@article {pmid39979287,
year = {2025},
author = {Tsenkova, M and Brauer, M and Pozdeev, VI and Kasakin, M and Busi, SB and Schmoetten, M and Cheung, D and Meyers, M and Rodriguez, F and Gaigneaux, A and Koncina, E and Gilson, C and Schlicker, L and Herebian, D and Schmitz, M and de Nies, L and Mayatepek, E and Haan, S and de Beaufort, C and Cramer, T and Meiser, J and Linster, CL and Wilmes, P and Letellier, E},
title = {Ketogenic diet suppresses colorectal cancer through the gut microbiome long chain fatty acid stearate.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1792},
pmid = {39979287},
issn = {2041-1723},
support = {OT2 OD030544/OD/NIH HHS/United States ; U2C DK119886/DK/NIDDK NIH HHS/United States ; },
mesh = {*Diet, Ketogenic ; *Gastrointestinal Microbiome/physiology ; Animals ; *Stearic Acids/metabolism ; *Colorectal Neoplasms/diet therapy/microbiology/pathology/metabolism ; Humans ; Mice ; Male ; Apoptosis ; Female ; Bacteria/metabolism/genetics ; Disease Models, Animal ; Colon/microbiology/pathology ; Cell Line, Tumor ; Fecal Microbiota Transplantation ; },
abstract = {Colorectal cancer (CRC) patients have been shown to possess an altered gut microbiome. Diet is a well-established modulator of the microbiome, and thus, dietary interventions might have a beneficial effect on CRC. An attenuating effect of the ketogenic diet (KD) on CRC cell growth has been previously observed, however the role of the gut microbiome in driving this effect remains unknown. Here, we describe a reduced colonic tumor burden upon KD consumption in a CRC mouse model with a humanized microbiome. Importantly, we demonstrate a causal relationship through microbiome transplantation into germ-free mice, whereby alterations in the gut microbiota were maintained in the absence of continued selective pressure from the KD. Specifically, we identify a shift toward bacterial species that produce stearic acid in ketogenic conditions, whereas consumers were depleted, resulting in elevated levels of free stearate in the gut lumen. This microbial product demonstrates tumor-suppressing properties by inducing apoptosis in cancer cells and decreasing colonic Th17 immune cell populations. Taken together, the beneficial effects of the KD are mediated through alterations in the gut microbiome, including, among others, increased stearic acid production, which in turn significantly reduces intestinal tumor growth.},
}

*Diet, Ketogenic
*Gastrointestinal Microbiome/physiology
Animals
*Stearic Acids/metabolism
*Colorectal Neoplasms/diet therapy/microbiology/pathology/metabolism
Humans
Mice
Male
Apoptosis
Female
Bacteria/metabolism/genetics
Disease Models, Animal
Colon/microbiology/pathology
Cell Line, Tumor
Fecal Microbiota Transplantation

@article {pmid40316177,
year = {2025},
author = {Yin, Y and Guan, M and Wu, S and Cui, C and Wang, R and Zhao, X and Yang, X and Qiao, L and Li, Y and Zhang, C},
title = {Young fecal microbiota transplantation improves working memory in aged recipient rats by increasing interleukin-4 and interleukin-17 levels.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neures.2025.04.005},
pmid = {40316177},
issn = {1872-8111},
abstract = {While transplanting the fecal microbiota from young to aged rodents has been extensively studied (that is, young FMT [yFMT]), its mechanism of alleviating working memory decline has not been fully elucidated. In this report, we aimed to investigate the effect of yFMT on the working memory of aged recipient rats performing delayed match-to-position (DMTP) tasks and the associated cellular and molecular mechanisms. The results revealed that yFMT mitigated the decline in DMTP task performance of aged recipients. This improvement was associated with a reshaped gut microbiota and increased levels of brain-derived neurotrophic factor, N-methyl-D-aspartate receptor subunit 1, and synaptophysin, enhancing synaptic formation and transmission. The remodeling of the gut microbiome influenced peripheral circulation and the hippocampus and medial prefrontal cortex by regulating the Th17/Treg ratio and microglial polarization. Ultimately, interleukin-4 and interleukin-17 emerged as potential key molecules driving the beneficial effects of FMT. These observations provide new insights into the gutbrain axis, emphasizing the connection between the gut and brain through the circulation system, and suggest an immunological mechanism that may help reverse age-related declines in the gut microbiota.},
}

@article {pmid40316082,
year = {2025},
author = {Qiu, MT and Zhou, L and Wang, XY and Li, ZP and Wei, MX and Zeng, ZH and Cheng, J and Xu, GH and Zhu, JX and Yi, LT},
title = {Anti-colitis comparison of polysaccharides and anthocyanins extracted from black wolfberry based on microbiomics, immunofluorescence and multi-cytokines profile analysis.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {143700},
doi = {10.1016/j.ijbiomac.2025.143700},
pmid = {40316082},
issn = {1879-0003},
abstract = {Black wolfberry (Lycium ruthenicum) is a widely consumed food known for its pharmacological properties, particularly its anti-inflammatory and antioxidant effects. This study investigates the therapeutic potential of black wolfberry polysaccharides (LRP) and anthocyanins (LRA) in treating ulcerative colitis, a chronic inflammatory bowel disease. Using a DSS-induced mouse model of colitis, we administered varying doses of LRP and LRA and evaluated their effects on disease activity, inflammation, gut barrier function, and microbiota composition. LRP demonstrated dose-dependent efficacy, with the 200 mg/kg dose showing the most significant reduction in the disease activity index (DAI), improvement in histopathology, and restoration of tight junction protein expression. In contrast, LRA exhibited an inverted U-shaped response, with the 100 mg/kg dose being the most effective. Additionally, LRP treatment modulated cytokine levels, promoting an anti-inflammatory response, and significantly restored gut microbiota balance by increasing Muribaculaceae and Limosilactobacillus while reducing Bacteroides and Helicobacter. Fecal microbiota transplantation (FMT) experiments further confirmed that the therapeutic effects of LRP are microbiota-dependent. These findings suggest that LRP, a polysaccharide derived from black wolfberry, offers a dietary intervention for colitis through immune modulation and gut microbiota restoration.},
}

@article {pmid40315641,
year = {2025},
author = {Wei, FH and Xie, WY and Zhao, PS and Ji, ZH and Gao, F and Chen, CZ and Zhang, Z and Gao, W and Yuan, B},
title = {Crataegus pinnatifida polysaccharide alleviates DSS-induced colitis in mice by regulating the intestinal microbiota and enhancing arginine biosynthesis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {142},
number = {},
pages = {156794},
doi = {10.1016/j.phymed.2025.156794},
pmid = {40315641},
issn = {1618-095X},
abstract = {BACKGROUND: The development of effective and safe dietary supplements is essential for both the prevention and management of ulcerative colitis (UC), as its pathogenesis is intricate and difficult to completely resolve. Crataegus pinnatifida, a medicinal food with a long history of use, has broad medicinal value. Recent research has revealed promising insights into the role of polysaccharide derived from Crataegus pinnatifida on modulating short-chain fatty acids (SCFAs) to alleviate UC inflammation. However, the mechanisms by which CPP regulates the intestinal microbiota and key metabolites during the antagonistic phase of UC have yet to be elucidated.

OBJECTIVE: This research elucidated the protective role of CPP in relation to UC, highlighted the mechanisms through which CPP operates, particularly regarding gut microbiota and metabolism, and offered a theoretical foundation for the potential use of CPP as a dietary supplement aimed at preventing UC.

METHODS: The impact of CPP on acute UC induced by 3 % DSS in mice was examined through the evaluation of the disease activity index, measurement of colon length, and observation of body weight changes. Enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory factor levels in both serum and colon, as well as to assess oxidative stress mediators. The intestinal histological damage, mucus layer damage and the level of tight junction protein were analyzed by histopathological staining and western blot (WB). The impact of gut microbiota on CPP in colitis was evaluated using 16S rRNA sequencing, microbiota depletion experiments, and fecal microbiota transplantation (FMT) studies. The key metabolic pathways and key metabolites affected by CPP in the treatment of UC were analyzed through untargeted metabolomics sequencing, ELISA, and WB assays.

RESULTS: Prophylactic dietary supplementation with Crataegus pinnatifida polysaccharide (CPP) notably reduced the fundamental clinical manifestations of UC induced by DSS, including DAI score, reduced colon length, and weight loss, as well as inflammation and oxidative stress. CPP promoted the expression of Claudin-1, ZO-1 and Occludin and promoted mucin secretion, which contributed to the mitigation of intestinal barrier damage caused by DSS. 16S sequencing results and metabolomics results revealed that CPP intervention upregulated the relative abundance of Lactobacillus, thereby reshaping the intestinal microbiota and activate the arginine biosynthesis pathway. The results of fecal microbiota transplantation and antibiotic clearance experiments indicated that the alleviating effect of CPP on UC was dependent on the intestinal microbiota and this alleviating effect was transferred through fecal microbiota transplantation. Mechanistically, CPP indirectly promoted the expression of the rate-limiting enzyme argininosuccinate synthase 1 (ASS1) in the intestinal Arginine biosynthesis pathway by reshaping the intestinal microbiota, thereby increasing intestinal Arginine level and alleviating the inflammatory response and oxidative stress induced by DSS and intestinal barrier damage.

