076},
issn = {2045-2322},
support = {2017/27/N/NZ6/02850//Narodowe Centrum Nauki/ ; },
abstract = {Halophilic archaea are a group distinct from Bacteria and Eukarya, which belong to extremophiles living in highly saline environments. However, they can also exist in the human microbiome. Their impact on the human immune system is poorly known. In this study we examined the interaction of Halorhabdus rudnickae WSM-64[T], isolated from the Barycz area of the Wieliczka Salt-Mine in Poland, and of Natrinema salaciae MDB25[T] from the brine of Lake Medee in Italy, with human monocyte-derived dendritic cells (Mo-DCs). We found that these halophilic archaea invade the cytoplasm and the nucleus of Mo-DCs, but, in contrast to intracellular bacterial pathogens, they do not cause cytotoxic effects on DCs, as no single- or double-stranded DNA breaks (SSB and DSB, respectively), nor chromatin aberrations were noted. Moreover, they did not induce cell cycle alterations, apoptosis or necrosis of DCs. Surprisingly, these halophiles were found to protect against genotoxic activities of Staphylococcus aureus enterotoxin B (SEB), as pre-incubation of the Mo-DCs with the halophilic archaea significantly reduced SEB-induced SSB and DSB, as well as cell cycle disturbance and apoptosis. Therefore, these halophilic archaea can be regarded as safe stimulators for the Mo-DCs to potentially be used as immunomodulators and protective agents for various disorders.},
}

@article {pmid40590527,
year = {2025},
author = {Bridy, PV and Cruz, JC and Covington, JL and Islam, TI and Hadley, CE and Tran, K and Fry, R and Sheffield, BA and Serrano, M and Buck, GA and Zhao, J and Tossas, KY and Meyers, C and Morgan, IM and James, CD and Jefferson, KK},
title = {Human papillomavirus 16 mitigates Sneathia vaginalis-induced damage to cervical keratinocytes.},
journal = {mSphere},
volume = {},
number = {},
pages = {e0015225},
doi = {10.1128/msphere.00152-25},
pmid = {40590527},
issn = {2379-5042},
abstract = {Sneathia vaginalis is a bacterial component of the vaginal microbiome that is of clinical interest because of its association with preterm birth and other obstetric complications. It produces a cytotoxin, but little is known about the mechanism through which it kills epithelial cells or the role that cytotoxicity plays in bacterial survival. Recent microbiome studies demonstrate an association between S. vaginalis and human papillomavirus (HPV) within the female reproductive tract, suggesting that HPV and S. vaginalis could interact in some way within this shared niche. We analyzed 16S rRNA survey and HPV typing data from our Vaginal Human Microbiome Project and found, in agreement with other reports, that S. vaginalis was associated with HPV infection. To test the hypothesis that HPV promotes the growth of S. vaginalis, growth and cytotoxicity of S. vaginalis in co-culture with HPV16-positive and HPV-negative human cervical keratinocytes (HCK) were quantitatively assessed. Organotypic HCK rafts expressing HPV16 were more resistant to S. vaginalis-induced damage, as assessed by histology, and supported increased bacterial growth relative to HPV-negative HCK rafts. When S. vaginalis was co-cultured with HPV16-positive and HPV-negative HCK monolayers, cytotoxicity was observed in both HPV16-positive and HPV-negative cells, but HPV16-positive cells were more resistant to the toxic effects of the bacteria and supported bacterial growth for an extended period of time. In conclusion, HPV16 may protect cervical keratinocytes from the cytotoxic effects of S. vaginalis, preventing the eradication of colonized cells and supporting bacterial growth, and this could underlie the association between S. vaginalis and HPV in vivo.IMPORTANCESneathia vaginalis (S. vaginalis) is a bacterial species that lives in the human vagina and can cause complications during pregnancy if it invades the uterus. It is capable of killing cervical epithelial cells. Human papillomaviruses (HPV) are sexually transmitted viruses that can cause genital lesions and cervical cancer. Recently, multiple reports describe an association between S. vaginalis and HPV. This study used cultured cervical epithelial cells expressing the high-risk HPV type, HPV16, and HPV-negative cells to determine whether HPV promotes the growth of S. vaginalis. We found that HPV16 promotes the survival of cervical epithelial cells that are exposed to S. vaginalis. Survival of cervical epithelial cells may benefit the growth of S. vaginalis, which adhere to and feed off of these cells to survive in the female reproductive tract.},
}

@article {pmid40586597,
year = {2025},
author = {Khatib, L and Song, SJ and Dilmore, AH and Sanders, JG and Brennan, C and Hernandez, AR and Myers, T and Oles, R and Farmer, S and Cowart, C and Birmingham, A and Diaz, EA and Nizet, O and Gilbert, K and Litwin, N and Das, P and Nowinski, B and Bryant, M and Tribelhorn, C and Sanders-Bodai, K and Chaumont, S and Knol, J and Roeselers, G and Laiola, M and Shetty, SA and Veiga, P and Tap, J and Derrien, M and Koutnikova, H and Cotillard, A and Lay, C and Tovar, AR and Torres, N and Arteaga, L and González, A and McDonald, D and Bartko, A and Knight, R},
title = {A three-country analysis of the gut microbiome indicates taxon associations with diet vary by taxon resolution and population.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0054425},
doi = {10.1128/msystems.00544-25},
pmid = {40586597},
issn = {2379-5077},
abstract = {UNLABELLED: Emerging research suggests that diet plays a vital role in shaping the composition and function of the gut microbiota. Although substantial efforts have been made to identify general patterns linking diet to the gut microbiome, much of this research has been concentrated on a small number of countries. Additionally, both diet and the gut microbiome have highly complex and individualized configurations, and there is growing evidence that tailoring diets to individual gut microbiota profiles may optimize the path toward improving or maintaining health and preventing disease. Using fecal metagenomic data from 1,177 individuals across three countries, we examine the relationship between diet and bacterial genera, focusing on Prevotella and Faecalibacterium, which have gained significant attention for their potential roles in human health and strong associations with dietary patterns. We find that these two genera in particular show significant associations with many aspects of diet but these associations vary in scale and direction, depending on the level of metagenomic resolution (i.e., genus level by reads and strain level by metagenome-assembled genomes) and the contextual population. These results highlight the growing importance of building metagenomic data sets that are standardized, comprehensive, and representative of diverse populations to increase our ability to tease apart the complex relationship between diet and the microbiome.

IMPORTANCE: An analysis of fecal microbiome data from individuals in the United States, United Kingdom, and Mexico shows that associations with dietary components vary both by country and by level of resolution (i.e., genus and strain). Our work sheds light on why there may be conflicting reports regarding microbial associations with diet, disease, and health.},
}

@article {pmid40586419,
year = {2025},
author = {Dason, MS and Corà, D and Re, A},
title = {Sequence modeling tools to decode the biosynthetic diversity of the human microbiome.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0033325},
doi = {10.1128/msystems.00333-25},
pmid = {40586419},
issn = {2379-5077},
abstract = {Understanding the biosynthetic potential of the human microbiome remains a significant challenge with far-reaching scientific and translational implications. Analyses of human-associated (meta)genomic sequencing data undeniably show that the biosynthetic diversity encoded in these genomes is largely underexplored. A crucial step in studying specialized metabolites involves the sequence-based identification of genes encoding biosynthetic pathways, typically organized into biosynthetic gene clusters (BGCs). In this review, we provide a concise and updated overview of the widening range of computational approaches that have effectively addressed the sequence-based identification of BGCs across both isolated genomes and complex microbial communities. These advancements are set to deepen our understanding of the biosynthetic potential and diversity of microorganisms residing in different human body sites.},
}

@article {pmid40585799,
year = {2025},
author = {Alty, JW and Barnes, CE and Nicoli, AM and Turner, BS and Beneman, EA and Dugan, AE and Brucks, SD and Kruger, AG and Schrock, RR and Ribbeck, K and Kiessling, LL},
title = {Synthetic Mucins as Glycan-Defined Prebiotics.},
journal = {ACS central science},
volume = {11},
number = {6},
pages = {918-926},
doi = {10.1021/acscentsci.5c00317},
pmid = {40585799},
issn = {2374-7943},
abstract = {The human microbiome contains at least as many bacterial cells as human cells. Some bacteria offer benefits, like improving gut barrier function, suppressing pathobiont growth, and modulating immunity. These benefits have popularized probiotics, but probiotic retention is often hindered by low colonization efficiency in the mucosal layer that lines all epithelial cells. Mucins, the primary components of mucus, are essential for the organization and regulation of microbial populations. The molecular mechanisms of mucin-probiotic interactions remain understudied due, in part, to the inability to incisively manipulate native mucin sequences or their glycans. Here, we used synthetic mucins with defined glycan presentations to interrogate glycan-dependent interactions between mucus and three probiotic lactobacilli species. The nutrient conditions under which bacteria were cultured influenced glycan binding preferences, suggesting mucin-probiotic interactions change with nutrient availability. The addition of synthetic mucins to native mucin increased Limosilactobacillus fermentum adherence. Additionally, an increase in glycosidase activity indicated that native and synthetic mucins function as prebiotics, as probiotic bacteria can cleave the displayed O-glycans. Thus, synthetic mucins can cultivate target probiotic bacteria and increase adhesion as binding sites, highlighting their value as tools for elucidating native mucin functions and as promising agents for promoting human health.},
}

@article {pmid40587084,
year = {2025},
author = {Li, Y and He, Z and Li, C and Huang, J and Yu, Z},
title = {Mechanisms of efficacy of drug therapy in type 2 diabetes: the role of microbiomes.},
journal = {Minerva endocrinology},
volume = {},
number = {},
pages = {},
doi = {10.23736/S2724-6507.25.04306-4},
pmid = {40587084},
issn = {2724-6116},
abstract = {The gut microbiota plays a crucial role in the human body and has an impact on the physiological function of the host. In particular, changes in the gut microbiota are especially pronounced in patients with type 2 diabetes. There is ample evidence that glucose-lowering drugs exert their therapeutic effects precisely through their interactions with the gut microbiota, but there is a lack of summarization. An overall comparison of the effects of each hypoglycemic agent on the gut flora can provide new inspiration for combinations. In this paper, we selected several representative glucose-lowering drugs, such as metformin, sodium-dependent glucose transporters 2 inhibitors (dapagliflozin), glucagon-like peptide-1 receptor agonists (semaglutide, liraglutide), and the traditional Chinese medicine (berberine), and illustrated how they can affect the disease process by regulating metabolic homeostasis, immune response, and gut barrier. We found that each of these four hypoglycemic agents can have conflicting effects on the gut flora depending on the timing and mode of administration. Meanwhile, the potential impact of gut microbiota on drug safety is explored, and an outlook for the optimization of future type 2 diabetes treatment regimens is presented.},
}

@article {pmid40575486,
year = {2025},
author = {Nieves, L and Roach, A and Hunter, J and Smeh, S and Islas, A and Islas, A and Blattman, J and Di Palma, M},
title = {Harnessing the microbiome to improve clinical outcomes for cancer, transplant, and immunocompromised patients in the intensive care unit (ICU).},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1577108},
pmid = {40575486},
issn = {2235-2988},
mesh = {Humans ; *Intensive Care Units ; *Neoplasms/microbiology/therapy/immunology ; *Immunocompromised Host ; *Microbiota ; Dysbiosis/microbiology ; *Transplant Recipients ; Treatment Outcome ; },
abstract = {In recent decades, there has been a growing emphasis on understanding how the architecture of the human microbiome can impact typical biological processes and patient clinical outcomes. In fact, microbiome modifications and modulations have not only been associated with impacts on general health and well-being but have also been shown to yield differences in patient responsiveness to vaccines, medications, and chemotherapeutic regimens. Much of this influence likely stems from how changes in the microbiome result in differences in microbial communities and the subsequent release of microbial-derived metabolites that can alter typical immunological processes. Understanding how microbial composition can impact patient responsiveness can be particularly important in the intensive care unit (ICU), where the efficacy of medications and treatments can result in negative patient outcomes if unsuccessful. Clinical scientists have further developed the concept of the pathobiome, a disease-promoting microbiome whose development can be associated with dysbiosis. Understanding how the microbiome and its associated components can impact patient responsiveness, especially in the ICU, must be further researched and understood. Here, we analyze what causes variances in the microbiome and pathobiome in significant immunocompromised populations, including cancer patients and transplant recipients, and how variances in the microbiome can impact patient outcomes in the ICU. Further, we detail potential future applications of how our understanding of what impacts the human microbiome during the treatment of these populations may be exploited to improve patient prognosis.},
}

Humans
*Intensive Care Units
*Neoplasms/microbiology/therapy/immunology
*Immunocompromised Host
*Microbiota
Dysbiosis/microbiology
*Transplant Recipients
Treatment Outcome

@article {pmid40574683,
year = {2025},
author = {},
title = {Correction to: Human microbiome: Impact of newly approved treatments on C. difficile infection.},
journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists},
volume = {},
number = {},
pages = {},
doi = {10.1093/ajhp/zxaf137},
pmid = {40574683},
issn = {1535-2900},
}

@article {pmid40572254,
year = {2025},
author = {Park, Y and Kyung, S and Mun, S and Yu, BS and Yun, K and Baek, C and Lee, DG and Kang, S and Kim, SR and Kim, JH and Lee, Y and Park, BC and Han, K},
title = {Comparative Analysis of Bacteriome in Hair Follicle Layers of Patients with Female Pattern Androgenic Alopecia.},
journal = {Microorganisms},
volume = {13},
number = {6},
pages = {},
pmid = {40572254},
issn = {2076-2607},
abstract = {Androgenetic alopecia (AGA) is the most common form of patterned hair loss, exhibiting gender-specific clinical features. Recent studies highlight the importance of the skin microbiome in maintaining skin health, but the relationship between the hair follicle microbiome and hair loss, particularly AGA, remains understudied. Hair follicle layer samples were collected directly from the crown region of female pattern hair loss (FPHL), male pattern hair loss (MPHL), and healthy adult women (control) groups. Microbial DNA was extracted and analyzed using Illumina 16S rRNA V3-V4 gene amplicon sequencing. Alpha-diversity and beta-diversity analyses and taxonomic and functional profiling were conducted through relative abundance, LEfSe, and PICRUSt2 analyses. The alpha-diversity analysis showed a significant decrease in microbial richness in the hair loss groups. Unweighted UniFrac-based beta-diversity analysis revealed significant clustering between the control group and the FPHL group. Taxonomic profiling and LEfSe analysis identified differences in microbial composition and biomarkers. PICRUSt2 analysis further revealed altered pathways related to porphyrin metabolism, fatty acid biosynthesis, and steroid hormone metabolism. Additionally, differences in microbiome composition and potential functions were found between the FPHL and MPHL groups. This study provides comprehensive insights into the hair follicle microbiome, revealing unique microbial patterns and functional alterations associated with FPHL. Understanding these microbiome characteristics may contribute to targeted approaches for addressing AGA. Further research is warranted.},
}

@article {pmid40571109,
year = {2025},
author = {Chen, H and Qiu, X and Lei, S and Zhao, Y and Zhang, M and Gao, M and Guo, R and Di, H and Huang, J and Yu, Z},
title = {Gut vs. Vaginal Microbiome in Diabetes Progression: Key Microbial Shifts and Implications.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {107833},
doi = {10.1016/j.micpath.2025.107833},
pmid = {40571109},
issn = {1096-1208},
abstract = {BACKGROUND: Dysiosis in gut and vaginal microbiome is implicated in type 2 diabetes (T2D) pathogenesis, but their contributions remain unclear. This study aims to compare their alterations and clinical relevance in diabetes development.

