@article {pmid41052982,
year = {2025},
author = {Cao, Y and Fan, X and Zang, T and Qiu, T and Fang, Q and Bai, J and Liu, Y},
title = {Prenatal depression-associated gut microbiota induces depressive-like behaviors and hippocampal neuroinflammation in germ-free mice.},
journal = {Translational psychiatry},
volume = {15},
number = {1},
pages = {383},
pmid = {41052982},
issn = {2158-3188},
support = {2023AFB710//Natural Science Foundation of Hebei Province (Hebei Provincial Natural Science Foundation)/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Female ; *Hippocampus/metabolism/pathology/immunology ; Mice ; Pregnancy ; Fecal Microbiota Transplantation ; *Depression/microbiology/metabolism ; *Dysbiosis/microbiology/complications ; Humans ; Lipopolysaccharides/blood ; Germ-Free Life ; *Neuroinflammatory Diseases/metabolism/microbiology ; Microglia ; *Pregnancy Complications/microbiology ; Disease Models, Animal ; Behavior, Animal ; Interleukin-6/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; },
abstract = {Numerous studies have described the role of the microbiome-gut-brain axis in depression. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of prenatal depression are limited. In this study, fecal microbiota from women with prenatal depression was transplanted into germ-free mice to investigate the potential causal relationships between the gut microbiota and depressive phenotypes. Shotgun metagenomic sequencing and untargeted metabolomics approaches were used to investigate the characteristics of gut microbiota and microbial metabolites. The levels of neuroinflammation in the brain were detected using immunofluorescence and real-time quantitative PCR. We found significant changes in gut microbiota composition and metabolites in mice with fecal microbiota transplantation (FMT) from women with prenatal depression, including decreased Ligilactobacillus, increased Akkermansia, and abnormal glycerophospholipid metabolism. Besides, significant increase in plasma lipopolysaccharide (LPS) levels and significant proliferation of microglia in the hippocampus were observed in mice receiving FMT from women with prenatal depression, accompanied by a significant increase in the expression of nuclear factor-κB (NF-κB) p65, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA. The gut microbiota and its metabolites were strongly associated with depressive-like behaviors, plasma LPS and neuroinflammation. Our study collectively demonstrates that dysbiosis of the gut microbiota may play a causal relationship in the development of prenatal depression. This process potentially involves the activation of neuroinflammation through the LPS-NF-κB signaling pathway.},
}

Animals
*Gastrointestinal Microbiome/physiology
Female
*Hippocampus/metabolism/pathology/immunology
Mice
Pregnancy
Fecal Microbiota Transplantation
*Depression/microbiology/metabolism
*Dysbiosis/microbiology/complications
Humans
Lipopolysaccharides/blood
Germ-Free Life
*Neuroinflammatory Diseases/metabolism/microbiology
Microglia
*Pregnancy Complications/microbiology
Disease Models, Animal
Behavior, Animal
Interleukin-6/metabolism
Tumor Necrosis Factor-alpha/metabolism

@article {pmid41052746,
year = {2025},
author = {Chen, Y and Yu, L and Zhang, L and Liu, C and You, Y and Guo, H and Li, Z and Yin, X and Hong, T and Ding, L and Fang, Q},
title = {Gut microbiota dysbiosis exacerbates post-stroke depression via microglial NLRP3 inflammasome activation.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115488},
doi = {10.1016/j.expneurol.2025.115488},
pmid = {41052746},
issn = {1090-2430},
abstract = {BACKGROUND: Post-stroke depression (PSD) is a neuropsychiatric complication prevalent among stroke survivors. Emerging evidence suggests that dysregulation of the microbiota-gut-brain axis is implicated in the pathogenesis of PSD. However, the exact mechanism is not clear and further research is necessary.

METHODS: Initially, Sprague-Dawley (SD) rats were randomly allocated into three experimental groups: Sham, Middle Cerebral Artery Occlusion (MCAO), and PSD. Behavioral tests were conducted to evaluate depressive-like behavior. Fecal samples from all groups underwent 16S rRNA sequencing for comprehensive gut microbiota analysis. Colonic tissues were collected from rats and subjected to immunohistochemical analysis for quantification of tight junction proteins (ZO-1, Occludin, and Claudin). Peripheral blood plasma was obtained for the determination of IL-1β, IL-6, TNF-α, and IL-18 levels using enzyme-linked immunosorbent assay (ELISA). Lastly, hippocampus tissues were harvested for molecular characterization of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and inflammatory cytokines expression through tripartite methodology: Reverse Transcription quantitative PCR (RT-qPCR), Western blot, and immunofluorescence. Concurrently, hippocampal concentrations of 5-HT, BDNF, and PSD-95 were also measured by ELISA. Subsequently, Fecal Microbiota Transplantation (FMT) was performed by administering fecal suspensions from PSD and Sham donor rats to healthy SD recipients via oral gavage. Then, use the above methods to test the same indicator.

RESULT: Comparative analyses showed that microbial species richness and diversity indices were significantly reduced in PSD model rats, along with a compositional imbalance of the gut microbiota. Concurrently, reduced expression of the colonic tight junction proteins ZO-1, Occludin, and Claudin was observed, accompanied by elevated levels of peripheral inflammatory cytokines. In PSD rats, NLRP3 inflammasome activation was detected in the ischemic hippocampus, along with increased expression of the inflammatory cytokines IL-18 and IL-1β, and decreased levels of 5-HT, BDNF, and PSD-95. Subsequently, using FMT technology, PSD rat feces were innovatively prepared into a fecal suspension and administered to healthy SD rats. Analysis revealed that FMT-PSD rats exhibited a disrupted gut microbiota structure, impaired colonic barrier integrity, activation of the hippocampal NLRP3 inflammasome, elevated inflammatory cytokine levels, and reduced neurotransmitter expression.

CONCLUSION: In summary, these data demonstrate that dysbiosis of the intestinal microbiota compromises gut barrier integrity and elicits systemic inflammation, which may subsequently activate the NLRP3 inflammasome in hippocampal microglia. This activation promotes the release of pro-inflammatory cytokines IL-18 and IL-1β, and coincides with dysregulation of emotion-related neurotransmitters, collectively contributing to the pathogenesis of PSD.},
}

@article {pmid41052446,
year = {2025},
author = {Sacks, HS and , },
title = {In primary CDI, fecal microbiota transplantation was noninferior to vancomycin for clinical cure at 14 d without recurrence at 60 d.},
journal = {Annals of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.7326/ANNALS-25-03648-JC},
pmid = {41052446},
issn = {1539-3704},
abstract = {GIM/FP/GP: [Formula: see text] Gastroenterology: [Formula: see text] Infectious Disease: [Formula: see text].},
}

@article {pmid41048505,
year = {2025},
author = {Yang, W and Jin, Q and Xiao, D and Li, X and Huang, D},
title = {Interaction mechanism and intervention strategy between metabolic dysfunction-associated steatotic liver disease and intestinal microbiota.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1597995},
pmid = {41048505},
issn = {1664-302X},
abstract = {The interaction between metabolic dysfunction-associated seatotic liver disease (MASLD) and gut microbiota regulates hepatic metabolic homeostasis through the gut-liver axis, and its mechanisms involve intestinal dysbiosis (decreased bacteroidetes, increased ratio of firmicutes/proteobacteria), bile acid metabolism reprogramming (secondary bile acids inhibit FXR signaling), short-chain fatty acid (SCFAs) deficiency, and endotoxin-mediated inflammatory activation (TLR4/NF-κB pathway). Among the intervention strategies, probiotics (such as Bifidobacteria) improved inflammation by regulating microbiota structure and intestinal barrier function, prebiotics such as resistant starch enriched butyric acid-producing bacteria and reduced liver lipid deposition, fecal microbiota transplantation (FMT) could remodel the microbiota but needed to optimize safety, restricted fructose intake and Mediterranean diet reduced liver damage by regulating microbiota metabolism, and metabolic surgery improved fibrosis through microbiota remodeling and bile acid signaling. In the future, it is necessary to combine multi-omics technology to analyze the microbiota-host interaction network, develop precision therapies such as phage targeted clearance or engineering bacterial delivery of metabolites, and promote the clinical transformation of personalized intervention programs.},
}

@article {pmid41047993,
year = {2025},
author = {Paaske, SE and Baunwall, SMD and Rubak, T and Rågård, N and Kelsen, J and Hansen, MM and Lødrup, AB and Lyhne, S and Glavind, E and Fernis, CMC and Hald, S and Erikstrup, LT and Vinter-Jensen, L and Lal, S and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL},
title = {Improving Clinical Outcomes of Encapsulated Faecal Microbiota Transplantation for Clostridioides difficile Infection Through Empirical Donor Selection and Optimised Dosing: A Quality Improvement Study.},
journal = {Alimentary pharmacology & therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1111/apt.70395},
pmid = {41047993},
issn = {1365-2036},
support = {8056-00006B//Innovationsfonden/ ; },
abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is effective for Clostridioides difficile infection (CDI), but real-world effectiveness data are warranted to refine treatment algorithms. We previously found that FMT effectiveness varied with donors, and the effect of a single capsule FMT administration was lower than expected.

AIMS: To improve FMT outcomes through empirical donor exclusion and application of an optimised capsule FMT dosing regimen.

METHODS: In this multi-site Danish quality improvement study, we included patients with CDI treated with capsule-based FMT from 24 June 2019 to 30 September 2024. The primary outcome was cure of C. difficile-associated diarrhoea (CDAD) 8 weeks after FMT. We assessed this using statistical process control charts monitored separately for the primary FMT centre and the external FMT sites. We used multivariable, mixed-effect logistic regression analysis to evaluate the impact of FMT dosing while adjusting for patient, donor and CDI-related factors.

RESULTS: We included 1176 patients (1707 FMT treatments). At external FMT sites, the cure rate from one FMT treatment changed from 50% (95% confidence interval (CI): 45%-56%) to 59% (55%-63%) following the exclusion of three low-performing donors in November 2022. After implementing a two-dose capsule FMT dosing regimen in February 2024, the cure rate increased to 72% (65%-77%). The impact of the two-dose capsule FMT dosing regimen remained statistically significant after adjustment (odds ratio 1.22; 95% CI 1.16-1.28; p < 0.001).

CONCLUSION: Empirical donor selection and a two-dose capsule FMT regimen improved clinical outcomes in a large-scale system treating patients with CDI.},
}

@article {pmid41047724,
year = {2025},
author = {de Groen, P and Fuhri Snethlage, CM and Wortelboer, K and Tokgöz, S and Davids, M and Verdoes, X and Westerbeke, FHM and Meijer, RI and Gotthardt, M and de Vos, WM and Herrema, H and Nieuwdorp, M and Hanssen, NMJ},
title = {Autologous fecal microbiota capsules are safe and potentially preserve beta-cell function in individuals with type 1 diabetes.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2563155},
doi = {10.1080/19490976.2025.2563155},
pmid = {41047724},
issn = {1949-0984},
mesh = {Humans ; *Diabetes Mellitus, Type 1/therapy ; *Insulin-Secreting Cells/physiology/metabolism ; Male ; Female ; Adult ; *Feces/microbiology ; Pilot Projects ; Capsules/administration & dosage ; *Fecal Microbiota Transplantation/adverse effects/methods ; Young Adult ; Middle Aged ; C-Peptide/blood/metabolism ; Adolescent ; Gastrointestinal Microbiome ; },
abstract = {This study investigated the safety and feasibility of daily ingestion of autologous lyophilized fecal microbiota capsules (a-LFMCs) for preserving beta-cell function in individuals with type 1 diabetes (T1D). We evaluated a-LFMC in an open-label, single-arm pilot study (NCT05323162) with 10 individuals with T1D. The study included a 3-month run-in period, 3 months of daily a-LFMC treatment, and a 3-month follow-up. Beta-cell function was assessed using mixed-meal stimulated C-peptide area under the curve (AUC). During the run-in period, beta-cell function significantly declined (mean ΔAUC -12.02 ± 5.09 nmol/L*min, p = 0.025). There was no decrease in beta-cell function during the a-LFMC treatment period (mean ΔAUC 0.76 ± 5.09 nmol/L*min, p = 0.88) and the follow-up period (mean ΔAUC 0.96 ± 5.09 nmol/L*min, p = 0.85). No serious adverse events occurred, though constipation increased during the treatment period (0% vs. 30%, p = 0.021). a-LFMC treatment was found to be safe and potentially contributes to preserving beta-cell function in T1D patients. A larger randomized placebo-controlled trial is needed to confirm these promising findings.},
}

Humans
*Diabetes Mellitus, Type 1/therapy
*Insulin-Secreting Cells/physiology/metabolism
Male
Female
Adult
*Feces/microbiology
Pilot Projects
Capsules/administration & dosage
*Fecal Microbiota Transplantation/adverse effects/methods
Young Adult
Middle Aged
C-Peptide/blood/metabolism
Adolescent
Gastrointestinal Microbiome

@article {pmid41046337,
year = {2025},
author = {Vogel, GF and Kathemann, S and Pietrobattista, A and Maggiore, G and Aldrian, D and Sciveres, M and Verkade, HJ and Sokal, E and Jannone, G and Salcedo, M and Rauschkolb, P and Maucksch, C and Valcheva, V and Lainka, E},
title = {Odevixibat after liver transplant in patients with progressive familial intrahepatic cholestasis type 1: A case series.},
journal = {Journal of pediatric gastroenterology and nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1002/jpn3.70227},
pmid = {41046337},
issn = {1536-4801},
support = {//Ipsen/ ; },
abstract = {OBJECTIVES: Patients with progressive familial intrahepatic cholestasis type 1 (PFIC1) who have undergone liver transplantation (LT) may have unmet needs and impacts on daily life due to post-LT complications, including diarrhea and hepatic steatosis. Here, we describe the effects of the ileal bile acid transporter inhibitor odevixibat on diarrhea and hepatic steatosis in a cohort of patients with PFIC1 post-LT.

METHODS: Treating physicians from six centers retrospectively collected data through July 2023 on patients with PFIC1 who received odevixibat post-LT. Data collected included demographics, medical history, and symptom presentation, characteristics of diarrhea, and liver imaging and/or histopathology.

RESULTS: Overall, nine male patients with PFIC1 (seven aged <18 years at initial completion of the case report form) were included. In most patients, the primary indication for odevixibat treatment was diarrhea and/or steatosis post-LT. Odevixibat was initiated at a daily dose of 30-120 µg/kg (median exposure: 13 months). All patients had post-LT diarrhea, which was generally associated with negative impacts on daily life (e.g., ability to attend school, needing to wear diapers due to fecal urgency). After odevixibat initiation, most patients had improved diarrhea and positive impacts on daily life. Among five patients with post-LT steatosis and data available before and after odevixibat initiation, steatosis appeared to improve in three and did not change in two.

CONCLUSIONS: Overall, the majority of patients with PFIC1 post-LT complications in this case series experienced improvements in diarrhea and daily activities with odevixibat. Treatment with odevixibat following LT also appeared to reduce steatosis in some patients. Further studies, particularly those with a prospective design, are needed to confirm these findings.},
}

@article {pmid41046274,
year = {2025},
author = {Sadeghloo, Z and Ebrahimi, S and Hakemi-Vala, M and Totonchi, M and Sadeghi, A and Fatemi, N},
title = {Fusobacterium nucleatum and non-coding RNAs: orchestrating oncogenic pathways in colorectal cancer.},
journal = {Gut pathogens},
volume = {17},
number = {1},
pages = {78},
pmid = {41046274},
issn = {1757-4749},
abstract = {Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with mounting evidence implicating the gut microbiome in its pathogenesis. Among the microbial agents, Fusobacterium nucleatum has emerged as a prominent contributor, frequently detected in CRC tissues and associated with advanced disease stages and poor prognosis. This review highlights the complex interplay between F. nucleatum and host non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in modulating CRC biology. F. nucleatum influences the expression of several ncRNAs, which in turn regulate key signaling pathways such as Wnt/β-catenin (e.g., miR-1246, miR-135b), PI3K/AKT (e.g., miR-22, miR-135b), and TLR4/NF-κB (e.g., miR-31, lnc-NEAT1). Through these mechanisms, F. nucleatum contributes to tumor cell proliferation, immune evasion, metastasis, and chemoresistance. Additionally, its impact on ncRNA expression is implicated in reduced efficacy of standard chemotherapy. Emerging microbiota-based therapies, including probiotics and fecal microbiota transplantation, show promise in modulating gut flora and potentially reversing ncRNA dysregulation; however, their mechanistic effects on the F. nucleatum-ncRNA axis require further investigation. This review underscores the critical role of F. nucleatum-regulated ncRNAs in CRC and presents new opportunities for biomarker discovery and targeted therapeutics.},
}

@article {pmid41045390,
year = {2025},
author = {Senthilkumar, H and Chauhan, SC and Arumugam, M},
title = {Unraveling the multifactorial pathophysiology of polycystic ovary syndrome: exploring lifestyle, prenatal influences, neuroendocrine dysfunction, and post-translational modifications.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {980},
pmid = {41045390},
issn = {1573-4978},
mesh = {Humans ; *Polycystic Ovary Syndrome/physiopathology/metabolism/genetics/etiology ; Female ; *Protein Processing, Post-Translational ; Life Style ; Pregnancy ; Neurosecretory Systems/metabolism/physiopathology ; Insulin Resistance/physiology ; Animals ; Oxidative Stress ; },
abstract = {Polycystic ovary syndrome (PCOS) is a complex, multifactorial metabolic and endocrine disorder in reproductive-age women. This review discusses the interlinked roles of lifestyle, metabolic dysregulation, insulin resistance, neuroendocrine impairment, genetic predisposition, and post-translational modifications (PTMs) in PCOS pathogenesis. Lifestyle components, especially those leading to obesity and insulin resistance, worsen the hyperandrogenism, ovulatory dysfunction, and inflammation. Dietary treatments such as, DASH diet and caloric restriction, particularly along with metformin, have been proven to improve metabolic and reproductive parameters. Environmental toxins, such as endocrine-disrupting chemicals (EDCs) and advanced glycation end-products (AGEs), further compromise ovarian function and hormone regulation. Oxidative stress and insulin resistance, driven by mitochondrial malfunction and chronic inflammation, create a self-perpetuating vicious cycle that compromises oocyte quality and worsens metabolic imbalance. Neuroendocrine disruption, characterized by increased GnRH and LH pulsatility, is initiated by dysregulated kisspeptin, dynorphin, and neurokinin B signaling in KNDy neurons, modified GABAergic input, and increased AMH and androgens. PTMs such as phosphorylation, methylation, acetylation, and ubiquitination also play essential roles in granulosa cell function, AR signaling, insulin sensitivity, and oocyte maturation. Current and novel treatment options vary from lifestyle modifications and pharmacological interventions (e.g., metformin, GLP-1 receptor agonists, myoinositol, vitamin D, and statins) to regenerative measures like mesenchymal stem cells and fecal microbiota transplantation. Newer therapies focusing on PTMs and neuroendocrine regulators remain the future hope. Multidisciplinary individualized management is critical for successful PCOS therapy and averting long-term complications.},
}

Humans
*Polycystic Ovary Syndrome/physiopathology/metabolism/genetics/etiology
Female
*Protein Processing, Post-Translational
Life Style
Pregnancy
Neurosecretory Systems/metabolism/physiopathology
Insulin Resistance/physiology
Animals
Oxidative Stress

@article {pmid41039216,
year = {2025},
author = {Ma, Y and Wang, D and Yu, X and Fan, Y and Yang, Z and Gao, X and Huang, X and Meng, J and Cheng, P and Liu, X and Liu, Z and Li, X},
title = {Moderate altitude exposure induced gut microbiota enterotype shifts impacting host serum metabolome and phenome.},
journal = {BMC microbiology},
volume = {25},
number = {1},
pages = {591},
pmid = {41039216},
issn = {1471-2180},
support = {2023YFE0114300//National key research and development program intergovernmental key projects/ ; No.2024A1515012697//Guangdong Provincial Basic and Applied Basic Research Fund Project/ ; No. 202206010044//Science and Technology Program of Guangzhou, China/ ; No. U24A20652//The Joint Funds of the Natural Science Foundation of China/ ; No. 82272246//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Consistent patterns of gut microbiota variations, particularly in relative abundance, have been identified in the adult human gut. Enterotype, another general measure of the gut microbiota, is a valuable approach for categorizing the human gut microbiota into distinct clusters. The impact of different enterotypes on human health varies, and the changes induced by moderate altitude exposure remain unclear. This study aimed to conduct a comprehensive investigation of the cascade effects triggered by enterotype shifts following moderate altitude exposure.

RESULTS: Using shotgun metagenome sequencing, participants before and after moderate-altitude exposure were classified into cluster BL (dominated by Blautia) and cluster BA (dominated by Bacteroides). Relative to cluster BL, cluster BA consisted predominantly of individuals exposed to moderate altitude. Compared to cluster BL, Cluster BA exhibited rewired metabolism of serum metabolites (i.e., amino acids, fatty acids and bile acids) and gut microbiota, lower inflammatory factor levels (i.e., tumor necrosis factor-α (TNF-α)), and sparser correlations among these parameters. Individuals with baseline BL enterotype who transitioned to the BA enterotype following moderate-altitude exposure showed prominent improvement in fasting blood glucose (FBG) levels, with higher abundance of Bacteroidetes species (e.g., Bacteroides thetaiotaomicron, and Bacteroides uniformis), but lower Proteobacteria species abundance (e.g., Escherichia coli) and decreased L-Glutamic acid levels. Furthermore, fecal microbiota transplantation (FMT) from moderate-altitude exposed individuals to high-fat diet (HFD) fed mice confirmed increased Bacteroides abundance shifts associated with improvements in glucose homeostasis regulation and rewired amino acid metabolism. In addition, significant increases in alanine aminotransferase (ALT) levels but decreased serum creatinine (Scr), arterial oxygen saturation (SaO2), 4-Hydroxyproline, L-Glutamic acid, L-Asparagine, L-Threonine, L-Citrulline, L-Lysine and Isovaleric acid levels were identified as potentially important signals for individuals upon moderate altitude exposure, regardless of the gut microbiota enterotype.

CONCLUSIONS: Moderate altitude exposure could induce enterotype switching, and a Bacteroides-dominant enterotype may be a beneficial pattern of the gut microbiome related to host metabolism. Moderate-altitude exposure has potential implications for glycemic control, suggesting new avenues for managing FBG levels in future.

GRAPHICAL ABSTRACT: [Image: see text]

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-025-04245-4.},
}

@article {pmid41043596,
year = {2025},
author = {Nasare, D and Bagade, S},
title = {The Gut-Lung Axis in Tuberculosis: A New Frontier in Immunomodulation and Microbiota-Directed Therapeutic Strategies.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {108087},
doi = {10.1016/j.micpath.2025.108087},
pmid = {41043596},
issn = {1096-1208},
abstract = {Tuberculosis (TB) is a transmissible disease that contributes to the global health burden due to drug resistance. The gut-lung axis is an emerging and promising frontier for understanding Mycobacterium tuberculosis (MTB) pathogenesis and disease progression via gut and lung bidirectional communication. Increasing evidence highlights that regulation in gut and lung microbial communities, termed dysbiosis, influences homeostatic conditions, innate and adaptive responses, and susceptibility to TB. Growing research has witnessed a paradigm shift toward the immunological interplay between gut microbiota and lung microbiota, and modulation in TB. This review deals with the interplay of immune cells and gut microbiota in TB, highlighting the importance of innate and adaptive responses in stabilizing the dysbiosis and inflammation. Host-directed therapies such as probiotics, prebiotics, synbiotics, short-chain fatty acids (SCFAs), and fecal microbiota transplantation support the stabilization of gut microbiota and maintain the disease severity. Moreover, personalized microbiota therapies, such as bacteriophage therapy, diagnostic agents, and biomarkers, are explored for their several roles in maintaining the eubiosis condition. We also highlight the future perspective of addressing the knowledge gap to develop a personalized and combined approach to novel drug delivery systems and host-directed therapies. This review provides an in-depth outline of the gut-lung axis as a potential therapeutic intervention, offering a conceptual framework for developing next-generation, microbiota-directed therapies to suppress and combat MTB infection.},
}

@article {pmid41043575,
year = {2025},
author = {Ahmed, LA and Al-Massri, KF},
title = {Insights into the Role of Gut Microbiota Modulation in the Management of Various Cardiovascular Diseases: A New Approach for Improving the Efficacy of Current Cardiovascular Medications.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {178210},
doi = {10.1016/j.ejphar.2025.178210},
pmid = {41043575},
issn = {1879-0712},
abstract = {Gut microbiome is an emerging contributor to various cardiovascular diseases (CVDs) where gut dysbiosis increases the risk of development and progression of atherosclerosis, coronary artery diseases, hypertension, and heart failure. Microbiota can also affect the metabolism of medications including cardiovascular drugs, resulting in alteration of their pharmacokinetics and pharmacodynamics or producing metabolites which can interfere with response of these drugs. Importantly, CVDs require prolonged pharmacological interventions with medications which may have impacts on the diversity and composition of gut microbiota. Gut microbiota modulation using diets, prebiotics, probiotics, fecal microbiota transplantation, and microbial trimethylamine-lyase inhibitors, has also shown benefits in the management of CVDs where gut microbiota and their metabolites have recently been studied as potential targets for the management of these diseases. Specifically, using innovative microbiota therapies in combination with traditional pharmacological agents have been evaluated for additional benefits in various CVDs. However, assessing the interactions among host factors, gut microbiome, and drug response will be essential for the development of new therapeutic targets for cardiovascular disorders, ultimately hoping better prognosis and patient's quality of life for those affected with CVDs.},
}

@article {pmid41043062,
year = {2025},
author = {Malogan, J and Hallowell, HA and Francis, B and Suez, J},
title = {Supplementation and Elimination of Microbiome-Produced Metabolites in the Treatment of Human Disease.},
journal = {Annals of the New York Academy of Sciences},
volume = {},
number = {},
pages = {},
doi = {10.1111/nyas.70103},
pmid = {41043062},
issn = {1749-6632},
abstract = {The human gut microbiome has a complex and influential relationship with host physiology that is governed through commensal-derived metabolites, small molecules, and endogenous microbial patterns. Indeed, microbial metabolites from the gut microbiome have been implicated in promoting health as well as contributing to the pathogenesis of microbiome-associated diseases. Live microbial therapeutics, such as probiotics and fecal microbiota transplantations, have been extensively utilized to establish health-promoting assemblages of bacteria and their associated beneficial metabolites. However, broad clinical use of live microbial therapeutics is limited by efficacy, specificity, and safety concerns. To circumvent this, a postbiotic approach can be taken, in which a beneficial effect may be achieved by direct administration of bacterially derived bioactive molecules. Alternatively, in cases where microbiome-derived metabolites drive disease, specific oral inhibitors can be used to restrict compound production. In this review, we examine the use of postbiotics to alleviate disease and highlight recent translational successes. Additionally, we discuss emerging approaches for precision elimination of disease-causing metabolites, as well as the exciting possibility of utilizing bacteriophages to modulate the production of metabolites in the microbiome.},
}