CONCLUSION: Our research findings demonstrate that CPP is a plant-derived polysaccharide that alleviates UC by modulating the gut microbiota and enhancing arginine biosynthesis.},
}

@article {pmid40314722,
year = {2025},
author = {Castagnoli, R and Pala, F and Subramanian, P and Oguz, C and Schwarz, B and Lim, AI and Burns, AS and Fontana, E and Bosticardo, M and Corsino, C and Angelova, A and Delmonte, OM and Kenney, H and Riley, D and Smith, G and Ott de Bruin, L and Oikonomou, V and Dos Santos Dias, L and Fink, D and Bohrnsen, E and Kimzey, CD and Marseglia, GL and Alva-Lozada, G and Bergerson, JRE and Brett, A and Brigatti, KW and Dimitrova, D and Dutmer, CM and Freeman, AF and Ale, H and Holland, SM and Licciardi, F and Pasic, S and Poskitt, LE and Potts, DE and Dasso, JF and Sharapova, SO and Strauss, KA and Ward, BR and Yilmaz, M and Kuhns, DB and Lionakis, MS and Daley, SR and Kong, HH and Segre, JA and Villa, A and Pittaluga, S and Walter, JE and Vujkovic-Cvijin, I and Belkaid, Y and Notarangelo, LD},
title = {Immunopathological and microbial signatures of inflammatory bowel disease in partial RAG deficiency.},
journal = {The Journal of experimental medicine},
volume = {222},
number = {8},
pages = {},
pmid = {40314722},
issn = {1540-9538},
support = {U01 DK062413/DK/NIDDK NIH HHS/United States ; HHSN316201300006W/75N93022F00001/HH/HHS/United States ; //National Institute of Allergy and Infectious Diseases/ ; U01DK062413/DK/NIDDK NIH HHS/United States ; DP1HL174182/HL/NHLBI NIH HHS/United States ; 831262//Crohn's & Colitis Foundation Career Development/ ; AI001222/NH/NIH HHS/United States ; DP1 HL174182/HL/NHLBI NIH HHS/United States ; //Fondazione Ghislieri/ ; //Cedars-Sinai Medical Center/ ; },
mesh = {Animals ; *Inflammatory Bowel Diseases/immunology/microbiology/pathology/genetics ; *Homeodomain Proteins/genetics ; Humans ; Mice ; Female ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome ; Bone Marrow Transplantation ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology ; Mice, Inbred C57BL ; },
abstract = {Partial RAG deficiency (pRD) can manifest with systemic and tissue-specific immune dysregulation, with inflammatory bowel disease (IBD) in 15% of the patients. We aimed at identifying the immunopathological and microbial signatures associated with IBD in patients with pRD and in a mouse model of pRD (Rag1w/w) with spontaneous development of colitis. pRD patients with IBD and Rag1w/w mice showed a systemic and colonic Th1/Th17 inflammatory signature. Restriction of fecal microbial diversity, abundance of pathogenic bacteria, and depletion of microbial species producing short-chain fatty acid were observed, which were associated with impaired induction of lamina propria peripheral Treg cells in Rag1w/w mice. The use of vedolizumab in Rag1w/w mice and of ustekinumab in a pRD patient were ineffective. Antibiotics ameliorated gut inflammation in Rag1w/w mice, but only bone marrow transplantation (BMT) rescued the immunopathological and microbial signatures. Our findings shed new light in the pathophysiology of gut inflammation in pRD and establish a curative role for BMT to resolve the disease phenotype.},
}

Animals
*Inflammatory Bowel Diseases/immunology/microbiology/pathology/genetics
*Homeodomain Proteins/genetics
Humans
Mice
Female
Male
Disease Models, Animal
Gastrointestinal Microbiome
Bone Marrow Transplantation
T-Lymphocytes, Regulatory/immunology
Th17 Cells/immunology
Mice, Inbred C57BL

@article {pmid40314681,
year = {2025},
author = {Li, X and Su, K and He, Y and Shao, S and Lan, L and Zhang, Q},
title = {Knowledge Mapping of International Microbiota Research: Analyzing Thirty-Year Citation Classics and Exploring Future Expectations.},
journal = {The new microbiologica},
volume = {48},
number = {1},
pages = {46-59},
pmid = {40314681},
issn = {1121-7138},
mesh = {Humans ; *Microbiota ; *Biomedical Research ; Bibliometrics ; Gastrointestinal Microbiome ; },
abstract = {Microbiota research has rapidly emerged as a pivotal field, with over 250,000 publications and more than ten million citations recorded in the Web of Science Core Collection database by 2024. There were 1682 original microbiota citation classics (each receiving 400 citations or more) identified over the past three decades, totaling 1,559,594 citations and averaging 927 citations per paper. Collaborative efforts in the production of these citation classics involved 87 out of 89 participating countries and 2107 out of 2142 institutions. The USA, various European countries, and China emerged as the leading contributors to this burgeoning research area. Jeffrey I. Gordon, Rob Knight, and Curtis Huttenhower were the prominent figures in microbiota research. Author keywords were analyzed, which revealed a notable shift in research focus from environmental microorganisms to human gut microbiota. Advances such as high-throughput 16S rRNA sequencing and metagenomics expanded the scope of investigations into host-microbiota interactions. Current research interests encompass exploring mechanisms underlying gut-X-axis conditions, including inflammatory bowel disease, obesity, diabetes, colorectal cancer, liver diseases, and neurological disorders. Moreover, environmental exposures have been evidenced to alter gut microbiota and metabolites, contributing a novel research direction. Future research direction is also anticipated to delve further into biosynthetic gene engineering technologies aimed at microbial interventions, including probiotics and fecal microbiota transplantation. This study outlines the evolving landscape of microbiota research and provides valuable insights to inform future investigations within the field.},
}

Humans
*Microbiota
*Biomedical Research
Bibliometrics
Gastrointestinal Microbiome

@article {pmid40314129,
year = {2025},
author = {Xiao, K and Li, K and Xiao, K and Yang, J and Zhou, L},
title = {Gut Microbiota and Hepatocellular Carcinoma: Metabolic Products and Immunotherapy Modulation.},
journal = {Cancer medicine},
volume = {14},
number = {9},
pages = {e70914},
pmid = {40314129},
issn = {2045-7634},
support = {21MC1930500//Shanghai Clinical Research Center of Traditional Chinese Medicine Oncology, Science and Technology Commission of Shanghai Municipality/ ; ZYYZDXK-2023063//High-Level Traditional Chinese Medicine Key Discipline Construction Project of the National Administration of Traditional Chinese Medicine/ ; //Youth Talent Project of Longhua Hospital, affiliated with Shanghai University of Traditional Chinese Medicine/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Carcinoma, Hepatocellular/therapy/immunology/microbiology/metabolism/pathology ; *Liver Neoplasms/therapy/immunology/microbiology/metabolism/pathology ; *Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; },
abstract = {BACKGROUND: The relationship between hepatocellular carcinoma (HCC) and gut microbiota has gained attention for its impact on HCC immunotherapy.

METHODS: Key gut microbial metabolites, including bile acids, toll-like receptor 4, short-chain fatty acids, and bacterial toxins, contribute to HCC progression and influence immune responses through the gut-liver axis. As immune checkpoint inhibitors (ICIs) become common in HCC treatment, modulating the gut microbiota offers new strategies to enhance ICIs efficacy. However, individual differences in microbial composition introduce challenges, with some HCC patients showing resistance to ICIs.

RESULTS: This review summarizes the latest findings on the role of gut microbiota in HCC and explores emerging therapeutic approaches, including fecal microbiota transplantation, probiotics, antibiotics, and natural compounds.