METHODS: Metagenomic sequencing was performed on vaginal and fecal samples from T2D patients. Differential feature selection and correlation model were used to dissect microbial contributions to diabetic markers.

RESULTS: Gut microbiota exhibited reduced diversity in T2D patients, with enrichment of Desulfovibrio desulfuricans and Adlercreutzia equolifaciens validated in public cohorts. Vaginal microbiota diversity remained unaffected. Furthermore, structural equation modeling revealed stronger gut microbiota associations with blood glucose and HbA1c. Notably, Romboutsia ilealis-derived pgm was enriched in the diabetes group, which could catalyze the production of glucose, suggesting that it may be involved in the progression of T2D.

CONCLUSION: Our findings establish the gut microbiome as the dominant driver of T2D progression, with R. ilealis emerging as a potential therapeutic target. This highlights the priority of gut-centric microbiota interventions in diabetes management.},
}

@article {pmid40569694,
year = {2025},
author = {Kasmanas, JC and Magnúsdóttir, S and Zhang, J and Smalla, K and Schloter, M and Stadler, PF and de Leon Ferreira de Carvalho, ACP and Rocha, U},
title = {Integrating comparative genomics and risk classification by assessing virulence, antimicrobial resistance, and plasmid spread in microbial communities with gSpreadComp.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf072},
pmid = {40569694},
issn = {2047-217X},
support = {2019/03,396-9//São Paulo Research Foundation/ ; 2022/03,534-5//São Paulo Research Foundation/ ; //Deutsche Forschungsgemeinschaft/ ; //International Development Research Centre/ ; },
mesh = {*Plasmids/genetics ; Humans ; *Genomics/methods ; Virulence/genetics ; *Drug Resistance, Bacterial/genetics ; Gastrointestinal Microbiome/genetics ; Virulence Factors/genetics ; Computational Biology/methods ; Software ; Genome, Bacterial ; *Bacteria/genetics/pathogenicity/drug effects ; },
abstract = {BACKGROUND: Comparative genomics, genetic spread analysis, and context-aware ranking are crucial in understanding microbial dynamics' impact on public health. gSpreadComp streamlines the path from in silico analysis to hypothesis generation. By integrating comparative genomics, genome annotation, normalization, plasmid-mediated gene transfer, and microbial resistance-virulence risk-ranking into a unified workflow, gSpreadComp facilitates hypothesis generation from complex microbial datasets.

FINDINGS: The gSpreadComp workflow works through 6 modular steps: taxonomy assignment, genome quality estimation, antimicrobial resistance (AMR) gene annotation, plasmid/chromosome classification, virulence factor annotation, and downstream analysis. Our workflow calculates gene spread using normalized weighted average prevalence and ranks potential resistance-virulence risk by integrating microbial resistance, virulence, and plasmid transmissibility data and producing an HTML report. As a use case, we analyzed 3,566 metagenome-assembled genomes recovered from human gut microbiomes across diets. Our findings indicated consistent AMR across diets, with diet-specific resistance patterns, such as increased bacitracin in vegans and tetracycline in omnivores. Notably, ketogenic diets showed a slightly higher resistance-virulence rank, while vegan and vegetarian diets encompassed more plasmid-mediated gene transfer.

CONCLUSIONS: The gSpreadComp workflow aims to facilitate hypothesis generation for targeted experimental validations by the identification of concerning resistant hotspots in complex microbial datasets. Our study raises attention to a more thorough study of the critical role of diet in microbial community dynamics and the spread of AMR. This research underscores the importance of integrating genomic data into public health strategies to combat AMR. The gSpreadComp workflow is available at https://github.com/mdsufz/gSpreadComp/.},
}

*Plasmids/genetics
Humans
*Genomics/methods
Virulence/genetics
*Drug Resistance, Bacterial/genetics
Gastrointestinal Microbiome/genetics
Virulence Factors/genetics
Computational Biology/methods
Software
Genome, Bacterial
*Bacteria/genetics/pathogenicity/drug effects

@article {pmid40568731,
year = {2025},
author = {Masetti, R and Barbara, G and Muratore, E and Marasco, G and Cremon, C and Marangoni, A and Brigidi, P and Putignani, L and Angelino, G and Quagliarella, F and Galaverna, F and Leardini, D and Lazzarotto, T and Gabelli, M and Savarino, E and Zecca, M and Faraci, M and Prete, A and Biffi, A and Locatelli, F and Merli, P},
title = {Fecal microbiota transplantation for decolonization from multidrug-resistant bacteria in pediatric allogeneic hematopoietic stem cell transplantation recipients: a retrospective real-word data study.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.288067},
pmid = {40568731},
issn = {1592-8721},
abstract = {Not available.},
}

@article {pmid40566568,
year = {2025},
author = {Papakonstantinou, A and Moustakli, E and Potiris, A and Zikopoulos, A and Tsarna, E and Christodoulaki, C and Tsakiridis, I and Dagklis, T and Panagopoulos, P and Drakakis, P and Stavros, S},
title = {Behind-the-Scenes Actors in Fertility: A Comprehensive Review of the Female Reproductive Tract Microbiome and Its Clinical Relevance.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/life15060916},
pmid = {40566568},
issn = {2075-1729},
abstract = {The study of the microbiome has rapidly progressed over the past few decades, capturing the interest of both scientists and the general public. Nevertheless, there is still no widely agreed-upon definition for the term "microbiome" despite tremendous advances in our knowledge. The international scientific literature consistently underscores the difference between the human microbiome and human microbiota. Recent research has emphasized the importance of the female reproductive tract microbiome in fertility, impacting natural conception and assisted reproductive technologies (ARTs). This review explores the relationship between infertility and the microbiota of the female reproductive tract through a thorough evaluation of research papers and large-scale studies published up to 2024. The objective of this review is to critically assess current evidence on the role of the reproductive tract microbiome in female infertility and ART outcomes. Relevant papers were identified and analyzed through the electronic medical databases PubMed/MEDLINE and Scopus. A comprehensive synthesis of data from 36 original studies was performed, including observational, case-control, cohort, and randomized trials. By focusing on the vagina, cervix, and endometrium, this study offers a comprehensive overview of the microbiome throughout the female reproductive tract. RIF and poor reproductive outcomes are strongly linked to dysbiosis, which is characterized by a reduction in Lactobacillus species. Lactobacillus crispatus, in particular, plays a significant role in protecting against bacterial vaginosis and infertility. A thorough understanding of how the microbiome impacts fertility and the development of clinical strategies to improve reproductive outcomes requires standardized microbiome investigation techniques and larger, randomized trials that account for diverse patient characteristics.},
}

@article {pmid40562845,
year = {2025},
author = {Shiner, YA and Caplan, S and Doweck, I},
title = {Actinomyces findings in tonsillectomy specimens- comparison between adults and pediatrics populations.},
journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery},
volume = {},
number = {},
pages = {},
pmid = {40562845},
issn = {1434-4726},
abstract = {BACKGROUND: Tonsillectomy is a common surgical procedure primarily performed for obstructive sleep apnea (OSA) and recurrent acute tonsillitis. Actinomyces are gram-positive, anaerobic bacteria commonly found in the oral cavity and known to form part of the human microbiome, occasionally associated with localized infections. While Actinomyces bacterial colonization in tonsils has been previously studied, its correlation with surgical indications and outcomes remains unclear.

OBJECTIVES: The study aimed to investigate the relationship between Actinomyces colonization in tonsillar specimens and surgical indications, and to examine whether Actinomyces presence influences tonsillectomy outcomes, specifically post-operative hemorrhage and hospital stay.

METHODS: This retrospective cohort study analyzed electronic medical records from Lady Davis Carmel Medical Centre between 2011 and 2021. The study included 1,333 patients who underwent extra-capsular tonsillectomies. Patient demographics, surgical indications, length of hospital stay, post-surgical complications, and pathological reports were collected and analyzed using IBM SPSS Statistics 28.0.

RESULTS: The study population consisted of 760 (57%) males and 573 (43%) females, with an age range of 0.98 to 67.5 years (mean 9.1 years). Actinomyces was present in 13.2% of specimens from patients with infectious indications compared to 4.5% in patients with obstructive indications (p < 0.001). A statistically significant age difference was observed between patients with (17.78 years) and without (8.55 years) Actinomyces. Multivariate analysis revealed that age was the most significant predictor of Actinomyces presence (OR 1.047, p < 0.0001).

CONCLUSIONS: The study found a significant correlation between Actinomyces presence, older age, and infectious surgical indications. While Actinomyces colonization did not demonstrate a direct influence on surgical complications, the findings suggest potential clinical relevance that merits further research to elucidate the bacterium's role in tonsillar pathology.},
}

@article {pmid40560509,
year = {2025},
author = {Andersen, C and Ebsen, TS and Thorup, CA and Reinholdt, KB and Kjaerulff, AMG and Udholm, N and Khalid, V and Madzak, A and Duez, C and Münch, H and Pauli, S and Danstrup, CS and Petersen, NK and Greve, T and Klug, TE},
title = {Next-generation sequencing of the tonsillar microbiome in severe acute tonsillitis: comparison with healthy controls and culture-based findings.},
journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology},
volume = {},
number = {},
pages = {},
pmid = {40560509},
issn = {1435-4373},
abstract = {PURPOSE: Previous culture-based studies suggest three significant pathogens in acute tonsillitis (AT): Streptococcus pyogenes, Fusobacterium necrophorum, and Streptococcus dysgalactiae. Next-generation sequencing (NGS) provides further insights into the human microbiome and may pinpoint additional pathogens in bacterial infections. We aimed to investigate the tonsillar microbiome and identify pathogens associated with AT by applying NGS to tonsillar swabs from patients with severe AT, comparing the findings with both healthy controls and culture-based results.

METHODS: Full-length sequencing of the 16S rRNA gene (16S tNGS) was performed on tonsillar swabs from 64 AT patients and 55 controls, who were prospectively enrolled at two Danish Ear-Nose-Throat Departments between June 2016 and December 2019.

RESULTS: The mean number of detected bacteria was significantly higher in patients analysed with 16S tNGS (36) than with culture methods (6.5, p < 0.001). The alpha diversity was lower in patients compared to controls (p < 0.001) and beta diversity showed separation of the two groups (p = 0.001). S. pyogenes (p = 0.001) and Bifidobacteriaceae (p = 0.002) were significantly more abundant in patients compared to controls. The three suggested pathogens were detected more frequently using 16S tNGS compared to culture: S. pyogenes (38% vs. 27%, p = 0.26), F. necrophorum (19% vs. 11%, p = 0.32), and S. dysgalactiae (14% vs. 11%, p = 0.79).

CONCLUSION: The tonsillar microbiome differed significantly between AT patients and healthy controls. Our findings confirm the role of S. pyogenes in AT, but did not identify additional likely pathogens. The addition of 16S tNGS to cultures increased the collective detection rate of three previously suggested pathogens from 48 to 70%.},
}

@article {pmid40550997,
year = {2025},
author = {Zhang, Y and Ke, S and Wang, XW and Sun, Y and Weiss, ST and Liu, YY},
title = {Association rule mining of the human gut microbiome.},
journal = {Science China. Life sciences},
volume = {},
number = {},
pages = {},
pmid = {40550997},
issn = {1869-1889},
abstract = {The human gut carries a vast and diverse microbial community that is essential for human health. Understanding the structure of this complex community is a crucial step toward comprehending human-microbiome interactions. Traditional co-occurrence and correlation analyses typically focus on pairwise relationships and ignore higher-order relationships. Association rule mining (ARM) is a well-developed technique in data mining and has been applied to human microbiome data to identify higher-order relationships. Yet, existing attempts suffer from small sample sizes and low taxonomic resolution. We developed an advanced ARM framework and systematically investigated the interactions between microbial species using a public large-scale uniformly processed human microbiome data from the curatedMetagenomicData (CMD) together with ARM. First, we inferred association rules in the gut microbiome samples of healthy individuals (n=2,815) in CMD. Then we compared those rules with those inferred from the individuals with different diseases: inflammatory bowel disease (IBD, n=768), colorectal cancer (CRC, n=368), impaired glucose tolerance (IGT, n=199), and type 2 diabetes (T2D, n=164). Finally, we demonstrated that ARM is an efficient feature selection tool that can improve the performance of microbiome-based disease classification. Together, this study illustrates the higher-order microbial relationships in the human gut microbiome and highlights the critical importance of incorporating association rules in microbiome-based disease classification.},
}

@article {pmid40550653,
year = {2025},
author = {Lai, P and He, Z},
title = {[Probiotics empower postoperative intestinal function recovery after colorectal surgery: mechanisms and clinical progress].},
journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery},
volume = {28},
number = {6},
pages = {619-626},
doi = {10.3760/cma.j.cn441530-20250310-00093},
pmid = {40550653},
issn = {1671-0274},
mesh = {Humans ; Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Recovery of Function ; *Colorectal Surgery ; Dysbiosis ; *Intestines/microbiology ; Postoperative Period ; Postoperative Complications/prevention & control ; },
abstract = {Gastrointestinal dysfunction is a common and significant complication in colorectal surgical practice, which is associated with gut microbiota dysbiosis caused by various perioperative interventions. Currently, enhanced recovery after surgery (ERAS) protocols have been increasingly adopted in clinical practice, greatly accelerating the recovery of postoperative intestinal function. However, there are still no effective interventions in the ERAS protocols to target surgery-induced gut microbiota dysbiosis. Probiotics, as a key treatment method targeting the gut microbiota, can stimulate intestinal motility, inhibit the colonization of pathogenic bacteria, enhance intestinal barrier function, among other effects. Based on these effects of probiotics, they are expected to resolve the neglected gut microbiota dysbiosis, further accelerating the postoperative recovery of intestinal function after colorectal surgery. This article reviews the mechanisms and clinical progress in postoperative bowel functional recovery after colorectal surgery.},
}

Humans
Gastrointestinal Microbiome
*Probiotics/therapeutic use
Recovery of Function
*Colorectal Surgery
Dysbiosis
*Intestines/microbiology
Postoperative Period
Postoperative Complications/prevention & control