@article {pmid41041846,
year = {2025},
author = {Zhao, Y and Yu, C and Zhang, J and Yao, Q and Zhu, X and Zhou, X},
title = {The gut‑skin axis: Emerging insights in understanding and treating skin diseases through gut microbiome modulation (Review).},
journal = {International journal of molecular medicine},
volume = {56},
number = {6},
pages = {},
doi = {10.3892/ijmm.2025.5651},
pmid = {41041846},
issn = {1791-244X},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Skin Diseases/therapy/microbiology ; *Skin/microbiology/pathology ; Probiotics/therapeutic use ; Animals ; Prebiotics ; },
abstract = {Emerging evidence indicates a significant association between the composition and functionality of the gut microbiome and various skin disorders, including psoriasis, atopic dermatitis, acne and several dermatological conditions. The gut‑skin axis theory describes a complex bidirectional communication network between the gut and the skin, providing mechanistic insights into the pathogenesis of certain cutaneous diseases. Specifically, the gut microbiome influences skin health through the regulation of systemic immunity, inflammatory responses and metabolic pathways. Advances in high‑throughput sequencing and bioinformatics technologies have substantially enhanced the understanding of the role of the gut microbiome in skin pathology. Clinical and preclinical studies have demonstrated that restoring gut microbial homeostasis via interventions such as faecal microbiota transplantation, probiotics and prebiotics can ameliorate symptoms of skin diseases. Furthermore, personalized microbiome‑based therapies, next‑generation probiotics and dietary modifications hold promise for refining gut‑skin interactions and advancing precision medicine in dermatology. Therapeutic strategies targeting the gut‑skin axis offer novel avenues for innovative dermatological treatments, with future breakthroughs potentially involving microbial community engineering, postbiotics and artificial intelligence in microbiome‑related diagnostics. This narrative review summarizes recent advances in gut‑skin axis research, explores its potential in the prevention and management of selected dermatoses and discusses future trends and scientific developments in the field.},
}

Humans
*Gastrointestinal Microbiome
*Skin Diseases/therapy/microbiology
*Skin/microbiology/pathology
Probiotics/therapeutic use
Animals
Prebiotics

@article {pmid41041667,
year = {2025},
author = {Tariq, H and Ramakrishnan, M and Portocarrero, P and Gupta, M and Herrera, N and Klein, J and Gupta, A and Cibrik, D},
title = {Fecal Impaction: An Unusual Cause of Acute Kidney Injury in a Kidney Transplant Recipient.},
journal = {Case reports in transplantation},
volume = {2025},
number = {},
pages = {5726025},
pmid = {41041667},
issn = {2090-6943},
abstract = {Acute kidney injury (AKI) is common in kidney transplant recipients, and the etiology varies depending on the time since transplantation. We present an uncommon case of AKI from obstructive uropathy 7 years posttransplant in a 47-year-old Caucasian male with moderate intellectual disability and end-stage kidney disease secondary to glomerulonephritis who received a deceased donor kidney transplant. He presented with abdominal pain, lethargy, hypercalcemia, and AKI. However, though his serum calcium level improved with intravenous fluid resuscitation, the AKI did not improve. Kidney transplant ultrasound showed hydronephrosis of the transplant ureter, and a noncontrast abdominal and pelvic computed tomography scan showed fecal impaction as the cause of obstruction of the transplanted ureter. The patient underwent fecal disimpaction resulting in the resolution of his hydronephrosis and return of his kidney function to baseline. Although a few case reports have been published of fecal impaction causing AKI due to obstruction of native ureters, to our knowledge, this is the first case describing AKI from fecal impaction in an adult kidney transplant recipient.},
}

@article {pmid41041075,
year = {2025},
author = {Zhu, S and Li, X and Yu, Y and Han, X and Yang, F and Lu, M and Dai, G and Guo, L and Xu, D},
title = {EZH2-mediated H3K27me3 links microbial inosine loss to depression: a gut-brain epigenetic switch.},
journal = {Theranostics},
volume = {15},
number = {18},
pages = {9969-9986},
pmid = {41041075},
issn = {1838-7640},
mesh = {Animals ; *Gastrointestinal Microbiome/genetics/physiology ; Mice ; *Enhancer of Zeste Homolog 2 Protein/metabolism/genetics ; *Epigenesis, Genetic ; *Depression/microbiology/metabolism/genetics ; *Histones/metabolism ; *Inosine/metabolism ; *Brain/metabolism ; Male ; Mice, Knockout ; Mice, Inbred C57BL ; Disease Models, Animal ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Apoptosis ; },
abstract = {Background: Depression, the second most prevalent neurological disorder globally, affects over 300 million people and presents an urgent public health challenge. While gut microbiota dysbiosis is increasingly recognized as a key contributor to depression, the molecular mechanisms linking microbial imbalance to brain dysfunction remain poorly defined. Methods: We investigated the role of EZH2 in gut microbiota-induced depressive behaviors in mice using the chronic unpredictable mild stress (CUMS), fecal microbiota transplantation, and conditional knockout of EZH2. CUT&Tag sequencing was employed to analyze EZH2-mediated H3K27me3 epigenetic reprogramming. Untargeted metabolomics and luciferase reporter assays were used to identify metabolites that upregulate EZH2 expression. 16S rRNA sequencing combined with metabolic tracing was conducted to trace the microbial origin of inosine. Additionally, natural compound screening identified coumaric acid (CA) as a novel EZH2-targeting degrader. Results: Conditional knockout of neuronal Ezh2 abolishes microbiota-induced depressive behaviors and neuronal apoptosis. Mechanistically, reduced abundance of specific microbiota (f_Lachnospiraceae, f_Oscillospiraceae, and f_Erysipelotricaceae) leads to inosine depletion. This depletion subsequently elevates EZH2 transcriptional activity by increasing H3K9ac modification at its locus, mediated through attenuation of the A2aR-cAMP-PKA-CREB-HDAC3 signaling axis. Subsequently, EZH2 silences serotonergic synapse-related genes (e.g., Tph2, Htr2a, Htr6) via H3K27me3 reprogramming, ultimately driving depressive behaviors and neuronal apoptosis in mice. Importantly, CA is identified as a first-in-class EZH2 degrader that binds lysine residues K623/K646 and recruits UBE3A for proteasomal degradation. CA treatment restores synaptic integrity and reverses depressive behaviors with minimal toxicity. Conclusions: Collectively, these findings define a novel "microbiota-inosine-EZH2" axis in depression pathogenesis and highlight EZH2 degradation as a promising therapeutic strategy for microbiota-associated neuropsychiatric disorders.},
}

Animals
*Gastrointestinal Microbiome/genetics/physiology
Mice
*Enhancer of Zeste Homolog 2 Protein/metabolism/genetics
*Epigenesis, Genetic
*Depression/microbiology/metabolism/genetics
*Histones/metabolism
*Inosine/metabolism
*Brain/metabolism
Male
Mice, Knockout
Mice, Inbred C57BL
Disease Models, Animal
Dysbiosis/microbiology
Fecal Microbiota Transplantation
Apoptosis

@article {pmid41040884,
year = {2025},
author = {Zhang, S and Zhang, T and Zhang, Y and Ye, C and Mu, L and He, Q and Huang, T and Wang, G and Li, Y and Xie, S and Tang, X},
title = {Akkermansia muciniphila regulates the gut microenvironment and alleviate periodontal inflammmation in mice with periodontitis.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1643691},
pmid = {41040884},
issn = {1664-302X},
abstract = {OBJECTIVE: Akkermansia muciniphila (A. muciniphila) is an emerging gut commensal known for its roles in host metabolism and immune modulation. While its involvement in metabolic and inflammatory disorders is well characterized, its potential association with oral diseases such as periodontitis remains poorly understood. This study aimed to explore whether modulation of the gut microbiota via fecal microbiota transplantation (FMT) from periodontally healthy donors could influence the abundance of A. muciniphila and contribute to the alleviation of periodontitis.

METHODS: Fecal samples were collected from human donors, including periodontally healthy individuals (H group, n = 16), untreated patients with severe periodontitis (P group, n = 12), and the same patients at two weeks (P2W) and three months (P3M) after periodontal therapy. Quantitative PCR was used to assess A. muciniphila abundance in these human samples. A germ-free mouse model of periodontitis was then established, and the mice received FMT using samples from human donor groups (P-PBS, P-H, and P-P). Gut microbiota composition, periodontal inflammation, gut barrier proteins (MUC2, ZO-1), and inflammatory cytokines (IL-6, TNF-α) were evaluated in the mice.

RESULTS: Compared to groups H, P2W, and P3M, the abundance of A. muciniphila in the gut was significantly lower in patients with severe periodontitis, but it was increased after periodontal therapy. In mice, FMT from healthy donors (P-H group) significantly enriched A. muciniphila, improved expression of gut barrier proteins, reduced inflammatory cytokine levels, and alleviated periodontal inflammation compared to other groups.

CONCLUSION: These findings suggest a previously underrecognized link between gut microbial composition particularly A. muciniphila and periodontal health. Targeting the gut microbiota via FMT may represent a novel strategy for modulating systemic and oral inflammation and supporting the prevention or adjunctive treatment of periodontitis.},
}

@article {pmid41039491,
year = {2025},
author = {Song, J and Yang, X and Liu, X and Li, J},
title = {Gut bacteria: protective mediators, pathogenic contributors and novel therapeutic targets in Candida albicans infections.},
journal = {Gut pathogens},
volume = {17},
number = {1},
pages = {77},
pmid = {41039491},
issn = {1757-4749},
support = {24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; },
abstract = {Candida albicans is an opportunistic pathogen that resides in the human gut alongside a diverse array of microorganisms, including enteric bacteria, archaea, and viruses, which collectively form the gut microbiota. Recent studies have shown that the development of Candida albicans infections involves both weakened host immunity and enhanced invasiveness of Candida albicans, with intestinal microecology serving as a critical mediator of these processes. It has been demonstrated that disturbances in the gut microbiome can potentiate the invasive capacity of Candida albicans. Moreover, a compromised immune system, along with the use of antibiotics and immunosuppressive drugs, can lead to gut microbiome imbalances. Consequently, modulators of the intestinal microecology represent promising therapeutic interventions for managing Candida albicans infections. In this review, we examine the mechanisms underlying the increased invasiveness of Candida albicans following significant disruption of intestinal bacteria and highlighting the interplay among immune dysfunction, antibiotic use, and their effects on gut microbiome imbalance and Candida albicans infection. Additionally, we summarize the roles of microbiome-based therapies, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), in addressing Candida albicans infections. This review provides a theoretical foundation and practical guidance for the development of more effective microecological therapeutic strategies in the future.},
}

@article {pmid41039079,
year = {2025},
author = {Barkai, T and Yakubovsky, O and Korem Kohanim, Y and Bahar Halpern, K and Shir, S and Oren, N and Fine, M and Kelmer, P and Talmon, A and Israeli, A and Pencovich, N and Pery, R and Nachmany, I and Itzkovitz, S},
title = {Transcriptomic profiling of shed cells enables spatial mapping of cellular turnover in human organs.},
journal = {Molecular systems biology},
volume = {},
number = {},
pages = {},
pmid = {41039079},
issn = {1744-4292},
support = {768956//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; 908/21//Israeli Science Foundation/ ; 3663/21//Israeli Science Foundation/ ; },
abstract = {Single-cell atlases provide valuable insights into gene expression states but lack information on cellular dynamics. Understanding cell turnover rates-the time between a cell's birth and death-can shed light on stemness potential and susceptibility to damage. However, measuring turnover rates in human organs has been a significant challenge. In this study, we integrate transcriptomic data from both tissue and shed cells to assign turnover scores to individual cells, leveraging their expression profiles in spatially resolved expression atlases. By performing RNA sequencing on shed cells from the upper gastrointestinal tract, collected via nasogastric tubes, we infer turnover rates in the human esophagus, stomach, and small intestine. In addition, we analyze colonic fecal washes to map turnover patterns in the human large intestine. Our findings reveal a subset of short-lived, interferon-stimulated colonocytes within a distinct pro-inflammatory microenvironment. Our approach introduces a dynamic dimension to single-cell atlases, offering broad applicability across different organs and diseases.},
}

@article {pmid41038971,
year = {2025},
author = {Bahar Halpern, K and Kent, I and Yakubovsky, O and Ben-Moshe, S and Barkai, T and Fine, M and Novoselsky, R and Israeli, A and Nachmany, I and Itzkovitz, S},
title = {Stool shed cell transcriptomics mirrors tumor biology and enables colorectal cancer diagnosis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {34413},
pmid = {41038971},
issn = {2045-2322},
support = {768956/ERC_/European Research Council/International ; },
mesh = {Humans ; *Colorectal Neoplasms/diagnosis/genetics/pathology ; *Feces/cytology ; Female ; *Transcriptome ; Male ; *Gene Expression Profiling/methods ; Aged ; Middle Aged ; Biomarkers, Tumor/genetics ; Case-Control Studies ; Gene Expression Regulation, Neoplastic ; Adult ; Early Detection of Cancer/methods ; },
abstract = {Screening and molecular characterization of human intestinal pathologies such as colorectal cancer (CRC) currently depends on colonoscopy, an invasive procedure associated with risks and poor adherence. A non-invasive method that captures host molecular changes could improve early detection and monitoring of intestinal diseases. Transcriptomic profiling of shed intestinal cells in stool has shown potential in neonates but is limited in adults by the dominance of bacterial RNA. To address this, we combined microbial ribosomal RNA (rRNA) depletion with unique molecular identifier (UMI)-based RNA sequencing to enrich and quantify human transcripts in stool. Applying this method to samples from 54 CRC patients and 24 healthy controls, we profiled thousands of human genes per sample. Stool-derived gene expression distinguished CRC from control samples with high accuracy (AUC = 0.86) and strongly correlated with matched tumor tissue signatures. Notably, stool transcriptomes reverted to control-like patterns after tumor resection. Our approach offers a powerful, non-invasive alternative to current CRC diagnostics and enables molecular insights into tumor biology. This method could complement or replace existing screening tools and may be applicable to other gastrointestinal diseases.},
}

Humans
*Colorectal Neoplasms/diagnosis/genetics/pathology
*Feces/cytology
Female
*Transcriptome
Male
*Gene Expression Profiling/methods
Aged
Middle Aged
Biomarkers, Tumor/genetics
Case-Control Studies
Gene Expression Regulation, Neoplastic
Adult
Early Detection of Cancer/methods

@article {pmid41038411,
year = {2025},
author = {Taoum, C and Devaux, A and Rouanet, P and Colombo, PE and Boucher, D and Bonnet, M},
title = {Gut microbiota and chemoradiotherapy response in rectal cancer: biomarker opportunities.},
journal = {Critical reviews in oncology/hematology},
volume = {},
number = {},
pages = {104974},
doi = {10.1016/j.critrevonc.2025.104974},
pmid = {41038411},
issn = {1879-0461},
abstract = {The gut microbiota is increasingly recognized as a key factor in rectal carcinogenesis. This review synthesizes current clinical and preclinical evidence linking specific microbial signatures, such as Fusobacterium nucleatum, Duodenibacillus massiliensis and colibactin-producing Escherichia coli (CoPEC) to chemoradiotherapy (CRT) treatment efficacy and resistance. Microbiota-driven mechanisms include immune modulation, inflammation, and drug metabolism. We highlight emerging microbial biomarkers and therapeutic strategies such as antibiotics, probiotics, and fecal microbiota transplantation. Integrating microbiome profiling into clinical workflows could refine patient stratification and enhance CRT efficacy in rectal cancer. Ongoing clinical trials aim to validate these associations and establish robust microbial biomarkers for CRT response prediction in rectal cancer.},
}

@article {pmid41038146,
year = {2025},
author = {Du, Y and Xu, J and Jia, J and Nong, Y and Lin, Y and Ye, Y and Zhong, Y and Tan, Q and Wei, Y and Huang, G and Mao, D and Huang, G and Lu, L and Peng, Y and Huang, H and Huang, J},
title = {Yuzhuo Zhixiao pill can treat non-alcoholic steatohepatitis through modulation of gut microbiota, bile acid and short-chain fatty acid metabolism.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {148},
number = {},
pages = {157348},
doi = {10.1016/j.phymed.2025.157348},
pmid = {41038146},
issn = {1618-095X},
abstract = {BACKGROUND: Yuzhuo Zhixiao Pill (YZZXP), a formulation in traditional Chinese medicine (TCM), exhibits therapeutic potential in non-alcoholic steatohepatitis (NASH). However, the mechanisms underlying its effects, particularly those involving gut microbiota-bile acid-short-chain fatty acid (GM-BA-SCFA) interactions, remain unclear. Current therapies present notable side effects and inadequately address the multifactorial etiology of NASH.

PURPOSE: To evaluate the anti-NASH efficacy of YZZXP and elucidate its mechanism, focusing on GM remodeling and BA/SCFA regulation.

STUDY DESIGN: This study established a NASH model in rats using a high-fat diet (HFD) and performed fecal microbiota transplantation (FMT) experiments.

METHODS: The therapeutic impacts of YZZXP on gut microbial structure (16S rDNA sequencing), SCFA concentrations, and BA profiles (analyzed by LC-MS and GC-MS) were assessed.

RESULTS: YZZXP administration alleviated HFD-induced obesity, hepatic steatosis, inflammatory responses, and disturbances in glycolipid metabolism. Microbial profiling via 16S rDNA sequencing revealed restored gut microbial diversity, marked by increased Akkermansia, Bacteroides, and Roseburia abundance. PROB and FMT interventions validated GM modulation as central to YZZXP 's effects. Targeted metabolomic analyses demonstrated elevated levels of SCFAs (notably butyrate and acetate) and substantial shifts in BA composition, accompanied by downregulation of intestinal FXR-FGF19 signaling and enhanced cholesterol excretion.

CONCLUSIONS: YZZXP exerts anti-NASH activity through a synergistic mechanism comprising GM restoration, BA metabolic reprogramming via FXR pathway inhibition, and SCFA-driven metabolic modulation. In contrast to monotherapy approaches, the multi-target strategy of YZZXP prevents compensatory dysbiosis and yields more durable metabolic benefits than PROB or FMT alone. By integrating microbiota-metabolite interplay into therapeutic design, YZZXP introduces a novel paradigm in traditional medicine for NASH management, addressing the limitations of synthetic agents while promoting metabolic homeostasis.},
}

@article {pmid41038145,
year = {2025},
author = {Guo, L and Yi, J and Zhang, A and Zheng, X and Wang, M and Yang, F and Kong, X and Meng, J},
title = {Zhenqi Fuzheng Granule targets the SCFAs-GPR109A axis to enhance PD-1 antibody efficacy via immunometabolic remodeling in colorectal cancer.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {148},
number = {},
pages = {157312},
doi = {10.1016/j.phymed.2025.157312},
pmid = {41038145},
issn = {1618-095X},
abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs), particularly PD-1 antibodies, represent a breakthrough in colorectal cancer (CRC) treatment. However, their clinical efficacy remains limited by tumour-induced immunosuppression. Traditional Chinese medicine (TCM) has attracted growing interest as a potential adjuvant to immunotherapy. Zhenqi Fuzheng Granule (ZQFZ) is a clinically approved herbal prescription widely used as an adjuvant therapy for CRC, yet its mechanistic underpinnings remain elusive.

OBJECTIVE: To investigate how ZQFZ improves the efficacy in CRC, with emphasis on gut microbiota modulation, SCFAs production, and downstream immunometabolic pathways involving GPR109A, and confirms that butyrate plays an important role in colorectal cancer inhibition.

METHODS: Phytochemical analysis of ZQFZ was conducted using LC-MS/MS and UPLC-MS/MS, identifying and quantifying seven major compounds. In vivo experiments, AOM/DSS-induced CRC mouse models were treated with ZQFZ, PD-1 antibody, or their combination. Tumour progression, body weight, and survival were monitored. Gut microbial composition and colonic SCFAs levels were assessed via 16S rRNA sequencing and gas chromatography. RT-qPCR was employed to validate the expression of key genes associated with the GPR109A/AKT/mTOR/HIF-1α signaling pathway. Molecular changes in the GPR109A/AKT/mTOR/HIF-1α pathway were evaluated through Western blotting, transcriptomic, and proteomic analyses. Immune cell infiltration and phenotypes were analyzed by flow cytometry. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and structural stability between GPR109A and AKT1. The interactions between GPR109A and AKT1, as well as between butyrate and GPR109A, were further validated in vitro using microscale thermophoresis (MST) assays. To evaluate the microbial basis of ZQFZ activity, antibiotic-pretreated mice received ZQFZ-derived fecal microbiota transplantation (FMT). In vitro experiments, to investigate the mechanism by which sodium butyrate (NaB), the major gut microbial metabolite of ZQFZ, inhibits glycolysis in colorectal cancer under hypoxic conditions, CCK-8 assays, flow cytometry, lactate measurements, and Western blotting were performed to assess cell viability, apoptosis, lactate production, and the expression of AKT/mTOR/HIF-1α and glycolysis-related proteins.

RESULTS: LC-MS/MS profiling identified multiple bioactive constituents in ZQFZ. Targeted UPLC-MS/MS quantification revealed that the formulation contained Adenosine (0.87mg/g), Salidroside (0.11 mg/g), Astragaloside IV (0.07 mg/g), Calycosin (0.03 mg/g), Formononetin (6.7 μg /g), Chlorogenic acid (1.4 μg/g), Apigenin (0.5 μg/g). In vivo studies, both ZQFZ and PD-1 antibody inhibited tumour growth, with the combination treatment exerting the most pronounced antitumour effects. ZQFZ reshaped the gut microbiota, increased the levels of short-chain fatty acids (SCFAs), particularly butyrate, and activated the GPR109A pathway, leading to downregulation of the AKT/mTOR/HIF-1α signaling axis, suppression of HK2 expression and lactate production, and consequent inhibition of glycolysis. Immune remodeling was also observed, including reduced infiltration of myeloid-derived suppressor cells (MDSCs), polarization of macrophages toward the M1 phenotype, restoration of the CD4⁺/CD8⁺ T cell ratio, and modulation of serum cytokines including upregulation of IL-2, IL-12, and IFN-γ, along with downregulation of IL-4 and IL-10. ZQFZ-derived FMT significantly inhibited tumour growth, suppressed glycolysis-related markers (PKM2, GLUT1, HIF-1α, LDHA), and remodeled the immune microenvironment by reducing MDSCs and enhancing M1 macrophages and CD8⁺ T cell infiltration. In hypoxia-mimicking in vitro experiments, sodium butyrate (NaB), the principal gut microbial metabolite of ZQFZ, suppressed colorectal cancer cell viability and induced apoptosis. Through activation of GPR109A, NaB inhibited the AKT/mTOR/HIF-1α pathway and glycolysis-related enzymes, reduced lactate production, and further suppressed glycolysis. Molecular docking and dynamics simulations suggested a stable interaction between GPR109A and AKT1, which was confirmed in vitro by MST showing high-affinity binding (Kd=74.5 ± 20.8 nM); MST also verified moderate-affinity binding between GPR109A and sodium butyrate (Kd=43.3 ± 6.5 μM), supporting a dual interaction model wherein butyrate activates GPR109A, which in turn directly binds AKT1 to inhibit downstream glycolytic signaling.

CONCLUSION: This study uncovers a novel integrated mechanism whereby ZQFZ enhances PD-1 antibody efficacy via the gut microbiota-SCFAs-GPR109A axis, and NaB-mediated glycolysis inhibition under hypoxia further confirms its immunometabolic mechanism against CRC.},
}

@article {pmid41037658,
year = {2025},
author = {Sun, W and Ma, L and Feng, X and Fan, Y and Cai, Y and Li, X},
title = {Efficacy of gut microbiota-based therapy for autism Spectrum Disorder and attention Deficit Hyperactivity Disorder: a systematic review and meta-analysis.},
journal = {Psychology, health & medicine},
volume = {},
number = {},
pages = {1-25},
doi = {10.1080/13548506.2025.2565181},
pmid = {41037658},
issn = {1465-3966},
abstract = {The gut-brain axis is an emerging therapeutic target for neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). However, the overall efficacy of gut microbiome-based interventions remains unclear. This systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, aimed to synthesize the evidence on these interventions. Fifteen randomized controlled trials (RCTs) were identified from 1,080 records across PubMed, Embase, Web of Science, Cochrane, PsycInfo, MEDLINE, and ClinicalTrials.gov through August 2024. Interventions included probiotics, prebiotics, dietary changes, and fecal transplants. Using random-effects models, pooled analysis showed a small but significant overall benefit of gut microbiota-based interventions (Standardized Mean Difference, SMD = -0.12; 95% Confidence Interval, CI: -0.19 to -0.04), with low heterogeneity (I[2] = 5.9%). Effects differed by disorder: ADHD demonstrated greater improvement (SMD = -0.24; 95% CI: -0.42 to -0.06; I[2] = 50.4%) compared to ASD (SMD = -0.05; 95% CI: -0.15 to 0.04; I[2] = 0%). Duration-specific effects emerged: 8-week interventions showed significant outcomes (SMD = -0.32; 95% CI: -0.58 to -0.06), while shorter or longer durations lacked significance. Acceptability analysis from eight studies revealed comparable dropout rates between intervention and control groups (ASD: Risk Ratio, RR = 1.002; ADHD: RR = 0.943), with no serious adverse events reported. Subgroup analyses identified participant age, diagnosis type, and geographic location as heterogeneity sources. Despite methodological limitations and small sample sizes, findings suggest gut microbiome modulation may offer a safe adjunctive therapy, particularly for ADHD, with optimal effects emerging at 8 weeks. The gut-brain axis appears promising for neurodevelopmental disorders, but current evidence remains preliminary. Future research should prioritize large-scale RCTs with standardized protocols, mechanistic investigations, and long-term follow-up to establish clinical guidelines and clarify biological pathways. Findings underscore the need to tailor interventions to specific disorders and optimize treatment duration.},
}

@article {pmid41036798,
year = {2025},
author = {Nobel, YR and Park, H and Tillman, AM and Seeram, D and Moallem, DH and Intara, A and Nandakumar, R and Annavajhala, MK and Gomez-Simmonds, A and Verna, EC and Uhlemann, AC},
title = {Fecal Microbiota and Bile Acid Profiles in Early-Stage Hepatocellular Carcinoma: A Matched Case-Control Study.},
journal = {Clinical and translational gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ctg.0000000000000928},
pmid = {41036798},
issn = {2155-384X},
abstract = {INTRODUCTION: Early identification of hepatocellular carcinoma (HCC) is critical to reduce mortality. Diagnostic tools are limited for early disease. Intestinal microbiota may contribute to HCC risk directly and via metabolites, particularly bile acids (BA), offering potential noninvasive biomarkers.

METHODS: This was a case-control study of patients with cirrhosis with or without early-stage HCC, matched based on liver disease severity. Comprehensive analyses of fecal microbiota composition and function were performed.

RESULTS: There were 98 patients in the study (49 patients per group). Subjects with HCC were older (median 64 vs. 60 years, p<0.01) and more likely to have Hepatitis C (78% vs. 43%, p<0.01). Alpha diversity, beta diversity, and genes and pathways related to BA metabolism did not differ between groups overall, but alpha diversity did differ within the subset of patients with metabolic-associated steatotic liver disease (MASLD). There was differential abundance of multiple taxa between groups, including higher abundance of Klebsiella pneumoniae in cases. Increased concentration of secondary BA, which are microbiota-dependent, was associated with higher odds of HCC (adjusted OR 2.4, p=0.02); however, addition of microbial or BA features to a model with clinical data alone did not improve HCC prediction.