CONCLUSIONS: The focus is on translating these insights into personalized medicine to optimize ICIs responses and improve HCC treatment outcomes.},
}

Humans
*Gastrointestinal Microbiome/immunology/drug effects
*Carcinoma, Hepatocellular/therapy/immunology/microbiology/metabolism/pathology
*Liver Neoplasms/therapy/immunology/microbiology/metabolism/pathology
*Immunotherapy/methods
Immune Checkpoint Inhibitors/therapeutic use/pharmacology
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Animals

@article {pmid40313405,
year = {2025},
author = {Zhao, H and Qiu, X and Wang, S and Wang, Y and Xie, L and Xia, X and Li, W},
title = {Multiple pathways through which the gut microbiota regulates neuronal mitochondria constitute another possible direction for depression.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1578155},
pmid = {40313405},
issn = {1664-302X},
abstract = {As a significant mental health disorder worldwide, the treatment of depression has long faced the challenges of a low treatment rate, significant drug side effects and a high relapse rate. Recent studies have revealed that the gut microbiota and neuronal mitochondrial dysfunction play central roles in the pathogenesis of depression: the gut microbiota influences the course of depression through multiple pathways, including immune regulation, HPA axis modulation and neurotransmitter metabolism. Mitochondrial function serves as a key hub that mediates mood disorders through mechanisms such as defective energy metabolism, impaired neuroplasticity and amplified neuroinflammation. Notably, a bidirectional regulatory network exists between the gut microbiota and mitochondria: the flora metabolite butyrate enhances mitochondrial biosynthesis through activation of the AMPK-PGC1α pathway, whereas reactive oxygen species produced by mitochondria counteract the flora composition by altering the intestinal epithelial microenvironment. In this study, we systematically revealed the potential pathways by which the gut microbiota improves neuronal mitochondrial function by regulating neurotransmitter synthesis, mitochondrial autophagy, and oxidative stress homeostasis and proposed the integration of probiotic supplementation, dietary fiber intervention, and fecal microbial transplantation to remodel the flora-mitochondrial axis, which provides a theoretical basis for the development of novel antidepressant therapies targeting gut-brain interactions.},
}

@article {pmid40312419,
year = {2025},
author = {Cao, M and Deng, Y and Hao, Q and Yan, H and Wang, QL and Dong, C and Wu, J and He, Y and Huang, LB and Xia, X and Gao, Y and Chen, HN and Zhang, WH and Zhang, YJ and Zhuo, X and Dai, L and Hu, H and Peng, Y and Zhang, F and Liu, Z and Huang, W and Zhang, H and Yang, L and Shu, Y and Zhang, W and Zhang, Y and Xu, H},
title = {Single-cell transcriptomic analysis reveals gut microbiota-immunotherapy synergy through modulating tumor microenvironment.},
journal = {Signal transduction and targeted therapy},
volume = {10},
number = {1},
pages = {140},
pmid = {40312419},
issn = {2059-3635},
support = {82273445//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome/immunology/genetics/drug effects ; *Tumor Microenvironment/immunology/genetics/drug effects ; Mice ; *Single-Cell Analysis ; *Immunotherapy ; CD8-Positive T-Lymphocytes/immunology ; Humans ; Gene Expression Profiling ; Transcriptome ; *Neoplasms/immunology/genetics/therapy/microbiology ; *Immune Checkpoint Inhibitors/pharmacology ; Mice, Knockout ; Macrophages/immunology ; },
abstract = {The gut microbiota crucially regulates the efficacy of immune checkpoint inhibitor (ICI) based immunotherapy, but the underlying mechanisms remain unclear at the single-cell resolution. Using single-cell RNA sequencing and subsequent validations, we investigate gut microbiota-ICI synergy by profiling the tumor microenvironment (TME) and elucidating critical cellular interactions in mouse models. Our findings reveal that intact gut microbiota combined with ICIs may synergistically increase the proportions of CD8[+], CD4[+], and γδ T cells, reduce glycolysis metabolism, and reverse exhausted CD8[+] T cells into memory/effector CD8[+] T cells, enhancing antitumor response. This synergistic effect also induces macrophage reprogramming from M2 protumor Spp1[+] tumor-associated macrophages (TAMs) to Cd74[+] TAMs, which act as antigen-presenting cells (APCs). These macrophage subtypes show a negative correlation within tumors, particularly during fecal microbiota transplantation. Depleting Spp1[+] TAMs in Spp1 conditional knockout mice boosts ICI efficacy and T cell infiltration, regardless of gut microbiota status, suggesting a potential upstream role of the gut microbiota and highlighting the crucial negative impact of Spp1[+] TAMs during macrophage reprogramming on immunotherapy outcomes. Mechanistically, we propose a γδ T cell-APC-CD8[+] T cell axis, where gut microbiota and ICIs enhance Cd40lg expression on γδ T cells, activating Cd40 overexpressing APCs (e.g., Cd74[+] TAMs) through CD40-CD40L-related NF-κB signaling and boosting CD8[+] T cell responses via CD86-CD28 interactions. These findings highlight the potential importance of γδ T cells and SPP1-related macrophage reprogramming in activating CD8[+] T cells, as well as the synergistic effect of gut microbiota and ICIs in immunotherapy through modulating the TME.},
}

Animals
*Gastrointestinal Microbiome/immunology/genetics/drug effects
*Tumor Microenvironment/immunology/genetics/drug effects
Mice
*Single-Cell Analysis
*Immunotherapy
CD8-Positive T-Lymphocytes/immunology
Humans
Gene Expression Profiling
Transcriptome
*Neoplasms/immunology/genetics/therapy/microbiology
*Immune Checkpoint Inhibitors/pharmacology
Mice, Knockout
Macrophages/immunology

@article {pmid40311999,
year = {2025},
author = {Liu, A and Wang, B and Wang, M and Tang, R and Xu, W and Xiao, W},
title = {L-theanine alleviates ulcerative colitis by repairing the intestinal barrier through regulating the gut microbiota and associated short-chain fatty acids.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {},
number = {},
pages = {115497},
doi = {10.1016/j.fct.2025.115497},
pmid = {40311999},
issn = {1873-6351},
abstract = {Ulcerative colitis (UC) is closely related to impaired intestinal barrier function and imbalanced gut microbial communities. L-theanine shows great potential in maintaining intestinal integrity and regulating the gut microbiota and associated short-chain fatty acids (SCFAs). However, whether L-theanine can alleviate UC by repairing the intestinal barrier through these regulatory processes remains unclear. In this study, L-theanine was used to optimize the gut microbiota, and the restorative effect and mechanism of L-theanine in UC by repairing the gut barrier through the gut microbiota and SCFAs were investigated via fecal microbiota transplantation. The findings revealed that L-theanine regulated the gut microbiota structure, increased SCFA contents, and promoted gut barrier repair in UC mice. Moreover, L-theanine upregulated the protein and mRNA expression of G-protein-coupled receptor 43 (GPR43), AKT, and phosphatidylinositide 3-kinase (PI3K). These results indicated that L-theanine alleviates UC by repairing the gut barrier via regulating the gut microbiota and SCFAs through the GPR43/PI3K/AKT signaling pathway activation. This study provides a method of preventing and treating UC via L-theanine as a safe food dietary supplement.},
}

@article {pmid40309228,
year = {2025},
author = {Li, Y and Wu, YT and Wu, H},
title = {Management of hepatic encephalopathy following transjugular intrahepatic portosystemic shunts: Current strategies and future directions.},
journal = {World journal of gastroenterology},
volume = {31},
number = {15},
pages = {103512},
pmid = {40309228},
issn = {2219-2840},
mesh = {Humans ; *Portasystemic Shunt, Transjugular Intrahepatic/adverse effects ; *Hepatic Encephalopathy/etiology/therapy/prevention & control/diagnosis ; *Hypertension, Portal/surgery/etiology ; *Liver Cirrhosis/complications/surgery ; *Postoperative Complications/therapy/etiology/prevention & control ; Quality of Life ; Stents ; Treatment Outcome ; Biomarkers/blood ; Fecal Microbiota Transplantation ; },
abstract = {Transjugular intrahepatic portosystemic shunts (TIPSs) are generally used for the management of complications of portal hypertension in patients with decompensated cirrhosis. However, hepatic encephalopathy (HE), which impairs neuropsychiatric function and motor control, remains the primary adverse effect of TIPS, limiting its utility. Prompt prevention and treatment of post-TIPS HE are critical, as they are strongly associated with readmission rates and poor quality of life. This review focuses on the main pathophysiological mechanisms underlying post-TIPS HE, explores advanced biomarkers and predictive tools, and discusses current management strategies and future directions to prevent or reverse HE following TIPS. These strategies include preoperative patient assessment, individualized shunt diameter optimization, spontaneous portosystemic shunt embolization during the TIPS procedure, postoperative preventive and therapeutic measures such as nutrition management, medical therapy, fecal microbiota transplantation, and stent reduction.},
}

Humans
*Portasystemic Shunt, Transjugular Intrahepatic/adverse effects
*Hepatic Encephalopathy/etiology/therapy/prevention & control/diagnosis
*Hypertension, Portal/surgery/etiology
*Liver Cirrhosis/complications/surgery
*Postoperative Complications/therapy/etiology/prevention & control
Quality of Life
Stents
Treatment Outcome
Biomarkers/blood
Fecal Microbiota Transplantation

@article {pmid40309194,
year = {2025},
author = {Tang, CT and Wu, Y and Tao, Q and Zeng, CY and Chen, YX},
title = {Thalidomide mitigates Crohn's disease colitis by modulating gut microbiota, metabolites, and regulatory T cell immunity.},
journal = {Journal of pharmaceutical analysis},
volume = {15},
number = {4},
pages = {101121},
pmid = {40309194},
issn = {2214-0883},
abstract = {Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of forkhead box P3[+] (FOXP3[+]) regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile, with an increased abundance of probiotics Bacteroides fragilis, while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL-17), IL-1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal B. fragilis was observed, correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1 (FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa238-335) and the FXR1 domain (aa82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3[+] Tregs and curbs pro-inflammatory pathways.},
}

@article {pmid40309103,
year = {2025},
author = {Cong, X and Liu, X and Zhou, D and Xu, Y and Liu, J and Tong, F},
title = {Characterization and comparison of the fecal bacterial microbiota in Red Back Pine Root Snake (Oligodon formosanus) and Chinese Slug-Eating Snake (Pareas chinensis).},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1575405},
pmid = {40309103},
issn = {1664-302X},
abstract = {INTRODUCTION: The gastrointestinal tracts and oral cavities of animals harbor complex microbial communities that assist hosts in nutrient absorption and immune responses, thereby influencing behavior, development, reproduction, and overall health.