@article {pmid40546285,
year = {2025},
author = {Pei, X and Liu, M and Yu, S},
title = {How is the human microbiome linked to kidney stones?.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1602413},
doi = {10.3389/fcimb.2025.1602413},
pmid = {40546285},
issn = {2235-2988},
abstract = {In recent years, the incidence of kidney stones has continued to rise worldwide, and conventional treatments have limited efficacy in treating stones associated with recurrent or metabolic abnormalities. The microbiome, as the 'second genome' of the host, is involved in the development of kidney stones through metabolic regulation, immune homeostasis and inflammatory response. Studies have shown that the urinary microbiome of healthy people is dominated by commensal bacteria such as Lactobacillus and Streptococcus, which maintain microenvironmental homeostasis, whereas patients with renal stones have a significantly reduced diversity of intestinal and urinary microbiomes, with a reduced abundance of oxalic acid-degrading bacteria (e.g., Bifidobacterium oxalicum, Bifidobacterium bifidum), and a possible concentration of pathogenic bacteria (e.g., Proteus mirabilis). The microbiome regulates stone formation through mechanisms such as metabolites (e.g., short-chain fatty acids), changes in urine physicochemical properties (e.g., elevated pH), and imbalances in the inflammatory and immune microenvironments. For example, urease-producing bacteria promote magnesium ammonium phosphate stone formation through the breakdown of urea, whereas dysbiosis of the intestinal flora increases urinary oxalic acid excretion and exacerbates the risk of calcium oxalate stones. Microbiome-based diagnostic markers (e.g., elevated abundance of Aspergillus phylum) and targeted intervention strategies (e.g., probiotic supplementation, faecal bacteria transplantation) show potential for clinical application. However, technical bottlenecks (e.g., sequencing bias in low-biomass samples), mechanistic complexity (e.g., multistrain synergism), and individual heterogeneity remain major challenges for future research. Integration of multi-omics data, development of personalised therapies and interdisciplinary research will be the core directions to decipher the relationship between microbiome and kidney stones.},
}

@article {pmid40538714,
year = {2025},
author = {Guan, Z and Wang, H and Feng, Q},
title = {Establishment and improvement of genetic manipulation tools for Fusobacterium nucleatum.},
journal = {Engineering microbiology},
volume = {5},
number = {1},
pages = {100192},
pmid = {40538714},
issn = {2667-3703},
abstract = {An imbalance in oral microbial homeostasis is significantly associated with the onset and progression of several systemic diseases. Fusobacterium nucleatum, a ubiquitous periodontitis-causing bacterium in the oral cavity, is frequently detected in focal sites and contributes to the pathogenesis of many extraoral diseases, including cancers, cardiovascular diseases, and adverse pregnancy outcomes (APOs). F. nucleatum is one of the few oral anaerobes that can be cultured purely in vitro and is a 'model species' for studying the impact of oral health on systemic health. The establishment and development of genetic manipulation tools for F. nucleatum and the construction of pathogenic gene-disrupted strains are important strategies for studying the pathogenicity of F. nucleatum. Here, we review the establishment and development of the genetic manipulation systems for F. nucleatum and summarize the characteristics of various genetic manipulation tools, such as suicide plasmid-based systems for gene inactivation, replicable plasmid-based systems controlling gene expression, and transposon-based random mutagenesis systems. Notably, we summarize and analyze their applications in the study of the pathogenic mechanisms of F. nucleatum. We hope to provide reference information and ideas for future research on genetic manipulation tools and the pathogenic mechanisms of F. nucleatum and other Fusobacterium species.},
}

@article {pmid40527211,
year = {2025},
author = {Ghosh, S and Nath, S and Chakraborty, A and Bhowmick, S and Majumdar, KK and Mukherjee, S and Pramanik, S},
title = {Long-term arsenic exposure perturbs gut microbial diversity, composition and predicts metabolic dysregulation.},
journal = {Journal of hazardous materials},
volume = {495},
number = {},
pages = {138836},
doi = {10.1016/j.jhazmat.2025.138836},
pmid = {40527211},
issn = {1873-3336},
abstract = {The present study documents significant alterations in human gut microbial composition in arsenic exposed populations of West Bengal, India through amplicon sequencing of human stool metagenomic DNA. A notable reduction in α-diversity underscored a reduced species richness and an altered predominance. β- diversity analysis revealed prominent inter-individual differences. Among the 26 phyla detected, significant perturbation was noted in Bacteroidetes, Actinobacteria, Proteobacteria, and Firmicutes. Species analysis identified significant increase in Bifidobacterium adolescentis, B.longum, Blautia luti, B.wexlerae, Clostridium saudiense, Romboutsia timonensis and Streptococcus salivarius whereas members of Faecalibacterium prausnitzii, Megasphaera elsdenii, Prevotella copri and P. stercorea were found to be highly diminished due to As stress. PICRUSt analysis predicted significant upregulation (pT-test< 0.05) in gene families associated with carbohydrate, amino acid, nucleotide and lipid metabolism along with fermentation and secondary metabolite/ vitamin synthesis pathways in exposed group confirmed through Linear Discriminant Analysis. B.longum, B.luti and S.salivarius were found to be associated with obesity and ulcerative colitis. Network interactions were also characterized with major disruptions in keystone species interaction. The major findings of this study shall drive future studies like community-based metagenomics, metabolomics and in-vitro microbial verifications for designing of microbial therapeutics targeting gut health to combat the harmful impact of As exposure.},
}

@article {pmid40526755,
year = {2025},
author = {Zheng, Q and Zhong, Y and Lian, H and Zhuang, J and Wang, L and Chen, J and Wang, H and Wang, H and Ye, X and Huang, Z and Yang, K},
title = {Gut Microbial Signatures Associated With Clinical Remission in Inflammatory Bowel Disease Treated With Biologics: A Comprehensive Multi-Cohort Analysis.},
journal = {United European gastroenterology journal},
volume = {},
number = {},
pages = {},
doi = {10.1002/ueg2.70064},
pmid = {40526755},
issn = {2050-6414},
support = {No. 82300619//National Natural Science Foundation of China/ ; 2023A04J2245//Science and Technology Project in Guangzhou/ ; No. 20231800936102//Dongguan Science and Technology of Social Development Program/ ; No. 2022E02125//Science and Technology Aid Project of Xinjiang Uygur Autonomous Region/ ; },
abstract = {BACKGROUND AND AIMS: The relationship between gut microbiota and biological treatment response in inflammatory bowel disease (IBD) remains incompletely understood. We sought to characterize microbial signatures associated with clinical remission and develop a prediction model for clinical remission.

METHODS: We analyzed 16 S rRNA gene sequencing data from two independent public cohorts (n = 231) treated with biologics (infliximab: n = 23; adalimumab: n = 22; ustekinumab: n = 186). Microbial diversity and taxonomic compositions were compared between the remission and non-remission groups. Random Forest algorithm was employed to construct a prediction model using differential genera and clinical features, with performance evaluated through cross-validation. The model was further validated in a local cohort (n = 29).

RESULTS: Significant differences in alpha and beta diversity were observed between the remission and non-remission groups (p < 0.05). MaAsLin2 analysis identified 25 differentially abundant genera (p < 0.05). Among these, we selected the top 10 genera with highest importance scores (Parabacteroides_B_862066, Agathobaculum, Ruminococcus_E, Sutterella, Clostridium_R_135822, Hominilimicola, Onthenecus, Butyricimonas, Bariatricus, Hominenteromicrobium) to build the Random Forest model, notably all enriched in remission patients. The model demonstrated robust predictive performance for clinical remission (AUC: 0.895), which was further validated in the local cohort (AUC: 0.750).

CONCLUSION: There is a relationship between gut microbial signatures and biological treatment outcomes in IBD patients. A predictive model based on gut microbiota composition may help stratify patients for treatment response. Further investigation of microbiome modulation strategies may enhance therapeutic efficacy.},
}

@article {pmid40524314,
year = {2025},
author = {Schumacher, J and Müller, P and Sulzer, J and Faber, F and Molitor, B and Maier, L},
title = {Proton-pump inhibitors increase C. difficile infection risk by altering pH rather than by affecting the gut microbiome based on a bioreactor model.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2519697},
doi = {10.1080/19490976.2025.2519697},
pmid = {40524314},
issn = {1949-0984},
mesh = {*Proton Pump Inhibitors/adverse effects/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Humans ; Hydrogen-Ion Concentration ; *Clostridioides difficile/drug effects/growth & development ; Omeprazole/pharmacology/adverse effects ; *Clostridium Infections/microbiology ; Bioreactors/microbiology ; Bacteria/drug effects/classification/genetics/growth & development/isolation & purification ; Feces/microbiology ; },
abstract = {Clostridioides difficile infections often occur after antibiotic use, but they have also been linked to proton-pump inhibitor (PPI) therapy. The underlying mechanism - whether infection risk is due to a direct effect of PPIs on the gut microbiome or changes in gastrointestinal pH - has remained unclear. To disentangle both possibilities, we studied the impact of the proton-pump inhibitor omeprazole and pH changes on key members of the human gut microbiome and stool-derived microbial communities from different donors in vitro. We then developed a custom multiple-bioreactor system to grow a model human microbiome community and a stool-derived community in chemostat mode and tested the effects of omeprazole exposure, pH changes, and their combination on C. difficile growth within these communities. Our findings show that changes in pH significantly affect the gut microbial community's biomass and the abundances of different bacterial taxa, leading to increased C. difficile growth within the community. However, omeprazole treatment alone did not result in such effects. These findings imply that the higher risk of C. difficile infection following proton-pump inhibitor therapy is probably because of alterations in gastrointestinal pH rather than a direct interaction between the drug and the microbiome. This understanding offers a new perspective on infection risks in proton-pump inhibitor therapy.},
}

*Proton Pump Inhibitors/adverse effects/pharmacology
*Gastrointestinal Microbiome/drug effects
Humans
Hydrogen-Ion Concentration
*Clostridioides difficile/drug effects/growth & development
Omeprazole/pharmacology/adverse effects
*Clostridium Infections/microbiology
Bioreactors/microbiology
Bacteria/drug effects/classification/genetics/growth & development/isolation & purification
Feces/microbiology

@article {pmid40524025,
year = {2025},
author = {Mallari, P and Rostami, LD and Alanko, I and Howaili, F and Ran, M and Bansal, KK and Rosenholm, JM and Salo-Ahen, OMH},
title = {The Next Frontier: Unveiling Novel Approaches for Combating Multidrug-Resistant Bacteria.},
journal = {Pharmaceutical research},
volume = {},
number = {},
pages = {},
pmid = {40524025},
issn = {1573-904X},
support = {190913//Svenska Kulturfonden/ ; 188147//Svenska Kulturfonden/ ; },
abstract = {BACKGROUND: The rapid occurrence of bacterial antibiotic resistance poses a significant threat to public health worldwide. Since particularly multidrug-resistant (MDR) pathogens are becoming untreatable with currently available antibiotics, new treatment modalities must be deployed.

OBJECTIVES: This review explores the recent advancements and the enduring challenges in new antibacterial development for drug-resistant organisms.

RESULTS: We describe how bacterial resistance to antibiotics arises and discuss why the traditional drug discovery routes are inefficient. The best alternative strategies to overcome these challenges might include exploring new bacterial pathways, utilizing compounds with antibacterial activities from the human microbiome, and repurposing existing drugs. Moreover, novel drug delivery mechanisms that leverage, for example, nanotechnology-based carriers may be breakthrough ideas that can increase antibiotic efficacy and, at the same time, reduce toxicity. Current clinical trials of next-generation drugs indicate that some treatments possess excellent potential to overcome the MDR issue.

CONCLUSION: Despite the substantial obstacles to getting bench findings to the patient, numerous scientists are still working towards this goal. Both the application of antibiotic stewardship principles and timely considerations through the regulatory pathways are needed to release the next generation of antibiotics that are suitable for the fight against superbugs.},
}

@article {pmid40520768,
year = {2025},
author = {Feng, Z and Burgermeister, E and Philips, A and Zuo, T and Wen, W},
title = {The gut virome in association with the bacteriome in gastrointestinal diseases and beyond: roles, mechanisms, and clinical applications.},
journal = {Precision clinical medicine},
volume = {8},
number = {2},
pages = {pbaf010},
pmid = {40520768},
issn = {2516-1571},
abstract = {The gut virome, an essential component of the intestinal microbiome, constitutes ∼0.1% of the total microbial biomass but contains a far greater number of particles than bacteria, with phages making up 90%-95% of this virome. This review systematically examines the developmental patterns of the gut virome, focusing on factors influencing its composition, including diet, environment, host genetics, and immunity. Additionally, it explores the gut virome's associations with various diseases, its interactions with gut bacteria and the immune system, and its emerging clinical applications.},
}

@article {pmid40520523,
year = {2025},
author = {Zaki, EA and Afifi, SM and Ammar, NM and Kadry, MO},
title = {Assembled human microbiome and metabolome in chronic kidney disease: Dysbiosis a double-edged sword interlinking Circ-YAP1, Circ-APOE & Circ-SLC8A1.},
journal = {Toxicology reports},
volume = {14},
number = {},
pages = {102058},
pmid = {40520523},
issn = {2214-7500},
abstract = {Dysbiosis is an alteration in microbiota diversity previously elucidated in patients with chronic kidney disease (CKD). Relationship between dysbiosis and CKD is bidirectional; Uremic milieu disturbs the human microbiota on the other hand, gut metabolites influence CKD development. As a result, we outline the possible contribution of microbiota in the pathophysiology, diagnosis and monitoring of CKD. A growing body of research indicates that changes in circular RNAs (circ-RNAs) were observed in CKD with pathogenic implications, including modifying intracellular signaling, exaggerating oxidative stress, cellular apoptosis and inflammation. Additionally, Circ-RNAs exhibit promising role in clinical settings for monitoring, diagnosis, prognostication, and treatment of CKD. Herein blood samples were collected from 60 Egyptian patients with CKD as well as 60 healthy volunteers who served as controls. Following clinical evaluations, OPLS-DA and PCA GC-MS analysis were performed to detect metabolite perturbations. The levels of toxic uremic metabolites, such as urea, hexanedioic acid, ribonic acid, dodecanoic acid, pyrimidine, 1H-indole, 1H-indole-3-acetic acid, butanoic acid, L-cystine, and benzaldehyde linked to renal fibrosis were found to be elevated. Conversely, Reno-protective metabolites, such as short-chain fatty acids; 1H-indole were found to be negatively correlated with indole propionic acid, acetic acid, 2-propenoic acid, tryptophan, tyrosine, and glucitol (AUC 0.65) derived from the gut flora. CKD patients clarified an alteration both gene and protein expression of circRNAs (Circ-YAP1, circ-APOE, and circ-SLC8A1)/mTOR. Moreover, these biomarkers had a significant correlation with clinical investigations such as Creatinine, Glomerular filtration rate (GFR) and albumin/Creatinine (A/C) ratio. These results shed some light on the metabolic biomarkers that are associated with CKD and novel insights into metabolomics/microbiota/Circ-YAP1/circ-APOE/circ-SLC8A1/mTOR interlinked with disease prognosis/diagnosis that could be translated into clinically relevance.},
}

@article {pmid40517367,
year = {2025},
author = {Xi, S and Lin, T and Haiyan, Z and Shiyue, Z and Qi, Q and Qiangqiang, X and Mingzhi, Z and Liu, L},
title = {Propionate ameliorates neural degeneration by modulating mitochondrial fission and fusion in nerve cells.},
journal = {Neurological research},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/01616412.2025.2520019},
pmid = {40517367},
issn = {1743-1328},
abstract = {BACKGROUND: Sporadic global cognitive decline is on the rise, and current drugs exhibit limited efficacy. Propionate, an SCFAs of the human microbiome, exhibits robust neuroprotective effects.