DISCUSSION: When accounting for liver disease severity, there were limited differences in intestinal microbiota composition and BA metabolism between subjects with or without early-stage HCC. Promising areas for future study of microbiota-based HCC biomarkers were identified, including a focus on the subpopulation of patients with MASLD.},
}

@article {pmid41036738,
year = {2025},
author = {Li, Y and Dong, J and Wang, S and Xiong, R and Kang, X},
title = {High flavonoid diet alleviates chronic stress in cancer patients by optimization of the gut microbiota.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5fo02560e},
pmid = {41036738},
issn = {2042-650X},
abstract = {Scope: Cancer patients face long-term psychological stress due to the fear of death, economic burden, and pain caused by the disease. The aim of this study is to explore the effects of flavonoid diets on chronic stress in cancer patients. Methods and results: In this study, cancer patients were subjected to a high flavonoid diet (n = 15) or normal diet (n = 15). Their chronic stress status, quality of life and immune function were evaluated at the beginning and end of a 12-week diet intervention. The high flavonoid diet significantly alleviated anxiety, depression, and perceived stress in cancer patients (p < 0.05). The stress indicators in their plasma and saliva also decreased after the flavonoid diet (p < 0.05). The anxiety and depression behaviors of mice improved after receiving fecal microbiota transplantation from cancer patients receiving a high flavonoid diet (p < 0.05). The distribution of the gut microbiota changed, and butyric acid levels increased significantly in the FMT mice from the high flavonoid group (p < 0.05). The selected components of flavonoid (quercetin) caused similar changes in the behavioral experiments and gut microbiota of chronic stress mice. Conclusion: High levels of flavonoid intake can significantly improve the chronic stress status and quality of life of cancer patients, and the effects may be mediated by the optimization of the gut microbiota and their metabolites.},
}

@article {pmid41036224,
year = {2025},
author = {Liu, T and Ou, G and Wu, J and Wang, S and Wang, H and Wu, Z and Jiang, Y and Chen, Y and Xu, H and Deng, L and Chen, X and Xu, L},
title = {Pingwei Powder alleviates high-fat diet-induced colonic inflammation by modulating microbial metabolites SCFAs.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1628488},
pmid = {41036224},
issn = {2235-2988},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diet, High-Fat/adverse effects ; *Fatty Acids, Volatile/metabolism ; Colon/pathology/drug effects/microbiology ; *Colitis, Ulcerative/drug therapy ; Male ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice ; Cytokines/metabolism ; Disease Models, Animal ; Signal Transduction/drug effects ; Powders ; Mice, Inbred C57BL ; Bacteria/metabolism/classification/genetics ; Inflammation/drug therapy ; RNA, Ribosomal, 16S/genetics ; TOR Serine-Threonine Kinases/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; },
abstract = {BACKGROUND: Pingwei Powder (PWP), a renowned traditional Chinese medicine (TCM) formula, it has demonstrated excellent therapeutic effects in ulcerative colitis (UC), yet its underlying pharmacological mechanisms remain unclear. This study aims to investigate the therapeutic effect of PWP on the aggravation of colonic inflammation induced by a high-fat diet and particularly focuses on its regulatory mechanisms on gut microbiota, which are closely related to UC.

METHODS: Network pharmacology analysis was employed to screen potential pharmacological targets of PWP for UC. Histological changes in colonic tissue were observed using hematoxylin and eosin (H&E) staining, and immunofluorescence staining was performed to evaluate the expression of tight junction proteins (ZO1 and Occludin). Western blotting was used to detect the expression levels of proteins related to the PI3K/AKT/mTOR pathway, ZO1, and Occludin. qRT-PCR was conducted to measure the relative expression of inflammatory cytokines (IL-1β, IL-17, IL-6, and TNF-α) in colonic tissue. Additionally, 16S rDNA sequencing was performed to analyze gut microbiota alterations, and GC/MS was used to quantify short-chain fatty acids (SCFAs) in gut contents. The gutMgene database was utilized to validate the mediating roles of gut microbiota metabolites in the pharmacological effects of PWP. And their mediating role in PWP efficacy was verified by fecal microbiota transplantation (FMT) and butyrate supplementation.

RESULTS: Network pharmacology analysis predicted that PWP may regulate the PI3K/AKT pathway to exert therapeutic effects in UC. Experimental validation showed that PWP significantly downregulated the levels of PI3K, pAKT/AKT, and pmTOR/mTOR in colonic tissue, thereby enhancing autophagy in colonic epithelial cells, as evidenced by decreased levels of P62 and increased LC3B-II/LC3B-I ratios. Furthermore, 16S rDNA sequencing combined with targeted SCFAs analysis of gut contents revealed that the pharmacological effects of PWP may be mediated by increasing the abundance of SCFAs-producing gut microbiota (Alistipes and Parabacteroides) and elevating the levels of SCFAs in the gut.

CONCLUSION: PWP enhances the abundance of SCFAs-producing bacteria (Alistipes and Parabacteroides) in the gut, increases the levels of butyrate, and inhibits the PI3K/AKT/mTOR pathway in the colon. These effects promote colonic autophagy and contribute to the resolution of colonic inflammation.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Diet, High-Fat/adverse effects
*Fatty Acids, Volatile/metabolism
Colon/pathology/drug effects/microbiology
*Colitis, Ulcerative/drug therapy
Male
*Drugs, Chinese Herbal/pharmacology/therapeutic use
Mice
Cytokines/metabolism
Disease Models, Animal
Signal Transduction/drug effects
Powders
Mice, Inbred C57BL
Bacteria/metabolism/classification/genetics
Inflammation/drug therapy
RNA, Ribosomal, 16S/genetics
TOR Serine-Threonine Kinases/metabolism
Phosphatidylinositol 3-Kinases/metabolism

@article {pmid41035886,
year = {2025},
author = {Tayyab, M and Zhao, Y and Zhang, Y},
title = {Microbiome engineering to enhance disease resistance in aquaculture: current strategies and future directions.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1625265},
pmid = {41035886},
issn = {1664-302X},
abstract = {Aquaculture, a cornerstone of global food security, faces critical threats from disease outbreaks, antimicrobial resistance, and ecological disruption. Through a narrative analysis of over 160 studies, this review synthesizes advances in microbiome engineering-a sustainable approach to enhancing disease resistance in aquatic animals-addressing key gaps: the inconsistent efficacy of conventional probiotics and prebiotics under field conditions, and the need for climate-resilient solutions. Critically, we highlight the emergence of precision microbiome engineering as a transformative paradigm. We integrate findings from genomics, metabolomics, clustered regularly interspaced short palindromic repeats, and artificial intelligence to identify microbial strategies that enhance host resilience. Genomic and multi-omics methods reveal health-associated microbes and metabolites, such as Vibrio-dominated dysbiosis markers in shrimp and butyrate-mediated immunity. Guided by these biomarkers, we describe precision-tailored probiotics-host-derived or genome-edited Bacillus subtilis strains whose adhesion factors, metabolic outputs (e.g., butyrate, bacteriocins), and heat stress tolerance are matched to the target species' gut niche. These are combined with complementary prebiotics (e.g., chitosan oligosaccharides) and synbiotics (e.g., Lactiplantibacillus plantarum plus king oyster mushroom extracts) that suppress pathogens through competitive exclusion and immune modulation. Ecologically rational innovations-interventions explicitly grounded in ecological theory (niche complementarity, K-selection) to stabilize resource-efficient microbiomes-such as fecal microbiota transplantation and synthetic consortia, demonstrate further disease control potential. Our synthesis reveals that translating microbiome engineering from laboratory to farm requires overcoming host-microbiome compatibility challenges and ecological risks. Policy alignment with the United Nations Sustainable Development Goals-Zero Hunger (Sustainable Development Goal 2), Climate Action (Sustainable Development Goal 13), and Life Below Water (Sustainable Development Goal 14)-is critical for sustainable adoption.},
}

@article {pmid41035652,
year = {2025},
author = {Kalopedis, EA and Zorgani, A and Zinovkin, DA and Barri, M and Wood, CD and Pranjol, MZI},
title = {Leveraging the role of the microbiome in endometriosis: novel non-invasive and therapeutic approaches.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1631522},
pmid = {41035652},
issn = {1664-3224},
mesh = {Humans ; *Endometriosis/therapy/microbiology/immunology/diagnosis/metabolism/etiology ; Female ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/therapy/immunology/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; Lactobacillus ; Biomarkers ; },
abstract = {Endometriosis (EMS) is an oestrogen-dependent condition characterised by ectopic endometrial-like tissue growth with a chronic and inflammatory nature leading to severe symptoms and reduced quality of life. Emerging evidence implicates gut microbiome dysbiosis in EMS pathogenesis, driving chronic inflammation, immune dysfunction, and altered bacterial taxa within patient gut microbiome. This review examines the intricate relationship between gut dysbiosis and EMS, with a focus on immunomodulatory mechanisms and the downstream consequences of the bacterial contamination theory. It evaluates recent findings regarding microbial imbalances and microbial diversity, pinpointing gaps in current research that mandate further understanding. For example, while microbial markers like Lactobacillus depletion and elevated Escherichia coli have been observed in patients, their diagnostic potential remains poorly defined. Additionally, it addresses the broader implications of EMS, including its physical, mental and healthcare burdens. Simultaneously, critiquing current drawbacks in diagnostic and therapeutic strategies such as their invasiveness and limited efficacy. The review further evaluates novel microbiome-based strategies namely Lactobacillus-based probiotics and faecal microbiota transplantation (FMT), assessing their potential in modulating immune responses and alleviating EMS symptoms while considering associated challenges. Lastly, it highlights the emerging role of metabolomics in identifying non-invasive and diagnostic biomarkers like short-chain fatty acids (SCFAs), implicated in the interplay between microbial metabolites and immune signalling pathways in EMS.},
}

Humans
*Endometriosis/therapy/microbiology/immunology/diagnosis/metabolism/etiology
Female
*Gastrointestinal Microbiome/immunology
Dysbiosis/therapy/immunology/microbiology
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Animals
Lactobacillus
Biomarkers

@article {pmid41035378,
year = {2025},
author = {Zhang, Q and Cui, J and Hou, Y and Guo, L and Li, H and Zhou, G and Wang, X and Zhu, B and Shi, K and Zhang, Y and Bi, Y and Li, Y and Sun, L and Feng, Y and Yuan, J and Wang, X},
title = {Alterations in Gut Microbiota and Metabolism in Cirrhotic Portal Hypertension: Implications for Disease Progression.},
journal = {Alimentary pharmacology & therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1111/apt.70392},
pmid = {41035378},
issn = {1365-2036},
support = {7232272//the Beijing Municipal Natural Science Foundation/ ; BJZYYB-2023-06//the Beijing Traditional Chinese Medicine Technology Development Fund Project/ ; 81774234//the National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Although gut microbiota has been implicated in various liver disorders, its relationship with cirrhotic portal hypertension (CPH) remains unclear.

AIMS: To investigate the structural and functional alterations of gut microbiota in patients with CPH and the potential role of these alterations in the progression of CPH.

METHODS: We collected faecal samples from 35 patients with CPH and 71 patients without CPH (controls) to conduct microbiome and metabolomic analyses. Gut microbes, faecal metabolites and their functional pathways associated with CPH were identified using multiple bioinformatics approaches. To understand the role of gut microbiota in the pathogenesis of CPH, we carried out faecal microbiota transplantation, CPH-characteristic bacterial transplantation and antibacterial experiments in mice.

RESULTS: Microbial diversity was diminished, and gut microbial structures were altered in patients with CPH compared to the controls, primarily manifested as increased abundance of lipopolysaccharide-producing bacteria and decreased abundance of anti-inflammatory bacteria. This dysbiosis of gut microbiota was accompanied by changes in the faecal metabolome, particularly in arginine biosynthesis and nitric oxide production. Transplantation of gut microbiota from CPH patients, as well as the transplantation of CPH-associated bacteria Veillonella nakazawae, was found to exacerbate CPH progression in mice. Antibiotic treatment significantly alleviated the CPH progression induced by N-dimethylnitrosamine in mice.

CONCLUSIONS: Our study reveals that gut microbiota dysbiosis is implicated in CPH progression, potentially providing new avenues for microbiome-based treatment for CPH.},
}

@article {pmid41035224,
year = {2025},
author = {Farini, A and Strati, F and Molinaro, M and Mostosi, D and Saccone, S and Tripodi, L and Troisi, J and Landolfi, A and Amoroso, C and Cassani, B and Blanco-Míguez, A and Leonetti, E and Bazzani, D and Bolzan, M and Fortunato, F and Caprioli, F and Facciotti, F and Torrente, Y},
title = {Immunoproteasome Inhibition Positively Impacts the Gut-Muscle Axis in Duchenne Muscular Dystrophy.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {16},
number = {5},
pages = {e70054},
doi = {10.1002/jcsm.70054},
pmid = {41035224},
issn = {2190-6009},
support = {M6/C2_CALL 2022//PNRR/ ; FRRB-2022//Unmet Medical Needs, Fondazione Regionale per la Ricerca Biomedica/ ; GJC21084//Cariplo Telethon Alliance GJC2021-2022/ ; //NextGenerationEU/ ; //MUR/ ; PR-0394//Gruppo familiari beta-sarcoglicanopatie/ ; PNC-E3-2022-23683266-CUP: C43C22001630001//Hub Life Science-Diagnostica Avanzata/ ; //Associazione Centro Dino Ferrari/ ; },
mesh = {Animals ; *Muscular Dystrophy, Duchenne/drug therapy/metabolism/pathology ; Mice ; Gastrointestinal Microbiome/drug effects ; *Proteasome Inhibitors/pharmacology/therapeutic use ; *Muscle, Skeletal/drug effects/metabolism ; Disease Models, Animal ; Mice, Inbred mdx ; Male ; *Proteasome Endopeptidase Complex/metabolism ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Duchenne Muscular Dystrophy (DMD) features immune-muscle crosstalk, where muscle fibre degeneration enhances pro-inflammatory macrophage infiltration, worsening inflammation and impairing regeneration.

METHODS: We investigated the impact of immunoproteasome (IP) inhibition on the gut-muscle axis in mdx mice, a well-established model of DMD. We employed microbiota perturbation models, including broad-spectrum antibiotic treatment (ABX) and faecal microbiota transplantation (FMT) from IP-inhibited mdx mice. IP inhibition effects were assessed by analysing gut microbiota composition, intestinal inflammation, muscle integrity and associated metabolic and inflammatory pathways.

RESULTS: IP inhibitor ONX-0914 significantly impacted the intestinal inflammatory microenvironment and gut microbiota of mdx mice. ONX-0914 treatment increased gastrointestinal transit (increased wet/dry faecal weights, p = 0.0486 and p = 0.0112, respectively) and partially restored intestinal barrier integrity (reduced FITC-dextran leakage, p = 0.0449). JAM-A was significantly upregulated (p < 0.0001). Colonic CD206+ M2 macrophages increased, while CD68 + M1 cells partially decreased. ONX-0914 downregulated IP isoforms in macrophages (PSMB8: p = 0.0022; PSMB9: p = 0.0186) as well as FOXO-1 (p = 0.0380) and TNF-α (p = 0.0487). Antibiotic-induced microbiota depletion abrogated these effects. Metagenomic analysis revealed significant differences in microbiota composition between C57Bl controls and mdx mice (PERMANOVA p < 0.001), with ONX-0914 inducing enrichment of stachyose degradation pathways. Metabolomic analysis showed enrichment of bacterial metabolites, fatty acid and sugar metabolism pathways, with increased glutathione, galactose, glycerol, glyceraldehyde and TCA cycle intermediates. ONX-0914 improved mitochondrial activity in skeletal muscle, as increased expression of ETC complexes (mdx vs. mdx+ONX: Complex II, p = 0.0338; Complex IV, p = 0.0023) and TCA enzymes (mdx vs. FTMmdx+ONX: IDH p = 0.0258; FH p = 0.0366). This led to a shift towards oxidative muscle fibres and improved muscle morphology (increased fibre size, p < 0.0001 mdx vs. mdx+ONX and mdx vs. FTMmdx+ONX). Muscle performance was enhanced with reduced CPK levels (p = 0.0015 mdx vs. mdx+ONX) and fibrosis (decreased TGFβ: mdx vs. mdx+ONX, p = 0.0248; mdx vs. FTMmdx+ONX, p = 0.0279). ONX-0914 reduced CD68+ (mdx vs. mdx+ONX, p = 0.0024; mdx vs. FTMmdx+ONX, p < 0.0001) and increased CD206+ (mdx vs. FTMmdx+ONX: p = 0.0083) macrophages in muscle, downregulated inflammatory genes (mdx vs. mdx+ONX: ccl2 p = 0.0327, vcam-1p = 0.0378) and reduced pro-inflammatory proteins (MCP1, mdx vs. mdx+ONX, p = 0.0442). Inflammatory cytokines and endothelial vessel density in ONX-0914 treated mdx were restored to wild type mice. These data demonstrate that ONX-0914 enhances muscle function through microbiota-dependent mechanisms.

CONCLUSIONS: Our study advances the understanding of the role of dysbiosis in DMD disease and identifies IP inhibition as a potential therapeutic strategy to modulate the dystrophic gut-muscle axis, offering new perspectives for microbiota-targeted therapies.},
}

Animals
*Muscular Dystrophy, Duchenne/drug therapy/metabolism/pathology
Mice
Gastrointestinal Microbiome/drug effects
*Proteasome Inhibitors/pharmacology/therapeutic use
*Muscle, Skeletal/drug effects/metabolism
Disease Models, Animal
Mice, Inbred mdx
Male
*Proteasome Endopeptidase Complex/metabolism
Mice, Inbred C57BL

@article {pmid41033875,
year = {2025},
author = {Kopple, JD and Bross, R and Ekramzadeh, M and Markovic, D and Lyzlov, A and Lodebo, BT and Mehrotra, R and Shah, AP},
title = {Lanthanum carbonate lowers serum phosphorus without altering body phosphorus burden in maintenance peritoneal dialysis patients: a randomized crossover trial.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2025.08.015},
pmid = {41033875},
issn = {1938-3207},
abstract = {BACKGROUND: Many studies show that intestinal phosphate binders reduce serum phosphorus concentrations in hyperphosphatemic patients with chronic kidney failure. To our knowledge, there are virtually no studies of the effect of these binders on fecal phosphate or body phosphate.

OBJECTIVES: This study examined the hypothesis that phosphate binders increase fecal phosphate and reduce body phosphorus burden.

METHODS: Seven adult patients undergoing maintenance peritoneal dialysis underwent full metabolic balance studies for phosphorus in a research ward while they ate a constant phosphorus diet. Patients were studied during a baseline period without phosphate binders and while they received, in random order, 3 doses of lanthanum carbonate (La2(CO3)3), 1.5, 3.0, and 4.5 g/d, in 3 divided daily doses for ∼12-14 d each. The total duration of study was 47-49 d in each patient. Dialysate, urine, and feces were collected continuously and serum intermittently for phosphorus measurements.

RESULTS: Serum phosphorus concentrations fell progressively and significantly as the La2(CO3)3 dose was increased (r = -0.47, P < 0.001). Fecal phosphorus concentrations rose progressively as La2(CO3)3 increased (r = 46.4, P < 0.001). However, there was a negative correlation between both dialysate (r = -17.2, P = 0.002) and urine (r = -18.5, P < 0.001) phosphorus and La2(CO3)3 dose. This decline in dialysate and urine phosphorus correlated with the fall in serum phosphorus concentration as the La2(CO3)3 dose increased. As the La2(CO3)3 dose rose, the increase in fecal phosphorus concentration was essentially counterbalanced by the fall in dialysate and urine phosphorus. Hence, body phosphorus balance did not change with increasing La2(CO3)3 doses.

CONCLUSIONS: La2(CO3)3 treatment lowered serum phosphorus concentration but did not change body phosphorus content. This trial was registered at clinicaltrials.gov as NCT01581996.},
}

@article {pmid41033511,
year = {2025},
author = {Bian, S and Zhu, S and Lu, J and Iqbal, M and Jamil, T and Kiani, FA and Dong, H and Dai, H and Zhang, X and Liu, F and Li, A},
title = {Targeting gut microbiota in non-alcoholic fatty liver disease (NAFLD): Pathogenesis and therapeutic insights: A review.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {147995},
doi = {10.1016/j.ijbiomac.2025.147995},
pmid = {41033511},
issn = {1879-0003},
abstract = {Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by hepatic steatosis associated with insulin resistance, oxidative stress, inflammatory responses, and other factors. The precise pathogenesis of NAFLD remains unclear. Although it has emerged as a global health burden, current therapeutic options for example, probiotics, prebiotics, synbiotics and fecal microbiota transplantation (FMT) have shown promising but varied efficacy. Moreover, use of traditional Chinese medicine (TCM) in NAFLD patients, has gained growing attention for its multi-targeted regulatory properties and several natural product formulations and their beneficial impacts on gut microbiota, lipid metabolism and hepatic health. The article highlights the role of gut microbiota dysbiosis in the pathogenesis of NAFLD and explores the therapeutic strategies emphasizing the need of personalized multimodal approaches and robust clinical trials to validate these interventions.},
}

@article {pmid41032750,
year = {2025},
author = {Gurer Kluge, EE and Meedt, E and Feicht, J and Cao, K and Hiergeist, A and Mamilos, A and Hirsch, D and Hoepting, M and Kattner, AS and Matos, C and Bülow, S and Thiele Orberg, E and Beckhove, P and Kandulski, A and Evert, M and Hildner, K and Kreutz, M and Edinger, M and Wolff, D and Herr, W and Poeck, H and Gessner, A and Weber, DA and Kehr, B and Holler, E and Ghimire, S},
title = {Mucosal calprotectin is associated with severity of aGI-GVHD and poor outcomes after allogeneic stem cell transplantation.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025029402},
pmid = {41032750},
issn = {1528-0020},
abstract = {Calprotectin, a calcium- and zinc-binding protein composed of the subunits S100A8 and S100A9, has been extensively studied as a biomarker of gastrointestinal (GI) inflammation through fecal and serum analyses. However, its role in intestinal tissue remains poorly understood due to limited availability of biopsies. In this study, we analyzed S100A8 and S100A9 mRNA expression in 579 intestinal biopsies from allogeneic stem cell transplant (ASCT) patients and observed a strong association with acute GI graft-versus-host disease (aGI-GvHD) (p<0.001). Neutrophil infiltration correlated with the severity of aGI-GvHD (p<0.001), and calprotectin expression was strongly linked to Toll-like receptor 4 (TLR4) (p<0.001) and TLR2 (p<0.001) expression. TLR4 and aGI-GvHD were associated with elevated calprotectin mRNA levels (p<0.001). When patients received broad-spectrum antibiotics at disease onset, expression of calprotectin was suppressed (S100A8, p=0.001; S100A9, p=0.01). Gastrointestinal site-specific differences in calprotectin expression were identified: during severe aGI-GvHD, levels increased up to 30-fold in the small intestine and up to 5-fold in the large intestine with respect to mild/no aGI-GVHD, while under homeostasis, the large intestine exhibited higher baseline calprotectin (p=0.001). The high clinical relevance is evident from the observation that calprotectin expression was prognostic for transplant-related mortality (TRM). Our study suggests that (a) calprotectin is a potential biopsy biomarker in aGI-GvHD, (b) calprotectin expression and neutrophil infiltration possibly indicate translocation of microbiota, which (c) may be modulated by antibiotics.},
}

@article {pmid41031618,
year = {2025},
author = {Xu, F and Yue, Y and Sun, D},
title = {Mechanism of the AMPK/SIRT1 pathway in gut dysbiosis-mediated postoperative cognitive dysfunction in aged mice.},
journal = {The international journal of neuropsychopharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1093/ijnp/pyaf066},
pmid = {41031618},
issn = {1469-5111},
abstract = {OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a prevalent complication in older patients who undergo surgery that requires anesthesia. This study explored the role of the AMPK/SIRT1 pathway in gut dysbiosis-mediated POCD in aged mice.

METHODS: POCD was induced in aged male mice via open tibial fracture surgery under isoflurane anesthesia. Mice then received the probiotic VSL#3, the SIRT1 inhibitor EX527, and the AMPK/SIRT1 activator resveratrol. Fecal microbiota transplantation was conducted in aged POCD mice. Mouse cognitive function was assessed using the Morris water maze and novel object recognition tests. Mouse histopathological changes were observed via HE staining. Iba1+/GFAP+ activation was assessed via immunofluorescence, and pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 [IL]-1β, IL-6) in the hippocampus were determined via ELISA. Gut microbiota compositions were detected via 16S rRNA sequencing. Hippocampal pAMPK/AMPK and SIRT1 levels were assessed by western blot.

RESULTS: Aged POCD mice exhibited prolonged escape latency, reduced platform crossings, and an impaired object discrimination rate on postoperative day 7. Severe hippocampal CA1 damage, increased Iba1+/GFAP+ cell numbers, elevated pro-inflammatory cytokines, and gut dysbiosis were also observed. The probiotic VSL#3 ameliorated gut dysbiosis, alleviated POCD, and reduced neuroinflammation. Gut microbiota from POCD mice exacerbated cognitive deficits and neuroinflammation in aged mice, while clearance of gut microbiota improved outcomes. VSL#3 improved POCD in aged mice by balancing gut microbiota through the AMPK/SIRT1 pathway. The AMPK/SIRT1 pathway activation mitigated POCD.

CONCLUSION: VSL#3 balanced gut microbiota and suppressed neuroinflammation in hippocampal CA1 region by activating the AMPK/SIRT1 pathway, thereby alleviating POCD in aged mice.},
}

@article {pmid41030553,
year = {2025},
author = {Xie, H and Zhu, S and Xue, P and Xie, F and Zhao, L and Chu, X},
title = {Yanggan Yizhong decoction prevents liver metastasis from colorectal cancer by targeting myeloid-derived suppressor cells through the regulation of bile acid metabolism in the gut microbiota.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1639442},
pmid = {41030553},
issn = {1664-302X},
abstract = {INTRODUCTION: Liver metastasis (LM) exhibits a high incidence in colorectal cancer (CRC), yet effective preventive therapies are still lacking. Based on the prophylactic principle of harmonizing the liver and spleen, Yanggan Yizhong (YGYZ) decoction has shown clinical effectiveness in preventing LM. This study aims to explore the active components and underlying mechanisms of YGYZ in the prevention and treatment of LM.

METHODS: The components of YGYZ were analyzed using Ultra-High Performance Liquid Chromatography coupled with High-Resolution Tandem Mass Spectrometry (UPLC-HR-MS/MS). The LM mouse model was established through intrasplenic injection of ct26-luc cells to evaluate the effect and safety of YGYZ on LM. Fecal microbiota transplantation (FMT) was performed to create microbiota-altered mice, and liver tissue morphology along with HE staining was utilized to dynamically monitor LM progression. Flow cytometry and inflammatory factor assays were conducted to assess the immune microenvironment (IME) of the liver pre-metastatic niche (PMN). Additionally, 16S rRNA sequencing and bile acid (BA) metabolomics were employed to investigate the role of YGYZ in modulating gut microbiota (GM) and BA. Western blot analysis was performed to identify key targets of YGYZ in the GM-BA-immunity pathway.

RESULTS: UPLC-HR-MS/MS analysis identified 95 compounds in YGYZ, Glycyrrhizic acid, Bergapten, and Icariin as the main compounds. YGYZ and its FMT inhibited LM of CRC with safety, inhibited CD11b+Ly6G+ and CD11b+Ly6C+ cells in the pre-metastatic stage, decreased CD11b+Ly6G+ cells in the metastatic stage, reduced immunosuppressive factors such as Arg-1, TGF-β, and IL-10, and improved the CD4+/CD8+ T-cell ratio, regulating liver PMN. YGYZ also improved the GM structure, particularly decreasing the abundance of Clostridium in the LM mice. For the hepatic BAs profile, YGYZ increased the content of primary BAs-Nor cholic acid (NorCA), Taurocholic acid, Taurochenodeoxycholic Acid, and Tauro β-Muricholic Acid, and secondary BAs-ursodeoxycholic acid (UDCA), with similar trends in FMT, while YGYZ decreased NorCA, α-Muricholic acid, Tauro α-Muricholic acid, and UDCA in the fecal BA profile. YGYZ and its FMT dampened the protein expression of IL-6, STAT3, and pSTAT3, but only YGYZ downregulated kruppel-like factor 15 (KLF15).