METHODS: We utilized metagenomic sequencing technology to conduct a detailed analysis of the fecal bacterial communities of six Red Back Pine Root Snakes (Oligodon formosanus, XT) and three Chinese Slug-Eating Snakes (Pareas chinensis, Z) individuals. The microbial composition was assessed through taxonomic profiling, alpha diversity analysis, and functional annotation using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.

RESULTS: The results indicated that Proteobacteria, Bacteroidetes, Firmicutes, Verrucomicrobia, Actinobacteria, and Fusobacteria were the dominant phyla in XT samples, while Z samples additionally contained Patescibacteria. Alpha diversity analysis revealed significant differences in species abundance at the family level, with Z samples exhibiting higher microbial richness than XT. Furthermore, KEGG analysis showed that XT had higher functional gene abundance in pathways related to transcription, translation, environmental adaptation, membrane transport, cellular communities (prokaryotes), motility, and replication/repair compared to Z.

DISCUSSION: This study provides a comparative analysis of their gut microbiomes, offering valuable insights for future research on zoonotic diseases, host-microbe interactions, and ecological, evolutionary, behavioral, and seasonal influences on snake microbiota. These findings contribute to a broader understanding of microbial ecology in reptiles and its implications for conservation and disease dynamics.},
}

@article {pmid40308808,
year = {2025},
author = {Wei, H and Mai, ZL and Ma, BT and Chang, B},
title = {Creeping fat: A promising radiological predictor in small bowel Crohn's disease.},
journal = {World journal of gastroenterology},
volume = {31},
number = {16},
pages = {105186},
pmid = {40308808},
issn = {2219-2840},
mesh = {Humans ; *Crohn Disease/diagnostic imaging/therapy/pathology ; *Intestine, Small/diagnostic imaging/pathology ; Treatment Outcome ; Fecal Microbiota Transplantation ; Predictive Value of Tests ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging ; *Adipose Tissue/diagnostic imaging/pathology ; Biological Products/therapeutic use ; },
abstract = {In this manuscript, we comment on the article by Hasnaoui et al. Specifically, we delve into the characteristic manifestation of Crohn's disease (CD) known as creeping fat (CF). Our primary focus is to investigate the potential of imaging features of CF in predicting the response of small bowel CD to biologic therapies and fecal microbiota transplantation. We believe that further research should be dedicated to developing methods for quantifying CF in order to provide more accurate predictive tools for the treatment of small bowel CD.},
}

Humans
*Crohn Disease/diagnostic imaging/therapy/pathology
*Intestine, Small/diagnostic imaging/pathology
Treatment Outcome
Fecal Microbiota Transplantation
Predictive Value of Tests
Tomography, X-Ray Computed
Magnetic Resonance Imaging
*Adipose Tissue/diagnostic imaging/pathology
Biological Products/therapeutic use

@article {pmid40307551,
year = {2025},
author = {Kennedy, MS and Freiburger, A and Cooper, M and Beilsmith, K and St George, ML and Kalski, M and Cham, C and Guzzetta, A and Ng, SC and Chan, FK and DeLeon, O and Rubin, D and Henry, CS and Bergelson, J and Chang, EB},
title = {Diet outperforms microbial transplant to drive microbiome recovery in mice.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {40307551},
issn = {1476-4687},
abstract = {A high-fat, low-fibre Western-style diet (WD) induces microbiome dysbiosis characterized by reduced taxonomic diversity and metabolic breadth[1,2], which in turn increases risk for a wide array of metabolic[3-5], immune[6] and systemic pathologies. Recent work has established that WD can impair microbiome resilience to acute perturbations such as antibiotic treatment[7,8], although little is known about the mechanism of impairment and the specific consequences for the host of prolonged post-antibiotic dysbiosis. Here we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) or WD, and find that only mice on RC undergo a rapid successional process of recovery. Metabolic modelling indicates that a RC diet promotes the development of syntrophic cross-feeding interactions, whereas in mice on WD, a dominant taxon monopolizes readily available resources without releasing syntrophic byproducts. Intervention experiments reveal that an appropriate dietary resource environment is both necessary and sufficient for rapid and robust microbiome recovery, whereas microbial transplant is neither. Furthermore, prolonged post-antibiotic dysbiosis in mice on WD renders them susceptible to infection by the intestinal pathogen Salmonella enterica serovar Typhimurium. Our data challenge widespread enthusiasm for faecal microbiota transplant (FMT) as a strategy to address dysbiosis, and demonstrate that specific dietary interventions are, at a minimum, an essential prerequisite for effective FMT, and may afford a safer, more natural and less invasive alternative.},
}

@article {pmid40307477,
year = {2025},
author = {Iyengar, A and Ramadass, B and Venkatesh, S and Mak, RH},
title = {Gut microbiota-targeted therapies in pediatric chronic kidney disease: gaps and opportunities.},
journal = {Pediatric nephrology (Berlin, Germany)},
volume = {},
number = {},
pages = {},
pmid = {40307477},
issn = {1432-198X},
abstract = {Given the complex relationship between the gut microbiome and chronic kidney disease (CKD), exploring the potential role and scope of microbiota-targeted therapies in pediatric CKD is highly relevant. We aim to provide an overview of gut-targeted therapeutic strategies, including nutritional interventions (fiber, phytochemicals, fermented foods, and traditional Chinese medicines), probiotics, synbiotics, oral absorbents, and fecal microbial transplantation. Enhancing physical activity and preventing constipation are additional strategies that may promote gut microbiome health. In a uremic environment, gut microbiota-targeted therapies could potentially rebalance the gut microbiota, improve gut barrier function, decrease uremic toxin concentrations, enhance the production of short-chain fatty acids (SCFA), and reduce inflammation. While research in adult CKD patients has provided insights into these approaches, there are limited data in children with CKD. This review aims to summarize potential targeted therapies for restoring a balanced gut microbiota, emphasizing the need for studies that evaluate their effects on clinical outcomes in pediatric CKD.},
}

@article {pmid40306604,
year = {2025},
author = {Lee, SH and Han, C and Shin, C},
title = {IUPHAR Review: Microbiota-Gut-Brain Axis and its role in Neuropsychiatric Disorders.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {107749},
doi = {10.1016/j.phrs.2025.107749},
pmid = {40306604},
issn = {1096-1186},
abstract = {The human gut microbiome, composed of a vast array of microorganisms that have co-evolved with humans, is crucial for the development and function of brain systems. Research has consistently shown bidirectional communication between the gut and the brain through neuronal, endocrine, and immunological, and chemical pathways. Recent neuroscience studies have linked changes in the microbiome and microbial metabolites to various neuropsychiatric disorders such as autism, depression, anxiety, schizophrenia, eating disorders, and neurocognitive disorders. Novel metagenome-wide association studies have confirmed these microbiome variations in large samples and expanded our understanding of the interactions between human genes and the gut microbiome. The causal relationship between gut microbiota and neuropsychiatric disorders is being elucidated through the establishment of large cohort studies incorporating microbiome data and advanced statistical techniques. Ongoing animal and human studies focused on the microbiota-gut-brain axis are promising for developing new prevention and treatment strategies for neuropsychiatric conditions. The scope of these studies has broadened from microbiome-modulating therapies including prebiotics, probiotics, synbiotics and postbiotics to more extensive approaches such as fecal microbiota transplantation. Recent systematic reviews and meta-analyses have strengthened the evidence base for these innovative treatments. Despite extensive research over the past decade, many intriguing aspects still need to be elucidated regarding the role and therapeutic interventions of the microbiota-gut-brain axis in neuropsychiatric disorders.},
}

@article {pmid40306274,
year = {2025},
author = {Kim, SH and White, Z and Gainullina, A and Kang, S and Kim, J and Dominguez, JR and Choi, Y and Cabrera, I and Plaster, M and Takahama, M and Czepielewski, RS and Yeom, J and Gunzer, M and Hay, N and David, O and Chevrier, N and Sano, T and Kim, KW},
title = {IL-10 sensing by lung interstitial macrophages prevents bacterial dysbiosis-driven pulmonary inflammation and maintains immune homeostasis.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2025.04.004},
pmid = {40306274},
issn = {1097-4180},
abstract = {Crosstalk between the immune system and the microbiome is critical for maintaining immune homeostasis. Here, we examined this communication and the impact of immune-suppressive IL-10 signaling on pulmonary homeostasis. We found that IL-10 sensing by interstitial macrophages (IMs) is required to prevent spontaneous lung inflammation. Loss of IL-10 signaling in IMs initiated an inflammatory cascade through the activation of classical monocytes and CD4[+] T cell subsets, leading to chronic lung inflammation with age. Analyses of antibiotic-treated and germ-free mice established that lung inflammation in the animals lacking IL-10 signaling was triggered by commensal bacteria. 16S rRNA sequencing revealed Delftia acidovorans and Rhodococcus erythropolis as potential drivers of lung inflammation. Intranasal administration of these bacteria or transplantation of human fecal microbiota elicited lung inflammation in gnotobiotic Il10-deficient mice. These findings highlight that IL-10 sensing by IMs contributes to pulmonary homeostasis by preventing lung inflammation caused by commensal dysbiosis.},
}