METHODS: We used CCK8 to evaluate neuronal proliferation, DCFH-DA fluorescence probe to quantify ROS production, ELISA to detect IL-1β and IL-6 release, MitoTracker to assess mitochondrial membrane potential, real-time quantitative PCR, and western blotting to analyze DRP1 and anti-Mfn2 protein expression. We also established an in vitro blood-brain barrier model and AD mouse model.

RESULTS: Propionate normalized the mitochondrial membrane potential in glutamate-treated HT22 cells, reversed growth suppression, ROS accumulation, and elevated IL-1 and IL-6 release. Propionate also decreases Drp1 expression and elevates Mfn2 expression via GRP41 receptor binding. In vitro blood-brain barrier models illustrated the potential of propionate to ameliorate glutamate-induced blood-brain barrier damage. In vivo, propionate notably improved the learning and memory capabilities of AD mice and mitigated AD-induced mitochondrial defects.

CONCLUSION: Supplementation with propionate provides neuroprotection against neurodegenerative diseases. Propionate supplementation may provide a novel strategy for early intervention of neurological disorders.},
}

@article {pmid40507344,
year = {2025},
author = {Gomes de Sousa, R and Guerreiro, CS and Santos, I and Cravo, M},
title = {The Knowledge Gap in Gut Microbiome Characterization in Early-Onset Colorectal Cancer Patients: A Systematic Scoping Review.},
journal = {Cancers},
volume = {17},
number = {11},
pages = {},
doi = {10.3390/cancers17111863},
pmid = {40507344},
issn = {2072-6694},
abstract = {BACKGROUND/OBJECTIVES: Over the past two decades, the incidence of early-onset colorectal cancer (EoCRC) has been increasing, although its underlying causes remain unclear. Gut microbiome is known to play a role in carcinogenesis of colorectal cancer. This scoping review aims to systematically map and synthetize current evidence on gut microbiome characterization in EoCRC (vs. late-onset colorectal cancer (LoCRC) and healthy individuals), describe the methodology used, and identify knowledge gaps to inform and guide future research.

METHODS: This systematic scoping review followed the Joanna Briggs Institute (JBI) methodology for scoping reviews. Searches were conducted in PubMed, Web of Science, and Scopus between January and February 2025. Two reviewers independently screened and selected the studies. One reviewer extracted the relevant information, using an adapted version of the JBI template.

RESULTS: Seven studies met eligibility criteria. Compared to healthy young adults, EoCRC patients had a predominance of lower α diversity, different β diversity, and greater abundance of Flavonifractor plautii, Akkermansia muciniphila, Bacteroides, and Fusobacteria. Comparisons with LoCRC showed that EoCRC had distinct β diversity and a higher abundance in Fusobacterium, Akkermansia, Bacteroides, and Actinomyces. Only three studies correlated the microbiota composition of EoCRC with clinicopathology features and suggested positive associations between Fusobacterium abundance, rectal tumors and lower survival and Akkermansia abundance with body mass index (BMI) ≥ 25 kg/m[2], rectal EoCRC, and better survival.

CONCLUSIONS: There is a lack of large, methodologically robust studies linking gut microbiota with clinicopathological, lifestyle, and tumor molecular features in EoCRC. Our review highlights critical knowledge gaps, the need for standardized methodologies, and key areas for future investigation.},
}

@article {pmid40505619,
year = {2025},
author = {Bakkeren, E and Piskovsky, V and Foster, KR},
title = {Metabolic ecology of microbiomes: Nutrient competition, host benefits, and community engineering.},
journal = {Cell host & microbe},
volume = {33},
number = {6},
pages = {790-807},
doi = {10.1016/j.chom.2025.05.013},
pmid = {40505619},
issn = {1934-6069},
mesh = {*Microbiota/physiology ; Humans ; *Nutrients/metabolism ; Animals ; *Bacteria/metabolism/genetics ; *Host Microbial Interactions ; Plants/microbiology ; },
abstract = {Many plants and animals, including humans, host diverse communities of microbes that provide many benefits. A key challenge in understanding microbiomes is that the species composition often differs among individuals, which can thwart generalization. Here, we argue that the key to identifying general principles for microbiome science lies in microbial metabolism. In the human microbiome and in other systems, every microbial species must find ways to harvest nutrients to thrive. The available nutrients in a microbiome interact with microbial metabolism to define which species have the potential to persist in a host. The resulting nutrient competition shapes other mechanisms, including bacterial warfare and cross-feeding, to define microbiome composition and properties. We discuss impacts on ecological stability, colonization resistance, nutrient provision for the host, and evolution. A focus on the metabolic ecology of microbiomes offers a powerful way to understand and engineer microbiomes in health, agriculture, and the environment.},
}

*Microbiota/physiology
Humans
*Nutrients/metabolism
Animals
*Bacteria/metabolism/genetics
*Host Microbial Interactions
Plants/microbiology

@article {pmid40501963,
year = {2025},
author = {Chouhan, D and Grossman, AS and Kerns, KA and Stocke, KS and Kim, M and Dong, PT and Kumar, A and Lei, L and Lamont, RJ and McLean, JS and He, X and Bor, B},
title = {Episymbiotic Saccharibacteria suppresses epithelial immunoactivation through Type IV pili and TLR2 dependent endocytosis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.05.30.656655},
pmid = {40501963},
issn = {2692-8205},
abstract = {Saccharibacteria are episymbionts that require host-bacteria to grow. They are positively associated with inflammatory diseases within the human microbiome, yet their mechanisms for interacting with the human host and contributing to diseases remain unknown. This study investigated interactions between a Saccharibacterium (Nanosynbacter lyticus), its host-bacteria (Schaalia odontolytica), and oral epithelial cells. The host-bacteria induced proinflammatory cytokines in epithelial cells, while Saccharibacteria were immune silent. Remarkably, Saccharibacteria dampened cytokine responses to host-bacteria during coinfection. This effect was driven by Saccharibacteria-induced clustering of TLR2 receptors, a process likely facilitated by type IV, ultimately leading to reduced TLR2-mediated cytokine signalling. High resolution imaging showed that Saccharibacteria were endocytosed by oral epithelial cells, and colocalized with endosome markers, eventually trafficking to lysosomes. Moreover, a subset of the Saccharibacteria survive endocytosis long-term, and retains their capability to reinfect host-bacteria, highlighting a mechanism for persistence in the oral microbiome and a vital role in mammalian immune system modulation.},
}

@article {pmid40498317,
year = {2025},
author = {Viets, C and Stevens, CA},
title = {Measuring and Analyzing Bacterial Movement in Mucus.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2942},
number = {},
pages = {187-197},
pmid = {40498317},
issn = {1940-6029},
mesh = {Humans ; *Mucus/microbiology/metabolism ; Mucins/metabolism ; *Time-Lapse Imaging/methods ; *Bacteria ; Microbiota ; },
abstract = {Humans are colonized by trillions of microbes that compose the human microbiome. Much of the microbiome inhabits the mucus layers. Mucus layers, covering digestive, reproductive, ocular, and respiratory tracts, are viscous networks consisting mainly of water and mucin glycoproteins. Mucins assemble into a dense, cross-linked network that can affect bacterial swimming patterns, and studying this behavior provides valuable insights into how the body regulates interactions with both harmful and beneficial microbes. Here we present the use of time-lapse imaging to track individual bacterial cells within mucin and discuss techniques for accurately extracting cell trajectory data from these images. By integrating theoretical and experimental approaches, we also describe how to quantify bacterial movement in terms of speed, persistence, and randomness.},
}

Humans
*Mucus/microbiology/metabolism
Mucins/metabolism
*Time-Lapse Imaging/methods
*Bacteria
Microbiota

@article {pmid40492849,
year = {2025},
author = {Coccolini, F and Kirkpatrick, AW and Cremonini, C and Sartelli, M},
title = {Source control in intra-abdominal infections: What you need to know.},
journal = {The journal of trauma and acute care surgery},
volume = {},
number = {},
pages = {},
doi = {10.1097/TA.0000000000004654},
pmid = {40492849},
issn = {2163-0763},
abstract = {Providing optimal source control (SC) for intra-abdominal sepsis (IAS) is a critically important surgical principle, yet one that remains nebulous in terms of strict definitions and required conduct. The entire concept of SC has evolved in the last decades. Contemporary SC is not only surgical but also embraces minimally invasive percutaneous and medical therapies. We propose that adequate SC has evolved from the mere anatomical control of enteric leakage, cleansing of obvious contaminants and necrosis, to a more comprehensive anatomo-phyiological-biochemical model. While any breaches in the integrity of the gastrointestinal tract should be addressed urgently, SC should ultimately aim to control the generation and propagation of systemic biomediators, bacterial toxins, and toxic catabolites that perpetuate multisystem organ failure and death. Much urgently needs to be learned to understand and hopefully mitigate the dysbiotic influences of IAS on the human microbiome. Finally, the therapy offered should always be individualized, recognizing patient's unique pathophysiology, clinical condition, comorbidities, and predeclared preferences regarding invasive therapies and life-support.},
}

@article {pmid40491241,
year = {2025},
author = {Stringari, A and Tlais, AZA and Tonini, S and Pinto, D and Mondadori, G and Filannino, P and Di Cagno, R and Gobbetti, M},
title = {Revitalising Brewers' Spent Grains and Enriching With Biogenic Compounds Through the Fermentation of Fructophilic Lactic Acid Bacteria and Yeasts.},
journal = {Microbial biotechnology},
volume = {18},
number = {6},
pages = {e70171},
doi = {10.1111/1751-7915.70171},
pmid = {40491241},
issn = {1751-7915},
support = {//Open Access Publishing Fund of the Free University of Bozen-Bolzano/ ; },
mesh = {Fermentation ; *Lactobacillales/metabolism ; *Edible Grain/metabolism/microbiology ; *Saccharomycetales/metabolism ; Filaggrin Proteins ; Antioxidants/metabolism ; Lactic Acid/metabolism ; },
abstract = {The large output of spent grains from the brewing industry presents environmental concerns but also offers promising nutritional and functional potential for valorization by researchers and industrial stakeholders. In this perspective, we investigated how non-conventional starters like Fructobacillus fructosus PL22 and Wickerhamomyces anomalus GY1 can drive the fermentation of brewer's spent grain (BSG), a solid by-product of the brewing industry, to enrich its portfolio of bioactive compounds. While sugar reduction was comparable between started- and unstarted-BSG, the effect of the fermentation became evident through the release of key microbial metabolites (lactic and acetic acids and ethanol). Both starters generated the highest number of unique peptides, with only one previously identified as antioxidant peptide found in BSG fermented with F. fructosus. During fermentation, most amino acids and phenolic compounds decreased, while BSG fermented with W. anomalus distinctly enhanced the release of Ala, Cys and GABA, and health-promoting phenolic compounds, such as gallic acid, gallocatechin, quercetin, naringenin, kaempferol, and isorhamnetin. These metabolic changes were associated with the enhanced antifungal and antioxidant properties, which in turn positively reflected on skin protection as shown by the increased proliferation of human keratinocytes, over-expression of the filaggrin (FLG) gene, and wound healing. The power of fermentation to revitalise BSG, giving it a second life chance through the improvement of its nutritional value and further multifunctionality, was demonstrated.},
}

Fermentation
*Lactobacillales/metabolism
*Edible Grain/metabolism/microbiology
*Saccharomycetales/metabolism
Filaggrin Proteins
Antioxidants/metabolism
Lactic Acid/metabolism

@article {pmid40488826,
year = {2025},
author = {Lee, CJ and Carpenter, PA},
title = {Modern-Era Challenges in the Clinical Management of Graft-Versus-Host Disease.},
journal = {Advances in experimental medicine and biology},
volume = {1475},
number = {},
pages = {103-128},
pmid = {40488826},
issn = {0065-2598},
mesh = {*Graft vs Host Disease/therapy/diagnosis/immunology/etiology ; Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Animals ; Disease Management ; },
abstract = {For several decades, graft-versus-host disease (GVHD) has been a long-standing barrier to successful allogenic hematopoietic cell transplantation and a significant cause of post-transplant morbidity and mortality. Initially described as secondary disease or wasting syndrome in transplanted mice, the pathobiology of GVHD is increasingly understood as a dynamic interplay between innate and adaptive immunity in response to initial tissue damage, leading to inflammation and end-organ damage. In parallel, more uniform symptom capture, diagnosis, and response criteria have facilitated rigorous clinical trial design and conduct; together, these advancements have facilitated the development of novel GVHD prevention and treatment strategies. While these advancements have improved the GVHD treatment paradigm, new questions arise within this complex patient population. This chapter discusses several of the most pertinent current clinical practice challenges in GVHD, including its earlier diagnosis, risk stratification, initial and more advanced stage management, as well as a renewed focus on supportive care, given our increased understanding of key roles played by the human microbiome.},
}

*Graft vs Host Disease/therapy/diagnosis/immunology/etiology
Humans
*Hematopoietic Stem Cell Transplantation/adverse effects
Animals
Disease Management

@article {pmid40488467,
year = {2025},
author = {Liu, Y and Qiu, Q and Chen, Y and Deng, Y and Huang, W and Sun, C and Shang, X and Chen, X and Wang, C and Han, L and Chen, S and Yuan, J and Xu, F and Yang, Z and Fang, X and Huang, L},
title = {Integrated multi-omics analysis reveals the functional signature of microbes and metabolomics in pre-diabetes individuals.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0145924},
doi = {10.1128/spectrum.01459-24},
pmid = {40488467},
issn = {2165-0497},
abstract = {Pre-diabetes (PD) represents a critical stage in the progression toward type 2 diabetes, with significant alterations observed in the human microbial community among pre-diabetic individuals in observational studies. However, understanding the interaction between human microbiota and the host during pre-diabetes remains limited. Therefore, this study aims to understand the alterations in the human microbial community during pre-diabetes, a critical stage toward type 2 diabetes. Using an integrated analysis of human microbiota and metabolomics data, we seek to identify the functional signature associated with PD and gain insights into potential mechanisms driving its progression to type 2 diabetes. These findings could inform the development of early intervention strategies for those at high risk. Samples were collected from pre-diabetes, diabetes, and healthy control groups. Through metagenome and 16S rRNA sequencing, we analyzed the gut microbial and tongue coating compositions, respectively. Untargeted metabolomics techniques were also applied for comprehensive plasma data. Using integrated multi-omics analysis, we aim to understand the metabolic potentials of the human microbiome, its molecular links with host targets, and their effects on pre-diabetes, thereby deepening our understanding of microbiome-host interactions in this context. The pre-diabetes group exhibited distinct clinical characteristics, particularly in blood glucose levels and a higher average level of γ-glutamyl transferase. We identified 509 intestinal bacterial species, with Megamonas funiformis and Parabacteroides merdae showing higher abundance in the PD group. In tongue coating samples, we found 1,122 bacterial genera, with the PD group showing altered levels of Corynebacterium and Johnsonella. Furthermore, we detected 795 metabolites, primarily involved in carbohydrate and lipid metabolism. Importantly, our integrated multi-omics analysis suggested Flavonifractor plautii's role in modulating blood glucose through influencing carbohydrate metabolism. Our integrated multi-omics analysis revealed significant alterations in several regulatory pathways associated with pre-diabetes, particularly emphasizing the impact of gut bacterium Flavonifractor plautii on blood glucose levels through its influence on carbohydrate metabolism. These intricate relationships among gut microbiota, metabolites, and blood glucose levels underscore the significance of personalized treatment approaches and preventive strategies for pre-diabetes. The insights gained from this research hold considerable promise for advancing our understanding and management of pre-diabetes.IMPORTANCEThis study investigates alterations in the human microbial community during PD, a critical stage leading to type 2 diabetes. Through integrated analysis of metagenomic and metabolomics data from pre-diabetes, diabetes, and healthy control groups, we identified distinct clinical characteristics in the PD group, including elevated blood glucose levels and γ-glutamyl transferase. A total of 509 intestinal bacterial species were identified, with Flavonifractor plautii playing a key role in modulating blood glucose levels via its influence on carbohydrate metabolism. Our findings underscore the complex interactions among gut microbiota, metabolites, and blood glucose levels, highlighting the potential for personalized treatment approaches and early intervention strategies for individuals at high risk of developing type 2 diabetes.},
}