CONCLUSION: YGYZ may prevent LM by remodeling the GM and synergistically inhibiting KLF15 to regulate the enterohepatic BA cycle, and suppressing the proliferation and activation of myeloid-derived suppressor cells through the IL-6/STAT3 pathway, thereby improving IME of liver PMN.},
}

@article {pmid41030253,
year = {2025},
author = {Bautista, J and Villegas-Chávez, JA and Bunces-Larco, D and Martín-Aguilera, R and López-Cortés, A},
title = {The microbiome as a therapeutic co-driver in melanoma immuno-oncology.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1673880},
pmid = {41030253},
issn = {2296-858X},
abstract = {Melanoma, one of the most aggressive skin cancers, remains a major clinical challenge due to its high metastatic potential, therapy resistance, and rising global incidence. Although immune checkpoint inhibitors have transformed management, variable responses and acquired resistance limit durable benefit. Emerging evidence positions the microbiome as a pivotal determinant of melanoma biology and therapeutic outcomes. Dysbiosis in the skin, gut, and oral compartments fosters tumor-promoting inflammation, immune evasion, and oncogenic signaling, whereas enrichment of specific commensals, such as Akkermansia muciniphila and Faecalibacterium prausnitzii, enhances antigen presentation and effector T cell activity, improving ICI efficacy. Mechanistically, microbial metabolites, including short-chain fatty acids, tryptophan derivatives, and bile acids, modulate epigenetic programs, G-protein-coupled receptor signaling, and oncogenic cascades such as PI3K-AKT and RAS-RAF-MEK-ERK. Beyond the gut, cutaneous microbiota such as Staphylococcus epidermidis exert direct antitumor effects, while pathogenic oral taxa propagate systemic inflammation that shapes the melanoma tumor microenvironment. These insights are driving the development of microbiome-targeted interventions, including fecal microbiota transplantation, defined consortia, probiotics, and dietary modulation, with early clinical studies showing the potential to overcome resistance to immunotherapy. Integration of circadian biology further suggests that host-microbiome-immune interactions are temporally regulated, opening new dimensions for therapeutic optimization. By synthesizing mechanistic, clinical, and translational advances, this review highlights the microbiome as both a biomarker and a therapeutic axis in melanoma, underscoring its promise to transform precision immuno-oncology.},
}

@article {pmid41028942,
year = {2025},
author = {Ma, S and Li, X and Shang, S and Zhai, Z and Wu, M and Song, Q and Chen, D},
title = {Targeting gut microbiota and metabolites in cancer radiotherapy.},
journal = {Clinical and translational medicine},
volume = {15},
number = {10},
pages = {e70481},
doi = {10.1002/ctm2.70481},
pmid = {41028942},
issn = {2001-1326},
mesh = {Humans ; *Gastrointestinal Microbiome/radiation effects/drug effects/physiology/immunology ; *Neoplasms/radiotherapy ; *Radiotherapy/methods/adverse effects ; Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation/methods ; },
abstract = {Radiotherapy (RT) is a cornerstone in cancer treatment, but often causes radiation-induced injury. Accumulating evidence points to the gut microbiota in modulating immune functions and maintaining intestinal integrity to impact RT efficacy. This review examines the current understanding of intestinal flora and their metabolites within the context of RT. We outlined the current research applications in how microbiota-targeted strategies such as probiotics, prebiotics, dietary interventions, and faecal microbiota transplantation could restore microbial balance, reduce toxicity, and improve patient prognosis. Microbial byproducts such as short-chain fatty acids, bile acids and tryptophan exhibit protective effects against radiation damage, supporting immune modulation and enhancing tumour radiosensitivity. These microbial products underscore the potential of gut microbiota-targeted therapies as adjunctive treatments in RT, with implications for reducing toxicity and personalizing cancer care. All these strategies targeting gut microbiota and metabolites potentially aim to develop innovative therapies that boost RT effectiveness while minimizing side effects, and finally revolutionizing personalized cancer treatment. KEY POINTS: RT alters gut microbiota composition and contributes to intestinal injury and systemic toxicity. Gut microbiota regulate mucosal integrity, immune responses and therapeutic outcomes of RT. Microbial metabolites, including SCFAs, BAs and tryptophan derivatives, protect against radiation injury and enhance tumour radiosensitivity. Microbiota-targeted interventions (e.g. probiotics, prebiotics, dietary strategies, FMT) show promise for reducing RT-related toxicity and improving patient prognosis.},
}

Humans
*Gastrointestinal Microbiome/radiation effects/drug effects/physiology/immunology
*Neoplasms/radiotherapy
*Radiotherapy/methods/adverse effects
Probiotics/therapeutic use
Prebiotics
Fecal Microbiota Transplantation/methods

@article {pmid41028744,
year = {2025},
author = {Chen, C and Su, Q and Zi, M and Hua, X and Zhang, Z},
title = {Harnessing gut microbiota for colorectal cancer therapy: from clinical insights to therapeutic innovations.},
journal = {NPJ biofilms and microbiomes},
volume = {11},
number = {1},
pages = {190},
pmid = {41028744},
issn = {2055-5008},
mesh = {Humans ; *Colorectal Neoplasms/therapy/microbiology ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; Fusobacterium nucleatum ; },
abstract = {Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality worldwide, yet improvements in survival have been modest despite advances in conventional therapies. The gut microbiota has emerged as a critical player in CRC pathogenesis and a promising therapeutic target to enhance clinical outcomes. Mounting evidence implicates specific microorganisms, notably Escherichia coli, Fusobacterium nucleatum, and Bacteroides fragilis, in tumor initiation and progression through DNA damage, inflammatory modulation, and immunosuppressive mechanisms. Clinical trials investigating microbiome modulators-including faecal microbiota transplantation, probiotics, prebiotics, and engineered biotherapeutics-highlight their potential to augment chemotherapy, radiotherapy, immunotherapy, and surgical recovery, with encouraging preliminary efficacy in treatment-resistant CRC subtypes. Nonetheless, translating microbiome interventions into standardized clinical practice requires rigorous mechanistic validation, robust biomarker development, and careful management of safety concerns. Future research must focus on integrating high-resolution multi-omics, spatial microbiome mapping, artificial intelligence analytics, and innovative microbiome-targeted nanotechnologies to precisely reshape gut microbial communities, thereby ushering in a new era of precision oncology in colorectal cancer management.},
}

Humans
*Colorectal Neoplasms/therapy/microbiology
*Gastrointestinal Microbiome
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Prebiotics/administration & dosage
Fusobacterium nucleatum

@article {pmid41027059,
year = {2025},
author = {Shan, R and Wang, K and Chen, Q and Bao, L and Wu, K and Zhao, Y and Han, Y and Gao, Y and Zhang, N and Hu, X and Fu, Y and Zhao, C and Bian, W},
title = {Phytosphingosine alleviates DSS-induced colitis by regulating the gut microbiota and inflammatory responses.},
journal = {International immunopharmacology},
volume = {166},
number = {},
pages = {115610},
doi = {10.1016/j.intimp.2025.115610},
pmid = {41027059},
issn = {1878-1705},
abstract = {Inflammatory bowel disease is becoming increasingly prevalent and represents a major concern in global public health. However, conventional therapies often come with various adverse effects. Phytosphingosine (PS), a key metabolite in sphingolipid metabolism, is widely found in plants and fungi and possesses notable anti-inflammatory properties. In this study, we aimed to evaluate the protective effects of PS against dextran sulfate sodium (DSS)-induced experimental colitis in mice and elucidate its underlying mechanisms. Our results showed that oral administration of PS significantly alleviated DSS-induced colonic injury and reduced levels of proinflammatory cytokines such as TNF-α and IL-1β. Additionally, PS improved intestinal barrier function disrupted by DSS, as indicated by increased expression of mucin-2 and tight junction proteins. Furthermore, PS suppressed the activation of the NF-κB signaling pathway, oxidative stress and enhanced PPARγ expression. We also observed that PS mitigated DSS-induced gut dysbiosis in mice, characterized by an increase in Bacteroidota and a decrease in Proteobacteria. To explore the role of the gut microbiota in PS-mediated protection against colitis, fecal microbiota transplantation (FMT) was conducted in DSS-treated mice. Recipients of FMT from PS-treated donors exhibited reduced inflammatory responses and improved intestinal integrity, accompanied by a higher abundance of Bacteroidota in the gut. Additionally, PS treatment modified the profile of short-chain fatty acids in the mice, with a notable increase in the levels of butyrate and propionate. Overall, our findings demonstrate that PS attenuates DSS-induced colitis in mice through modulation of the gut microbiota, providing a potential strategy for IBD intervention via microbiota regulation.},
}

@article {pmid41024986,
year = {2025},
author = {Singla, N and Singla, K and Attauabi, M and Aggarwal, D},
title = {Gut-skin axis: Emerging insights for gastroenterologists-a narrative review.},
journal = {World journal of gastrointestinal pathophysiology},
volume = {16},
number = {3},
pages = {108952},
pmid = {41024986},
issn = {2150-5330},
abstract = {The gut-skin axis (GSA) embodies a complex, bidirectional interaction between the gastrointestinal (GI) system and skin, driven by immune modulation, systemic inflammation, and gut microbiota dynamics. Disruptions in gut homeostasis, including dysbiosis and increased intestinal permeability, are increasingly recognized as contributing factors to dermatological conditions such as acne, psoriasis, and atopic dermatitis. For gastroenterologists, appreciating this interplay is essential, as diseases and their treatments frequently present with cutaneous manifestations, offering diagnostic and therapeutic insights. This review explores the underlying mechanisms of the GSA, focusing on the microbiome and its metabolites as key regulators of inflammation and immunity. It underscores the clinical importance of microbiome-targeted therapies, such as probiotics, prebiotics, and dietary modifications, in addressing both GI and dermatological disorders. Furthermore, the review examines the influence of GI conditions, including inflammatory bowel disease and celiac disease on skin health. This article seeks to equip gastroenterologists with practical insights for identifying, diagnosing, and managing skin conditions associated with GI health. The article also highlights the current limitations in knowledge regarding the GSA. The GSA represents a promising avenue for therapeutic advancements, encouraging interdisciplinary collaboration between gastroenterology and dermatology to optimize patient care.},
}

@article {pmid41024984,
year = {2025},
author = {Marano, G and Anesini, MB and Milintenda, M and Acanfora, M and d'Abate, C and Lisci, FM and Pirona, I and Traversi, G and Pola, R and Gaetani, E and Mazza, M},
title = {Discovering a new paradigm: Gut microbiota as a central modulator of sexual health.},
journal = {World journal of gastrointestinal pathophysiology},
volume = {16},
number = {3},
pages = {107823},
pmid = {41024984},
issn = {2150-5330},
abstract = {The gut microbiota plays a pivotal role in human health, influencing diverse physiological processes, including those related to sexual health. Emerging evidence suggests a bidirectional relationship between the gut microbiota and sexual health, mediated by its impact on systemic inflammation, hormonal regulation, and immune function. A balanced gut microbiota supports optimal levels of sex hormones, such as estrogen and testosterone, which are critical for sexual function and reproductive health. Additionally, gut-derived metabolites such as short-chain fatty acids contribute to maintaining mucosal barrier integrity and regulating immune responses, which are essential for protecting against infections that may impair sexual health. Conversely, dysbiosis, an imbalance in gut microbial composition, has been linked to conditions such as erectile dysfunction, polycystic ovary syndrome, and reduced libido, emphasizing its role in sexual dysfunction. Lifestyle factors, including diet, stress, and antibiotic use, can modulate the gut microbiota and, consequently, sexual health outcomes. Recent therapeutic approaches, such as probiotics, prebiotics, and fecal microbiota transplantation, offer potential for restoring gut balance and improving sexual health. This review highlights the central role of the gut microbiota in sexual health, emphasizing its importance as a target for therapeutic interventions to enhance overall well-being.},
}

@article {pmid41024883,
year = {2025},
author = {Abdelwahab, MM and Ghattas, AS and Tawheed, A},
title = {Implications of gut microbiota in hepatic and pancreatic diseases: Gut-liver-pancreas axis.},
journal = {World journal of hepatology},
volume = {17},
number = {9},
pages = {109965},
pmid = {41024883},
issn = {1948-5182},
abstract = {The gut-liver-pancreas axis (GLPA) is a critical network shaped by gut microbiota (GM) and their metabolites, essential for maintaining metabolic and immune balance. Disruption of this microbial equilibrium, known as dysbiosis, contributes to the development and progression of various hepatic and pancreatic diseases. Through mechanisms such as increased intestinal permeability and exposure to microbial products-including lipopolysaccharide, trimethylamine-N-oxide, and secondary bile acids-dysbiosis promotes inflammation, oxidative stress, insulin resistance, and carcinogenesis. These changes are linked to conditions including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cirrhosis, hepatocellular carcinoma, pancreatitis, pancreatic ductal adenocarcinoma, and diabetes. Emerging tools like stool metagenomics and serum metabolomics help identify microbial biomarkers for diagnosis and risk stratification. While interventions such as probiotics, dietary changes, and fecal microbiota transplantation aim to restore microbial balance, their success remains inconsistent. This work aims to highlight the pathogenic role of GM across the GLPA, with special emphasis on the underexplored gut-pancreas connection. Advancing our understanding of the GLPA can unlock novel microbiota-targeted approaches for early diagnosis and treatment of hepatopancreatic diseases.},
}

@article {pmid41024876,
year = {2025},
author = {Mishra, AK and Goel, A},
title = {Stratification and selection of therapies to improve survival in severe alcoholic hepatitis.},
journal = {World journal of hepatology},
volume = {17},
number = {9},
pages = {109118},
pmid = {41024876},
issn = {1948-5182},
abstract = {Severe alcoholic hepatitis (SAH) is associated with high short-term mortality. The SAH population exhibits extreme heterogeneity in disease severity, clinical presentation, decompensations, and outcomes. Nonetheless, improving outcomes and preventing adverse events is a major challenge when selecting an appropriate treatment for alcoholic hepatitis. Currently, steroids are the standard of care for SAH with Maddrey's discriminant function > 32 and model for end stage liver disease > 20; however, they have limited usage due to ineligibility in approximately two-third of such patients. Approximately 25% of patients do not respond to steroids and require alternative therapies. An array of evolving therapies, such as granulocyte colony-stimulating factors, plasma exchange, fecal microbiota transplantation, antibiotics, anti-cytokine therapies, and N-acetylcysteine, showing variable success, are emerging. Hence, it is also crucial to select appropriate therapy. The present review discusses the standard of care, the existing therapies, risk stratification for outcomes, and the selection of appropriate therapy to improve survival in SAH patients.},
}

@article {pmid41024767,
year = {2025},
author = {Ezzat, WM},
title = {Machine learning as an artificial intelligence application in management of chronic hepatitis B virus infection.},
journal = {World journal of gastroenterology},
volume = {31},
number = {35},
pages = {109776},
pmid = {41024767},
issn = {2219-2840},
mesh = {Humans ; *Hepatitis B, Chronic/therapy/microbiology/diagnosis/virology ; *Machine Learning ; *Gastrointestinal Microbiome ; *Hepatitis B virus/pathogenicity ; Algorithms ; Artificial Intelligence ; Antiviral Agents/therapeutic use ; Supervised Machine Learning ; },
abstract = {Let's review the role of gut microbiota in pathogenesis of chronic hepatitis B infection as addressed in by Zhu et al. Zhu et al used high-throughput technology to characterize the microbial ecosystems, which led to an explosion of various types of molecular profiling data, such as metagenomics, metatranscriptomics, and metabolomics. To analyze such data, machine learning (ML) algorithms have shown to be useful for identifying key molecular signatures, discovering potential patient stratifications, and, particularly, for generating models that can accurately predict phenotypes. Strong evidence suggests that such gut microbiome-based stratification could guide customized interventions to benefit human health. Supervised learning includes designing an algorithm to fix a pre-identified problem. To get an answer, ML software must access data that have been nominated. On the other hand, unsupervised learning does not address any pre-defined problems. Bias should be eliminated as much as possible. In unsupervised learning, an ML algorithm works to identify data patterns without any prior operator input. This can subsequently lead to elements being identified that could not be conceived by the operator. At the intersection between supervised and unsupervised learning is semi-supervised ML. Semi-supervised learning includes using a partially labeled data set. The ML algorithm utilizes unsupervised learning to label data (that has not yet been labelled) by drawing findings from the labeled data. Then, supervised techniques can be used to solve defined problems involving the labeled data. Reinforcement learning, which is similar to supervised learning in the meaning, is goal-oriented. Reinforcement learning does not need labeled data, instead, it is provided with a set of regulations on a problem. An algorithm will carry out operations to try to answer questions involving the problem. Based on obtained data of gut microbiota, various therapeutic modalities can be applied: Prebiotics, probiotics, postbiotics, engineered bacteria, bacteriophage, and novel microbe-materials therapeutic system and fecal transplantation. In conclusion, ML is an artificial intelligence application that helps in providing new perspectives on tailored therapy. Furthermore, assessing the impact of gut microbiota modification is a critical step in advanced liver disease management. These new artificial intelligence techniques although promising, still require further analysis and validation in future studies.},
}

Humans
*Hepatitis B, Chronic/therapy/microbiology/diagnosis/virology
*Machine Learning
*Gastrointestinal Microbiome
*Hepatitis B virus/pathogenicity
Algorithms
Artificial Intelligence
Antiviral Agents/therapeutic use
Supervised Machine Learning

@article {pmid41024761,
year = {2025},
author = {Quiñones-Calvo, M and Alvarado-Jara, R and García-Renedo, P and Stallings, E and Grifol-Clar, E and Fernández-Rodríguez, CM},
title = {Beyond corticosteroids: A systematic review of novel therapeutic strategies in severe alcoholic hepatitis and 90-day survival.},
journal = {World journal of gastroenterology},
volume = {31},
number = {35},
pages = {109987},
pmid = {41024761},
issn = {2219-2840},
mesh = {Humans ; *Hepatitis, Alcoholic/mortality/therapy ; Liver Transplantation ; *Adrenal Cortex Hormones/therapeutic use ; Treatment Outcome ; Severity of Illness Index ; Time Factors ; Nutritional Support/methods ; },
abstract = {BACKGROUND: Severe alcoholic hepatitis (SAH) carries a 90-day mortality rate approaching 50%. Management includes corticosteroids, nutritional support, and early liver transplantation in selected cases. However, the mid-term impact of available therapies remains unclear. This systematic review provides a critical evaluation of treatments for SAH, specifically focusing on survival or mortality at 90 days as an essential window that captures short- and mid-term outcomes. The 90-day window is clinically significant, as it reflects the remission of systemic inflammation, early liver recovery, and minimizes confounding long-term behaviors such as alcohol relapse.

AIM: To review the effect of different treatments for SAH on survival and mortality at 90 days.

METHODS: A systematic search of PubMed and EMBASE (last updated March 2025) was performed without language restrictions, focusing on studies published in the last decade. Study selection and data extraction were performed independently by at least two reviewers. Risk of bias was assessed using RoB 2.0 and Risk-of Bias in Non-Randomized Studies of Interventions tools. Due to heterogeneity in study designs and interventions, a meta-analysis was not feasible. A qualitative synthesis was conducted using narrative summaries and evidence tables.

RESULTS: Searches in the databases yielded 645 citations in PubMed and 1516 in EMBASE. Of these 2161 studies, 618 were duplicates and therefore removed. A total of eight studies were included in qualitative synthesis. Among the included publications, six were randomized control trials (RCT) and two were retrospective cohort studies. These studies evaluated 90-day mortality or survival in SAH patients treated with corticosteroids (n = 2), pentoxifylline (n = 1), anakinra plus zinc (n = 2), granulocyte colony-stimulating factor (n = 1), amoxicillin-clavulanate (n = 1), fecal microbiota transplantation (n = 1) or extracorporeal liver assist device (n = 1). While most studies were conducted in Western countries, two had a global scope.

CONCLUSION: Steroids remain the first-line therapy for SAH despite reports of them not having any 90-day survival benefit. These results highlight the need for multicenter, biomarker-guided RCTs evaluating emerging treatments to improve mid-term survival in SAH.},
}

Humans
*Hepatitis, Alcoholic/mortality/therapy
Liver Transplantation
*Adrenal Cortex Hormones/therapeutic use
Treatment Outcome
Severity of Illness Index
Time Factors
Nutritional Support/methods

@article {pmid41024199,
year = {2025},
author = {Yang, G and Gao, L and Liu, Y and Xu, X and Yang, W},
title = {The impact of altered intestinal microbiota on intestinal immune function after acute exhaustive exercise in mice.},
journal = {BMC sports science, medicine & rehabilitation},
volume = {17},
number = {1},
pages = {279},
pmid = {41024199},
issn = {2052-1847},
support = {ZL22018//2022 Campus-Level Talent Special Project/ ; },
abstract = {PURPOSE: Long-term training or intense exercise alters gut microbiota. This study aimed to determine the effects of microbiota on colonic permeability and immune function in mice subjected to acute exhaustive exercise.

METHODS: C57BL/6 mice were randomly divided into the blank control (C), no exercise experience (NE), under a training protocol (E), phosphate-buffered saline (PBS) transplantation (PT), and fecal microbiota transplantation (FMT) groups. The E group underwent 14 weeks of moderate intensity training. At the end of the 14th week, fecal suspensions were prepared from mice in Group E and transplanted into Group FMT via enema, while Group PT received PBS enemas twice daily for 7 days. Prior to transplantation, both Groups PT and FMT were gavaged with antibiotics for 7 days, followed by 3 days of polyethylene glycol bowel cleansing. The C group was euthanized after a rest period, and the other groups were euthanized after acute exhaustive exercise. Colonic zonulin, occludin, ZO-1, CD14, TLR-4, MD-2, and TNF-α protein levels were detected via western blot, and enzyme-linked immunosorbent assays were used to detect serum LPS, IL-6, and colonic sIgA.

RESULTS: Colonic zonulin protein expression was significantly higher (P < 0.01) and occludin and ZO-1 expression levels were significantly lower in the NE, PT, and FMT groups compared with the C group (P < 0.01). ZO-1 was significantly higher in the FMT group compared with the PT group (P < 0.05). Colonic MD-2, TLR-4, and CD14 expression levels were significantly lower in the FMT group compared with the PT group (P < 0.01, P < 0.05, and P < 0.05, respectively). Serum LPS and IL-6 expression levels were significantly lower in the FMT group compared with the PT group (P < 0.01). Colonic sIgA levels were significantly lower in the NE, E, PT, and FMT groups compared with the C group (P < 0.01), and levels in the FMT group were significantly higher than the levels in the PT group (P < 0.01).

CONCLUSION: Fecal microbiota transplantation attenuated the increased intestinal permeability, enhanced intestinal immune function, and reduced systemic inflammation induced by acute exhaustive exercise in mice without prior exercise experience.},
}

@article {pmid41024120,
year = {2025},
author = {Huang, J and Tang, J and Wang, Z and Zhang, H and Wang, F and Tang, X and Zhou, X},
title = {Efficacy and safety of fecal microbiota transplantation for ulcerative colitis: protocol for an umbrella review of systematic reviews.},
journal = {Systematic reviews},
volume = {14},
number = {1},
pages = {182},
pmid = {41024120},
issn = {2046-4053},
support = {YN2024GZRPY030//Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province/ ; },
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Systematic Reviews as Topic ; *Colitis, Ulcerative/therapy ; Research Design ; Meta-Analysis as Topic ; Treatment Outcome ; },
abstract = {INTRODUCTION: A growing number of systematic reviews and meta-analyses (SRs/MAs) based on randomized clinical trials have been carried out to assess the efficacy of fecal flora transplantation (FMT) in the treatment of ulcerative colitis (UC). An overview of SRs/MAs will be conducted with the aim of systematically compiling, evaluating, and synthesizing the evidence regarding FMT for UC. This is a protocol for an overview of SRs/MAs. We will search eight public electronic databases for the studies of FMT on UC. SRs/MAs of clinical trials evaluating the effect of FMT on UC will be included. Two independent authors will screen titles and abstracts retrieved in the literature search and select reviews meeting the eligibility criteria for full-text review. The methodological quality, reporting quality, and evidence quality of the included studies will be assessed, using, respectively, the AMSTAR-2 tool, PRISMA checklists, and GRADE system.

RESULTS: From this study, the methodological quality, reporting quality, and evidence quality of the included SRs/MAs will be evaluated. We will also evaluate the efficacy of FMT in patients with UC.

IMPLICATIONS: We will ascertain the efficacy of FMT in UC patients to provide evidence to guide the treatment of UC with FMT in the future.

ETHICS AND DISSEMINATION: As a secondary study based on SRs/MAs, this study does not contain any individual patient information or violate participant rights. It is therefore not necessary to obtain ethics approval. We will report our findings in peer-reviewed journals or disseminate them at relevant conferences.

TRAIL REGISTRATION: Systematic review registration. PROSPERO CRD42023388682.},
}

Humans
*Fecal Microbiota Transplantation/methods
Systematic Reviews as Topic
*Colitis, Ulcerative/therapy
Research Design
Meta-Analysis as Topic
Treatment Outcome

@article {pmid41022353,
year = {2025},
author = {Belvončíková, P and Gardlík, R},
title = {Faecal microbiota transplantation for urinary tract infections.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmi.2025.09.018},
pmid = {41022353},
issn = {1469-0691},
abstract = {BACKGROUND: Recurrent urinary tract infections (rUTIs) are a major clinical burden, increasingly complicated by multidrug-resistant organisms (MDROs) and antibiotic overuse. Growing evidence implicates gut microbiota dysbiosis as a key contributor to UTI susceptibility, with the gastrointestinal tract acting as a reservoir for uropathogens.

OBJECTIVES: This review examines the emerging role of faecal microbiota transplantation (FMT) as a therapeutic strategy for rUTIs. We synthesize findings from human studies and case reports, evaluate microbiological and clinical outcomes post-FMT, and discuss mechanistic insights, safety concerns, and future research directions.

SOURCES: We reviewed peer-reviewed publications up to May 2025 using PubMed and Web of Science. Included sources comprised clinical trials, cohort studies, case reports, economic analyses, and expert reviews concerning FMT and UTIs.

CONTENT: FMT has shown promise in reducing rUTI episodes, particularly in patients with underlying gut dysbiosis or MDRO colonization. Clinical studies and case reports consistently report decreased UTI frequency, lower MDRO burden, and increased gut microbiota diversity post-FMT. Patients previously refractory to antibiotic prophylaxis achieved prolonged infection-free periods. Microbiome analyses often reveal reductions in uropathogen abundance and shifts toward donor-like microbial communities. However, outcomes vary and some patients experience persistence or transmission of uropathogens from donor stool, underscoring safety and screening concerns.