@article {pmid40305972,
year = {2025},
author = {Jiang, ZM and Fang, ZY and Yang, X and Ji, XX and Zhao, YY and Lin, BY and Weng, ZB and Liu, EH},
title = {Glycyrrhetinic acid ameliorates gastric mucosal injury by modulating gut microbiota and its metabolites via Thbs1/PI3K-Akt/p53 pathway.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {142},
number = {},
pages = {156745},
doi = {10.1016/j.phymed.2025.156745},
pmid = {40305972},
issn = {1618-095X},
abstract = {BACKGROUND: Dysbiosis of the gut microbiota is pivotal in the development of gastric mucosa injury (GMI). Glycyrrhetinic acid (GA) is a bioactive triterpenoid compound abundantly present in licorice roots. Although GA's potential in mitigating GMI is recognized, its precise mechanism remains elusive, particularly concerning the role of gut microbiota.

PURPOSE: This study aimed to explore the protective effects and mechanisms of GA in preventing HCl/ethanol-induced GMI in rats.

RESULTS: This study demonstrated the protective effects of GA on gastric mucosa, evidenced by enhanced morphology and structure as revealed through H&E staining. Utilizing fecal microbiota transplantation, GA was found to significantly mitigate oxidative damage, inflammation, and expression of apoptosis-related genes in GMI rats by a gut microbiota-dependent mechanism. 16S rRNA sequencing and metabolomics profiling revealed that GA ameliorated HCl/ethanol-triggered intestinal dysbiosis and imbalances in sphingolipid, arginine, and tryptophan metabolism. By promoting the prevalence of Bifidobacterium longum subsp. infantis (B. infantis) in the gut microbiota, GA improved metabolic disturbances linked to injury. Furthermore, its action mechanism was related to the inhibition of the Thbs1/PI3K-Akt/p53 signaling pathway.

CONCLUSION: The administration of GA improves GMI by mitigating intestinal dysbiosis and fostering colonization of B. infantis. GA offers therapeutic potential for GMI by modulating the Thbs1/PI3K-Akt/p53 pathway, thus alleviating inflammatory responses associated with gut microbiota imbalance.},
}

@article {pmid40305678,
year = {2025},
author = {Wang, Y and Wang, X and Chen, Z and Zheng, J and Liu, X and Zheng, Y and Zheng, Z and Xu, Z and Zhang, Y and Chen, K and Zhang, Y and Yu, L and Ding, Y},
title = {Akkermansia muciniphila exacerbates acute radiation-induced intestinal injury by depleting mucin and enhancing inflammation.},
journal = {The ISME journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/ismejo/wraf084},
pmid = {40305678},
issn = {1751-7370},
abstract = {Dysbiosis of gut microbiota plays a crucial role in acute radiation-induced intestinal injury. However, studies on the influence of gut microbiota on acute radiation-induced intestinal injury are inconsistent. In this study, we established an acute radiation-induced intestinal injury mouse model and performed fecal microbiota transplantation to explore the role of the gut microbiota in acute radiation-induced intestinal injury. We observed a significant increase in Akkermansia muciniphila following irradiation, whereas fecal microbiota transplantation effectively reduced Akkermansia muciniphila levels. Contrary to expectations, Akkermansia muciniphila supplementation increased acute radiation-induced intestinal injury and mortality. Mechanistically, post-radiation Akkermansia muciniphila upregulates mucin metabolism genes and consumes mucin, thinning the mucosal barrier and promoting the adhesion and translocation of potential pathogens to epithelial cells, thus exacerbating acute radiation-induced intestinal injury. This enables Akkermansia muciniphila to use mucin as an energy source. Additionally, Akkermansia muciniphila increases the inflammatory macrophage changes and secretion of inflammatory cytokines, leading to a decrease in epithelial stem cell density and inhibition of goblet cell differentiation, further exacerbating acute radiation-induced intestinal injury. Our findings suggest that in certain intestinal environments, the addition of Akkermansia muciniphila may worsen radiation-induced intestinal damage; thus, alternative approaches to reverse the dysbiosis associated with radiotherapy should be explored.},
}

@article {pmid40305219,
year = {2025},
author = {Alves Costa Silva, C and Almonte, AA and Zitvogel, L},
title = {Oncobiomics: Leveraging Microbiome Translational Research in Immuno-Oncology for Clinical-Practice Changes.},
journal = {Biomolecules},
volume = {15},
number = {4},
pages = {},
pmid = {40305219},
issn = {2218-273X},
mesh = {Humans ; *Neoplasms/immunology/microbiology/therapy/metabolism ; *Translational Research, Biomedical ; *Microbiota ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/microbiology/immunology ; },
abstract = {Growing evidence suggests that cancer should not be viewed solely as a genetic disease but also as the result of functional defects in the metaorganism, including disturbances in the gut microbiota (i.e., gut dysbiosis). The human microbiota plays a critical role in regulating epithelial barrier function in the gut, airways, and skin, along with host metabolism and systemic immune responses against microbes and cancer. Collaborative international networks, such as ONCOBIOME, are essential in advancing research equity and building microbiome resources to identify and validate microbiota-related biomarkers and therapies. In this review, we explore the intricate relationship between the microbiome, metabolism, and cancer immunity, and we propose microbiota-based strategies to improve outcomes for individuals at risk of developing cancer or living with the disease.},
}

Humans
*Neoplasms/immunology/microbiology/therapy/metabolism
*Translational Research, Biomedical
*Microbiota
*Gastrointestinal Microbiome/immunology
Dysbiosis/microbiology/immunology

@article {pmid40304829,
year = {2025},
author = {Alum, EU and Uti, DE and Ugwu, OP and Alum, BN and Edeh, FO and Ainebyoona, C},
title = {Unveiling the microbial orchestra: exploring the role of microbiota in cancer development and treatment.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {646},
pmid = {40304829},
issn = {2730-6011},
abstract = {The human microbiota comprises a diverse microbial ecosystem that significantly impacts health and disease. Among its components, the gut microbiota plays a crucial role in regulating metabolic, immunologic, and inflammatory responses. Dysbiosis, an imbalance in microbial composition, has been linked to carcinogenesis through mechanisms such as chronic inflammation, metabolic disturbances, epigenetic modifications, and immune system dysregulation. Additionally, dysbiosis influences the efficacy and toxicity of cancer therapies. Given these associations, there is growing interest in leveraging the microbiota as a biomarker for cancer detection and outcome prediction. Notably, distinct microbial signatures have been identified across various cancer types, suggesting their potential as diagnostic markers. Furthermore, modulation of the microbiota presents a promising avenue for improving cancer treatment outcomes through strategies such as antibiotics, prebiotics, probiotics, fecal microbiota transplantation, dietary interventions, small-molecule inhibitors, and phage therapy. To explore these relationships, we conducted a comprehensive literature review using Web of Science, Scopus, PubMed, MEDLINE, Embase, and Google Scholar as our primary online databases, focusing on indexed peer-reviewed articles up to the present year. This review aims to elucidate the role of dysbiosis in cancer development, examine the molecular mechanisms involved, and assess the impact of microbiota on cancer therapies. Additionally, we highlight microbiota-based therapeutic strategies and discuss their potential applications in cancer management. A deeper understanding of the intricate interplay between the microbiota and cancer may pave the way for novel approaches to cancer prevention, early detection, and treatment optimization.},
}

@article {pmid40302307,
year = {2025},
author = {Hoffmann, DE and Javitt, GH and Kelly, CR and Keller, JJ and Baunwall, SMD and Hvas, CL},
title = {Fecal microbiota transplantation: a tale of two regulatory pathways.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2493901},
doi = {10.1080/19490976.2025.2493901},
pmid = {40302307},
issn = {1949-0984},
mesh = {*Fecal Microbiota Transplantation/history/methods/standards/adverse effects ; Humans ; *Gastrointestinal Microbiome ; United States ; Europe ; },
abstract = {Fecal microbiota transplantation (FMT) is a procedure involving the transfer of intestinal microbiota from a healthy donor to a patient to restore a functional intestinal microbiome. First described in modern science in 1958, the use of FMT has been practiced for decades, but only during the past dozen years have clinical frameworks and legal regulations from competent authorities been developed. Future development of microbiota-derived medical therapies will be shaped by the regulatory frameworks of various jurisdictions. This review examines the historical development and status of FMT regulations in the United States and Europe, with particular attention to their respective approaches to ensuring the safety and quality of the therapeutic product and patient access.},
}