@article {pmid40482318,
year = {2025},
author = {Häggqvist, IM and Jernman, J and Snellman, E and Kärhä, P and Pasternack, R and Partonen, T and Karisola, P},
title = {Infrared-A (IR-A) modulates the p53 pathway and diurnal clock in human skin and subcutaneous adipose tissue in vivo.},
journal = {Journal of photochemistry and photobiology. B, Biology},
volume = {269},
number = {},
pages = {113199},
doi = {10.1016/j.jphotobiol.2025.113199},
pmid = {40482318},
issn = {1873-2682},
abstract = {Infrared-A (IR-A) radiation is thought to protect the skin from damage due to ultraviolet radiation and alter its carcinogenic potential, possibly by preventing keratinocyte apoptosis via p53 pathway modulation. Solar radiation, including IR-A, is a major factor in contributing to the entrainment of circadian rhythms. We examined the impacts of IR-A on the intrinsic clock and transcriptomics in individuals with different diurnal preference to understand the mechanisms by which IR-A acts in the human skin and subcutaneous adipose tissue. IR-A caused multiple gene expressional changes, mainly as immediate stress responses in 15 min, that were reversed within 24 h. IR-A irradiation increased the skin surface temperature (mean peak temperature 42.9 °C). In skin, the zinc finger proteins ZNF490 and ZNHIT2 correlated negatively with the maximum skin surface temperature. In adipose tissue, CDKN1A, which codes p21 protein, had a negative correlation with the skin surface temperature change. In the skin immunohistochemical staining, the circadian regulators CRY1 and CRY2 increased significantly 24 h after the irradiation, CRY1 already in 15 min. According to the diurnal preferences, morning-type individuals develop mostly innate immune responses, whereas evening-type of individuals had more pronounced responses through p53 pathway modulation, apoptosis, and autophagy.},
}

@article {pmid40479572,
year = {2025},
author = {Lee, PJ and Lo, YC and Chen, YY and Hu, CJ and Lin, YK and Trang Pham, QT and Sim, NK and Then, CK and Shen, SC},
title = {Short-Chain Fatty Acids Improve Hippocampal Atrophy, Ventricular Dilatation and Cognitive Function Decline in Aged Mice.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.0426},
pmid = {40479572},
issn = {2152-5250},
abstract = {Many countries are becoming aged or super-aged societies. This demographic shift causes substantial social, economic, and personal costs directly and indirectly attributable to cognitive decline. Recent studies have shown that dietary fiber can slow down memory decline, with short-chain fatty acids being the primary metabolites produced by gut microbiota from the fermentation of dietary fiber. Despite this, there are limited studies investigating the effect of SCFAs on age-related cognitive function and morphological changes of the brain. In this study, we used B6C3F1 male mice at the age of 3 months and treated them with water, low dose, and high dose SCFAs for 9 months. We assessed their short- and long-term cognitive functions using the Novel Object Recognition test, Morris Water Maze, and Rotarod test. Their brain structure was assessed by 7 Tetra Magnetic Resonance Imaging (7TMRI) and gut microbiota analyzed by 16S rRNA sequencing. Our results show that both short-term and long-term SCFA treatment significantly improve cognitive deficits in the Novel Objective Recognition test and Morris Water Maze tests. Additionally, the 7T MRI results show that SCFAs mitigated hippocampal atrophy compared to the control group. These improvements were accompanied by alteration of gut microbiota composition. We also found that, after treatment, the beneficial gut microbiota Alloprevotella was positively correlated with hippocampal volume. Therefore, we propose that SCFAs may be a promising therapeutic strategy to counteract age-related cognitive decline.},
}

@article {pmid40476583,
year = {2025},
author = {Jang, JY and Seo, JH and Choi, JJ and Ryu, HJ and Yun, H and Ha, DM and Yang, J},
title = {Insight into microbial extracellular vesicles as key communication materials and their clinical implications for lung cancer (Review).},
journal = {International journal of molecular medicine},
volume = {56},
number = {2},
pages = {},
doi = {10.3892/ijmm.2025.5560},
pmid = {40476583},
issn = {1791-244X},
mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Lung Neoplasms/microbiology/metabolism/pathology/etiology ; Microbiota ; Animals ; Cell Communication ; *Bacteria/metabolism ; Dysbiosis ; Lung/microbiology ; },
abstract = {The complexity of lung cancer, driven by multifactorial causes such as genetic, environmental and lifestyle factors, underscores the necessity for tailored treatment strategies informed by recent advancements. Studies highlight a significant association between the lung microbiome and lung cancer, with dysbiosis potentially contributing to disease development via inflammation, immune response alterations and bacterial metabolite production. Furthermore, exposure to airborne bacteria may influence lung health by introducing pathogenic species or altering the human microbiome, thereby implicating certain dominant airborne bacteria in lung diseases, including the exacerbation of lung cancer. Extracellular vesicles (EVs) facilitate cell‑to‑cell communication, penetrating mucosal barriers to impact various organs, notably the lung. Epidemiological evidence suggests a strong relationship between the presence of microbial EVs (MEVs) in the air and chronic pulmonary diseases, with indications of a potential risk for lung cancer. MEVs play a significant role in pulmonary disease development by inducing airway inflammation and affecting lung function. The microbiome and MEVs offer considerable potential as novel tools in precision medicine for lung cancer. Biological data analysis and artificial intelligence technology advancements are pivotal for fully realizing their diagnostic and therapeutic capabilities. These developments can potentially shape the future landscape of lung cancer diagnostics, therapeutics and prevention strategies.},
}

Humans
*Extracellular Vesicles/metabolism
*Lung Neoplasms/microbiology/metabolism/pathology/etiology
Microbiota
Animals
Cell Communication
*Bacteria/metabolism
Dysbiosis
Lung/microbiology

@article {pmid40476157,
year = {2025},
author = {Rashid, M and Pereira, HS and Alissa, A and Keraidi, S and Wipf, N and Sowa, AM and McDonnell, JM and Darwish, S and Butler, JS},
title = {Microbiome dysbiosis in spinal pathology: Mechanisms, evidence, and research limitations.},
journal = {Brain & spine},
volume = {5},
number = {},
pages = {104272},
pmid = {40476157},
issn = {2772-5294},
abstract = {INTRODUCTION: The microbiome's relevance has become increasingly discussed amid the rising prevalence of chronic illnesses. Microbiome research to date focuses predominantly on its relationship with the GI tract while largely ignoring any impact on the rest of the body. This narrative review aims to lay a foundation of knowledge to fill this gap in the literature and discuss other microbiomes within the human body and their relation to spinal health.

RESEARCH QUESTION: What is the relationship between the human microbiome and spinal pathologies?

MATERIALS AND METHODS: A narrative review of all available literature (written or translated to English) was performed using PubMed, MEDLINE, and Google Scholar using relevant search terms including: "microbiome", "spine", "spinal pathology", "ankylosing spondylitis", and "seronegative arthropathies".

RESULTS: This review found that with dysbiosis, specific bacterial such as Bacteroidaceae and Rikenellaceae proliferate, altering the cytokine microenvironment and subsequently increasing gut wall permeability. This immune overactivation and improper cell function results in an increased susceptibility to autoimmunity; specifically ankylosing spondylitis and seronegative arthropathies. This review also highlights the significant gaps in the available literature.

DISCUSSION AND CONCLUSION: This review aims to equip clinicians with an understanding of how the collection of microbiomes in the human body have specific implications for spinal health. By building on the current literature and integrating this knowledge into practice, more patient-specific practices in the treatment of spinal pathologies can be implemented, ultimately improving and optimizing patient care in a field in which the microbiome is not currently at the forefront of pathology.},
}

@article {pmid40474070,
year = {2025},
author = {Boodaghidizaji, M and Jungles, T and Chen, T and Zhang, B and Yao, T and Landay, A and Keshavarzian, A and Hamaker, B and Ardekani, A},
title = {Machine learning based gut microbiota pattern and response to fiber as a diagnostic tool for chronic inflammatory diseases.},
journal = {BMC microbiology},
volume = {25},
number = {1},
pages = {353},
pmid = {40474070},
issn = {1471-2180},
abstract = {Gut microbiota has been implicated in the pathogenesis of multiple gastrointestinal (GI) and systemic metabolic and inflammatory disorders where disrupted gut microbiota composition and function (dysbiosis) has been found in multiple studies. Thus, human microbiome data holds significant potential as a source of information for diagnosing and characterizing diseases-such as phenotypes, disease course, and therapeutic response-associated with dysbiotic microbiota communities. However, multiple attempts to leverage gut microbiota taxonomic data for diagnostic and disease characterization have failed due to significant inter-individual variability of microbiota community and overlap of disrupted microbiota communities among multiple diseases. One potential approach is to look at the microbiota community pattern and response to microbiota modifiers like dietary fiber in different disease states. This approach has become feasible with the advent of machine learning, which can uncover hidden patterns in human microbiome data and enable disease prediction. Accordingly, the aim of our study was to test the hypothesis that machine learning algorithms can distinguish stool microbiota patterns-and their responses to fiber-across diseases with previously reported overlapping dysbiotic microbiota profiles. Here, we applied machine learning algorithms to distinguish between Parkinson's disease, Crohn's disease (CD), ulcerative colitis (UC), human immune deficiency virus (HIV), and healthy control (HC) subjects in the presence and absence of fiber treatments. We demonstrated that machine learning algorithms can classify diseases with accuracy as high as 95%. Furthermore, applying machine learning to microbiome data to distinguish UC from CD yielded a prediction accuracy of up to 90%.},
}

@article {pmid40473134,
year = {2025},
author = {Sadeghi, S and Faramarzi, MA and Siroosi, M},
title = {Design of Novel Human Microbiome-Derived Peptides for Inhibition of OXA-48 Carbapenemase: An In-Silico and In-Vitro Approach.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {107779},
doi = {10.1016/j.micpath.2025.107779},
pmid = {40473134},
issn = {1096-1208},
abstract = {Drug-resistant bacteria have become a global healthcare challenge, especially due to their acquisition of resistance to last-resort antibiotics. OXA-48 carbapenemase is one of the notorious enzymes that inactivates carbapenems through hydrolysis. The emergence of OXA-48 and OXA-48-like carbapenemases is a significant concern as they are responsible for many outbreaks of hospital-acquired infections in various countries, with limited treatment options available. Thus, targeting this enzyme and inhibiting its activity can be an attractive therapeutic strategy. In this study, a rational computer-aided approach was applied to design effective inhibitory peptides against OXA-48 carbapenemase. The primary library was constructed based on peptides derived from the Human Antimicrobial Peptide (HAMP) database. The binding of peptides to the enzyme was investigated through molecular docking studies using ClusPro. After each screening step, numerous targeted amino acid substitutions were performed to enhance the affinity and physicochemical properties of the selected peptides. The final selected peptides, in complex with the enzyme, were subjected to 200 ns Molecular Dynamics (MD) simulations using the GROMACS package, and MM/PBSA analysis was conducted to evaluate the binding free energy of the enzyme-peptide complexes. Finally, the inhibitory effects of the designed peptides were also computationally assessed on OXA-48-like carbapenemases. Homology modeling was used to generate 3D structures of the enzymes whose structures were not solved experimentally. Results indicated that the two final selected peptides effectively interacted with the important residues of OXA-48 carbapenemase and spatially blocked its active site. These peptides also demonstrated high binding affinity to the most common OXA-48-like carbapenemases in silico. In vitro studies on the efficacy of one of the designed peptides, M104, demonstrated that this peptide enhanced the activity of meropenem against a meropenem-resistant, clinical Klebsiella pneumoniae strain harboring the gene blaOXA48 by reducing its minimum inhibitory concentration (MIC) by 4-fold. In an era where effective inhibitors against OXA-48 carbapenemase are limited, present study addressed this urgent need by rationally designed novel peptides.},
}

@article {pmid40470258,
year = {2025},
author = {Demirci, M and Gadhave, K},
title = {Editorial: Human microbiome and COVID-19.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1613825},
pmid = {40470258},
issn = {2235-2988},
}

@article {pmid40468659,
year = {2025},
author = {Hossain, MS and Seo, H and Lee, KA and Ul-Haq, A and Kim, S and Jo, S and Rahim, MA and Tajdozian, H and Ghorbanian, F and Yoon, Y and Barman, I and Shuvo, MSH and Kim, HS and Song, HY},
title = {Microbiome therapeutic PMC72 through reverse translational research in gout.},
journal = {Journal of microbiology (Seoul, Korea)},
volume = {63},
number = {5},
pages = {e2501002},
doi = {10.71150/jm.2501002},
pmid = {40468659},
issn = {1976-3794},
support = {RS-202300219563//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; 2020R1I1A-3072680//Ministry of Education/ ; //Soonchunhyang University Research Fund/ ; },
mesh = {Animals ; *Gout/therapy/microbiology/chemically induced ; Humans ; Mice ; *Gastrointestinal Microbiome/drug effects ; Hyperuricemia/chemically induced/therapy ; Uric Acid/blood/metabolism ; Disease Models, Animal ; Translational Research, Biomedical ; Dysbiosis ; Male ; Feces/microbiology ; Febuxostat/therapeutic use ; Oxonic Acid ; Oxidative Stress ; },
abstract = {Gout is an inflammatory arthritis resulting from the deposition of monosodium urate crystals. Urate-lowering therapies for gout have limitations, including side effects and limited efficacy, highlighting the need for novel therapeutic approaches to improve patient outcomes. In this context, our research team conducted a microbiome analysis of fecal samples from healthy individuals and gout patients, identifying Bifidobacterium as a key biomarker. Subsequently, we isolated and identified this strain, B. longum PMC72, and demonstrated its efficacy in a gout mouse model. In potassium oxonate (PO)-induced hyperuricemia mice, PMC72 significantly alleviated nausea, gait disturbances, ankle inflammation, and improved renal health. These effects were associated with marked reductions in oxidative stress markers, including serum uric acid, blood urea nitrogen, hepatic xanthine oxidase, and malondialdehyde (MDA) levels in serum, liver, and joint samples, as well as the downregulation of inflammation and uric acid transport-related gene expression in kidney samples. These benefits were comparable to those treated with Febuxostat, a standard urate-lowering therapy for gout. Furthermore, gut microbiome analysis revealed that PMC72 restored dysbiosis induced by hyperuricemia, contrasting with the reduced microbial diversity observed with febuxostat alone, and showed a complete recovery to eubiosis when combined with Febuxostat. These findings position PMC72 as a promising microbial therapeutic candidate for gout management, demonstrating significant development potential and serving as a benchmark for reverse translational microbiome-based therapeutic research.},
}