IMPLICATIONS: FMT represents a promising microbiome-based intervention for managing rUTIs, particularly in complex or antibiotic-resistant cases. Randomized controlled trials are needed to assess efficacy, define optimal protocols, and address safety concerns. Standardized practices will be essential to integrate FMT into routine UTI care.},
}

@article {pmid40737907,
year = {2025},
author = {Bilal, M and Si, W and Vitienes, I and El-Fateh, M and Ahmed, N and Lin, H and Willie, BM and Zhao, X},
title = {Cohousing-mediated microbiota transfer promotes bone health and modulates gut integrity, and immunity in young broiler chickens.},
journal = {Poultry science},
volume = {104},
number = {10},
pages = {105587},
pmid = {40737907},
issn = {1525-3171},
mesh = {Animals ; *Chickens/immunology/physiology/microbiology/growth & development ; *Gastrointestinal Microbiome ; *Bone and Bones/physiology ; Male ; *Fecal Microbiota Transplantation/veterinary ; *Animal Husbandry/methods ; Cytokines ; Random Allocation ; },
abstract = {The intestine hosts a complex microbiota, which plays a crucial role in health and development. This study investigated the impact of cohousing day-old broilers with 14-day-old (CH14) or 42-day-old (CH42) broiler chickens and their fecal material for a week, compared to a non-cohoused control group. Birds were raised for 42 days, and bone traits, gut integrity and microbiota, cytokine and antimicrobial peptide profiles, and T cell immunity subsets were assessed at days 14 and 42. Production parameters were recorded weekly, and mortality daily. Both treatment groups exhibited significantly improved tibial bone length, cortical bone volume, and mineral density, with reduced pore volume and diameter. These effects were more pronounced in CH42 birds at day 14. Pro-inflammatory (IL-6, IL-17, IL-1β, IL-2, AvBD-4, AvBD-7) and anti-inflammatory (IL-10, TGF-β) markers were monitored, with CH42 birds showing significantly higher levels of both IL-10 and TGF-β at day 42. CH42 birds had higher CD4+CD25+ T regulatory cells and lower CD4+ T cells, while CD8+ T cells remained unchanged. Gut integrity markers (Claudin-2, Occludin, ZO-1, JAM-2) were improved in both groups. CH42 birds showed increased microbiota alpha and beta diversity and Firmicutes dominance by day 42. Cohousing and fecal material transfer improved bone development, gut integrity and microbiota, and immune homeostasis, highlighting the potential of older birds' microbiota and inspiring the development of microbiota-based approaches to enhance poultry health, welfare, and management.},
}

Animals
*Chickens/immunology/physiology/microbiology/growth & development
*Gastrointestinal Microbiome
*Bone and Bones/physiology
Male
*Fecal Microbiota Transplantation/veterinary
*Animal Husbandry/methods
Cytokines
Random Allocation

@article {pmid41020845,
year = {2025},
author = {Borrego-Ruiz, A and Borrego, JJ},
title = {Microbial Metabolomes in Alzheimer's Disease: From Pathogenesis to Therapeutic Potential.},
journal = {Current issues in molecular biology},
volume = {47},
number = {9},
pages = {},
doi = {10.3390/cimb47090724},
pmid = {41020845},
issn = {1467-3045},
abstract = {BACKGROUND: Accumulating evidence underscores the potential role of the gut microbiome in the pathogenesis of Alzheimer's disease, but much remains to be clarified. This review examines current evidence linking gut microbiome dysbiosis to Alzheimer's disease, focusing on microbial metabolomes and their mechanistic role, as well as on the potential of therapeutic approaches targeting the gut microbiome.

METHODS: A narrative, non-systematic examination of the literature was conducted to provide a comprehensive overview of the subject under examination. Database searches were performed in PubMed, Scopus, and Web of Science between June and July 2025.

RESULTS: Alzheimer's disease is linked to reduced gut microbial diversity and altered bacterial taxa. Gut microbiome shifts correlate with inflammation and may drive Alzheimer's disease progression via the microbiota-gut-brain axis. Microbial amyloids and bacterial products can cross both the intestinal and blood-brain barrier, triggering neuroinflammation and promoting amyloid and tau pathologies. Short-chain fatty acids produced by the gut microbiome regulate neuroinflammation, lipid metabolism, and gene expression, impacting Alzheimer's disease pathology. Therapeutics targeting the gut microbiome, including probiotics, prebiotics, and fecal microbiota transplantation, show promise in modulating neuroinflammation, reducing amyloid and tau pathology, and improving cognitive function in Alzheimer's disease.

CONCLUSIONS: The gut microbiome significantly influences Alzheimer's disease pathogenesis, and its modulation offers potential to slow progression. However, further research is required to validate effective clinical interventions.},
}

@article {pmid41019955,
year = {2025},
author = {Hajjar, J and Voigt, AY and Conner, ME and Swennes, AG and Fowler, S and Calarge, C and Mendonca, DD and Armstrong, D and Chang, CY and Walter, JE and Butte, MJ and Savidge, T and Oh, J and Kheradmand, F and Petrosino, JF},
title = {Gut dysbiosis patterns in CVID patients with noninfectious complications observed in a germ-free mouse model through fecal microbiota transplantation.},
journal = {Journal of human immunity},
volume = {1},
number = {1},
pages = {},
pmid = {41019955},
issn = {3065-8993},
abstract = {Patients with common variable immunodeficiency (CVID) who develop noninfectious complications (NIC) have worse clinical outcomes than those with infections only (INF). While gut microbiome aberrations have been linked to NIC, reductionist animal models that accurately recapitulate CVID are lacking. Our aim in this study was to uncover potential microbiome roles in the development of NIC in CVID. We performed whole-genome shotgun sequencing on fecal samples from CVID patients with NIC, INF, and their household controls. We also performed fecal microbiota transplants from CVID patients to germ-free mice. We found potentially pathogenic microbes Streptococcus parasanguinis and Erysipelatoclostridium ramosum were enriched in gut microbiomes of CVID patients with NIC. In contrast, Fusicatenibacter saccharivorans and Anaerostipes hadrus, known to suppress inflammation and promote healthy metabolism, were enriched in gut microbiomes of INF CVID patients. Fecal microbiota transplant from NIC, INF, and their household controls into germ-free mice revealed gut dysbiosis patterns only in recipients from CVID patients with NIC, but not in those from INF CVID or household controls recipients. Our findings provide a proof of concept that fecal microbiota transplant from CVID patients with NIC to germ-free mice recapitulates microbiome alterations observed in the donors.},
}

@article {pmid41019532,
year = {2025},
author = {Li, Z and Zhang, L and Wan, Z and Liu, H and Zhang, T and Li, Y},
title = {Therapeutic potential of the gut commensal bacterium Parabacteroides goldsteinii in human health and disease treatment.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1618892},
pmid = {41019532},
issn = {1664-302X},
abstract = {The gut microbiota, as a critical guardian of human health, maintains physiological homeostasis, modulating immunity, and facilitates nutrient metabolism. Parabacteroides goldsteinii, a probiotic gut commensal, has garnered increasing scientific attention. This review systematically examines its biological characteristics, then analyzes mechanisms promoting health (immunomodulation, metabolic regulation, and intestinal barrier reinforcement), and finally evaluates disease associations (metabolic disorders, neurological diseases, inflammatory conditions, and malignancies). Current evidence shows that therapeutic efficacy against obesity, non-alcoholic fatty liver disease, inflammatory bowel disease, autism spectrum disorder, and colorectal cancer via short-chain fatty acids secretion, bile acid transformation, and host immunity modulation. Dietary factors (e.g., inulin), pharmacological agents (e.g., metformin, aspirin), and lifestyle interventions (e.g., exercise synbiotics) dynamically regulate its abundance, underscoring therapeutic potential. Despite translational challenges-like optimizing cultivation, dose-response characterization, and genetic tool development-emerging applications (engineered probiotics, fecal microbiota transplantation, and synthetic biology) highlight broad prospects. Future research should prioritize context-dependent mechanisms across diseases and refined translation strategies for microbiome-based precision medicine.},
}

@article {pmid41018102,
year = {2025},
author = {Wang, L and Qiao, W and Zhen, X and Zhang, Y and Dong, Z},
title = {Targeting the gut-liver axis in cholangiocarcinoma: mechanisms, therapeutic advances, and future directions.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1646897},
pmid = {41018102},
issn = {2234-943X},
abstract = {Cholangiocarcinoma (CCA), a highly aggressive biliary tract malignancy, exhibits rising incidence rates and an extremely poor prognosis. Recent studies reveal that gut-liver axis dysregulation drives CCA progression through gut microbiota dysbiosis, bile acid (BA) metabolic disturbances, and immune microenvironment remodeling. Clinical evidence highlights significant alterations in the gut and biliary microbial composition of CCA patients, which correlate with tumor stage, vascular invasion, and survival outcomes. Dysregulated BA metabolism in CCA, characterized by accumulation of primary conjugated BAs, promotes tumor invasiveness via interaction with specific BA receptors and fosters an immunosuppressive microenvironment. Emerging therapeutic strategies include antibiotics for pathogenic microbiota modulation, probiotics for microbial homeostasis restoration, fecal microbiota transplantation, and BA pathway modulators. Future directions necessitate integrating synthetic biology (engineered microbiota), multi-omics, and artificial intelligence to develop precision therapies. Targeting the gut-liver axis offers novel therapeutic perspectives for CCA; however, clinical translation demands deeper mechanistic insights and standardized protocols to address challenges such as microbiota heterogeneity and receptor signaling duality.},
}

@article {pmid41017540,
year = {2025},
author = {Ticinesi, A and Spaggiari, R and Passaro, A and Volpato, S},
title = {Gut microbiota dysbiosis and its relation to osteoporosis and sarcopenia in older people.},
journal = {Current opinion in clinical nutrition and metabolic care},
volume = {},
number = {},
pages = {},
doi = {10.1097/MCO.0000000000001173},
pmid = {41017540},
issn = {1473-6519},
abstract = {PURPOSE OF REVIEW: Gut microbiome is increasingly recognized as a modulator of the biology of aging. Several preclinical studies suggest that dysbiosis, typically arising in the older age, is associated with osteoporosis and sarcopenia. This review examines the recent findings on the mechanistic aspects of the gut-bone and gut-muscle axes in aging and provides a critical overview on their translation to clinical practice.

RECENT FINDINGS: Gut microbiome can modulate the pathophysiology of osteoporosis and sarcopenia through multiple mechanisms, particularly involving the production of bioactive mediators such as short-chain fatty acids (SCFAs), bile acids and tryptophan metabolites. Dysbiosis increases the risk of osteoporosis, fragility fractures and muscle wasting, with possible sex-specific differences, but the definition of GM traits associated with each condition is inconsistent across studies. Short-term microbiome-modifying treatments, including probiotics and functional foods, slowed down the age-related decline in bone mineral density and improved muscle function in a handful of small-sized clinical studies.

SUMMARY: Gut microbiome remains a very promising therapeutic target against osteoporosis and sarcopenia, but no recommendations can be made for clinical practice at the current state-of-art. Microbiome-targeted strategies may soon emerge as valuable adjuvant therapies in the management of age-related musculoskeletal decline.},
}

@article {pmid41017030,
year = {2025},
author = {Jones, JC and García, OG and Villalba, JA and Hinojosa, R and Taylor, ML and Annambhotla, P and Kapturczak, MH and Mayes, B and Karpathy, SE and Gleaton, AN and Moon, L and Singleton, J and Basavaraju, SV and Paddock, CD},
title = {Organ Donor Transmission of Rickettsia typhi to Kidney Transplant Recipients, Texas, USA, 2024.},
journal = {Emerging infectious diseases},
volume = {31},
number = {10},
pages = {1893-1900},
doi = {10.3201/eid3110.250961},
pmid = {41017030},
issn = {1080-6059},
abstract = {Murine typhus, a fleaborne disease caused by the bacterium Rickettsia typhi, is found throughout temperate and tropical regions of the world. Transmission of R. typhi to humans involves several species of fleas, and most infections result from direct inoculation of R. typhi-infected flea feces into abrasions in the skin. We describe the transmission of R. typhi from an organ donor in Texas, USA, to 2 kidney transplant recipients. The donor and 1 recipient died from the infection. The occurrence of R. typhi transmission via transplantation is a harbinger for the reemergence of murine typhus in some of the most densely populated metropolitan areas of the United States. Our findings reinforce the need to improve healthcare provider and public awareness of this life-threatening but treatable infection.},
}

@article {pmid41016812,
year = {2025},
author = {Huang, L and Li, H and Yang, W and Huang, L and Chen, Q and Li, S and Zou, Z and Zhao, L and Zeng, Z},
title = {L-Theanine Ameliorates Metabolic Dysregulation and Adverse Fetal Outcomes in a Mice Model of Gestational Obesity: Association with FXR/FGF15 Signaling.},
journal = {Journal of microbiology and biotechnology},
volume = {35},
number = {},
pages = {e2504017},
doi = {10.4014/jmb.2504.04017},
pmid = {41016812},
issn = {1738-8872},
mesh = {Animals ; Female ; Pregnancy ; Mice ; Gastrointestinal Microbiome/drug effects ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; *Glutamates/pharmacology/therapeutic use ; *Fibroblast Growth Factors/metabolism/genetics ; *Receptors, Cytoplasmic and Nuclear/metabolism ; Signal Transduction/drug effects ; Pregnancy Outcome ; Humans ; *Pregnancy in Obesity/metabolism/drug therapy ; Mice, Inbred C57BL ; *Obesity/metabolism ; Mice, Obese ; Placenta ; },
abstract = {In this study, we investigated whether L-theanine (LTA) ameliorates adverse pregnancy outcomes in high-fat diet (HFD)-induced gestational obesity mice. Gestational obese mice models received HFD and fecal microbiota transplantation (FMT) from pregnant obese women, followed by LTA treatment. Gut microbiota DNA from six obese and six normal pregnant women was analyzed. Also assessed were lipid profiles, inflammatory factors, gut permeability, FXR/FGF15 expression, pup weight, and placental function. Alpha- and beta-diversity analyses showed reduced gut microbial diversity in the obese pregnant women. Postpartum hemorrhage, cholesterol, and triglycerides inversely correlated with Weissella, while BMI was positively associated with Escherichia-Shigella. Neonatal weight correlated positively with Subdoligranulum and negatively with Megamonas. Fasting glucose was significantly positively associated with Bacteroides vulgatus, whereas neonatal body weight inversely correlated with Eubacterium ramulus. In gestational obesity mice, LTA administration reduced weight gain, visceral/gonadal adiposity, metabolic markers (fasting glucose/insulin/cholesterol), gut barrier dysfunction (TNF-α, IL-6, IL-8, Claudin-2), and linked to FXR/FGF15 pathway alterations. Furthermore, LTA intervention suppressed MCP-1, IL-1β, F4/80 and hepatic lipid metabolism regulators (CD36, SREBP1c, SCD1, GLUT4, Cyp7a1, IRS-1), while also mitigating placental tissue junction zone abnormalities and pup weight. To sum up, LTA-mediated attenuation of adverse pregnancy outcomes associates with FXR/FGF15 pathway alterations, concomitant with restoration of metabolic homeostasis and inflammation suppression.},
}

Animals
Female
Pregnancy
Mice
Gastrointestinal Microbiome/drug effects
Diet, High-Fat/adverse effects
Disease Models, Animal
*Glutamates/pharmacology/therapeutic use
*Fibroblast Growth Factors/metabolism/genetics
*Receptors, Cytoplasmic and Nuclear/metabolism
Signal Transduction/drug effects
Pregnancy Outcome
Humans
*Pregnancy in Obesity/metabolism/drug therapy
Mice, Inbred C57BL
*Obesity/metabolism
Mice, Obese
Placenta

@article {pmid41016739,
year = {2025},
author = {Zheng, D and Chen, S and Feng, H and Zhang, S and Zhang, C and Wang, Y and Tan, W and Qing, Q and Liu, L and Liu, X and Wang, Z and Liang, L and Sun, J and Chen, Y},
title = {Oral administration of low-molecular-weight heparin ameliorates colitis by enhancing the gut mucus barrier via microbial tryptophan metabolites.},
journal = {British journal of pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bph.70209},
pmid = {41016739},
issn = {1476-5381},
support = {2021YFA0717000//National Key R&D Program of China/ ; 81800460//National Natural Science Foundation of China/ ; 82270581//National Natural Science Foundation of China/ ; KCXFZ20211020163558024//Shenzhen Science and Technology Innovation Program/ ; ZDSYS20220606100800002//Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease/ ; },
abstract = {BACKGROUND AND PURPOSE: Previous studies have reported that oral low-molecular-weight heparin (LMWH) ameliorated colitis by undefined mechanisms in ulcerative colitis (UC) patients. Our study explored the mechanisms of LMWH on colitis from the perspective of gut microbiota and its metabolites.

EXPERIMENTAL APPROACH: Dextran sulfate sodium (DSS; 2.5%) was used to induce colitis in mouse model, and LMWH was administered by either oral gavage, intracolonic delivery or subcutaneous injection to compare their therapeutic effects. Pseudo-germ-free mice was established by using antibiotic cocktail, and faecal microbial transplantation (FMT) was performed to verify the role of microbiota in LMWH actions. Alcian blue staining, fluorescence in situ hybridization of EUB338 and immunohistochemical staining were performed to evaluate the integrity of gut mucus barrier. Amplicon sequencing, transcriptome sequencing and untargeted metabolome studies were used to explore LMWH mechanisms. The ameliorating effect of indole-3-propionic acid (IPA) was verified in vitro and in vivo.

KEY RESULTS: Oral, but not subcutaneous, administration of LMWH alleviated colitis and enhanced the gut mucus barrier. Pseudo-germ-free mice and FMT assays confirmed that therapeutic effects of oral LMWH were dependent on gut microbiota. Oral LMWH increased Firmicutes abundance and decreased Escherichia/Shigella abundance, subsequently increasing microbial tryptophan metabolites, especially IPA. The protective effects of oral LMWH were reproduced by IPA supplementation, with mucus barrier enhancing through regulating the Wnt/β-catenin pathway.

CONCLUSION AND IMPLICATIONS: The results provide new insights into the signalling mechanisms associated with the therapeutic potential of LMWH in colitis, and highlight the application of IPA for UC treatment.},
}

@article {pmid41015495,
year = {2025},
author = {Castells-Nobau, A and Fumagalli, A and Del Castillo-Izquierdo, Á and Rosell-Díaz, M and de la Vega-Correa, L and Samulėnaitė, S and Motger-Albertí, A and Arnoriaga-Rodríguez, M and Garre-Olmo, J and Puig, J and Ramos, R and Burokas, A and Coll, C and Zapata-Tona, C and Perez-Brocal, V and Ramio, L and Moya, A and Swann, J and Martín-García, E and Maldonado, R and Fernández-Real, JM and Mayneris-Perxachs, J},
title = {Gut microbial modulation of 3-hydroxyanthranilic acid and dopaminergic signalling influences attention in obesity.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2025-336391},
pmid = {41015495},
issn = {1468-3288},
abstract = {BACKGROUND: Obesity-related alterations in the gut microbiota have been linked to cognitive decline, yet their relationship with attention remains poorly understood.

OBJECTIVE: To evaluate the possible relationships among gut metagenomics, plasma metabolomics and attention.

DESIGN: We conducted faecal shotgun metagenomics and targeted plasma tryptophan metabolomics across three independent cohorts (n=156, n=124, n=804) with functional validations in preclinical models, including three faecal microbiota transplantation (FMT) experiments in mice and Drosophila melanogaster.

RESULTS: Obesity was consistently associated with reduced attention. Metagenomics analyses identified Proteobacteria species and microbial functions related to tryptophan biosynthesis from anthranilic acid (AA) as negatively associated with attention in obesity. Plasma tryptophan metabolic profiling and machine learning revealed that 3-hydroxyanthranilic acid (3-HAA) was positively associated with attention, particularly in obesity, while AA showed a negative association. Bariatric surgery improved attention and enriched microbial species linked to attention. In mice, diet-induced obesity (DIO) and microbiota depletion reduced 3-HAA and 5-hydroxy-indole acetic acid (5-HIAA) concentrations in the prefrontal cortex (PFC), which were restored by FMT. Global metabolic profiling (>600 metabolites) of PFC from the FMT group identified 3-HAA and the tryptophan and tyrosine pathways among the most significant in mice receiving microbiota from high-attention donors. A second FMT experiment also revealed a consistent enrichment of the tryptophan and tyrosine metabolism at the transcriptional level in the PFC, with Haao (3-hydroxyantrhanilic acid dioxygenase) and Aox4 (aldehyde oxidase 4), key in 3-HAA and 5-HIAA degradation, among the significantly regulated genes. In a third FMT study, attentional traits were transmitted from humans to mice alongside modulation of serotonergic and dopaminergic pathways. In Drosophila, mono-colonisation with Enterobacter cloacae and DIO induced attention deficit-like behaviours, which were mitigated by 3-HAA supplementation.

CONCLUSIONS: We have identified the microbiota and 3-HAA as potential therapeutic targets to improve attention, especially in obesity.},
}

@article {pmid41013319,
year = {2025},
author = {Igbo, CA and Ezeano, C and Adeniran, O and Taha, M and Annan, AA and Nriagu, VC and Boateng, S and Williams, MC and Onyali, C},
title = {The impact of fecal microbiota transplantation on refractory ulcerative colitis: A systematic review and Meta-Analysis of randomised controlled trials.},
journal = {BMC gastroenterology},
volume = {25},
number = {1},
pages = {654},
pmid = {41013319},
issn = {1471-230X},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; },
abstract = {BACKGROUND: Refractory ulcerative colitis (UC), characterized by persistent disease activity despite optimized medical therapy, poses a significant therapeutic challenge. Fecal microbiota transplantation (FMT) has shown promise in inducing remission in active ulcerative colitis (UC) by restoring gut microbial balance; however, its efficacy in refractory cases remains unclear. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of FMT in achieving clinical and endoscopic remission in patients with refractory UC, based on evidence from randomized controlled trials (RCTs).

METHODS: We searched PubMed, Scopus, Google Scholar Cochrane CENTRAL, and Web of Science up to February 2025 for RCTs comparing FMT to placebo or standard care in adults with refractory UC (Mayo Score ≥ 3 despite treatment). Primary outcomes were clinical remission (Mayo Score ≤ 2, no subscore > 1) and endoscopic remission (Mayo endoscopic subscore ≤ 1). Data were pooled using a random-effects model, with heterogeneity assessed via I² and Q-tests. Subgroup analyses explored age at diagnosis and disease duration as moderators. The review followed PRISMA guidelines and was registered with PROSPERO (CRD420250651790).

RESULTS: Six RCTs were included. FMT showed no significant effect on clinical remission (pooled estimate - 0.2584; 95% CI - 0.9031 to 0.3863; p = 0.4321) or endoscopic remission (pooled estimate - 0.2229; 95% CI - 0.8811 to 0.4353; p = 0.5069), with no heterogeneity (I² = 0.00%). Subgroup analyses revealed no moderation by age or disease duration (p > 0.27). Adverse events were mild and transient.

CONCLUSION: FMT does not significantly improve clinical or endoscopic remission in refractory UC, suggesting limited efficacy in this population despite a favorable safety profile. Larger, standardized trials are warranted.},
}

Humans
*Fecal Microbiota Transplantation/methods
*Colitis, Ulcerative/therapy
Randomized Controlled Trials as Topic
Remission Induction
Treatment Outcome

@article {pmid41012834,
year = {2025},
author = {Liu, S and Zhou, B and Liu, L and Zhong, J and Zhang, X and Jiang, W and Liu, H and Zhou, Z and Peng, G and Zhong, Y and Zhang, K and Zhong, Z},
title = {Effects and Microbiota Changes Following Oral Lyophilized Fecal Microbiota Transplantation Capsules in Canine with Chronic Enteropathy After Parvovirus Infection: Case Report.},
journal = {Veterinary sciences},
volume = {12},
number = {9},
pages = {},
doi = {10.3390/vetsci12090909},
pmid = {41012834},
issn = {2306-7381},
support = {CGF2024001//the Study on Key Technologies for Conservation of Wild Giant Panda Populations and Its Habitats within Giant Panda National Park System/ ; },
abstract = {(1) Background: Chronic enteropathy (CE) in canines is associated with persistent microbiome dysbiosis, and conventional therapies (e.g., special diets, antimicrobials, and immunosuppressive drugs) are sometimes ineffective. Currently, fecal microbiota transplantation (FMT) has proven successful in treating CE in canines via invasive methods (e.g., enemas or endoscopy) or via oral frozen liquid capsules, which must be stored at -80 °C. However, due to the invasiveness of the administration methods and the storage constraints of the liquid capsules, FMT is not widely used in veterinary clinical practice. (2) Methods: The case of a four-year-old Siberian Husky with a three-year history of CE following canine parvovirus infection received lyophilized FMT capsules for thirty days. Stool samples were collected for metagenomic sequencing and quantification of fecal short-chain fatty acids (SCFAs), both pre- and post-FMT. Blood samples were analyzed using complete blood count (CBC) and biochemical testing. Ultrasound was used to assess the wall thickness of the stomach, duodenum, jejunum, and colon. (3) Results: Post-FMT, improvements in clinical outcomes were observed: fecal scores improved from 6 (unformed stools with mucus) to 2 (formed stool), and body weight increased by 8.3% (from 24.2 kg to 26.2 kg). Abnormal CBC and biochemical parameters were restored to reference ranges, including hematocrit (from 60.6% to 55.7%), hemoglobin (from 208 g/L to 190 g/L), creatinine (from 167 μmol/L to 121 μmol/L), and urea (from 11.9 mmol/L to 7.1 mmol/L). Ultrasound results showed that colonic wall thickness decreased from 0.23 ± 0.03 cm (pathological) to 0.18 ± 0.01 cm (physiological). Metagenomic analysis revealed that microbial richness (operational taxonomic units (OTUs) from 151 to 183) and diversity (Shannon and Simpson indices from 3.16 to 4.8 and from 0.87 to 0.94, respectively) all increased. The microbiota composition of the recipient exhibited a decline in the relative abundance of Firmicutes, falling from 99.84% to 35.62%, concomitant with an increase in Actinobacteria (from 0.08% to 4.78%), indicating a convergence toward a donor-like profile. Fecal SCFAs analysis revealed a 251.4% increase in propionate (from 0.0833 to 0.2929 mg/g) and elevated acetate (from 0.4425 to 0.4676 mg/g). These changes are functionally linked to enriched propanoate metabolism (Z = 0.89) in KEGG pathways. (4) Conclusions: Oral lyophilized FMT capsules resolved clinical signs of CE, enhanced microbial diversity and richness, and restored donor-like abundances of gut microbiota, particularly SCFA-producing taxa. Microbial restructuring increased microbial metabolite output, notably SCFA concentrations, and enriched functional metabolic pathways. Importantly, lyophilized FMT overcomes storage limitations and administration barriers, demonstrating its high clinical viability for treating canine CE.},
}

@article {pmid41011544,
year = {2025},
author = {Dai, K and Ding, L and Yang, X and Wang, S and Rong, Z},
title = {Gut Microbiota and Neurodevelopment in Preterm Infants: Mechanistic Insights and Prospects for Clinical Translation.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/microorganisms13092213},
pmid = {41011544},
issn = {2076-2607},
abstract = {Preterm birth remains a significant global health challenge and is strongly associated with heightened risks of long-term neurodevelopmental impairments, including cognitive delays, behavioural disorders, and emotional dysregulation. In recent years, accumulating evidence has underscored the critical role of the gut microbiota in early brain development through the gut-brain axis. In preterm infants, microbial colonisation is frequently delayed or disrupted due to caesarean delivery, perinatal antibiotic exposure, formula feeding, and prolonged stays in neonatal intensive care units (NICUs), all of which contribute to gut dysbiosis during critical periods of neurodevelopment. This review synthesises current knowledge on the sources, temporal patterns, and determinants of gut microbiota colonisation in preterm infants. This review focuses on the gut bacteriome and uses faecal-sample bacteriome sequencing as its primary method of characterisation. We detail five mechanistic pathways that link microbial disturbances to adverse neurodevelopmental outcomes: immune activation and white matter injury, short-chain fatty acids (SCFAs)-mediated neuroprotection, tryptophan-serotonin metabolic signalling, hypothalamic-pituitary-adrenal (HPA) axis modulation, and the integrity of intestinal and blood-brain barriers (BBB). We also critically examine emerging microbiota-targeted interventions-including probiotics, prebiotics, human milk oligosaccharides (HMOs), antibiotic stewardship strategies, skin-to-skin contact (SSC), and faecal microbiota transplantation (FMT)-focusing on their mechanisms of action, translational potential, and associated ethical concerns. Finally, we identify key research gaps, including the scarcity of longitudinal studies, limited functional modelling, and the absence of standardised protocols across clinical settings. A comprehensive understanding of microbial-neurodevelopmental interactions may provide a foundation for the development of targeted, timing-sensitive, and ethically sound interventions aimed at improving neurodevelopmental outcomes in this vulnerable population.},
}