*Fecal Microbiota Transplantation/history/methods/standards/adverse effects
Humans
*Gastrointestinal Microbiome
United States
Europe

@article {pmid40301246,
year = {2025},
author = {Liu, X and Cui, J and Tan, X and Yu, Y and Niu, J and Wang, Q},
title = {Short-Chain Fatty Acids Alleviate Perioperative Neurocognitive Disorders Through BDNF/PI3K/Akt Pathway in Middle-Aged Rats.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {40301246},
issn = {1559-1182},
support = {246Z7702G//Central Government - Guided Local Science and Technology Development Fund/ ; },
abstract = {Perioperative neurocognitive disorders (PND), characterized by persistent cognitive impairment lasting from days to years, present substantial clinical challenges in elderly surgical populations, profoundly compromising functional independence, quality of life, and long-term prognosis. We aimed to investigate the effects of short-chain fatty acids (SCFAs) treatment on PND via mediating Brain-derived neurotrophic factor (BDNF)/Phosphatidylinositol3-kinase (PI3K)/Protein kinase B (Akt) pathway. Using 16S rDNA sequencing targeting the V3-V4 hypervariable regions, we first demonstrated significant gut microbiota dysbiosis in PND model rats, accompanied by altered SCFAs profiles. Subsequent fecal microbiota transplantation (FMT) experiments established causal relationships between PND-associated microbial alterations and spatial cognitive deficits. Mechanistically, SCFAs supplementation attenuated neuronal damage and restored synaptic plasticity, as evidenced by Nissl staining quantification (reduced chromatolysis), TUNEL assay (decreased apoptosis rate), and immunohistochemical analysis (upregulated NeuN expression). Molecular investigations revealed that SCFAs-mediated cognitive improvement involved BDNF upregulation and subsequent PI3K/Akt pathway activation, ultimately enhancing neuronal survival and synaptic integrity. Notably, PND animals exhibited characteristic neuropathological features including synaptic density reduction (PSD-95 downregulation), neuroinflammation amplification (IL-6 elevation), and apoptosis activation-all significantly reversed by SCFA intervention. Our findings establish a novel gut-brain axis mechanism wherein microbiota-derived SCFAs may exert neuroprotection through BDNF-dependent PI3K/Akt signaling, and offer potential therapeutic strategies for PND management.},
}

@article {pmid40301116,
year = {2025},
author = {Kamath, S and Bryant, RV and Costello, SP and Day, AS and Forbes, B and Haifer, C and Hold, G and Kelly, CR and Li, A and Pakuwal, E and Stringer, A and Tucker, EC and Wardill, HR and Joyce, P},
title = {Translational strategies for oral delivery of faecal microbiota transplantation.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2025-335077},
pmid = {40301116},
issn = {1468-3288},
abstract = {Faecal microbiota transplantation (FMT) has emerged as a transformative therapy for Clostridioides difficile infections and shows promise for various GI and systemic diseases. However, the poor patient acceptability and accessibility of 'conventional' FMT, typically administered via colonoscopies or enemas, hinders its widespread clinical adoption, particularly for chronic conditions. Oral administration of FMT (OralFMT) overcomes these limitations, yet faces distinct challenges, including a significant capsule burden, palatability concerns and poor microbial viability during gastric transit. This review provides a comprehensive analysis of emerging strategies that aim to advance OralFMT by: (1) refining processing technologies (eg, lyophilisation) that enable manufacturing of low-volume FMT formulations for reducing capsule burden and (2) developing delivery technologies that improve organoleptic acceptability and safeguard the microbiota for targeted colonic release. These advancements present opportunities for OralFMT to expand its therapeutic scope, beyond C. difficile infections, towards chronic GI conditions requiring frequent dosing regimens. While this review primarily focuses on optimising OralFMT delivery, it is important to contextualise these advancements within the broader shift towards defined microbial consortia. Live biotherapeutic products (LBPs) offer an alternative approach, yet the interplay between OralFMT and LBPs in clinical practice remains unresolved. We postulate that continued innovation in OralFMT and LBPs via a multidisciplinary approach can further increase therapeutic efficacy and scalability by enabling disease site targeting, co-delivery of therapeutic compounds and overcoming colonisation resistance. Realising these goals positions OralFMT as a cornerstone of personalised care across a range of diseases rooted in microbiome health.},
}

@article {pmid40300858,
year = {2025},
author = {Almonte, AA and Zitvogel, L},
title = {Gut reactions: harnessing microbial metabolism to fuel next-generation cancer immunotherapy.},
journal = {Journal for immunotherapy of cancer},
volume = {13},
number = {4},
pages = {},
doi = {10.1136/jitc-2025-011540},
pmid = {40300858},
issn = {2051-1426},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology ; },
abstract = {Immunotherapies, including immune checkpoint inhibitors and chimeric antigen receptor-T cell therapies, depend heavily on a healthy and diverse gut microbiome for optimal efficacy. Dysbiosis, or an imbalance in gut microbial composition and function, can diminish immunotherapy responses by altering immune cell trafficking and metabolic output. Key microbial metabolites such as short-chain fatty acids and modified bile acids shape host immunity and influence T-cell function, while their disruption can foster an immunosuppressive microenvironment. Emerging strategies to restore a balanced microbiome and boost treatment outcomes include dietary interventions, supplementation with beneficial microbes, and fecal microbiota transplantation. Despite these advances, challenges remain in defining dysbiosis, identifying reliable biomarkers, and tailoring microbiota-centered interventions. Nevertheless, as our understanding evolves, the gut microbiome holds promise as an integral component of personalized cancer immunotherapy.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Immunotherapy/methods
*Neoplasms/therapy/immunology

@article {pmid40300731,
year = {2025},
author = {Mahmoud, AA and Wang, X and Liao, X and Zhang, S and Ding, T and Ahn, J},
title = {Impact of prophages on gut microbiota and disease associations.},
journal = {Microbial pathogenesis},
volume = {204},
number = {},
pages = {107642},
doi = {10.1016/j.micpath.2025.107642},
pmid = {40300731},
issn = {1096-1208},
abstract = {The gut microbiota plays an important role in maintaining host health by affecting various physiological functions. Among the diverse microbial communities in the gut, prophages are integral components of bacterial genomes, contributing significantly to bacterial evolution, ecology and pathogenicity. Prophages are capable of switching to lytic cycles in response to various internal and external factors. Factors that induce prophage induction include DNA damage, oxidative stress, nutrient availability, host immune response, quorum sensing, diet, secondary metabolites, antibiotics, and lifestyle changes. Prophage induction could contribute to both gut homeostasis and dysbiosis. Importantly, the connections between prophage induction and disorders such as inflammatory bowel disease, ulcerative colitis, and bacterial vaginosis highlight the dual roles of prophages in both health and disease. Although therapeutic approaches such as phage therapy (PT), fecal microbiota transplants (FMT), and fecal virome transplants (FVT) have gained attention, the concept of dietary prophage induction therapy offers a novel, targeted method to modulate gut microbiota. In spite of recent advances in understanding the role of prophages in gut health, the exact mechanisms by which they influence gut health remain only partially understood. Therefore, further research is needed to elucidate additional molecular mechanisms of prophage induction pathways and to explore their implications for gut microbiota dynamics and disease associations. This review discusses the molecular mechanisms and key factors that trigger prophage induction in the gut. Insights into these processes could lead to innovative therapeutic strategies that utilize prophages to support gut health.},
}

@article {pmid40303777,
year = {2023},
author = {De Sabato, L and Ianiro, G and Alborali, GL and Kroneman, A and Grierson, SS and Krumova-Valcheva, GL and Hakze-van der Honing, RW and Johne, R and Kolackova, I and Kozyra, I and Gyurova, E and Pavoni, E and Reisp, K and Sassu, EL and Schilling-Loeffler, K and Smith, RP and Vasickova, P and Żmudzki, J and Rzeżutka, A and Di Bartolo, I},
title = {Molecular Characterization and Phylogenetic Analysis of Hepatitis E Virus (HEV) Strains from Pigs Farmed in Eight European Countries between 2020 and 2022.},
journal = {Transboundary and emerging diseases},
volume = {2023},
number = {},
pages = {2806835},
pmid = {40303777},
issn = {1865-1682},
mesh = {Animals ; *Hepatitis E virus/genetics/isolation & purification/classification ; Swine ; *Hepatitis E/veterinary/virology/epidemiology ; *Swine Diseases/virology/epidemiology ; Phylogeny ; Europe/epidemiology ; Feces/virology ; Genotype ; },
abstract = {In high-income countries, the hepatitis E virus (HEV) is considered an emerging threat causing autochthonous acute hepatitis in humans, with an increased number of reported cases over the last 10 years and related increased burden of chronic hepatitis in immunocompromised and transplant patients. Pigs are the main reservoir of the HEV-3 genotype, which is the most common in Europe, and can be transmitted to humans through the consumption of raw and undercooked pork products. Extensive sequencing revealed the existence of several HEV-3 subtypes in both humans and pigs, confirming a broad heterogeneity of the virus, with some subtypes, such as 3e, 3f, and 3c, which are predominant in Europe. In this study, 291 HEV sequences were obtained from pig feces sampled in more than 74 farms located in Austria, Bulgaria, Czech Republic, Germany, Italy, Poland, the United Kingdom, as well as an unknown number of farms in Netherlands. Of the 99 nonidentical sequences (99/291), 90 were assigned to seven established HEV-3 subtypes: 3a, 3c, 3e, 3f, 3g (here named 3g-like), 3i, and 3l (named 3l-like), already described in Europe, while nine sequences of HEV-3 could not be assigned to any existing subtype (here named 3 [∗]). The 3e subtype was the most common, detected in six out of eight countries, followed by 3f and 3c, which were also present in several countries; 3g-like, 3i, and 3l-like subtypes showed only a limited circulation. The distribution of frequently (3e, 3f, and 3c) and rarely (3g-like, 3i, and 3l-like) detected HEV-3 subtypes in pigs was correlated with their detection rates in human patients in Europe. The results from this study confirm the wide circulation of several HEV-3 strains in European pigs and confirm that sequencing is needed to monitor the different strains and to identify possible zoonotic transmission paths.},
}