Animals
*Gout/therapy/microbiology/chemically induced
Humans
Mice
*Gastrointestinal Microbiome/drug effects
Hyperuricemia/chemically induced/therapy
Uric Acid/blood/metabolism
Disease Models, Animal
Translational Research, Biomedical
Dysbiosis
Male
Feces/microbiology
Febuxostat/therapeutic use
Oxonic Acid
Oxidative Stress

@article {pmid40467859,
year = {2025},
author = {Ferretti, P and Johnson, K and Priya, S and Blekhman, R},
title = {Genomics of host-microbiome interactions in humans.},
journal = {Nature reviews. Genetics},
volume = {},
number = {},
pages = {},
pmid = {40467859},
issn = {1471-0064},
abstract = {The human microbiome is a complex ecosystem of microorganisms that inhabit the human body and have a crucial role in human health. Microbiome composition is shaped by its interaction with many factors, including human genetics. Advances in genomic technologies are improving the ability to quantify the effect of human genetics on the microbiome through improved heritability studies and microbiome genome-wide association studies (GWAS). Complementary studies using transcriptomic analyses are providing a more comprehensive view of the bidirectional relationship between host gene expression and the microbiome. The resulting insights into the genetic mechanisms driving host-microbiome interactions will ultimately contribute to the development of personalized medicine and targeted therapies.},
}

@article {pmid40467839,
year = {2025},
author = {Chen, YA and Kawashima, H and Park, J and Mohsen, A and Hosomi, K and Nakagata, T and Murakami, H and Nanri, H and Miyachi, M and Kunisawa, J and Mizuguchi, K},
title = {NIBN Japan Microbiome Database, a database for exploring the correlations between human microbiome and health.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {19640},
pmid = {40467839},
issn = {2045-2322},
support = {22AC5002//Ministry of Health, Labour and Welfare/ ; 22AC5002//Ministry of Health, Labour and Welfare/ ; 20AC5004//Ministry of Health, Labour and Welfare/ ; 20AC5004//Ministry of Health, Labour and Welfare/ ; },
abstract = {Recent research has highlighted the substantial impact of gut microbiome on various aspects of human health, such as obesity, inflammation, infectious diseases, and cancer. As a result, gut microbiota composition is increasingly recognized as a potential health indicator and biomarker for disease. Numerous factors, including lifestyle, diet, and physical fitness, are known to shape the composition of the human microbiome. However, a significant challenge in elucidating the relationships between these factors and the gut microbiome lies in needing a comprehensive database that integrates diverse human microbiome profiles with extensive sample metadata. To address this issue, we developed an extensive human microbiome database for healthy individuals. This initiative led to the establishment of the NIBN Japan Microbiome Database (NIBN JMD), one of the largest resources of its kind, encompassing up to 1,000 metadata points and more than 2,000 microbiome samples, including data from longitudinal studies. In this article, we describe the creation and features of NIBN JMD, detailing the data collection, processing, and database implementation. NIBN JMD is publicly accessible at https://jmd.nibn.go.jp/ .},
}

@article {pmid40456421,
year = {2025},
author = {Talukdar, D and Raju, YJ and Jana, P and Sharma, K and Babele, P and Kothidar, A and Ahrodia, T and Narendrakumar, L and Shyam, KR and Singh, U and Tanwar, S and Harle, S and Chaudhuri, S and Raghavan, S and Wadhwa, N and Mukherjee, S and Bhatnagar, S and Das, B and , },
title = {Genomic insights into the potency and functional roles of Lactobacillus species in term and preterm births.},
journal = {Genomics},
volume = {},
number = {},
pages = {111063},
doi = {10.1016/j.ygeno.2025.111063},
pmid = {40456421},
issn = {1089-8646},
abstract = {The vaginal microbiome, typically dominated by Lactobacillus species, plays a key role in reducing the risk of preterm birth (PTB) by protecting against infections. In this study, we sequenced 133 Lactobacillus genomes isolated from the reproductive tracts of pregnant Indian women. Genomic analysis identified genes linked to pathogen resistance and anti-inflammatory functions. Further proteome analysis of cell-free supernatant revealed antimicrobial properties, including lysin and bacteriocin, while antibacterial tests confirmed their ability to inhibit reproductive tract pathogens. These findings suggest that Lactobacillus strains protect against harmful microbes, potentially reducing infection risks and PTB. This Lactobacillus consortium holds promise for developing biotherapeutics aimed at improving maternal health.},
}

@article {pmid40456384,
year = {2025},
author = {Nayyar, J and Bedu-Ferrari, C and Patangia, D and Hurley, E and Feeley, L and Ross, RP and Stanton, C and Brady, P},
title = {Gut and oral microbial profile associations to oral cancer.},
journal = {Journal of dentistry},
volume = {},
number = {},
pages = {105848},
doi = {10.1016/j.jdent.2025.105848},
pmid = {40456384},
issn = {1879-176X},
abstract = {The human microbiome is widely known to be associated with health and disease. The oral microbiome has been linked with oral diseases and infections, though not many studies have explored the relation between oral and gut microbiome with oral cancer based on lesion histology METHODS: This study uniquely explores the oral and gut microbiota in 30 participants (n=30) divided into three groups based on histology; Benign (B) (n=15), Potentially Malignant (PM) (n=8), and Malignant (M) (n=7) oral lesions. Using shotgun metagenomic sequencing, we analysed microbiota profiles to determine their potential as biomarkers for oral malignancy RESULTS: Distinct gut microbial profiles were observed between Benign and Malignant groups and the association of specific microbes in oral saliva, such as Haemophilus parainfluenzae, Veillonella parvula, Fusobacterium nucleatum and Rothia mucilaginosa were strongly associated with malignancy CONCLUSION: The data from this exploratory study suggest that oral and gut microbiomes could act as possible biomarkers and aid in early detection and assessment of oral cancer risk. With regard to potentially malignant lesions, future research could study individual Oral Potentially Malignant Disorders (OPMDs) as distinct entities due to the wide variation in clinical and histological presentation. Further research is required to develop definitive biomarkers in both potentially malignant and malignant oral lesions CLINICAL SIGNIFICANCE: While smoking and alcohol are known risk factors for oral cancer, a biomarker such as the saliva/stool microbiome profile could help identify a risk indicator or a potential risk factor. Additionally such a biomarker could help identify patients with OPMDs that are likely to undergo malignant transformation.},
}

@article {pmid40455399,
year = {2025},
author = {Qayyum, H and Raziq, MF and Manzoor, H and Zaidi, SSA and Ali, A and Kayani, MUR},
title = {Efficient De Novo Assembly and Recovery of Microbial Genomes from Complex Metagenomes Using a Reduced Set of k-mers.},
journal = {Interdisciplinary sciences, computational life sciences},
volume = {},
number = {},
pages = {},
pmid = {40455399},
issn = {1867-1462},
abstract = {De novo assembly and genome binning are fundamental steps for genome-resolved metagenomics analyses. However, the availability of limited computational resources and extensive processing time limit the broader application of these analyses. To address these challenges, the optimization of the parameters employed in these processes can improve the effective utilization of available metagenomics tools. Therefore, this study tested three sets of k-mers (default, reduced, and extended) for their efficiency in metagenome assembly and suitability in recovering metagenome-assembled genomes. The results demonstrate that the reduced set of k-mers outperforms the other two sets in computational efficiency and the quality of results. The assemblies from the default set are comparable with those from the reduced set; however, less complete and highly contaminated metagenome-assembled genomes are obtained at the expense of higher processing time. The extended set of k-mers yields less contiguous but computationally expensive assemblies. This set takes approximately 3-times more processing time than the reduced k-mers and recovers the lowest proportions of high and medium-quality metagenome-assembled genomes. Contrarily, the reduced set produces better assemblies, substantially improving the number and quality of the recovered metagenome-assembled genomes in significantly reduced processing time. Validation of the reduced k-mer set on previously published metagenome datasets further demonstrates its effectiveness not only for human metagenomes but also for the metagenomes of environmental origin. These findings underscore that the reduced k-mer set is optimal for efficient metagenome analyses of varying complexities and origins. This optimization of the k-mer set used in metagenome assemblers significantly reduces computational time while improving the quality of the assemblies and recovered metagenome-assembled genomes. This efficient solution will facilitate the widespread application of genome-resolved analyses, even in resource-limited settings, and help the recovery of better-quality metagenome-assembled genomes for downstream analyses.},
}

@article {pmid40454482,
year = {2025},
author = {Koletic, C and Mrad, A and Martin, A and Devkota, S},
title = {Diet's impact on gut microbial assemblage in health and disease.},
journal = {The Journal of clinical investigation},
volume = {135},
number = {11},
pages = {},
doi = {10.1172/JCI184319},
pmid = {40454482},
issn = {1558-8238},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Diet ; Animals ; Chronic Disease ; },
abstract = {The gut microbiome has been linked to everything from human behavior to athletic performance to disease pathogenesis. And yet, few universal truths have emerged regarding how the microbiome exerts its effects or responds to the host environment except for one: gut microbiota are exquisitely sensitive to human diets. What we eat from birth onward shapes our gut microbiome composition and function, and this is likely an evolutionarily conserved interaction that benefits the microbe and often the host. However, modern diets and lifestyles have created discordance between our slowly evolving human genome and rapidly adaptable microbiome, and have been implicated in the rise of chronic diseases over the past 75 years. Diet and microbiome interactions have been reviewed extensively, so here we focus on areas of microbiome research that have most illuminated natural and disruptive dietary forces over time in humans, and where we may have opportunities to restore the natural balance of host with microbes in our modern world.},
}

Humans
*Gastrointestinal Microbiome
*Diet
Animals
Chronic Disease

@article {pmid40448869,
year = {2025},
author = {Dash, HR and Al-Snan, NR},
title = {DNA forensics at forty: the way forward.},
journal = {International journal of legal medicine},
volume = {},
number = {},
pages = {},
pmid = {40448869},
issn = {1437-1596},
abstract = {Forensic DNA analysis has transformed criminal investigations since its inception in 1985. Over four decades, this field has evolved through various phases-from the early stages of exploration to today's highly sophisticated methodologies. Key advancements such as the development of rapid DNA analysis techniques, microchip-based systems, and next-generation sequencing have improved the speed, reliability, and utility of DNA forensics. However, despite these technological advances, the field still faces considerable challenges, particularly with increasing case backlogs, limited population-specific databases, and the difficulties associated with analyzing degraded or challenging samples like bones and touch DNA. Emerging technologies such as single-cell genomic analysis, lineage markers, proteomics, and human microbiome analysis offer promising solutions to these challenges. Furthermore, the integration of artificial intelligence (AI) and machine learning (ML) in forensic workflows is enhancing the ability to analyze complex DNA samples efficiently, paving the way for faster and more accurate results. As forensic DNA analysis enters its next phase, the focus will be on expanding databases, refining quality control and assurance protocols, and standardizing training for forensic professionals worldwide. The journey of forensic DNA analysis over the past 40 years demonstrates a field in continuous development. Although significant progress has been made, there remain opportunities for further innovation, particularly in overcoming the current limitations and addressing ethical and legal concerns. By doing so, forensic DNA analysis will continue to play a pivotal role in the future of criminal justice.},
}

@article {pmid40448308,
year = {2025},
author = {Gu, BH and Jung, HY and Rim, CY and Kim, TY and Lee, SJ and Choi, DY and Park, HK and Kim, M},
title = {Comparative Colonisation Ability of Human Faecal Microbiome Transplantation Strategies in Murine Models.},
journal = {Microbial biotechnology},
volume = {18},
number = {6},
pages = {e70173},
doi = {10.1111/1751-7915.70173},
pmid = {40448308},
issn = {1751-7915},
support = {2024-ER2113-00//the Korea National Institute of Health (KNIH) research project/ ; 20019505//the Ministry of Trade, Industry & Energy (MOTIE, Korea)/ ; },
mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Humans ; Mice ; *Gastrointestinal Microbiome ; *Feces/microbiology ; Disease Models, Animal ; *Bacteria/classification/growth & development/isolation & purification/genetics ; Dysbiosis/therapy/microbiology ; Male ; Models, Animal ; },
abstract = {The gut microbiome plays a crucial role in maintaining intestinal homeostasis and influencing immune-mediated diseases. Human faecal microbiota transplantation (FMT) is often employed in murine models to investigate the role of human microbes in disease regulation, but methods for effective colonisation require refinement. This study aimed to assess the colonisation efficiency of human microbiota in a murine model using FMT with human faeces, focusing particularly on the impact of gut microbiota depletion via polyethylene glycol (PEG) and comparing oral-gastric gavage with enema administration routes. Our findings revealed that PEG-induced depletion enhanced human microbiome colonisation in mice. Oral-gastric gavage prolonged colonisation, while enema administration facilitated quicker resolution of dysbiosis, both inducing selective human microbial colonisation in a time-dependent manner. Notably, genera such as Bacteroides, Blautia, Medicaternibacter and Bifidobacteria were successfully colonised, whereas Roseburia, Anaerostipes, Anaerobutyricum and Faecalibacterium failed to establish in the murine gut post-FMT. These findings highlight the challenges of replicating human gut microbiota in murine models and underscore the importance of selecting appropriate FMT methods based on desired outcomes. This study provides valuable insights into the colonisation dynamics of human microbiota in mice, contributing to the development of more effective FMT strategies for disease treatment.},
}

Animals
*Fecal Microbiota Transplantation/methods
Humans
Mice
*Gastrointestinal Microbiome
*Feces/microbiology
Disease Models, Animal
*Bacteria/classification/growth & development/isolation & purification/genetics
Dysbiosis/therapy/microbiology
Male
Models, Animal