@article {pmid41011526,
year = {2025},
author = {Roberts, JL and Park, CC},
title = {Emerging Roles of the Gut Microbiome in Musculoskeletal Injury and Repair.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/microorganisms13092193},
pmid = {41011526},
issn = {2076-2607},
support = {5P30AR003783-04/NH/NIH HHS/United States ; IK1RX003783//US Department of Veterans Affairs/ ; RFGA2024-022-010//Arizona Biomedical Research Centre/ ; },
abstract = {Over the past decade, significant attention has been directed toward understanding the role of the gut microbiome in health and disease. The gut microbiota, comprising a complex and diverse community of microorganisms, has been linked to numerous conditions, including metabolic disorders, gastrointestinal diseases, and inflammatory or autoimmune conditions. Recently, a growing body of evidence has revealed a compelling relationship between gut microbiota composition and musculoskeletal injury recovery, highlighting its potential as a novel therapeutic target. Musculoskeletal injuries, including fractures, post-traumatic osteoarthritis, and tendon or ligament injuries, commonly lead to changes in the community structure of the gut microbiota, intestinal permeability, and systemic inflammation, processes known to negatively influence tissue repair. Preclinical studies demonstrate that microbiota-targeted interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, effectively restore gut barrier integrity, modulate inflammation, and normalize gut-derived metabolite profiles. Despite these promising findings, critical gaps remain in translating these effects into clinical practice, particularly regarding the mechanisms linking specific microbiota changes to improved musculoskeletal healing outcomes. Future research incorporating rigorous clinical trials, multi-omics analyses, and advanced predictive tools, including artificial intelligence and microbiome-informed digital twins, is urgently needed to fully harness the therapeutic potential of microbiome-based interventions in musculoskeletal injury recovery. This narrative review provides insights into our evolving understanding of the relationship between the gut microbiota and musculoskeletal injury and explores the potential of gut microbiota-targeted therapies for improved healing outcomes.},
}

@article {pmid41011482,
year = {2025},
author = {Zhu, H and Yan, X and Shi, H and Chen, Y and Huang, C and Zhou, Y and Yan, S and Zhang, N and Wang, J and Zhang, J and Han, C and Chen, Q and Zhao, J and Cao, M},
title = {The Role of Gut Microbiota and Its Metabolites in Mitigating Radiation Damage.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/microorganisms13092151},
pmid = {41011482},
issn = {2076-2607},
support = {No. 2024ZYD0194//Central Guidance on Local Science and Technology Development Fund of Sichuan Province/ ; No. SZKF202309//Open Project Program of Panxi Crops Research and Utilization Key Laboratory of Sichuan Province/ ; No. 2024LQRD0045//Science and Technology Plan Project of Chengdu Longquanyi District/ ; },
abstract = {With the widespread use of ionizing radiation (IR) in medical and industrial settings, irradiation has become increasingly common, posing significant risks to human health. Among the various organs affected, the gut is particularly sensitive to radiation-induced damage, leading to conditions such as radiation-induced intestinal damage (RIID). Recent studies have emphasized the critical role of gut microbiota and its metabolites in mitigating radiation-induced injury. This review discusses the effects of IR on the mammalian and human gut microbiota. We examine the dynamics of gut microbiota composition during and after irradiation, and emphasize the protective role of the gut flora and the metabolites in the pathophysiological mechanisms exhibited during radiation injury. In addition, this article investigates how specific metabolites, such as short-chain fatty acids and indole derivatives, may contribute to the mitigation of inflammation and promotion of gut barrier integrity. In addition, various therapeutic strategies based on modulating the gut microbiota, such as probiotics, antibiotics, and fecal microbiota transplantation, are discussed to understand their potential to prevent or mitigate RIID. Understanding the interactions between IR, gut microbiota and their metabolites provides new avenues for developing innovative therapeutic approaches to improve patient outcomes during and after radiotherapy. Future research directions could focus on optimizing microbiota-based therapies and exploring the role of diet and lifestyle in enhancing intestinal health during irradiation.},
}

@article {pmid41011478,
year = {2025},
author = {Cortés, M and Olate, P and Rodriguez, R and Diaz, R and Martínez, A and Hernández, G and Sepulveda, N and Paz, EA and Quiñones, J},
title = {Human Microbiome as an Immunoregulatory Axis: Mechanisms, Dysbiosis, and Therapeutic Modulation.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/microorganisms13092147},
pmid = {41011478},
issn = {2076-2607},
support = {N° 21231033//Agencia Nacional de Investigación y Desarrollo/ ; },
abstract = {The human microbiome plays a central role in modulating the immune system and maintaining immunophysiological homeostasis, contributing to the prevention of immune-mediated diseases. In particular, the gut microbiota is a key ecosystem for immune system maturation, especially in early life. This review aimed to analyze the molecular and cellular mechanisms linking the microbiome to immune and neuronal functions, as well as the impact of dysbiosis and emerging therapeutic strategies targeting the microbiome. The analysis was based on scientific databases, prioritizing studies published since 2000, with special emphasis on the past decade. The microbiome influences immune signaling through microorganism-associated molecular patterns (MAMPs) and pattern recognition receptors (PRRs), including Toll-like receptors (TLRs). Additionally, microbial metabolites-such as short-chain fatty acids (SCFAs), tryptophan derivatives, and secondary bile acids-exert significant immunomodulatory effects. The intestinal epithelial barrier is also described as an active immunological interface contributing to systemic regulation. The literature highlights innovative therapies, including fecal microbiota transplantation (FMT), probiotics, and microbiome editing with CRISPR-Cas technologies. These strategies aim to restore microbial balance and improve immune outcomes. The growing body of evidence positions the microbiome as a valuable clinical and diagnostic target, with significant potential for application in personalized medicine.},
}

@article {pmid41011464,
year = {2025},
author = {Cano, Á and Ruiz Arabi, E and Ruiz, L and Nadales, BJ and Baumela, A and Recio, M and Machuca, I and Castón, JJ and Pérez-Nadales, E and Torre Cisneros, J},
title = {Compassionate Use of Encapsulated MKB-01 Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection: A Single-Center Experience.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/microorganisms13092134},
pmid = {41011464},
issn = {2076-2607},
abstract = {Fecal microbiota transplantation (FMT) is a safe and effective treatment for recurrent Clostridiodes difficile infection (rCDI). However, experience with the oral biologic product MKB-01 remains limited. We describe a series of 13 patients with rCDI treated with FMT using MKB-01 capsules administered orally. Each patient received a single dose of 4 capsules (≥2.1-2.5 × 10[11] microorganisms) with water after a 2 h fasting period. Antibiotic therapy was discontinued pre FMT. Clinical evaluation was performed at weeks 8 and 12. The mean number of prior recurrences was 1.5 (range: 1-3 episodes). In 12 patients (92.3%), FMT was administered after resolution of the current episode; in one patient (7%), it was administered on day 3 of fidaxomicin therapy, prior to symptom resolution. At week 8, clinical cure (Absence of baseline symptoms for at least 72 h) was achieved in 11 patients (84.6%). An additional patient (7%) responded to a second FMT. One recurrence occurred at 8 weeks and was resolved with a second FMT. Therefore, the overall clinical response rate after one or more FMTs was 12 out of 13 patients (92.3%). The procedure was well tolerated; only one patient experienced self-limited diarrhea. These findings support oral FMT with MKB-01 capsules as a safe and effective option for treating rCDI.},
}

@article {pmid41011331,
year = {2025},
author = {Alexandrescu, L and Tofolean, IT and Tofolean, DE and Nicoara, AD and Twakor, AN and Rusu, E and Preotesoiu, I and Dumitru, E and Dumitru, A and Tocia, C and Herlo, A and Alexandrescu, DM and Popescu, I and Cimpineanu, B},
title = {Ethanol-Induced Dysbiosis and Systemic Impact: A Meta-Analytical Synthesis of Human and Animal Research.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/microorganisms13092000},
pmid = {41011331},
issn = {2076-2607},
abstract = {BACKGROUND: Chronic ethanol consumption is a major global health concern traditionally associated with liver disease. Ethanol disrupts gut microbial communities, compromises intestinal barrier function, and contributes to hepatic, metabolic, and neurocognitive disorders.

METHODS: We conducted a systematic PubMed search and meta-analysis of 11 human and 19 animal studies evaluating ethanol-induced gut microbiota alterations. Studies were assessed for microbial diversity, taxonomic shifts, barrier integrity, and systemic effects. Effect sizes were calculated where possible, and interventional outcomes were examined.

RESULTS: Across species, ethanol exposure was consistently associated with reduced microbial diversity and depletion of beneficial commensals such as Faecalibacterium, Lactobacillus, Akkermansia, and Bifidobacterium, alongside an expansion of proinflammatory taxa (Proteobacteria, Enterococcus, Veillonella). Our analysis uniquely highlights discrepancies between human and animal studies, including opposite trends in specific genera (e.g., Akkermansia and Bifidobacterium) and the impact of confounders such as antibiotic exposure in human cohorts. We also demonstrate that microbiota-targeted interventions can partially restore diversity and improve clinical or behavioral outcomes.

CONCLUSIONS: This meta-analysis highlights reproducible patterns of ethanol-induced gut dysbiosis across both human and animal studies.},
}

@article {pmid41011314,
year = {2025},
author = {Meacci, D and Bruni, A and Cocquio, A and Dell'Anna, G and Mandarino, FV and Marasco, G and Cecinato, P and Barbara, G and Zagari, RM},
title = {Microbial Landscapes of the Gut-Biliary Axis: Implications for Benign and Malignant Biliary Tract Diseases.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/microorganisms13091980},
pmid = {41011314},
issn = {2076-2607},
abstract = {Next-generation sequencing has overturned the dogma of biliary sterility, revealing low-biomass microbiota along the gut-biliary axis with metabolic and immunologic effects. This review synthesizes evidence on composition, function, and routes of colonization across benign and malignant disease. In cholelithiasis, Proteobacteria- and Firmicutes-rich consortia provide β-glucuronidase, phospholipase A2, and bile salt hydrolase, driving bile supersaturation, nucleation, and recurrence. In primary sclerosing cholangitis, primary biliary cholangitis, and autoimmune hepatitis, intestinal dysbiosis and disturbed bile acid pools modulate pattern recognition receptors and bile acid signaling (FXR, TGR5), promote Th17 skewing, and injure cholangiocytes; bile frequently shows Enterococcus expansion linked to taurolithocholic acid. Distinct oncobiomes characterize cholangiocarcinoma subtypes; colibactin-positive Escherichia coli and intratumoral Gammaproteobacteria contribute to DNA damage and chemoresistance. In hepatocellular carcinoma, intratumoral microbial signatures correlate with tumor biology and prognosis. We critically appraise key methodological constraints-sampling route and post-sphincterotomy contamination, antibiotic prophylaxis, low biomass, and heterogeneous analytical pipelines-and outline a translational agenda: validated microbial/metabolomic biomarkers from bile, tissue, and stent biofilms; targeted modulation with selective antibiotics, engineered probiotics, fecal microbiota transplantation, and bile acid receptor modulators. Standardized protocols and spatial, multi-omic prospective studies are required to enable risk stratification and microbiota-informed therapeutics.},
}

@article {pmid41011192,
year = {2025},
author = {Cerrito, L and Galasso, L and Iaccarino, J and Pizzi, A and Termite, F and Esposto, G and Borriello, R and Ainora, ME and Gasbarrini, A and Zocco, MA},
title = {Present and Future Perspectives in the Treatment of Liver Fibrosis.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {9},
pages = {},
doi = {10.3390/ph18091321},
pmid = {41011192},
issn = {1424-8247},
abstract = {BACKGROUND/OBJECTIVES: Liver fibrosis is a progressive consequence of chronic liver injury that can evolve into cirrhosis, liver failure, or hepatocellular carcinoma, representing a major global health burden. Fibrogenesis is driven by hepatic stellate cell (HSC) activation, excessive extracellular matrix deposition, and structural disruption of liver tissue, with transforming growth factor-β (TGF-β) signaling and inflammatory mediators as central pathways. Current therapies primarily target the underlying causes, which may halt disease progression but rarely reverse established fibrosis. This review aims to outline current and emerging therapeutic strategies for liver fibrosis, informing both clinical practice and future research directions.

METHODS: A narrative synthesis of preclinical and clinical evidence was conducted, focusing on pharmacological interventions, microbiota-directed strategies, and innovative modalities under investigation for antifibrotic activity.

RESULTS: Bile acids, including ursodeoxycholic acid and derivatives, modulate HSC activity and autophagy. Farnesoid X receptor (FXR) agonists, such as obeticholic acid, reduce fibrosis but are limited by adverse effects. Fatty acid synthase inhibitors, exemplified by denifanstat, show promise in metabolic dysfunction-associated steatohepatitis (MASH). Additional strategies include renin-angiotensin system inhibitors, omega-3 fatty acids, and agents targeting the gut-liver axis. Microbiota-directed interventions-probiotics, prebiotics, symbiotics, antibiotics (e.g., rifaximin), and fecal microbiota transplantation-are emerging as potential modulators of barrier integrity, inflammation, and fibrogenesis, though larger clinical trials are required. Reliable non-invasive biomarkers and innovative trial designs, including adaptive platforms, are essential to improve patient selection and efficiently evaluate multiple agents and combinations.

CONCLUSIONS: Novel modalities such as immunotherapy, gene editing, and multi-targeted therapies hold additional potential for fibrosis reversal. Continued translational efforts are critical to establish safe, effective, and accessible treatments for patients with liver fibrosis.},
}

@article {pmid41011021,
year = {2025},
author = {Savvidis, C and Maggio, V and Rizzo, M and Zabuliene, L and Ilias, I},
title = {The Gut Microbiota Axis in Social Jetlag: A Novel Framework for Metabolic Dysfunction and Chronotherapeutic Innovation.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {9},
pages = {},
doi = {10.3390/medicina61091630},
pmid = {41011021},
issn = {1648-9144},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Circadian Rhythm/physiology ; *Jet Lag Syndrome/complications/physiopathology/microbiology/therapy ; *Metabolic Diseases/etiology ; *Chronotherapy/methods ; Melatonin/therapeutic use ; },
abstract = {Social jetlag, the misalignment between internal circadian rhythms and socially imposed schedules, is increasingly recognized as a risk factor for metabolic disorders such as obesity, type 2 diabetes (T2D), and cardiovascular disease. Recent evidence implicates the gut microbiota as a key mediator in this relationship, operating through a microbiota-gut-metabolic axis that influences host metabolism, immune function, and circadian regulation. Mechanistic studies reveal that social jetlag disrupts microbial rhythmicity, reduces short-chain fatty acid (SCFA) production, impairs intestinal barrier function, and promotes systemic inflammation, which contribute to insulin resistance and metabolic dysfunction. Clinical and preclinical interventions, including time-restricted feeding (TRF)/time-restricted eating (TRE), probiotics or melatonin supplementation, and fecal microbiota transplantation (FMT), demonstrate the potential to restore microbial and metabolic homeostasis by realigning host and microbial rhythms. This review synthesizes mechanistic insights with emerging human and clinical evidence, highlighting the gut microbiota as a novel target for chronotherapeutic strategies aimed at mitigating the metabolic consequences of circadian disruption. Recognizing and treating circadian-microbiome misalignment may provide a clinically actionable pathway to prevent or reverse chronic metabolic diseases in modern populations.},
}

Humans
*Gastrointestinal Microbiome/physiology
Circadian Rhythm/physiology
*Jet Lag Syndrome/complications/physiopathology/microbiology/therapy
*Metabolic Diseases/etiology
*Chronotherapy/methods
Melatonin/therapeutic use

@article {pmid41010985,
year = {2025},
author = {Petrelli, F and Ghidini, A and Dottorini, L and Ghidini, M and Zaniboni, A and Tomasello, G},
title = {Clinical Evidence for Microbiome-Based Strategies in Cancer Immunotherapy: A State-of-the-Art Review.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {9},
pages = {},
doi = {10.3390/medicina61091595},
pmid = {41010985},
issn = {1648-9144},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Immunotherapy/methods ; *Neoplasms/therapy ; Immune Checkpoint Inhibitors/therapeutic use ; Probiotics/therapeutic use ; },
abstract = {The gut microbiome has emerged as a critical determinant of immune-checkpoint inhibitor (ICI) efficacy. A narrative review of 95 clinical studies (2015-2025) shows that patients with greater gut microbial diversity and relative enrichment of commensals such as Akkermansia, Ruminococcus, and other short-chain fatty acid producers experience longer progression-free and overall survival, particularly in melanoma and non-small-cell lung cancer. Broad-spectrum antibiotics given within 30 days of ICI initiation and over-the-counter mixed probiotics consistently correlate with poorer outcomes. Early phase I/II trials of responder-derived fecal microbiota transplantation in ICI-refractory melanoma achieved objective response rates of 20-40%, while pilot high-fiber or plant-forward dietary interventions improved immunologic surrogates such as CD8[+] tumor infiltration. Machine-learning classifiers that integrate 16S or metagenomic profiles predict ICI response with an area under the ROC curve of 0.83-0.92. Methodological heterogeneity across sampling, sequencing, and clinical endpoints remains a barrier, underscoring the need for standardization and larger, well-powered trials.},
}

Humans
*Gastrointestinal Microbiome/drug effects/immunology
*Immunotherapy/methods
*Neoplasms/therapy
Immune Checkpoint Inhibitors/therapeutic use
Probiotics/therapeutic use

@article {pmid41010510,
year = {2025},
author = {Petropoulos, A and Stavropoulou, E and Tsigalou, C and Bezirtzoglou, E},
title = {Microbiota Gut-Brain Axis and Autism Spectrum Disorder: Mechanisms and Therapeutic Perspectives.},
journal = {Nutrients},
volume = {17},
number = {18},
pages = {},
doi = {10.3390/nu17182984},
pmid = {41010510},
issn = {2072-6643},
support = {//Democritus University of Thrace/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Autism Spectrum Disorder/microbiology/therapy/physiopathology ; Dysbiosis/microbiology/therapy ; *Brain/physiopathology ; Animals ; *Brain-Gut Axis ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; Gastrointestinal Diseases/microbiology ; },
abstract = {Background/Objectives: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition often accompanied by gastrointestinal (GI) symptoms and gut microbiota imbalances. The microbiota-gut-brain (MGB) axis is a bidirectional communication network linking gut microbes, the GI system, and the central nervous system (CNS). This narrative review explores the role of the MGB axis in ASD pathophysiology, focusing on communication pathways, neurodevelopmental implications, gut microbiota alteration, GI dysfunction, and emerging therapeutics. Methods: A narrative review methodology was employed. We searched major scientific databases including PubMed, Scopus, and Google Scholar for research on MGB axis mechanisms, gut microbiota composition in ASD, dysbiosis, leaky gut, immune activation, GI disorders, and intervention (probiotics, prebiotics, fecal microbiota transplantation (FMT), antibiotics and diet). Key findings from recent human, animal and in vitro studies were synthesized thematically, emphasizing mechanistic insights and therapeutic outcomes. Original references from the initial manuscript draft were retained and supplemented for comprehensiveness and accuracy. Results: The MGB axis involves neuroanatomical, neuroendocrine, immunological, and metabolic pathways that enable microbes to influence brain development and function. Individuals with ASD commonly exhibit gut dysbiosis characterized by reduced microbial diversity (notably lower Bifidobacterium and Firmicutes) and overpresentation of potentially pathogenic taxa (e.g., Clostridia, Desulfovibrio, Enterobacteriaceae). Dysbiosis is associated with increased intestinal permeability ("leaky gut") and newly activated and altered microbial metabolite profiles, such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPSs). Functional gastrointestinal disorders (FGIDs) are prevalent in ASD, linking gut-brain axis dysfunction to behavioral severity. Therapeutically, probiotics and prebiotics can restore eubiosis, fortify the gut barrier, and reduce neuroinflammation, showing modest improvements in GI and behavioral symptoms. FMT and Microbiota Transfer Therapy (MTT) have yielded promising results in open label trials, improving GI function and some ASD behaviors. Antibiotic interventions (e.g., vancomycin) have been found to temporarily alleviate ASD symptoms associated with Clostridiales overgrowth, while nutritional strategies (high-fiber, gluten-free, or ketogenic diets) may modulate the microbiome and influence outcomes. Conclusions: Accumulating evidence implicates the MGB axis in ASD pathogenesis. Gut microbiota dysbiosis and the related GI pathology may exacerbate neurodevelopmental and behavioral symptoms via immune, endocrine and neural routes. Interventions targeting the gut ecosystem, through diet modification, probiotics, symbiotics, or microbiota transplants, offer therapeutic promise. However, heterogeneity in findings underscores the need for rigorous, large-scale studies to clarify causal relationships and evaluate long-term efficacy and safety. Understanding MGB axis mechanisms in ASD could pave the way for novel adjunctive treatments to improve the quality of life for individuals with ASD.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Autism Spectrum Disorder/microbiology/therapy/physiopathology
Dysbiosis/microbiology/therapy
*Brain/physiopathology
Animals
*Brain-Gut Axis
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Prebiotics/administration & dosage
Gastrointestinal Diseases/microbiology

@article {pmid41010468,
year = {2025},
author = {Forcina, G and Di Filippo, P and De Biasio, D and Cesaro, FG and Frattolillo, V and Massa, A and De Cesare, M and Marzuillo, P and Miraglia Del Giudice, E and Di Sessa, A},
title = {Targeting the Gut Microbiota in Pediatric Obesity: A Paradigm Shift in Prevention and Treatment? A Comprehensive Review.},
journal = {Nutrients},
volume = {17},
number = {18},
pages = {},
doi = {10.3390/nu17182942},
pmid = {41010468},
issn = {2072-6643},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Pediatric Obesity/microbiology/therapy/prevention & control ; Probiotics/therapeutic use/administration & dosage ; Child ; Prebiotics/administration & dosage ; Fecal Microbiota Transplantation ; Dysbiosis/therapy ; Synbiotics/administration & dosage ; },
abstract = {Pediatric obesity represents a growing global health challenge, closely associated with increased cardiometabolic risk and long-term adverse outcomes. Although lifestyle modifications remain the cornerstone of treatment, sustained success is often limited. Emerging evidence suggests that the gut microbiota (GM) plays a pivotal role in the pathogenesis of obesity, influencing host metabolism, energy homeostasis, and systemic inflammation. This narrative review aims to provide a comprehensive and up-to-date overview of the complex interplay between GM and pediatric obesity, with a particular emphasis on microbiota-targeted interventions. These include probiotics, prebiotics, synbiotics, postbiotics, dietary modulation, and fecal microbiota transplantation (FMT). Findings from preclinical studies and early-phase clinical trials indicate that gut dysbiosis may contribute to obesity-related mechanisms, such as altered nutrient absorption, increased adiposity, and dysregulated appetite control. Interventions targeting the microbiota have shown promise in modulating inflammatory pathways and improving metabolic profiles. While preliminary findings underscore the potential of the GM as a novel adjunctive target in managing pediatric obesity, current evidence remains heterogeneous, and robust clinical pediatric data are limited. Further research is needed to clarify the therapeutic efficacy, safety, and long-term outcomes of microbiota-modulating strategies in children with obesity.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Pediatric Obesity/microbiology/therapy/prevention & control
Probiotics/therapeutic use/administration & dosage
Child
Prebiotics/administration & dosage
Fecal Microbiota Transplantation
Dysbiosis/therapy
Synbiotics/administration & dosage

@article {pmid41010451,
year = {2025},
author = {Jiang, Z and Zhu, J and Shen, Z and Gao, L and Chen, Z and Zhang, L and Wang, Q},
title = {The Microecological-Immune Axis in Pediatric Allergic Diseases: Imbalance Mechanisms and Regulatory Interventions.},
journal = {Nutrients},
volume = {17},
number = {18},
pages = {},
doi = {10.3390/nu17182925},
pmid = {41010451},
issn = {2072-6643},
support = {(2025KYCX1-A04//Wuhan Yaxin General Hospital Scientific Research and Innovation Fund Key Projects/ ; WCYY2022K02//Wuhan Wuchang Hospital Scientific Research and Innovation Fund Key Projects/ ; },
mesh = {Humans ; *Hypersensitivity/immunology/microbiology/therapy ; Child ; *Dysbiosis/immunology ; *Gastrointestinal Microbiome/immunology ; Probiotics/administration & dosage ; Prebiotics/administration & dosage ; *Microbiota/immunology ; Lung/immunology/microbiology ; Skin/immunology/microbiology ; Asthma/immunology/microbiology ; },
abstract = {In recent years, the global prevalence of pediatric allergic diseases-including atopic dermatitis, allergic rhinitis, and asthma-has increased significantly. Accumulating evidence underscores the pivotal role of the microbiota-immune axis in the regulation of immune tolerance, wherein microbial dysbiosis is a critical driver in the onset and progression of these conditions. Notably, reduced microbial diversity and imbalanced proportions can also cause immune dysregulation and cross-organ signaling. The skin-lung-gut axis has emerged as a key conduit for multi-organ immune communication. Microbial communities at barrier sites not only mediate local immune homeostasis but also influence distant organs through metabolite production and immune signaling pathways, forming a complex network of organ crosstalk. This mechanism is integral to the maintenance of both innate (e.g., epithelial barrier integrity and phagocytic activity) and adaptive (e.g., the Type 1/Type 2 cytokine balance and regulatory T cell function) immunity, thereby suppressing allergic inflammation. Early microbial colonization is crucial for immune system maturation, and its perturbation is strongly linked to abnormal allergic immune responses. As such, the skin-lung-gut axis functions as a cross-organ microecological-immune regulatory network that is particularly relevant in the context of infantile allergic disorders. Intervention strategies targeting the microbiota-including probiotics, prebiotics, synbiotics, and postbiotics-have demonstrated potential in modulating host immunity. Furthermore, emerging approaches such as engineered probiotics, advanced delivery systems, and fecal microbiota transplantation (FMT) offer promising therapeutic avenues. This review provides a comprehensive overview of microbiota development in early life, its association with allergic disease pathogenesis, and the current progress in microbiota-targeted interventions, offering a theoretical foundation for individualized prevention and treatment strategies.},
}

Humans
*Hypersensitivity/immunology/microbiology/therapy
Child
*Dysbiosis/immunology
*Gastrointestinal Microbiome/immunology
Probiotics/administration & dosage
Prebiotics/administration & dosage
*Microbiota/immunology
Lung/immunology/microbiology
Skin/immunology/microbiology
Asthma/immunology/microbiology

@article {pmid41009869,
year = {2025},
author = {Kocsis, B and Szabó, D and Sipos, L},
title = {Gut Microbiome and Intestinal Colonization with Multidrug-Resistant Strains of Enterobacterales: An Interplay Between Microbial Communities.},
journal = {Antibiotics (Basel, Switzerland)},
volume = {14},
number = {9},
pages = {},
doi = {10.3390/antibiotics14090890},
pmid = {41009869},
issn = {2079-6382},
support = {No "0272//HUN-REN-SU, Human Microbiota Study Group/ ; Janos Bolyai Scholarship (BO/00286/22/5)//Hungarian Academy of Sciences./ ; 952491-AmReSu//European Union's Horizon 2020/ ; },
abstract = {Background: The intestinal tract is a host to a high number of diverse bacteria, and the presence of multidrug-resistant (MDR) Enterobacterales strains acts as a reservoir and a source of infection. The interactions between the intestinal microbiome and colonizer Enterobacterales strains influence long-lasting colonization. Aims: In this narrative review, we summarize available data about the intestinal colonization of MDR Enterobacterales strains and correlations between colonization and the intestinal microbiome. Results: Several endogenous and exogenous factors influence the intestinal colonization of MDR Enterobacterales strains. On the gut microbiome level, the intestinal microbial community is composed of the Lachnospiraceae family (e.g., Lachnoclostridium, Agathobacter, Roseburia, Tyzzerella), which indicates a protective role against colonizer MDR Enterobacterales strains; by contrast, a high abundance of Enterobacterales correlates with the colonization of MDR Enterobacterales strains. In specific patient groups, striking differences in microbiome composition can be detected. Among hematopoietic stem-cell-transplanted patients colonized by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, a greater abundance of Bifidobacterium, Blautia, Clostridium, Coprococcus, L-Ruminococcus, Mogibacteriaceae, Peptostreptococceae and Oscillospira was observed compared to patients not colonized by ESBL-producing strains, who had a greater abundance of Actinomycetales. In liver transplant patients, a reduction in the alpha-diversity of the intestinal microbiome in fecal samples correlates with the carriage of MDR Enterobacterales. Conclusions: Intestinal colonization with MDR Enterobacterales is a multifactorial process that involves the MDR strain (e.g., its plasmids, fimbria), host and mucosal factors (e.g., IgA and defensin) and exogenous factors (e.g., use of antibiotics, hospitalization). On the gut microbiome level, the Lachnospiraceae family is dominant among intestines not colonized by MDR strains, but a high abundance of Enterobacterales was correlated with colonization with MDR Enterobacterales strains.},
}