Animals
*Hepatitis E virus/genetics/isolation & purification/classification
Swine
*Hepatitis E/veterinary/virology/epidemiology
*Swine Diseases/virology/epidemiology
Phylogeny
Europe/epidemiology
Feces/virology
Genotype

@article {pmid40300372,
year = {2025},
author = {Liu, Z and Zhang, H and Wang, J and Yao, Y and Wang, X and Liu, Y and Fang, W and Liu, X and Zheng, Y},
title = {Clca1 deficiency exacerbates colitis susceptibility via impairment of mucus barrier integrity and gut microbiota homeostasis.},
journal = {Microbiological research},
volume = {297},
number = {},
pages = {128191},
doi = {10.1016/j.micres.2025.128191},
pmid = {40300372},
issn = {1618-0623},
abstract = {The intestinal mucus barrier has emerged as a promising therapeutic target for inflammatory bowel disease. Understanding its regulatory mechanisms is critical for elucidating ulcerative colitis (UC) pathogenesis, improving diagnostics, guiding treatments, and preventing relapse. Chloride Channel Accessory 1 (Clca1), a constituent of the mucus layer, remains understudied in colitis. Here, we investigated Clca1's role in mucosal immunity and intestinal homeostasis using experimental colitis models. Clca1-deficient (Clca1[-/-]) mice displayed compromised mucus layer integrity, reduced neutrophil infiltration, and gut microbiota dysbiosis. Notably, Clca1[-/-] mice exhibited exacerbated colitis severity following dextran sulfate sodium (DSS) challenge, accompanied by a diminished goblet cell populations. Fecal microbiota transplantation (FMT) studies revealed that gut microbiota critically modulates divergent phenotypic outcomes between genotypes. Our findings establish Clca1 as a multifunctional regulator of mucus barrier integrity through mechanisms involving goblet cell maintenance, neutrophil-mediated immunity, and host-microbiota crosstalk. These results advance the understanding of UC pathogenesis and identify Clca1-associated pathways as potential targets for barrier restoration therapies.},
}

@article {pmid40299998,
year = {2025},
author = {Cao, J and Wang, X and Lei, Y and Jiang, X and Kannan, K and Li, M},
title = {Health Risks of Low-Dose Dietary Exposure to Triphenyl Phosphate and Diphenyl Phosphate in Mice: Insights from the Gut-Liver Axis.},
journal = {Environmental science & technology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.est.4c08270},
pmid = {40299998},
issn = {1520-5851},
abstract = {Aryl phosphate esters have been detected throughout the natural environment and in human blood samples, making it important to determine the health risks associated with exposure to triphenyl phosphate (TPHP) and its metabolite diphenyl phosphate (DPHP). Here, C57BL/6J male mice were exposed to TPHP or DPHP for 12 weeks at estimated daily intake doses of 0.1 and 7 μg/kg bw/day. TPHP intake affected the levels of short-chain fatty acids and bile acids in the gut, enhancing the production of 29 medium- and long-chain fatty acids in the liver by 3.72-fold and significantly increasing hepatic lipid and cholesterol levels. Metabolomic and molecular analysis confirmed that elevated liver cholesterol levels persisted after an 8 week recovery period. Gut microbiota-dependent cholesterol alterations were the toxic end points observed in TPHP-fed mice, as supported by the results of fecal microbiota transplantation. In DPHP-fed mice, serotonergic and glutamatergic synapses were simultaneously altered in the liver and intestine, corresponding to the reduction of five brain neurotransmitters (15.4-60.8%). Decreased liver carbohydrate levels and insulin resistance were observed in the DPHP-fed mice. These results suggest that TPHP and DPHP affect metabolism via different toxic modes, mediated through the gut-liver axis, providing novel insights into the mechanisms of organophosphate-ester-mediated metabolic disruption.},
}

@article {pmid40299512,
year = {2025},
author = {Eslami, M and Adampour, Z and Fadaee Dowlat, B and Yaghmayee, S and Motallebi Tabaei, F and Oksenych, V and Naderian, R},
title = {A Novel Frontier in Gut-Brain Axis Research: The Transplantation of Fecal Microbiota in Neurodegenerative Disorders.},
journal = {Biomedicines},
volume = {13},
number = {4},
pages = {},
pmid = {40299512},
issn = {2227-9059},
abstract = {The gut-brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous system (CNS) and the gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, and metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In recent years, fecal microbiota transplantation (FMT) has gained attention as an innovative therapeutic approach, aiming to restore microbial balance in the gut while influencing neuroinflammatory and neurodegenerative pathways. This review explores the mechanisms by which FMT impacts the gut-brain axis. Key areas of focus include its ability to reduce neuroinflammation, strengthen gut barrier integrity, regulate neurotransmitter production, and reinstate microbial diversity. Both preclinical and clinical studies indicate that FMT can alleviate motor and cognitive deficits in PD and AD, lower neuroinflammatory markers in MS, and enhance respiratory and neuromuscular functions in ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, and inconsistencies in clinical outcomes. Innovations such as synthetic microbial communities, engineered probiotics, and AI-driven analysis of the microbiome hold the potential to improve the precision and effectiveness of FMT in managing neurodegenerative conditions. Although FMT presents considerable promise as a therapeutic development, its widespread application for neurodegenerative diseases requires thorough validation through well-designed, large-scale clinical trials. It is essential to establish standardized protocols, refine donor selection processes, and deepen our understanding of the molecular mechanisms behind its efficacy.},
}

@article {pmid40299326,
year = {2025},
author = {Hauser, G and Benjak Horvat, I and Rajilić-Stojanović, M and Krznarić-Zrnić, I and Kukla, M and Aljinović-Vučić, V and Mikolašević, I},
title = {Intestinal Microbiota Modulation by Fecal Microbiota Transplantation in Nonalcoholic Fatty Liver Disease.},
journal = {Biomedicines},
volume = {13},
number = {4},
pages = {},
pmid = {40299326},
issn = {2227-9059},
abstract = {Numerous factors are involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which are responsible for its development and progression as an independent entity, but also thanks to their simultaneous action. This is explained by the hypothesis of multiple parallel hits. These factors are insulin resistance, lipid metabolism alteration, oxidative stress, endoplasmic reticulum stress, inflammatory cytokine liberation, gut microbiota dysbiosis or gut-liver axis activation. This is a systematic review which has an aim to show the connection between intestinal microbiota and the role of its disbalance in the development of NAFLD. The gut microbiota is made from a wide spectrum of microorganisms that has a systemic impact on human health, with a well-documented role in digestion, energy metabolism, the stimulation of the immune system, synthesis of essential nutrients, etc. It has been shown that dysbiosis is associated with all three stages of chronic liver disease. Thus, the modulation of the gut microbiota has attracted research interest as a novel therapeutic approach for the management of NAFLD patients. The modification of microbiota can be achieved by substantial diet modification and the application of probiotics or prebiotics, while the most radical effects are observed by fecal microbiota transplantation (FMT). Given the results of FMT in the context of metabolic syndrome (MetS) and NAFLD in animal models and scarce pilot studies on humans, FMT seems to be a promising treatment option that could reverse intestinal dysbiosis and thereby influence the course of NAFLD.},
}

@article {pmid40298931,
year = {2025},
author = {Gao, X and Fu, N and Ben, Q and Bu, X},
title = {A Meta-Analysis of the Effects of Gut Microbiota-Based Interventions on Gastrointestinal and Behavioral Symptoms in Children With Autism Spectrum Disorder.},
journal = {Nutrition reviews},
volume = {},
number = {},
pages = {},
doi = {10.1093/nutrit/nuaf050},
pmid = {40298931},
issn = {1753-4887},
abstract = {CONTEXT: Despite an increasing body of research showing gut microbiota-based interventions can improve gastrointestinal (GI) symptoms and behavioral symptoms in both humans and animals, there are still disagreements about its impact on autism spectrum disorder (ASD) in children.