@article {pmid40441709,
year = {2025},
author = {Dang, T and Fuji, Y and Kumaishi, K and Usui, E and Kobori, S and Sato, T and Narukawa, M and Toda, Y and Sakurai, K and Yamasaki, Y and Tsujimoto, H and Hirai, MY and Ichihashi, Y and Iwata, H},
title = {I-SVVS: integrative stochastic variational variable selection to explore joint patterns of multi-omics microbiome data.},
journal = {Briefings in bioinformatics},
volume = {26},
number = {3},
pages = {},
doi = {10.1093/bib/bbaf132},
pmid = {40441709},
issn = {1477-4054},
support = {JP21J21850//JSPS KAKENHI/ ; JPMJCR1602//JST-CREST Program/ ; JPMJMI120C7//JST-Mirai Program/ ; JPMJAN23D1//JST ALCA-Next Program/ ; },
mesh = {*Microbiota ; Mice ; Animals ; Humans ; Stochastic Processes ; Bayes Theorem ; Glycine max/microbiology ; *Metabolomics/methods ; Algorithms ; *Computational Biology/methods ; Metabolome ; Cluster Analysis ; Multiomics ; },
abstract = {High-dimensional multi-omics microbiome data play an important role in elucidating microbial community interactions with their hosts and environment in critical diseases and ecological changes. Although Bayesian clustering methods have recently been used for the integrated analysis of multi-omics data, no method designed to analyze multi-omics microbiome data has been proposed. In this study, we propose a novel framework called integrative stochastic variational variable selection (I-SVVS), which is an extension of stochastic variational variable selection for high-dimensional microbiome data. The I-SVVS approach addresses a specific Bayesian mixture model for each type of omics data, such as an infinite Dirichlet multinomial mixture model for microbiome data and an infinite Gaussian mixture model for metabolomic data. This approach is expected to reduce the computational time of the clustering process and improve the accuracy of the clustering results. Additionally, I-SVVS identifies a critical set of representative variables in multi-omics microbiome data. Three datasets from soybean, mice, and humans (each set integrated microbiome and metabolome) were used to demonstrate the potential of I-SVVS. The results indicate that I-SVVS achieved improved accuracy and faster computation compared to existing methods across all test datasets. It effectively identified key microbiome species and metabolites characterizing each cluster. For instance, the computational analysis of the soybean dataset, including 377 samples with 16 943 microbiome species and 265 metabolome features, was completed in 2.18 hours using I-SVVS, compared to 2.35 days with Clusternomics and 1.12 days with iClusterPlus. The software for this analysis, written in Python, is freely available at https://github.com/tungtokyo1108/I-SVVS.},
}

*Microbiota
Mice
Animals
Humans
Stochastic Processes
Bayes Theorem
Glycine max/microbiology
*Metabolomics/methods
Algorithms
*Computational Biology/methods
Metabolome
Cluster Analysis
Multiomics

@article {pmid40436194,
year = {2025},
author = {Chang, VC and Purandare, V and Li, S and Andreotti, G and Hua, X and Wan, Y and Dagnall, CL and Jones, K and Hicks, BD and Hutchinson, A and Yano, Y and Dalton, KR and Lee, M and Parks, CG and London, SJ and Sandler, DP and Gail, MH and Shi, J and Hofmann, JN and Sinha, R and Abnet, CC and Vogtmann, E and Beane Freeman, LE},
title = {Animal farming and the oral microbiome in the Agricultural Health Study.},
journal = {Environmental research},
volume = {},
number = {},
pages = {121964},
doi = {10.1016/j.envres.2025.121964},
pmid = {40436194},
issn = {1096-0953},
abstract = {BACKGROUND: Raising farm animals imparts various exposures that may shape the human microbiome. The oral microbiome has been increasingly implicated in disease development. Animal farming has also been associated with certain chronic diseases such as cancer; however, underlying biological mechanisms are unclear. We investigated associations between raising farm animals and the oral microbiome in the Agricultural Health Study.

METHODS: This analysis included 1,245 participants (865 farmers and 380 spouses) who provided oral wash specimens and information on types and numbers of specific animals raised on their farms within 2 years before sample collection. The oral microbiome was measured by sequencing the V4 region of the 16S ribosomal RNA gene. We evaluated associations of farm animal exposures with alpha and beta diversity metrics (within- and between-sample diversity, respectively), as well as presence and relative abundance of specific bacterial genera. All analyses adjusted for potential confounders (e.g., age, sex, smoking, alcohol consumption).

RESULTS: Overall, 63% of participants raised farm animals, most commonly cattle (46%) and hogs (20%). Those who raised a large number of hogs (≥2,000 vs. no hogs) had higher alpha diversity. Conversely, raising sheep/goats and raising larger numbers of poultry were associated with lower alpha diversity. Beta diversity was not significantly different between participants with and without any farm animals. Participants raising any farm animals had higher relative abundance of Porphyromonas and lower relative abundances of Prevotella and Ruminococcaceae UCG-014. Several genera were more likely to be absent with specific animal exposures (e.g., Capnocytophaga for cattle and sheep/goats; Corynebacterium, Dialister, Stomatobaculum, and Solobacterium for sheep/goats and poultry).

CONCLUSIONS: This was the largest study of farm animal exposures and the human microbiome to date. Findings suggest that raising specific farm animals may influence the oral microbiome, supporting the need to further investigate the potential role of animal farming in disease etiology.},
}

@article {pmid40434093,
year = {2025},
author = {Koldaş, SS and Sezerman, OU and Timuçin, E},
title = {Exploring the role of microbiome in cystic fibrosis clinical outcomes through a mediation analysis.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0019625},
doi = {10.1128/msystems.00196-25},
pmid = {40434093},
issn = {2379-5077},
abstract = {UNLABELLED: Human microbiome plays a crucial role in host health and disease by mediating the impact of environmental factors on clinical outcomes. Mediation analysis is a valuable tool for dissecting these complex relationships. However, existing approaches are primarily designed for cross-sectional studies. Modern clinical research increasingly utilizes long follow-up periods, leading to complex data structures, particularly in metagenomic studies. To address this limitation, we introduce a novel mediation framework based on structural equation modeling that leverages linear mixed-effects models using penalized quasi-likelihood estimation with a debiased lasso. We applied this framework to a 16S rRNA sputum microbiome data set collected from patients with cystic fibrosis over 10 years to investigate the mediating role of the microbiome in the relationship between clinical states, disease aggressiveness phenotypes, and lung function. We identified richness as a key mediator of lung function. Specifically, Streptococcus was found to be significantly associated with mediating the decline in lung function on treatment compared to exacerbation, while Gemella was associated with the decline in lung function on recovery. This approach offers a powerful new tool for understanding the complex interplay between microbiome and clinical outcomes in longitudinal studies, facilitating targeted microbiome-based interventions.

IMPORTANCE: Understanding the mechanisms by which the microbiome influences clinical outcomes is paramount for realizing the full potential of microbiome-based medicine, including diagnostics and therapeutics. Identifying specific microbial mediators not only reveals potential targets for novel therapies and drug repurposing but also offers a more precise approach to patient stratification and personalized interventions. While traditional mediation analyses are ill-equipped to address the complexities of longitudinal metagenomic data, our framework directly addresses this gap, enabling robust investigation of these increasingly common study designs. By applying this framework to a decade-long cystic fibrosis study, we have begun to unravel the intricate relationships between the sputum microbiome and lung function decline across different clinical states, yielding insights that were previously unknown.},
}

@article {pmid40433658,
year = {2025},
author = {Śmiga, M and Olczak, T},
title = {HmuY proteins of the Porphyromonas genus show diversity in heme-binding properties.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1560779},
pmid = {40433658},
issn = {2235-2988},
mesh = {*Heme/metabolism ; *Bacterial Proteins/metabolism/genetics/chemistry ; Humans ; *Porphyromonas gingivalis/metabolism/genetics ; Protein Binding ; *Porphyromonas/metabolism/genetics ; Computational Biology ; Phylogeny ; Iron/metabolism ; Protoporphyrins/metabolism ; Binding Sites ; },
abstract = {INTRODUCTION: Bacteria of the Porphyromonas genus, belonging to the Bacteroidota phylum, colonize various host niches in health and disease. As heme auxotrophs, they rely on heme uptake for iron and protoporphyrin IX. A key heme acquisition system in Porphyromonas gingivalis is the Hmu system, where the hemophore-like HmuY[Pg] protein plays a major role. HmuY[Pg] coordinates heme-iron using two histidines, whereas other known HmuY proteins produced by other Bacteroidota members prefer a pair of histidine-methionine or two methionines. Some of them bind heme via the protoporphyrin ring without heme-iron coordination, similar to the P. gingivalis HusA protein.

METHODS: This study used bioinformatics, spectroscopic, and electrophoretic methods to compare the genomic organization of the Hmu system and the structural and functional properties of HmuY proteins within the Porphyromonas genus.

RESULTS AND DISCUSSION: We revealed variations in the heme-binding properties of proteins belonging to the HmuY family and susceptibility to modifications in their heme-binding pockets. These findings suggest that HmuY proteins may have undergone evolutionary adaptations to enhance bacterial survival in the human microbiome, contributing to dysbiosis and disease development. These evolutionary changes may explain the superior heme-binding ability of P. gingivalis HmuY[Pg] compared to HmuY homologs produced by other Porphyromonas species.},
}

*Heme/metabolism
*Bacterial Proteins/metabolism/genetics/chemistry
Humans
*Porphyromonas gingivalis/metabolism/genetics
Protein Binding
*Porphyromonas/metabolism/genetics
Computational Biology
Phylogeny
Iron/metabolism
Protoporphyrins/metabolism
Binding Sites

@article {pmid40430019,
year = {2025},
author = {Kozhakhmetov, S and Kossumov, A and Zhakupova, T and Polyakova, T and Imambayeva, N and Syzdykova, B and Rakhmankulova, A and Dalibayeva, G and Kovenskiy, A and Jarmukhanov, Z and Issilbayeva, A and Vinogradova, E and Kushugulova, A},
title = {Characterization of Gut Microbiome Composition in Depression and Completed Suicide.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
doi = {10.3390/ijms26104880},
pmid = {40430019},
issn = {1422-0067},
support = {AP19676162//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome ; Male ; Female ; *Depression/microbiology ; Middle Aged ; Adult ; *Suicide, Completed/psychology ; Feces/microbiology ; Dysbiosis/microbiology ; Energy Metabolism ; },
abstract = {Growing evidence supports a bidirectional relationship between the gut microbiome and mental health. This study investigated the association between gut microbiota, depression, and suicidal behavior by analyzing fecal samples from 35 individuals with varying depression levels and 36 completed suicide cases. Standardized psychometric assessments were used for depression evaluation. Analysis revealed significant taxonomic differences between groups, with increased abundance of Firmicutes, Clostridia, Lachnospiraceae, Blautia, and Dorea in suicide cases, which also positively correlated with depression severity. Metabolic pathway analysis demonstrated a notable dichotomy: suicide cases showed elevated pathways related to infection processes, inflammation, and antibiotic resistance, while the control group exhibited higher energy metabolism and vitamin synthesis pathways. The findings establish specific microbiome profiles associated with both depression symptoms and suicidal behavior, suggesting that gut dysbiosis may influence mental health through altered energy metabolism and inflammatory processes, potentially offering new perspectives for diagnostic and therapeutic approaches.},
}

Humans
*Gastrointestinal Microbiome
Male
Female
*Depression/microbiology
Middle Aged
Adult
*Suicide, Completed/psychology
Feces/microbiology
Dysbiosis/microbiology
Energy Metabolism

@article {pmid40423870,
year = {2025},
author = {Zhang, M and Zhang, H and Hong, A and Huang, J and Yang, L and Long, Y and Yu, Z},
title = {Dynamic changes of dental plaque and saliva microbiota in OSCC progression.},
journal = {Clinical oral investigations},
volume = {29},
number = {6},
pages = {314},
pmid = {40423870},
issn = {1436-3771},
support = {32170071//This work was funded by the National Natural Science Foundation of China/ ; 82273466//This work was funded by the National Natural Science Foundation of China/ ; 2023ZJ1120//Hunan Provincial Science and Technology Department/ ; 2024JJ2039//Natural Science Foundation of Hunan Province/ ; 2024JJ8117//Natural Science Foundation of Hunan Province/ ; },
mesh = {Humans ; *Saliva/microbiology ; Disease Progression ; *Dental Plaque/microbiology ; *Mouth Neoplasms/microbiology/pathology ; *Carcinoma, Squamous Cell/microbiology/pathology ; Female ; *Microbiota ; Male ; Middle Aged ; Neoplasm Staging ; Metagenomics ; },
abstract = {OBJECTIVES: To elucidate the changes in microbial composition and genomics in saliva and dental plaque during the progression of Oral Squamous Cell Carcinoma (OSCC), and to identify virulence factors and pathways associated with tumor differentiation in OSCC patients.

MATERIALS AND METHODS: Using metagenomic sequencing, 64 saliva and dental plaque samples from OSCC patients at different stages of differentiation were examined.

RESULTS: The results showed notable differences in the microbial composition and genomic profiles across ecological regions and differentiation degrees. Notably, the relative abundance of specific microbes, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Haemophilus parainfluenzae, increased in poorly differentiated OSCC. Microbial alpha diversity in dental plaque and saliva correlates with tumor T staging. Dental plaque microbiota shows higher specialization, especially in poorly differentiated tumors. Both microbiota types become more stable with advanced T staging. Genomic analysis reveals increased virulence factors in poorly differentiated stages.Subsequently, functional pathway analysis and tracing of pathogens reveal specific microbial mechanisms in oral cancer pathogenesis. Certain oral pathogens may promote tumorigenesis by secreting factors like GAPDH (glyceraldehyde-3-phosphate dehydrogenase), GspG (a gingipain precursor), and AllS (a lysine-specific gingipain precursor).

CONCLUSIONS: OSCC progression is associated with altered microbial composition, diversity, and genomic profiles in saliva and dental plaque. Poorly differentiated stages show higher abundance of pathogens and virulence factors, implicating them in tumorigenesis.