@article {pmid41009471,
year = {2025},
author = {Miftode, IL and Vâţă, A and Miftode, RŞ and Oancea, AF and Pasăre, MA and Parângă, TG and Miftode, EG and Mititiuc, IL and Radu, VD},
title = {The Gut Microbiome and Colistin Resistance: A Hidden Driver of Antimicrobial Failure.},
journal = {International journal of molecular sciences},
volume = {26},
number = {18},
pages = {},
doi = {10.3390/ijms26188899},
pmid = {41009471},
issn = {1422-0067},
mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Colistin/pharmacology/therapeutic use ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Animals ; *Drug Resistance, Bacterial/genetics ; Gene Transfer, Horizontal ; },
abstract = {Colistin, a polymyxin antibiotic reintroduced as a last-resort therapy against multidrug-resistant Gram-negative bacteria, is increasingly being compromised by the emergence of plasmid-mediated colistin resistance genes (mcr-1 to mcr-10). The human gut microbiota serves as a major reservoir and transmission hub for these resistance determinants, even among individuals without prior colistin exposure. This review explores the mechanisms, dissemination, and clinical implications of mcr-mediated colistin resistance within the gut microbiota, highlighting its role in horizontal gene transfer, colonization, and environmental persistence. A comprehensive synthesis of the recent literature was conducted, focusing on epidemiological studies, molecular mechanisms, neonatal implications and decolonization strategies. The intestinal tract supports the enrichment and exchange of mcr genes among commensal and pathogenic bacteria, especially under antibiotic pressure. Colistin use in agriculture has amplified gut colonization with resistant strains in both animals and humans. Surveillance gaps remain, particularly in neonatal populations, where colonization may occur early and persist silently. Promising interventions, such as fecal microbiota transplantation and phage therapies, are under investigation but lack large-scale clinical validation. The gut microbiome plays a central role in the global spread of colistin resistance. Mitigating this threat requires integrated One Health responses, improved diagnostics for gut colonization, and investment in microbiome-based therapies. A proactive, multisectoral approach is essential to safeguard colistin efficacy and address the expanding threat of mcr-mediated resistance.},
}

*Gastrointestinal Microbiome/drug effects
Humans
*Colistin/pharmacology/therapeutic use
*Anti-Bacterial Agents/pharmacology/therapeutic use
Animals
*Drug Resistance, Bacterial/genetics
Gene Transfer, Horizontal

@article {pmid41008952,
year = {2025},
author = {Huang, W and Lv, Y and Zou, C and Ge, C and Zhan, S and Shen, X and Wu, L and Wang, X and Yuan, H and Lin, G and Yu, D and Liu, B},
title = {Mangosteen Pericarp Extract Mitigates Diquat-Induced Hepatic Oxidative Stress by NRF2/HO-1 Activation, Intestinal Barrier Integrity Restoration, and Gut Microbiota Modulation.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {9},
pages = {},
doi = {10.3390/antiox14091045},
pmid = {41008952},
issn = {2076-3921},
support = {32402779//National Natural Science Foundation of China/ ; ZCLMS25C1701//Zhejiang Provincial Natural Science Foundation/ ; 2024GZ39//Public Welfare and Applied Research Project of Huzhou Science and Technology Bureau/ ; },
abstract = {Poultry production exposes birds to diverse environmental and physiological stressors that disrupt redox balance, impair gut-liver axis function, and undermine health and productivity. This study investigated the hepatoprotective and antioxidative effects of mangosteen pericarp extract (MPE) in an experimental model of diquat-induced oxidative stress in laying hens. A total of 270 Hy-Line White laying hens were randomly assigned to three groups: control group (CON), diquat-challenged group (DQ), and MEP intervention with diquat-challenged group (MQ), with six replicates of 15 birds each. The results showed that MPE supplementation effectively mitigated the hepatic oxidative damage caused by diquat, as evidenced by the increased ALT and AST activity, improved lipid metabolism, and reduced hepatic fibrosis. Mechanistically, MPE activated the NRF2/HO-1 antioxidant pathway, thus enhancing the liver's ability to counteract ROS-induced damage and reducing lipid droplet accumulation in liver tissue. MPE supplementation restored intestinal barrier integrity by upregulating tight junction protein expression (Occludin-1 and ZO-1), enhancing MUC-2 expression, and thereby decreasing gut microbiota-derived LPS transferring from the intestine. Additionally, MPE also modulated gut microbiota composition by enriching beneficial bacterial genera such as Lactobacillus and Ruminococcus while suppressing the growth of potentially harmful taxa (e.g., Bacteroidales and UCG-010). Fecal microbiota transplantation (FMT) from MPE-treated donors into diquat-exposed recipients reproduced these beneficial effects, further highlighting the role of gut microbiota modulation in mediating MPE's systemic protective actions. Together, these findings demonstrated that MPE alleviated DQ-induced liver injury and oxidative stress through a combination of antioxidant activity, protection of intestinal barrier function, and modulation of gut microbiota, positioning MPE as a promising natural strategy for mitigating oxidative stress-related liver damage by regulating the gut microbiota and gut-liver axis in poultry.},
}

@article {pmid41008344,
year = {2025},
author = {Logan, AC and Cordell, B and Pillai, SD and Robinson, JM and Prescott, SL},
title = {From Bacillus Criminalis to the Legalome: Will Neuromicrobiology Impact 21st Century Criminal Justice?.},
journal = {Brain sciences},
volume = {15},
number = {9},
pages = {},
doi = {10.3390/brainsci15090984},
pmid = {41008344},
issn = {2076-3425},
abstract = {The idea that gut microbes or a "bacillus of crime" might promote criminal behavior was popularized in the early 20th century. Today, advances in neuromicrobiology and related omics technologies are lending credibility to the idea. In recent cases of dismissal of driving while intoxicated charges, courts in the United States and Europe have acknowledged that gut microbes can manufacture significant amounts of systemically available ethanol, without a defendant's awareness. Indeed, emergent research is raising difficult questions for criminal justice systems that depend on prescientific notions of free moral agency. Evidence demonstrates that gut microbes play a role in neurophysiology, influencing cognition and behaviors. This may lead to justice involvement via involuntary intoxication, aggression, anger, irritability, and antisocial behavior. Herein, we discuss these 'auto-brewery syndrome' court decisions, arguing that they portend a much larger incorporation of neuromicrobiology and multi-omics science within the criminal justice system. The legalome, which refers to the application of gut microbiome and omics sciences in the context of forensic psychiatry/psychology, will likely play an increasing role in 21st century criminal justice. The legalome concept is bolstered by epidemiology, mechanistic bench science, fecal transplant studies, multi-omics and polygenic research, Mendelian randomization work, microbiome signature research, and human intervention trials. However, a more robust body of microbiota-gut-brain axis research is needed, especially through the lens of prevention, intervention, and rehabilitation. With ethical guardrails in place, greater inclusion of at-risk or justice-involved persons in brain science and microbiome research has the potential to transform justice systems for the better.},
}

@article {pmid41007859,
year = {2025},
author = {Wang, J and Chao, J},
title = {Alveolar Epithelial Cell Dysfunction in Acute Respiratory Distress Syndrome: Mechanistic Insights and Targeted Interventions.},
journal = {Biomedicines},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/biomedicines13092299},
pmid = {41007859},
issn = {2227-9059},
support = {82373547//National Natural Science Foundation of China/ ; BF2024054//Jiangsu Province Science and Technology Plan Project/ ; },
abstract = {Acute respiratory distress syndrome (ARDS) is a life-threatening condition with high mortality. A central driver in its pathogenesis is alveolar epithelial cell (AEC) dysfunction, which leads to disruption of the epithelial barrier, impaired fluid clearance, and dysregulated inflammatory responses. This review summarizes the key mechanisms underlying AEC injury, including programmed cell death (apoptosis, pyroptosis, necroptosis, ferroptosis), oxidative stress, mitochondrial dysfunction, epigenetic reprogramming (DNA methylation, histone modifications), metabolic rewiring (succinate accumulation), and spatiotemporal heterogeneity revealed by single-cell sequencing and spatial transcriptomics. Multicellular crosstalk involving epithelial-immune-endothelial networks and the gut-lung axis further shapes disease progression. Building on these mechanistic foundations, we evaluate emerging AEC-targeted interventions such as pharmacologic agents (antioxidants, anti-inflammatories), biologics (mesenchymal stem cells and engineered exosomes), and gene-based approaches (adeno-associated virus and CRISPR-Cas9 systems delivered via smart nanocarriers). Complementary strategies include microbiome modulation through probiotics, short-chain fatty acids, or fecal microbiota transplantation, and biomarker-guided precision medicine (e.g., sRAGE, exosomal miRNAs) to enable promise individualized regimens. We also discuss translational hurdles, including nanotoxicity, mesenchymal stem cell (MSC) heterogeneity, and gene-editing safety, and highlight future opportunities involving AI-driven multi-omics, lung-on-chip platforms, and epithelium-centered regenerative therapies. By integrating mechanistic insights with innovative therapeutic strategies, this review aims to outline a roadmap toward epithelium-targeted, precision-guided therapies for ARDS.},
}

@article {pmid41007736,
year = {2025},
author = {Borrego-Ruiz, A and Borrego, JJ},
title = {The Gut Microbiome in Human Obesity: A Comprehensive Review.},
journal = {Biomedicines},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/biomedicines13092173},
pmid = {41007736},
issn = {2227-9059},
abstract = {An estimated 2.6 billion individuals are currently living with overweight or obesity, and this number is projected to exceed 4 billion by 2035. Consequently, unless this increasing trajectory is effectively addressed, the trend is expected to continue in the coming years. The gut microbiome has emerged as a central regulator of host metabolism and energy homeostasis, making its detailed characterization crucial for the advancement of innovative therapeutic strategies and for elucidating mechanisms underlying metabolic health and disease. This review examines human obesity through the lens of the gut microbiome, providing a comprehensive overview of its role by addressing gut microbiome alterations, microbiome-driven mechanisms, dietary influences, prebiotic effects, microbiome-based therapeutics, and other approaches in the treatment of obesity and related metabolic disorders. The composition of the gut microbiome is altered in obesity and characterized by reduced microbial diversity and inconsistent shifts in dominant bacterial phyla, which collectively contribute to metabolic dysregulation. The gut microbiome influences obesity through multiple mechanisms. These include regulating energy balance and insulin sensitivity via short-chain fatty acids, inducing chronic inflammation, modulating metabolic and appetite genes, altering bile acid signaling, and promoting fat storage by inhibiting fasting-induced adipose factor. Dietary patterns exert a profound influence on gut microbiome composition and function, with plant-based diets conferring protective effects against obesity and its comorbidities. Microbiome-based therapeutics, including probiotics, synbiotics, and fecal microbiota transplantation, have demonstrated potential in modulating key metabolic and inflammatory pathways associated with obesity. As the scientific understanding of the human gut microbiome continues to advance, the integration of microbiome-based therapies into standard clinical practice is poised to become increasingly feasible and therapeutically transformative, particularly for obesity, a complex condition that demands innovative and customized interventions.},
}

@article {pmid41007706,
year = {2025},
author = {Caserta, S and Alvaro, ME and Penna, G and Fazio, M and Stagno, F and Allegra, A},
title = {Gut Microbiota Dysbiosis and Dietary Interventions in Non-Hodgkin B-Cell Lymphomas: Implications for Treatment Response.},
journal = {Biomedicines},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/biomedicines13092141},
pmid = {41007706},
issn = {2227-9059},
abstract = {Non-Hodgkin B-cell lymphomas are a heterogeneous group of lymphoid malignancies with variable biological behavior, clinical presentation and treatment response. While chemoimmunotherapy remains the cornerstone of their management, growing evidence implicates the gut microbiota as a critical modulator of both lymphomagenesis and therapeutic efficacy. Gut microbiota dysbiosis, characterized by reduced microbial diversity and pathogenic taxonomic shifts, has been observed also in newly diagnosed patients and not just after therapy. This microbial imbalance contributes to mucosal barrier disruption, systemic inflammation, and altered immune responses, affecting treatment outcomes and toxicity profiles. Antibiotic exposure, especially broad-spectrum agents, exacerbates dysbiosis and has been associated with inferior responses to immunochemotherapy and CAR T-cell therapy. Conversely, certain commensal taxa, like Faecalibacterium prausnitzii and Lactobacillus johnsonii, may exert protective effects by preserving mucosal homeostasis and promoting antitumor immunity. Targeted interventions, including prudent antibiotic stewardship, prebiotics, probiotics, dietary modulation, and fecal microbiota transplantation, are under investigation to restore eubiosis and improve clinical outcomes. Preliminary clinical trials suggest a strong correlation between baseline microbiome composition and therapeutic response. Further mechanistic studies and randomized trials are warranted to define the causal role of the microbiome in non-Hodgkin B-cell lymphomas pathophysiology and to develop personalized microbiome-modulating strategies as adjuncts to standard treatment.},
}

@article {pmid41007667,
year = {2025},
author = {Dziedziak, M and Mytych, A and Szyller, HP and Lasocka, M and Augustynowicz, G and Szydziak, J and Hrapkowicz, A and Dyda, M and Braksator, J and Pytrus, T},
title = {Gut Microbiota in Psychiatric and Neurological Disorders: Current Insights and Therapeutic Implications.},
journal = {Biomedicines},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/biomedicines13092104},
pmid = {41007667},
issn = {2227-9059},
abstract = {Recent studies increasingly highlight the complex interaction between gut microbiota and mental health, drawing attention to the role of the microbiota-gut-brain axis (MGBA) in the pathophysiology of mental and neurodevelopmental disorders. Changes in the composition of the gut microbiota-dysbiosis-are associated with conditions such as depression, schizophrenia, bipolar disorder (BD), autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and neurodegenerative diseases such as Parkinson's and Alzheimer's. These microbial imbalances can affect brain function through a variety of mechanisms, including activation of the immune system, alteration of intestinal permeability, modulation of the digestive and central nervous systems, and changes in the production of neuroactive metabolites such as short-chain fatty acids, serotonin, and tryptophan derivatives. The aim of this paper is to review the current state of knowledge on therapeutic strategies targeting the gut microbiome-including probiotics, prebiotics, synbiotics, personalized dietary interventions, and fecal microbiota transplantation (FMT)-which are becoming promising adjuncts or alternatives to conventional psychopharmacology, offering a forward-looking and individualized approach to mental health treatment. Understanding the bidirectional and multifactorial nature of MGBA may pave the way for new, integrative treatment paradigms in psychiatry and neurology, requiring further research and exploration of their scope of application.},
}

@article {pmid40716981,
year = {2025},
author = {Wang, Y and Bao, J and Chen, B and Zhang, F and Cui, B},
title = {Successful management of oral manifestations of Behcet's disease and Sjogren's disease using washed microbiota transplantation: a case report.},
journal = {Oral surgery, oral medicine, oral pathology and oral radiology},
volume = {140},
number = {5},
pages = {e147-e152},
doi = {10.1016/j.oooo.2025.06.017},
pmid = {40716981},
issn = {2212-4411},
mesh = {Humans ; *Behcet Syndrome/complications/therapy ; Female ; *Sjogren's Syndrome/complications/therapy ; Adult ; *Oral Ulcer/therapy/etiology/microbiology ; Xerostomia/therapy/etiology ; *Fecal Microbiota Transplantation ; Dry Eye Syndromes/therapy/etiology ; },
abstract = {Recurrent oral ulcers is a characteristic of Behcet's disease (BD), while xerostomia typifies Sjogren's disease (SD), with emerging evidence implicating gut dysbiosis in their pathogenesis through oral-gut axis interactions. This case report describes a 36-year-old woman with BD and SD who presented with refractory oral ulcers, xerostomia, and dry eyes. Despite conventional therapy, her symptoms persisted until she underwent washed microbiota transplantation (WMT) to address concurrent gut dysbiosis. Remarkably, within 3 months, the frequency of oral ulcers decreased with quicker healing, and dry eye symptoms resolved completely. Two years later, sustained improvement was confirmed, allowing for discontinuation of hydroxychloroquine. Microbial analyses showed a significant difference in the gut and oral microbiota before and after WMT. These findings suggest WMT may offer a novel therapeutic approach for refractory oral manifestations in BD and SD.},
}

Humans
*Behcet Syndrome/complications/therapy
Female
*Sjogren's Syndrome/complications/therapy
Adult
*Oral Ulcer/therapy/etiology/microbiology
Xerostomia/therapy/etiology
*Fecal Microbiota Transplantation
Dry Eye Syndromes/therapy/etiology

@article {pmid41006438,
year = {2025},
author = {Prylińska-Jaśkowiak, M and Tabisz, H and Kujawski, S and Godlewska, BR and Słomko, J and Januszko-Giergielewicz, B and Murovska, M and Morten, KJ and Sokołowski, Ł and Zalewski, P},
title = {The gut microbial composition is different in chronic fatigue syndrome than in healthy controls.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33075},
pmid = {41006438},
issn = {2045-2322},
abstract = {The pathogenesis of Chronic Fatigue Syndrome (CFS) is yet unknown. This study aimed to assess the gut microbial composition in CFS patients versus in healthy controls (HCs). The composition of fecal bacteria was examined in twenty-five CFS patients and sixteen HCs using Illumina sequencing of 16 S rRNA gene amplicons targeting the V3-V4 bacterial gene regions. 143 (46%) of the microbial genera were found only in the CFS. In addition, the gut microbial composition in the CFS patients contained a much higher proportion of the 10 most commonly found bacteria compared to the HCs group. A significantly lower observed number of operational taxonomic units (OTUs) was noted in CFS compared to HCs (p = 0.045). Significant between-group differences in the gut microbial composition in CFS compared to HCs were noted. The three most discriminating Amplicon Sequencing Variants (ASVs): ASV 191, ASV 44, and ASV 75, were identified as significantly more abundant in the healthy control group compared to the patient group. In addition, the Neural Network (multilayer perceptron) was able to discriminate gut microbial composition from CFS versus HCs with excellent performance (AUC = 0.935). The gut microbial composition is different in CFS patients compared to HCs. Further studies should assess the pathophysiological consequences of these differences as well as the effectiveness of therapies aimed at modifying the gut microbial composition in CFS patients.},
}

@article {pmid41005300,
year = {2025},
author = {Zhao, CN and Li, SS and Yau, T and Chen, WQ and Ji, R and Guan, XY and Kong, FS},
title = {Phocaeicola vulgatus induces immunotherapy resistance in hepatocellular carcinoma via reducing indoleacetic acid production.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {102370},
doi = {10.1016/j.xcrm.2025.102370},
pmid = {41005300},
issn = {2666-3791},
abstract = {Immunotherapy has made remarkable achievements in various cancers, but response rates in hepatocellular carcinoma (HCC) remain highly variable. Understanding mechanisms behind this heterogeneity and identifying responsive patients are urgent clinical challenges. In this study, the metagenomic analysis of 65 HCC patients reveals distinct gut microbiota profiles distinguishing responders (Rs) from non-responders (NRs). These findings are further validated through fecal microbiota transplantation (FMT) in mouse models. Notably, Phocaeicola vulgatus (P. vulgatus) is enriched in NRs and diminishes anti-PD-1 efficacy in both syngeneic and orthotopic tumor models. Mechanistically, P. vulgatus suppresses the production of indoleacetic acid (IAA), thereby weakening interferon (IFN)-γ[+] and granzyme B (GzmB)[+]CD8[+] T cells and impairing the antitumor immune response. Furthermore, supplementation with IAA restores CD8[+] T cell cytotoxicity and counteracts the immune-suppressive effects of P. vulgatus. Our findings establish a causal relationship between P. vulgatus and anti-PD-1 resistance in HCC, highlighting IAA as a potential therapeutic target to enhance immunotherapy outcomes.},
}

@article {pmid41005008,
year = {2025},
author = {Jia, R and Xiao, CX and Zhang, YH and Hu, LY and Jun-Jun, Y and Zuo, R and Hu, YF and Xie, YH and Ma, XL and Li, Q and Hou, KJ},
title = {Microbiota in drug resistance.},
journal = {Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy},
volume = {84},
number = {},
pages = {101311},
doi = {10.1016/j.drup.2025.101311},
pmid = {41005008},
issn = {1532-2084},
abstract = {Drug resistance, particularly those of anticancer drugs and antibiotics, poses a significant challenge in the treatment of diseases, severely compromising therapeutic efficacy and patient survival rates. In recent years, an increasing number of studies have highlighted the dual role of microbiota in either promoting or mitigating drug resistance. The microbiome exists in symbiosis with the host, playing a crucial role in maintaining physiological functions and regulating immune responses. However, dysbiosis within the microbial community may induce or exacerbate drug resistance. While antibiotic-mediated depletion of gut microbiota has been proposed as a strategy to combat resistance, it may paradoxically lead to increased resistance or even worsen treatment outcomes. In this review, we focus on anticancer and antimicrobial agents as representative examples to elucidate the association of microbiome and drug resistance. We provide a detailed discussion on the mechanisms by which microbial dysbiosis contributes to development of drug resistance. Additionally, we systematically summarize the latest advancements in microbiota-targeted therapeutic strategies aimed at overcoming resistance, including fecal microbiota transplantation, probiotics and prebiotics, and bacterial engineering approaches. Finally, we discuss the potential clinical applications of microbiota-modulating strategies for overcoming drug resistance and examine the current challenges and future research directions in this field.},
}

@article {pmid41004024,
year = {2025},
author = {Longo, M and Rubio, T and Lamelas, A and Jericó, D and Rodenes-Gavidia, A and Cervero, J and Martínez-Blanch, J and Chenoll, E and Martorell, P and Paolini, E and Meroni, M and Riezu-Boj, JI and Solares, I and Sampedro, A and Urigo, F and Collantes, M and Battistin, M and Gatti, S and Quincoces, G and Peñuelas, I and Moreno-Aliaga, MJ and Ávila, MA and Di Pierro, E and Ramón, D and Milagro, FI and Dongiovanni, P and Fontanellas, A},
title = {Oral lipoteichoic and lipoic acids improve insulin resistance and body composition in porphyria mice on a high-carbohydrate diet.},
journal = {Journal of physiology and biochemistry},
volume = {},
number = {},
pages = {},
pmid = {41004024},
issn = {1877-8755},
abstract = {Acute intermittent porphyria (AIP) is a genetic metabolic disorder characterized by neurovisceral attacks. Although high-carbohydrate diets or intravenous glucose administration can help alleviate incipient attacks in patients, these interventions may also promote insulin resistance and increase metabolic risk. This study explored targeted dietary interventions to manage hyperinsulinemia and to enhance glucose uptake in insulin-sensitive organs under high-carbohydrate diet. Body composition and fecal microbiota profile were also investigated in a murine model of the disease. Wild-type and AIP mice (n = 6/group) were supplemented with tapioca maltodextrin in drinking water for 12 weeks, alongside heat-treated Bifidobacterium animalis subsp. lactis CECT-8145 (BPL1®HT), its by-product lipoteichoic acid (LTA), or the insulin-sensitizing agent α-lipoic acid (α-LA). Liver-targeted therapies, previously assessed in AIP mice, were also included in this study. AIP mice on a high-carbohydrate diet exhibited hyperinsulinemia and tissue-specific differences in glucose uptake compared to wild-type mice. Dysbiosis, marked by reduced fecal Dorea spp. and Adlercreutzia muris, alongside higher abundance of Escherichia coli, was also showed. Supplementation with α-LA and LTA revealed superior ability to improve glucose tolerance test and skeletal muscle glucose uptake, reduce hyperinsulinemia, and enhance body composition by increasing lean mass relative to fat, compared to gene therapy or liver-targeted insulin administration. Notably, LTA restored fecal microbiota profiles resembling those of wild-type mice. In conclusion, supplementation with LTA from BPL1®HT and α-LA may represent promising dietary interventions to manage glucose tolerance, improve insulin sensitivity in muscle and adipose tissues, and potentially ameliorate body composition in AIP patients under a high-carbohydrate diet.},
}

@article {pmid41003873,
year = {2025},
author = {Sadeghloo, Z and Sadeghi, A},
title = {Gut microbiota as a hidden modulator of chemotherapy: implications for colorectal cancer treatment.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {1717},
pmid = {41003873},
issn = {2730-6011},
abstract = {Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide, with chemotherapy remaining a cornerstone of treatment. Emerging evidence reveals that the gut microbiota significantly influences the metabolism, efficacy, and toxicity of chemotherapeutic agents such as 5-fluorouracil, irinotecan, and oxaliplatin. Microbial enzymes-most notably β-glucuronidases-can reactivate drug metabolites, contributing to adverse effects like mucositis and diarrhea. Additionally, certain bacterial species promote chemoresistance by modulating host immune responses and tumor microenvironments. This review highlights the critical role of the gut microbiota in shaping the efficacy and toxicity of chemotherapy in colorectal cancer, with a focus on microbial metabolism, chemoresistance, and microbiota-targeted therapies. Microbiota-targeted interventions-including probiotics, prebiotics, fecal microbiota transplantation (FMT), and enzyme inhibitors-represent promising strategies to improve treatment outcomes and mitigate toxicity. Enhanced understanding of microbiota-drug interactions is crucial for personalizing chemotherapy regimens, optimizing therapeutic efficacy, and minimizing adverse effects. The gut microbiota thus serves as both a key modulator and a potential therapeutic target in CRC.},
}

@article {pmid41002952,
year = {2025},
author = {Ji, M and Ji, M and Zhong, Y and Shao, L},
title = {Gut Microbiota in Acute Myeloid Leukemia: From Biomarkers to Interventions.},
journal = {Metabolites},
volume = {15},
number = {9},
pages = {},
doi = {10.3390/metabo15090568},
pmid = {41002952},
issn = {2218-1989},
abstract = {Acute myeloid leukemia (AML), the most common acute leukemia among adults, poses significant therapeutic challenges due to diagnostic limitations and the frequent development of treatment resistance. While genomics-based approaches have advanced, DNA aberrations do not always reflect the expression levels of genes and proteins, which are more tightly connected to disease phenotypes. Recently, the role of the gut microbiota in AML has gained increasing attention. AML patients often exhibit gut microbiota dysbiosis, which is linked to disease progression and heightened infection risk. Mounting evidence indicates that gut microbiota metabolism influences hematopoiesis and immune function via the "gut-bone marrow axis," with microbiota composition and diversity significantly affecting treatment outcomes and prognosis. High-throughput sequencing and metabolomics have identified correlations between gut microbiota composition and its metabolic products with AML clinical characteristics, paving the way for new biomarkers in diagnosis and prognosis. Additionally, treatments such as fecal microbiota transplantation (FMT) show promise in enhancing chemotherapy efficacy and improving patient outcomes. This review highlights recent advances in understanding the role of the gut microbiota in AML and explores new perspectives for its diagnosis and treatment.},
}