CLINICAL RELEVANCE: Understanding the microbial and genomic changes in saliva and dental plaque during OSCC progression could aid in developing new diagnostic biomarkers and targeted therapies, potentially enhancing early detection, treatment efficacy, and patient prognosis. Maintaining oral microbiota homeostasis may also help prevent oral cancer.},
}

Humans
*Saliva/microbiology
Disease Progression
*Dental Plaque/microbiology
*Mouth Neoplasms/microbiology/pathology
*Carcinoma, Squamous Cell/microbiology/pathology
Female
*Microbiota
Male
Middle Aged
Neoplasm Staging
Metagenomics

@article {pmid40420833,
year = {2025},
author = {Clasen, F and Yildirim, S and Arıkan, M and Garcia-Guevara, F and Hanoğlu, L and Yılmaz, NH and Şen, A and Celik, HK and Neslihan, AA and Demir, TK and Temel, Z and Mardinoglu, A and Moyes, DL and Uhlen, M and Shoaie, S},
title = {Microbiome signatures of virulence in the oral-gut-brain axis influence Parkinson's disease and cognitive decline pathophysiology.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2506843},
doi = {10.1080/19490976.2025.2506843},
pmid = {40420833},
issn = {1949-0984},
mesh = {Humans ; *Parkinson Disease/microbiology/physiopathology ; *Cognitive Dysfunction/microbiology/physiopathology ; *Gastrointestinal Microbiome ; *Mouth/microbiology ; *Brain/physiopathology/microbiology ; Male ; Female ; Aged ; *Bacteria/genetics/classification/pathogenicity/isolation & purification ; Metagenomics ; Virulence ; Virulence Factors/genetics/metabolism ; Saliva/microbiology/chemistry ; Middle Aged ; },
abstract = {The human microbiome is increasingly recognized for its crucial role in the development and progression of neurodegenerative diseases. While the gut-brain axis has been extensively studied, the contribution of the oral microbiome and gut-oral tropism in neurodegeneration has been largely overlooked. Cognitive impairment (CI) is common in neurodegenerative diseases and develops on a spectrum. In Parkinson's Disease (PD) patients, CI is one of the most common non-motor symptoms but its mechanistic development across the spectrum remains unclear, complicating early diagnosis of at-risk individuals. Here, we generated 228 shotgun metagenomics samples of the gut and oral microbiomes across PD patients with mild cognitive impairment (PD-MCI) or dementia (PDD), and a healthy cohort, to study the role of gut and oral microbiomes on CI in PD. In addition to revealing compositional and functional signatures, the role of pathobionts, and dysregulated metabolic pathways of the oral and gut microbiome in PD-MCI and PDD, we also revealed the importance of oral-gut translocation in increasing abundance of virulence factors in PD and CI. The oral-gut virulence was further integrated with saliva metaproteomics and demonstrated their potential role in dysfunction of host immunity and brain endothelial cells. Our findings highlight the significance of the oral-gut-brain axis and underscore its potential for discovering novel biomarkers for PD and CI.},
}

Humans
*Parkinson Disease/microbiology/physiopathology
*Cognitive Dysfunction/microbiology/physiopathology
*Gastrointestinal Microbiome
*Mouth/microbiology
*Brain/physiopathology/microbiology
Male
Female
Aged
*Bacteria/genetics/classification/pathogenicity/isolation & purification
Metagenomics
Virulence
Virulence Factors/genetics/metabolism
Saliva/microbiology/chemistry
Middle Aged

@article {pmid40418963,
year = {2025},
author = {Tyson-Carr, J and Leng, J and Scott, M and Adams, S and Hoptroff, M and Murphy, B and Fallon, N and Paterson, S and Thomas, A and Giesbrecht, T and Roberts, C},
title = {Body-site specific associations between human skin microbiome composition and psychological wellbeing.},
journal = {The British journal of dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1093/bjd/ljaf177},
pmid = {40418963},
issn = {1365-2133},
abstract = {BACKGROUND/OBJECTIVES: There is increasing scientific interest in understanding the interplay between psychological wellbeing and the human microbiome, with a particular focus on the gut microbiome's impact on psychological health. However, the role of the skin microbiome remains underexplored. The current study addresses this gap by investigating the relationship between the human skin microbiome at various body sites (face, scalp, forearm, axilla) and psychological wellbeing. This unique multi body site investigation aims to provide an understanding of the skin microbiome's role in psychological health.

METHODS: Fifty-three participants underwent microbiome sampling via skin swabbing from four body regions (forearm, face, scalp, and axilla) and completed psychological measures of global/general wellbeing (Affect Grid, Sleep Quality, Stress NRS-11, PSS-10) and body site-related wellbeing (Hair & ScalpCARE, SkinCARE, UnderarmCARE). All bacterial DNA extracts were analysed using quantitative polymerase chain reaction (qPCR) and Illumina sequencing of the V1 - V2 region of the 16S gene. Microbial diversity was computed as Shannon diversity and Faith's Phylogenetic diversity. Correlations were determined between psychological measures, microbial diversity, and genera for each body site.

RESULTS: The current study uncovered that specific bacterial genera were associated with aspects of wellbeing. Specifically, Cutibacterium showed consistent associations with psychological wellbeing across multiple body locations. Key findings showed increased Cutibacterium on the face and axilla was associated with reduced stress, increased Cutibacterium in the axilla was associated with increased mood pleasantness.

CONCLUSIONS: These findings highlight, for the first time, the nuanced relationship between skin microbiome and psychological wellbeing. Increased Cutibacterium across multiple body-sites was consistently associated with positive wellbeing outcomes. This underscores the need for further investigation into specific bacterial taxa that may be involved in a skin-brain axis, as well as the importance of specific microbial communities on the body and their potential influence on this connection.},
}

@article {pmid40417982,
year = {2025},
author = {Brown, SE and He, X and Magder, L and Johnston, ED and Morgan, D and Ravel, J and Mark, K and Ghanem, KG and Brotman, RM},
title = {Bacterial vaginosis incidence following a single hyperosmolal vaginal lubricant exposure: A comparison of two observational cohorts.},
journal = {Sexually transmitted diseases},
volume = {},
number = {},
pages = {},
doi = {10.1097/OLQ.0000000000002184},
pmid = {40417982},
issn = {1537-4521},
abstract = {BACKGROUND: Hyperosmolal lubricants may negatively affect the vaginal microenvironment, increasing the risk for bacterial vaginosis (BV). We compared the incidence of Amsel-defined BV in reproductive-age women exposed to hyperosmolal lubricant during transvaginal ultrasound to those without recent lubricant exposure.

METHODS: We analyzed two observational cohorts over 10 weeks: 58 lubricant-exposed women from the Gynecology and Lubricants Effects study and 59 lubricant-unexposed women from a University of Alabama Birmingham cohort linked to the University of Maryland Human Microbiome Project. BV was diagnosed using Amsel criteria at baseline, mid-study (lubricant-exposed: week 2, lubricant-unexposed: week 5), and final visit (week 10), and categorized by symptomatology. Risks for incident BV and Amsel criteria were assessed using modified Poisson regression with robust standard errors. An additional outcome of new-onset/newly-symptomatic BV included those with baseline asymptomatic BV. A secondary analysis focused on Black participants (N = 73) due to an observed higher BV incidence.

RESULTS: Baseline demographics and behaviors were similar between the cohorts. Among all participants, lubricant was not associated with new-onset BV (adjusted relative risk (aRR):1.32, 95% CI:0.58-3.01). 88% (23/26) of all new-onset/newly-symptomatic BV cases occurred in Black participants. Among Black participants, exposure to lubricant doubled the risk of developing new-onset BV (aRR:2.18, 95% CI:1.16-4.11) and new-onset/newly-symptomatic BV (aRR:1.91, 95% CI: 1.04-3.51), and increased the risk for new-onset clue cells (aRR:2.18, 95% CI:1.17 - 4.06) versus no lubricant exposure.

CONCLUSION: Hyperosmolal lubricants was associated with BV incidence in Black women. Factors contributing to this elevated risk require further research.},
}

@article {pmid40415928,
year = {2025},
author = {Karimianghadim, R and Satokari, R and Yeo, S and Arkkila, P and Kao, D and Pakpour, S},
title = {Prolonged effect of antibiotic therapy on the gut microbiota composition, functionality, and antibiotic resistance genes' profiles in healthy stool donors.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1589704},
pmid = {40415928},
issn = {1664-302X},
abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is highly effective in preventing Clostridioides difficile recurrence by restoring gut microbiota composition and function. However, the impact of recent antibiotic use, a key exclusion criterion for stool donors, on gut microbiota recovery is poorly understood.

METHODS: We investigated microbial recovery dynamics following antibiotic use in three long-term stool donors from Canada and Finland. Using longitudinal stool sampling, metagenomic sequencing, and qPCR, we assessed changes in bacterial diversity, community composition, microbial functions, the gut phageome, and the risk of transmitting antibiotic-resistant genes (ARGs).

RESULTS: Antibiotics caused lasting disruption to bacterial communities, significantly reducing important taxa like Bifidobacterium bifidum, Blautia wexlerae, Akkermansia muciniphila, Eubacterium sp. CAG 180, and Eubacterium hallii, with effects persisting for months. Functional analyses revealed alterations in housekeeping genes critical for energy production and biosynthesis, with no direct links to key health-related pathways. Antibiotics also disrupted viral populations, decreasing diversity and increasing crAssphage abundance, reflecting disrupted host-bacteriophage dynamics. No significant increase in clinically important ARGs was detected.

DISCUSSION: These findings highlight the unpredictable and complex recovery of gut microbiota post-antibiotics. Individualized suspension periods in donor programs, guided by metagenomic analyses, are recommended to optimize FMT outcomes in various indications by considering antibiotic spectrum, duration, and host-specific factors.},
}

@article {pmid40414632,
year = {2025},
author = {Srinivasan, S},
title = {Disruption in the human microbiome causing behavioural changes in bipolar disorder.},
journal = {International review of neurobiology},
volume = {180},
number = {},
pages = {157-187},
doi = {10.1016/bs.irn.2025.04.001},
pmid = {40414632},
issn = {2162-5514},
mesh = {Humans ; *Bipolar Disorder/microbiology/physiopathology/psychology ; *Gastrointestinal Microbiome/physiology ; *Microbiota/physiology ; },
abstract = {This chapter explores the intriguing and complex relationship between the human microbiome and Bipolar Disorder (BD). The microbiome, notably the gut microbiota, has been increasingly recognised as a key performer in brain health and disease. This is due to its role in the gut-brain axis, a bidirectional communication between the gastrointestinal tract and the central nervous system. Disruptions in the gut microbiota due to factors such as diet, and stress, may influence this axis and potentially trigger or exacerbate psychiatric conditions. Hence, we investigate into the present interpretation of the microbiome's role in mental health, concentrating on its impact on mood regulation and cognitive function. Consequently, we also explore the possible mechanisms through which microbiome disruption may pay to the behavioural changes observed in BD. Further exploration understand the complex interplay between the microbiome and BD and translate these findings into effective therapeutic plans.},
}

Humans
*Bipolar Disorder/microbiology/physiopathology/psychology
*Gastrointestinal Microbiome/physiology
*Microbiota/physiology

@article {pmid40414631,
year = {2025},
author = {Krishnan, D and Ghosh, P and Lakshman, N and Justin, A and Ramasamy, S},
title = {Oro-pharyngeal mucosal microbiome alternations causing immune system dysregulation in schizophrenia.},
journal = {International review of neurobiology},
volume = {180},
number = {},
pages = {125-156},
doi = {10.1016/bs.irn.2025.03.003},
pmid = {40414631},
issn = {2162-5514},
mesh = {Humans ; *Schizophrenia/immunology/microbiology ; *Microbiota/immunology/physiology ; *Oropharynx/microbiology/immunology ; *Mouth Mucosa/microbiology/immunology ; },
abstract = {Schizophrenia is a chronic and thoughtful psychological disorder that affects a person's thinking, feelings, and behaviours. Multi-factorial genetic, environmental, and neurological variables cause it. Recently, more research focused on the human microbiome, which alters the immune system and develops adverse health effects on the human body. The study discusses a possible relationship between the oropharyngeal microbiome and schizophrenia. According to recent studies, the oropharyngeal microbiome may alter the immune system in the human body and cause various psychiatric disorders, including schizophrenia. The oropharyngeal microbiome can cause schizophrenia either by affecting the genes, chromosomes, and immune system in the human body. Additionally, it examines the combined mechanism of how the oropharyngeal microbiome's alterations lead to genetic abnormalities and immune dysregulation in schizophrenia. By combining the various approaches, this chapter offers a comprehensive view of the oropharyngeal microbiome's role in schizophrenia and suggests that microbial alterations could serve as biomarkers or therapeutic targets for the disorder.},
}

Humans
*Schizophrenia/immunology/microbiology
*Microbiota/immunology/physiology
*Oropharynx/microbiology/immunology
*Mouth Mucosa/microbiology/immunology

@article {pmid40411603,
year = {2025},
author = {Georgakis, N and Premetis, GE and Pantiora, P and Varotsou, C and Bodourian, CS and Labrou, NE},
title = {The impact of metagenomic analysis on the discovery of novel endolysins.},
journal = {Applied microbiology and biotechnology},
volume = {109},
number = {1},
pages = {126},
pmid = {40411603},
issn = {1432-0614},
support = {4036//HFRI/ ; },
mesh = {*Metagenomics/methods ; *Endopeptidases/genetics/isolation & purification/pharmacology/metabolism ; Bacteriophages/enzymology/genetics ; Anti-Bacterial Agents/pharmacology ; Computational Biology ; Humans ; },
abstract = {Metagenomics has revolutionized enzyme discovery by enabling the study of genetic material directly from environmental samples, bypassing the need for microbial cultivation. This approach is particularly effective for identifying novel endolysins, phage-derived enzymes with antibacterial properties suited for therapeutic and industrial applications. Diverse ecosystems, such as biofilms, human microbiome, hot springs, and geothermal areas, serve as rich reservoirs for endolysins with traits like thermostability, broad-spectrum activity, specificity and resistance to harsh conditions. Functional metagenomics, complemented by bioinformatics, enables the discovery and annotation of previously uncharacterized endolysins. Examples of endolysins discovered from metagenomics analysis are discussed. Despite the challenges of analyzing complex microbial ecosystems and isolating target genes, metagenomics holds immense potential for uncovering innovative endolysins, paving the way for developing new biotechnological applications. KEY POINTS: • Endolysins offer antibacterial potential for therapeutic and industrial use. • Metagenomics enables discovery of novel endolysins from diverse ecosystems. • Advances in tools and methods have accelerated novel endolysins discovery.},
}

*Metagenomics/methods
*Endopeptidases/genetics/isolation & purification/pharmacology/metabolism
Bacteriophages/enzymology/genetics
Anti-Bacterial Agents/pharmacology
Computational Biology
Humans

@article {pmid40411594,
year = {2025},
author = {Dash, HR and Patel, A},
title = {Genealogically bewildered individuals and forensic identification: a review of current and emerging solutions.},
journal = {International journal of legal medicine},
volume = {},
number = {},
pages = {},
pmid = {40411594},
issn = {1437-1596},
abstract = {The increasing use of assisted reproductive technologies (ART) with donor gametes is driven by rising infertility rates, delayed parenthood, and the need to prevent hereditary diseases. Greater social acceptance of diverse family structures, advancements in reproductive medicine, and improving success rates also contribute. Accessibility, affordability, and cross-border reproductive care further expand ART's reach, making donor gametes a preferred option for many individuals and couples worldwide. The widespread application of ART has led to an increasing number of donor-conceived individuals, many of whom are now reaching reproductive maturity. This demographic shift introduces significant challenges for traditional forensic genetic identification methods, which rely on biological reference samples from genetically related individuals. The absence of such samples complicates the identification process, particularly for individuals conceived via gamete donation or adoption, where biological and legal parentage are incongruent. Conventional forensic genetic analyses, including short tandem repeat (STR) and single nucleotide polymorphism (SNP) profiling of autosomal, Y-chromosome, X-chromosome, and mitochondrial DNA, exhibit limited efficacy in these scenarios. While these methods can sometimes identify individuals conceived using a single donor gamete, they are insufficient for cases involving dual donor gametes or mitochondrial replacement therapy. Emerging methodologies such as forensic genetic genealogy, DNA methylation profiling, and human microbiome analysis offer innovative approaches but necessitate further clinical validation and standardization.},
}