@article {pmid41001760,
year = {2025},
author = {Jiang, L and Li, M and Zhao, Z},
title = {Intra-tumoral microbial heterogeneity of breast cancer: roles in tumorigenesis, therapeutic responses, and future directions.},
journal = {Journal of applied microbiology},
volume = {136},
number = {9},
pages = {},
doi = {10.1093/jambio/lxaf230},
pmid = {41001760},
issn = {1365-2672},
support = {82274296//National Natural Science Foundation of China/ ; 82473449//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Breast Neoplasms/microbiology/therapy/pathology ; Female ; *Carcinogenesis ; *Microbiota ; Tumor Microenvironment ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Gastrointestinal Microbiome ; },
abstract = {Recent advances in microbiome research have revealed that tumor-resident microbiota are not passive bystanders but active contributors to the progression of breast cancer. Similar to the well-characterized gut-breast microbiota axis, emerging evidence points to intricate interactions between intra-tumoral microbiota and breast cancer with implications for carcinogenesis, therapeutic response, and future directions. Intra-tumoral microbes have been shown to initiate inflammation, modulate tumor microenvironment, alter drug metabolism, and produce bioactive metabolites that influence tumor cell proliferation, apoptosis, and epithelial-mesenchymal transition. Distinct microbial signatures have been associated with specific molecular subtypes of breast cancer and may serve as predictive biomarkers for prognosis. Furthermore, dysbiosis within the tumor-resident microbiota has been linked to the development of treatment resistance, including chemotherapy, immunotherapy, and endocrine therapy. Preclinical studies support the feasibility of modulating the microbiota via using antibiotics, probiotics, fecal microbiota transplantation, or bacteriophage-based strategies to enhance antitumor efficacy and overcome resistance. This review summarizes current knowledge on the biological roles of tumor-resident microbiota in breast cancer, highlights subtype-specific microbial patterns and host-microbe interactions, and explores microbiota-targeted interventions as promising adjuncts in overcoming drug resistance.},
}

Humans
*Breast Neoplasms/microbiology/therapy/pathology
Female
*Carcinogenesis
*Microbiota
Tumor Microenvironment
Dysbiosis/microbiology
Probiotics/therapeutic use
Gastrointestinal Microbiome

@article {pmid41001122,
year = {2025},
author = {Bahitham, W and Banoun, Y and Aljahdali, M and Almuaiqly, G and Bahshwan, SM and Aljahdali, L and Sanai, FM and Rosado, AS and Sergi, CM},
title = {"Trust your gut": exploring the connection between gut microbiome dysbiosis and the advancement of Metabolic Associated Steatosis Liver Disease (MASLD)/Metabolic Associated Steatohepatitis (MASH): a systematic review of animal and human studies.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1637071},
pmid = {41001122},
issn = {2296-861X},
abstract = {Metabolic Associated Steatosis Liver Disease (MASLD) and its advanced form, Metabolic Associated Steatohepatitis (MASH), represent growing global health concerns closely linked to obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. The gut microbiome has emerged as a key modulator in MASLD pathogenesis through the gut-liver axis, influencing hepatic fat accumulation, inflammation, and fibrosis via microbial metabolites and immune responses. Dysbiosis-characterized by altered microbial diversity and composition-contributes to hepatic lipid dysregulation, systemic inflammation, and impaired bile acid signaling. Metabolites such as short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and ethanol play critical roles in disease progression. Recent innovations in precision medicine, including microbiome profiling, metabolomics, and genomics, offer promising diagnostic and therapeutic strategies. Targeted probiotics, fecal microbiota transplantation (FMT), and personalized dietary interventions are under investigation for modulating the gut microbiome. This systematic review, conducted in accordance with PRISMA 2020 guidelines, is the first to comprehensively integrate both animal and human studies on MASLD/MASH-related gut microbiome alterations. It uniquely synthesizes microbial taxa, functional metabolites, and region-specific patterns-including data from underrepresented MENA populations. Eligible studies from PubMed, Scopus, and Web of Science evaluated microbial composition, metabolite profiles, and associations with steatosis, inflammation, and fibrosis. The findings underscore the diagnostic and therapeutic potential of microbiome modulation and emphasize the need for longitudinal, mechanistically driven studies. This systematic review is the first to integrate both animal and human studies on MASLD/MASH-related gut microbiome alterations. Unlike previous reviews, it uniquely emphasizes microbial taxa, functional metabolites, and region-specific patterns, including underrepresented MENA populations. By synthesizing findings from diverse cohorts, this review highlights diagnostic and therapeutic opportunities while identifying persistent gaps in longitudinal data, regional representation, and multi-omics integration.},
}

@article {pmid41000801,
year = {2025},
author = {Soriano, S and Marshall, A and Holcomb, M and Flinn, H and Burke, M and Kara, G and Scalzo, P and Villapol, S},
title = {Sex-specific effects of fecal microbiota transplantation on TBI-exacerbated Alzheimer's pathology in mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.09.11.675717},
pmid = {41000801},
issn = {2692-8205},
abstract = {BACKGROUND: Traumatic brain injury (TBI) accelerates Alzheimer's disease (AD) pathology and neuroinflammation, potentially via gut-brain axis disruptions. Whether restoring gut microbial homeostasis mitigates TBI-exacerbated AD features remains unclear, particularly with respect to sex differences.

OBJECTIVE: The goal of our study was to test whether fecal microbiota transplantation (FMT) modifies amyloid pathology, neuroinflammation, gut microbial composition, metabolites, and motor outcomes in male and female 5xFAD mice subjected to TBI.

METHODS: Male and female 5xFAD mice received sham treatments or controlled cortical impact, followed 24 hours later by vehicle (VH) or sex-matched FMT from C57BL/6 donors. Assessments at baseline, 1, and 3 days post-injury included Thioflavin-S and 6E10 immunostaining for Aβ, Iba-1 and GFAP for glial activation, lesion volume, rotarod performance, 16S rRNA sequencing for microbiome profiling, serum short-chain fatty acids (SCFAs), and gut histology.

RESULTS: TBI increased cortical and dentate gyrus Aβ burden, with females showing greater vulnerability. FMT reduced Aβ deposition in sham animals and shifted plaque morphology but did not attenuate TBI-induced amyloid escalation. FMT differentially modulated glial responses by sex and region (reduced microgliosis in males) without altering lesion volume. Rotarod performance was better in sham females compared to males and declined in FMT-treated TBI females. Fecal microbiome alpha diversity and richness were unchanged, while beta diversity revealed marked, time-dependent community shifts after TBI that were slightly altered by FMT. Gut morphology remained broadly intact, but crypt width increased after TBI, particularly in males.

CONCLUSION: In 5xFAD mice, TBI drives sex-dependent worsening of amyloid pathology, neuroinflammation, and dysbiosis. Acute FMT partially restores microbial composition and plaque features in sham animals but fails to reverse TBI-induced neuroinflammation or motor deficits. These findings underscore the context- and sex-dependence of microbiome interventions and support longer-term, sex-specific strategies for AD with comorbid TBI.},
}

@article {pmid41000396,
year = {2025},
author = {Liu, C and Wang, J and Lei, L and Li, L and Yuan, X},
title = {Gut microbiota therapy for chronic kidney disease.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1660226},
pmid = {41000396},
issn = {1664-3224},
mesh = {Humans ; *Renal Insufficiency, Chronic/therapy/microbiology/etiology ; *Gastrointestinal Microbiome ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation/methods ; Animals ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; },
abstract = {Chronic kidney disease (CKD), affecting 13% of the global population, is increasingly linked to gut microbiota dysbiosis, a condition driven by uremic toxins accumulation, metabolic alterations, and dietary factors. This mini review explores gut microbiota modulation as a therapeutic strategy to alleviate CKD symptoms, focusing on interventions that target gut microbiota composition and function. Prebiotics, such as resistant starch, have been shown to lower uremic toxins and reduce inflammation, while dietary adjustments, including low-protein and gluten-free diets, modulate microbial diversity and improve renal biomarkers. Fecal microbiota transplantation (FMT), which stabilizes creatinine levels and shifts gut microbiota toward beneficial taxa, represents another promising approach. However, limitations persist: synbiotics, which often induce gut microbiota shifts, frequently lack clinical impact; probiotics, which enhance glucose control and oxidative stress mitigation, exhibit variable efficacy; and interventions such as propolis or cranberry extract, which have been tested, prove ineffective. The causal relationship between gut microbiota dysbiosis and CKD progression, which remains unclear, is further complicated by methodological heterogeneity across studies. Emerging strategies, including phage therapy and artificial intelligence-driven multi-omics integration, which hold significant promise, require further validation. Future research must prioritize longitudinal studies, maternal gut microbiota optimization, and personalized approaches, which are essential for advancing CKD management. While gut microbiota modulations hold therapeutic potential, translating these findings into clinical practice demands rigorous trials to address inconsistencies and establish mechanistic links, ultimately shifting CKD management from reactive treatment to precision-based prevention.},
}

Humans
*Renal Insufficiency, Chronic/therapy/microbiology/etiology
*Gastrointestinal Microbiome
Dysbiosis/therapy
*Fecal Microbiota Transplantation/methods
Animals
Probiotics/therapeutic use
Prebiotics/administration & dosage

@article {pmid40999363,
year = {2025},
author = {Pan, Y and Luo, Y and Wu, G and Lu, Y and Yang, P and Kong, P and Zheng, C and Wang, C and Yang, L and Li, X},
title = {Gut microbiota dysbiosis promotes coronary heart disease comorbid with depression through lipopolysaccharides and Toll-like receptor 4.},
journal = {BMC microbiology},
volume = {25},
number = {1},
pages = {588},
pmid = {40999363},
issn = {1471-2180},
support = {2021GXNSFBA196059//the Guangxi Young Scientists Fund/ ; 2022GXNSFDA035086//the Key Project of the Guangxi Natural Science Foundation/ ; 82060835//the National Natural Science Foundation of China/ ; 82360900//the National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Toll-Like Receptor 4/metabolism/genetics ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/complications ; *Lipopolysaccharides/metabolism ; Rats ; Male ; *Coronary Disease/microbiology/metabolism/etiology ; Fecal Microbiota Transplantation ; *Depression/microbiology/metabolism ; Disease Models, Animal ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects ; Myeloid Differentiation Factor 88/metabolism ; Comorbidity ; NF-kappa B/metabolism ; Signal Transduction ; RNA, Ribosomal, 16S/genetics ; Sulfonamides ; },
abstract = {Coronary heart disease (CHD) and depression often coexist and complicate patient care. The gut microbiota plays a crucial role in overall health and is involved in both conditions. Dysbiosis, particularly, increased levels of lipopolysaccharides (LPSs), can activate the Toll-like receptor 4 (TLR4), triggering inflammatory pathways associated with CHD and depression. Although some associations have been observed, the direct mechanistic association among gut dysbiosis, LPSs, TLR4 activation, and comorbidity of CHD and depression remains unclear. Thus, in the present study, we aimed to explore this association and the potential of modulating gut microbiota as a therapeutic strategy. METHODS: A rat model of CHD and depression was established using a high-fat diet and chronic unpredictable mild stress and verified by electrocardiogram, behavioral assessments, and cardiac marker analysis. Fecal microbiota transplantation (FMT) was performed by transferring microbiota from diseased rats to healthy rats (FMT-Disease group); the fecal microbiota of the rats from the FMT-Disease and FMT-Normal groups were compared. The TLR4 inhibitor TAK-242 was administered, creating the Disease + TAK-242 and FMT-Disease-TAK-242 groups. Gut microbiota composition was analyzed using 16 S rRNA high-throughput sequencing; LPS levels were measured using enzyme-linked immunosorbent assay. Polymerase chain reaction and western blotting were used to detect the expression of genes and proteins related to the TLR4/MYD88/NF-κB pathway in the heart and hippocampus, respectively. RESULTS: We confirmed that in the FMT-Disease group, the gut microbiota of diseased rats altered the gut microbial composition of healthy rats in terms of β-diversity, α-diversity, and community structure. Notably, LPS levels in the serum of FMT-Disease rats were elevated, thereby activating the TLR4/MYD88/NF-κB inflammatory pathway and increasing susceptibility to CHD comorbid with depression. Additionally, after receiving fecal microbiota from healthy rats, the Disease group showed a restoration of gut microbiota balance, improvement in general condition, and normalization of pathological, biochemical, and inflammatory indicators, indicating a suppressive effect on the progression of CHD with depression. CONCLUSION: Our findings further clarify the interrelationship between gut microbiota and CHD comorbid with depression, enhancing our understanding of its pathogenesis. Moreover, we propose a potential novel therapeutic strategy that focuses on modulating gut microbiota composition to block the TLR4/MYD88/NF-κB inflammatory pathway.},
}

Animals
*Toll-Like Receptor 4/metabolism/genetics
*Gastrointestinal Microbiome/physiology
*Dysbiosis/microbiology/complications
*Lipopolysaccharides/metabolism
Rats
Male
*Coronary Disease/microbiology/metabolism/etiology
Fecal Microbiota Transplantation
*Depression/microbiology/metabolism
Disease Models, Animal
Rats, Sprague-Dawley
Diet, High-Fat/adverse effects
Myeloid Differentiation Factor 88/metabolism
Comorbidity
NF-kappa B/metabolism
Signal Transduction
RNA, Ribosomal, 16S/genetics
Sulfonamides

@article {pmid40998619,
year = {2025},
author = {Metri, AA and Faghih, M and Thompson, E and Noë, M and Mannan, R and Kalyani, R and Gunzelman, E and Afghani, E and Cheesman, L and Akshintala, VS and Gurakar, M and Yousefli, Z and Warren, D and Desai, NM and Sun, Z and Walsh, C and Makary, MA and Hruban, RH and He, J and Zaheer, A and Singh, VK},
title = {Clinical predictors of pancreatic fibrosis in patients with recurrent acute and chronic pancreatitis.},
journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pan.2025.09.021},
pmid = {40998619},
issn = {1424-3911},
abstract = {OBJECTIVES: Fibrosis is considered the criterion standard for diagnosing chronic pancreatitis (CP) but adequate tissue specimens are difficult to obtain, carry risk and are often obtained at the time of surgery in advanced stages of CP. Noninvasive biomarkers that correlate with fibrosis across the continuum of pancreatitis are needed. Our aim was to determine which clinical variables are associated with fibrosis in patients with recurrent acute pancreatitis (RAP) or CP undergoing total pancreatectomy with islet autotransplantation (TPIAT).

METHODS: The demographic, clinical and radiologic data for patients undergoing TPIAT for RAP or CP between 2011 and 2023 were reviewed. Excisional biopsies from the proximal and distal pancreas were each scored from 0 to 6 for both perilobular and intralobular fibrosis, and the score of each biopsy was the sum of perilobular and intralobular fibrosis (0-12). The fibrosis score (FS), ranging from 0 to 12, was the mean FS from the proximal and distal pancreas.

RESULTS: There were 88 patients with a mean age 38 ± 14 years and 46 (52.3 %) were female. There were 35 (39.8 %) and 53 (60.2 %) with RAP and CP, respectively. Genetic (52.3 %) and idiopathic (37.5 %) were the most common etiologies. The mean FS was 6.52 ± 3.53. Large duct CP (β = 3, p = 0.001), exocrine pancreatic insufficiency (EPI) (β = 1.5, p = 0.037) and a genetic etiology (β = 1.6, p = 0.03) were significant predictors of fibrosis after adjusting for age, BMI, disease duration and use of oral hypoglycemic drugs and/or insulin.

CONCLUSION: Large duct CP, genetic etiology and EPI are all independent predictors of pancreatic fibrosis in a cohort of patients undergoing TPIAT. Computed tomography (CT) imaging and fecal elastase-1 (FE-1) concentration may be sufficient to estimate fibrosis without acquisition of a tissue specimen.},
}

@article {pmid40997947,
year = {2025},
author = {Bonilla-Moreno, M and Medina-Gómez, C and Guevara-Núñez, D and Saiz-Escobedo, L and Martí, S and Domínguez, MÁ and Carrera-Salinas, A and Rodríguez-Sevilla, G},
title = {Assessing healthcare workers as potential stool donors for faecal microbiota transplantation: a cross-sectional study of antimicrobial-resistant gut bacteria and enteropathogenic microorganisms.},
journal = {The Journal of hospital infection},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jhin.2025.09.004},
pmid = {40997947},
issn = {1532-2939},
abstract = {BACKGROUND: Faecal Microbiota Transplantation (FMT) is a procedure designed to modulate the gut microbiome, but identifying reliable stool donors remains challenging. We conducted a study at Bellvitge University Hospital to assess the prevalence of enteropathogenic microorganisms (EPs) and antimicrobial-resistant (AMR) gut bacteria among healthcare workers (HCWs) and evaluate their potential as stool donors.

METHODS: From November 2022 to April 2023, 106 HCWs were enrolled. Stool samples were tested for a range of EPs using real-time PCR and conventional methods, while AMR gut bacteria were screened using selective culture media. 16SrRNA sequencing was performed, and alpha-diversity was assessed using the Shannon index.

FINDINGS: EPs were found in 48.1% of samples (51/106), with protozoa being the most prevalent (37.7%, 40/106), followed by bacteria (10.4%, 11/106) and viruses (4.7%, 5/106). Blastocystis hominis (33%, 35/106) and Dientamoeba fragilis (18.8%, 20/106) were the most common protozoa, while Enteropathogenic Escherichia coli was the most frequent bacterial pathogen (3.8%, 4/106). Extended spectrum β-lactamase-producing E. coli was found in 2.8% of samples (3/106). Carbapenemase-producing bacteria, vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus or Clostridioides difficile were not present in any sample. HCWs with B. hominis had significantly higher Shannon alpha-diversity than those without (p < 0.01).

CONCLUSION: The prevalence of EPs and AMR gut bacteria among HCWs supports the inclusion of HCWs as potential stool donors for FMT, provided they meet health and screening criteria. This approach could help address the shortage of suitable stool donors for FMT programs.},
}

@article {pmid40997843,
year = {2025},
author = {Kao, D and Wong, K and Lee, C and Steiner, T and Franz, R and McDougall, C and Silva, M and Schmidt, TSB and Walter, J and Loebenberg, R and Monaghan, TM and Giebelhaus, RT and Harynuk, JJ and Xu, H and Yaskina, M and MacDonald, KV and Marshall, DA and Louie, T},
title = {Effects of lyophilised faecal filtrate compared with lyophilised donor stool on Clostridioides difficile recurrence: a multicentre, randomised, double-blinded, non-inferiority trial.},
journal = {The lancet. Gastroenterology & hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2468-1253(25)00190-6},
pmid = {40997843},
issn = {2468-1253},
abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection. However, it is not known whether live microbes are necessary in mediating FMT efficacy. This study aims to determine whether lyophilised sterile faecal filtrate (LSFF), free of live bacteria, is non-inferior to lyophilised donor stool (LFMT) in efficacy.

METHODS: This multicentre, randomised, double-blinded, non-inferiority trial was done at four academic centres in Canada. Eligible patients were adults aged 18 years or older with recurrent C difficile infection (at least two recurrences). Eligible patients were randomly assigned (1:1 using a prespecified computer-generated randomisation list with permutation blocks of 2 and 4, stratified by age >65 years or <65 years) to receive oral LSFF or LFMT. Each treatment dose consisted of 15 capsules that appeared identical. Participants and investigators were masked to treatment allocation. The primary outcome was the proportion of participants without recurrent C difficile infection (absence of more than three Bristol type 6 or 7 bowel movements per 24 h persisting more than 2 consecutive days) at 8 weeks. Analysis was done in the per protocol population, in which participants with unknown outcome status at 8 weeks due to death or loss to follow-up were excluded. Non-inferiority was established if the lower bound of the one-sided 95% CI for the difference in proportions of participants without recurrent C difficile between the LSFF and LFMT groups was above the non-inferiority margin of -10%. This trial was registered at ClinicalTrials.gov, NCT03806803, and is complete.

FINDINGS: Between March 27, 2019, and Nov 6, 2023, we assessed 409 patients for eligibility. 271 were excluded and the remaining 138 were enrolled and randomly assigned to receive LSFF (n=72) or LFMT (n=66). Participants' mean age was 61·2 years (SD 18·6); 91 (66%) of 138 patients were women and 47 (34%) were male. 127 participants (92%) were White. 130 (94%) of 138 participants completed the trial. At the planned interim analysis, 47 (65%) of 72 participants in the LSFF group and 57 (88%) of 65 participants in the LFMT group did not have C difficile recurrence at 8 weeks (difference -23%, one-sided 95% CI -33·8% to infinity; p=0·96). Given the pre-specified non-inferiority margin of -10%, non-inferiority of LSFF to LFMT could not be established and the study was terminated at the recommendation of the data safety monitoring board. Serious adverse events included one death (LFMT group) and five hospitalisations (four unrelated, one possibly related to interventions [LSFF group]). One event occurred before treatment and all others 2-20 weeks after study intervention. The most common adverse events were abdominal discomfort (48 [67%] of 72 patients in the LSFF group and 36 (55%) of 66 patients in the LFMT group) and nausea (13 [18%] in the LSFF group and 21 [32%] in LFMT group).

INTERPRETATION: Among adults with recurrent C difficile infection, non-inferiority of LSFF to LFMT was not established for the prevention of recurrent C difficile infection over 8 weeks, supporting the crucial role of live microbes in mediating clinical efficacy.

FUNDING: Canadian Institutes of Health Research; University of Alberta Hospital Foundation; Alberta Health Services; Weston Foundation.},
}

@article {pmid40996680,
year = {2025},
author = {Luo, YM and Dong, L and Li, YL and Lin, M and Xie, DY and Gao, JM and Zhang, YD and Zhu, YZ and Gong, QH},
title = {Icariside II Ameliorates Depression Induced by High-Fat Diet via the Microbiota-Gut-Brain Axis in Mice.},
journal = {Phytotherapy research : PTR},
volume = {},
number = {},
pages = {},
doi = {10.1002/ptr.70103},
pmid = {40996680},
issn = {1099-1573},
support = {ZYSE-2022-02//Future techelite talent development program from Zunyi Medical University/ ; 82160756//Natural Science Foundation of China/ ; GCC[2023]042//hundred level of high-level innovative talents in Guizhou Province/ ; Zunshi Kehe HZ Zi (2023) 170. Qianke Platform Talent [2021] 1350-006//Zunyi Science and Technology and Big Data Bureau, Zunyi Medical University 2023 Science and Technology Joint Fund Project/ ; },
abstract = {Obesity can lead to depression via the microbiota-gut-brain axis. Icariside II (ICS II), a flavonoid compound derived from the traditional Chinese medicine Herbal Epimedium, exerts excellent neuroprotective effects. However, the pharmacological effects and underlying mechanisms of ICS II in obesity-induced depression remain unexplored. The present study aims to investigate whether ICS II can mitigate depression induced by a high-fat diet (HFD) in mice through modulating the microbiota-gut-brain axis. Metabolic parameters were reflected through changes in body weight and blood lipids, while depressive phenotypes were evaluated through behavioral tests and neurotransmitter analysis. The microbiota composition was analyzed by 16S ribosomal RNA gene sequencing, and short chain fatty acids (SCFAs) were detected by liquid chromatography-tandem mass spectrometry. The gut barrier and brain blood barrier (BBB) functions were observed by pathological methods. Fecal microbiota transplantation was used to demonstrate the causality of microbiota-mediated effects. The results showed that ICS II alleviated obesity status and depressive-like behaviors. ICS II reshaped gut microbiota and increased SCFAs. Meanwhile, ICS II relieved gut barrier impairment and systemic inflammation. In the brain, ICS II alleviated neuroinflammation and BBB injury. Intriguingly, fecal microbiota from ICS II-treated HFD mice improved depressive-like behaviors, intestinal barrier dysfunction, and BBB damage compared with those receiving microbiota from HFD mice. Our findings reveal for the first time that ICS II improves the obesity-related metabolic dysregulation and alleviates HFD-induced depression via the microbiota-gut-brain axis. Overall, this study indicates that ICS II is a potential candidate compound for treating obesity-related mental diseases.},
}

@article {pmid40996271,
year = {2025},
author = {Wong, MK and Armstrong, E and Heirali, AA and Schneeberger, PHH and Chen, H and Cochrane, K and Sherriff, K and Allen-Vercoe, E and Siu, LL and Spreafico, A and Coburn, B},
title = {Assessment of ecological fidelity of human microbiome-associated mice in observational studies and an interventional trial.},
journal = {mBio},
volume = {},
number = {},
pages = {e0190425},
doi = {10.1128/mbio.01904-25},
pmid = {40996271},
issn = {2150-7511},
abstract = {Composition and function of the gut microbiome are associated with diverse health conditions and treatment responses. Human microbiota-associated (HMA) mouse models are used to establish causal links for these associations but have important limitations. We assessed the fidelity of HMA mouse models in recapitulating ecological responses to a microbial consortium using stools collected from a human clinical trial. HMA mice were generated using different routes of consortium exposure, and their ecological features were compared to human donors by metagenomic sequencing. HMA mice resembled other mice more than their respective human donors in gut microbial composition and function, with taxa including Akkermansia muciniphila and Bacteroides spp. enriched in mouse recipients. A limited repertoire of microbes was able to engraft into HMA mice regardless of route of consortium exposure. In publicly available HMA mouse data sets from four distinct health conditions, we confirmed our observation that a taxonomically restricted set of microbes reproducibly engrafts in HMA mice and observed that stool microbiome composition of HMA mice was more like other mice than their human donor. Our data suggest that HMA mice are limited models for assessing the ecological impact of microbial consortia, with ecological effects in HMA mice being more strongly associated with host species than donor stool ecology or ecological responses to treatment in humans. Comparisons to published studies suggest this may be due to comparatively large host-species effects that overshadow ecological effects of treatments in humans that HMA models aim to recapitulate.IMPORTANCEHMA mice are models that better represent human gut ecology compared to conventional laboratory mice and are commonly used to test the effects of the gut microbiome on disease or treatment response. We evaluated the fidelity of using HMA mice as avatars of ecological response to a human microbial consortium, Microbial Ecosystem Therapeutic 4. Our results show that HMA mice in our cohort and across other published studies are more similar to each other than the human donors or inoculum they are derived from and harbor a taxonomically restricted gut microbiome. These findings highlight the limitations of HMA mice in evaluating the ecological effects of complex human microbiome-targeting interventions, such as microbial consortia.},
}

@article {pmid40994135,
year = {2025},
author = {Li, S and Li, Z and Tuo, Y and Mu, G and Jiang, S},
title = {Mechanisms of Casein-Derived Immunomodulatory Peptides Maintaining Immune Homeostasis via Regulating Gut Microbiota in a Cyclophosphamide-Induced Mouse Model.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c07986},
pmid = {40994135},
issn = {1520-5118},
abstract = {Two immunomodulatory signature peptides (PFPEVFG and SPAQILQW) were obtained from casein hydrolysates produced by Kluyveromyces marxianus JY-1 in our previous studies with the aid of virtual screening. However, their mechanisms for improving the composition of the gut microbiota in immunosuppressed mice remain unknown. The aim of this study was to reveal the mechanisms of immunomodulation and improvement of gut microbiota composition mediated by the casein peptides PFPEVFG and SPAQILQW through a cyclophosphamide (Cy)-induced immunosuppression and intestinal mucosal injury mouse model. The casein peptides PFPEVFG and SPAQILQW reversed Cy-induced intestinal structural damage and could correct for Cy-induced intestinal flora disorders. Importantly, fecal microbiota transplantation (FMT) confirmed that the casein peptides PFPEVFG and SPAQILQW attenuate immunosuppression by targeting participation in the dynamic balance of the gut microbiota. These results indicated that the casein peptides PFPEVFG and SPAQILQW have the potential to be used as natural medicines for the treatment of immunosuppression.},
}