OBJECTIVE: The goal of this systematic review and meta-analysis was to fully investigate the effects of gut microbiota-based interventions (eg, fecal microbiota transplantation, probiotics, prebiotics) on GI and behavioral symptoms in children with ASD.

DATA SOURCES: The PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, and Scopus databases were searched from inception to August 25, 2024.

DATA EXTRACTION: Data were extracted by 2 reviewers independently, and discrepancies in authors' judgments were resolved by discussion or consulting a third author.

DATA ANALYSIS: The scale score of GI and behavioral symptoms before and after the intervention was extracted from included trials to evaluate the therapeutic effects of gut microbiota-based therapy in children with autism.

RESULTS: A total of 5722 records were identified, of which 13 included in narrative synthesis and 8 studies included a meta-analysis. The nonsignificant overall effect size of gut microbiota-based intervention on GI symptoms (standardized mean difference [SMD] = -0.34 [95% CI, -0.76 to 0.07]; P = .11) and behavioral symptoms (SMD = -0.18 [95% CI, -0.37 to 0.02]; P = .08) was observed. Nevertheless, we observed a significant effect size on behavioral symptoms in the subgroup of the intervention duration (SMD = -0.26 [95% CI, -0.49 to -0.03]; P = .02).

CONCLUSIONS: In children with autism, the proof supporting the validity of gut microbiota-based intervention on GI and behavioral symptoms should be interpreted cautiously. More randomized controlled trials with rigorous methodological quality are required to precisely confirm the curative benefits of gut microbiota-based interventions on GI and behavioral symptoms in children with autism.

PROSPERO registration no. CRD42024583213.},
}

@article {pmid40298495,
year = {2025},
author = {Cusumano, G and Flores, GA and Venanzoni, R and Angelini, P},
title = {The Impact of Antibiotic Therapy on Intestinal Microbiota: Dysbiosis, Antibiotic Resistance, and Restoration Strategies.},
journal = {Antibiotics (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
pmid = {40298495},
issn = {2079-6382},
abstract = {The human gut microbiota-an intricate and dynamic ecosystem-plays a pivotal role in metabolic regulation, immune modulation, and the maintenance of intestinal barrier integrity. Although antibiotic therapy is indispensable for managing bacterial infections, it profoundly disrupts gut microbial communities. Such dysbiosis is typified by diminished diversity and shifts in community structure, especially among beneficial bacterial genera (e.g., Bifidobacterium and Eubacterium), and fosters antibiotic-resistant strains and the horizontal transfer of resistance genes. These alterations compromise colonization resistance, increase intestinal permeability, and amplify susceptibility to opportunistic pathogens like Clostridioides difficile. Beyond gastrointestinal disorders, emerging evidence associates dysbiosis with systemic conditions, including chronic inflammation, metabolic syndrome, and neurodegenerative diseases, underscoring the relevance of the microbiota-gut-brain axis. The recovery of pre-existing gut communities post-antibiotic therapy is highly variable, influenced by drug spectrum, dosage, and treatment duration. Innovative interventions-such as fecal microbiota transplantation (FMT), probiotics, synbiotics, and precision microbiome therapeutics-have shown promise in counteracting dysbiosis and mitigating its adverse effects. These therapies align closely with antibiotic stewardship programs aimed at minimizing unnecessary antibiotic use to preserve microbial diversity and curtail the spread of multidrug-resistant organisms. This review emphasizes the pressing need for microbiota-centered strategies to optimize antibiotic administration, promote long-term health resilience, and alleviate the disease burden associated with antibiotic-induced dysbiosis.},
}

@article {pmid40297591,
year = {2025},
author = {Pei, X and Liu, L and Han, Y},
title = {Advances in human microbiome and prostate cancer research.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1576679},
pmid = {40297591},
issn = {1664-3224},
mesh = {Humans ; *Prostatic Neoplasms/microbiology/therapy/immunology/metabolism/etiology ; Male ; *Microbiota ; *Gastrointestinal Microbiome ; Tumor Microenvironment/immunology ; Animals ; },
abstract = {Prostate cancer (PCa) is the second most common malignant tumor in men worldwide, and its metastatic and heterogeneous nature makes it significantly more difficult to treat. Recent studies have revealed the critical role of microbiota in PCa occurrence, progression, and treatment. Accumulating evidence from 16S rRNA and metagenomic sequencing suggests the presence of specific microbiota in prostate tissues and macrogenomics techniques: cancerous tissues are enriched with pro-inflammatory genera (e.g., Fusobacterium, Propionibacterium acnes), whereas commensal bacteria (e.g., Pseudomonas) are more common in paracancerous tissues. The microbiota drive tumor progression through activation of the NF-κB/STAT3 pathway to induce chronic inflammation, modulation of the immune microenvironment (e.g., Treg/Th17 imbalance and M2-type macrophage polarization), and metabolite (e.g., LPS, short-chain fatty acids)-mediated hormonal and epigenetic regulation. In terms of clinical translation, urinary microbiota characterization combined with metabolomics analysis may enhance diagnostic specificity, while gut flora modulation (e.g., probiotic interventions or fecal transplants) may improve resistance to androgen deprivation therapy. Current challenges include sequencing accuracy of low-biomass samples, limitations of causal mechanism validation models, and large cohort heterogeneity. In the future, it will be necessary to integrate multi-omics technologies to explore the bidirectional regulation of the "gut-prostate axis" and develop personalized therapeutic strategies targeting microorganisms. In this paper, we systematically review the interactions between microbiota and PCa and their clinical potentials to provide a theoretical basis for precision diagnosis and treatment.},
}

Humans
*Prostatic Neoplasms/microbiology/therapy/immunology/metabolism/etiology
Male
*Microbiota
*Gastrointestinal Microbiome
Tumor Microenvironment/immunology
Animals

@article {pmid40297203,
year = {2025},
author = {Nguyen, JDK and Yohannes, KG and Setiady, I and Phillips, EC and Hays, RA and Behm, BW and Warren, CA and Shin, JH},
title = {Factors associated with failure of fecal microbiota transplant for recurrent Clostridioides difficile infection.},
journal = {Therapeutic advances in gastroenterology},
volume = {18},
number = {},
pages = {17562848251334517},
pmid = {40297203},
issn = {1756-283X},
abstract = {BACKGROUND: Clostridioides difficile infection (CDI) has emerged as a prevalent and recurrent antibiotic-associated infection. Fecal microbiota transplantation (FMT) is the most effective treatment for recurrent CDI (rCDI). Despite high success rates, FMT is ineffective in 5%-20% of cases. Factors associated with failure have not been clearly defined.

OBJECTIVES: In this study, we seek to identify factors predictive of FMT failure.

DESIGN: Retrospective cohort study.

METHODS: A retrospective chart review was conducted on adult patients who were screened at the Complicated C. difficile Clinic at the University of Virginia Health System and received FMT for rCDI between 2013 and 2022. The primary outcome was failure of FMT, defined as either rCDI or all-cause death within 1 year.

RESULTS: In total, 240 patients underwent FMT: 70.4% were female, the median age was 68, and the median episode of CDI was 4. A total of 24.6% experienced failure within 1 year (18.3% had rCDI and 7.1% died). Age 70 or older (odds ratio (OR) = 2.66 (1.29-5.67)), ⩾4 episodes of CDI (OR = 3.13 (1.47-7.09)), and diabetes mellitus (OR = 2.82 (1.25-6.50)) were associated with failure on multivariate analysis.

CONCLUSION: Our study shows that FMT remains an effective treatment for rCDI. We highlight several factors associated with FMT failure, such as older age, ⩾4 episodes of CDI, and diabetes mellitus, and the need for additional research to clearly define causality.},
}

@article {pmid40296251,
year = {2025},
author = {Zheng, H and Chen, Y and Lu, S and Liu, Z and Ma, Y and Zhang, C and Zhang, Y and Zhang, J and Liu, C and Chu, M and Pei, F and Liu, S and Duan, L},
title = {Mechanosensory Piezo2 regulated by gut microbiota participates in the development of visceral hypersensitivity and intestinal dysmotility.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2497399},
doi = {10.1080/19490976.2025.2497399},
pmid = {40296251},
issn = {1949-0984},
mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Humans ; Mice ; *Irritable Bowel Syndrome/microbiology/physiopathology/metabolism/therapy ; *Ion Channels/metabolism/genetics ; Male ; Female ; Fecal Microbiota Transplantation ; *Gastrointestinal Motility ; Adult ; Middle Aged ; Colon/metabolism ; Mice, Inbred C57BL ; Feces/microbiology ; Fusobacterium/physiology ; Dysbiosis/microbiology ; Disease Models, Animal ; Ganglia, Spinal/metabolism ; Akkermansia ; },
abstract = {The gut microbiota plays a crucial role in the manifestation of intestinal dysfunction associated with irritable bowel syndrome (IBS). The mechanosensory Piezo2 has been implicated in the regulation of intestinal function. However, it remains unclear whether Piezo2 is modulated by the gut microbiota, thus contributing to the development of visceral hypersensitivity and gut dysmotility. The study enrolled patients with diarrhea-predominant IBS (IBS-D) alongside healthy controls (HC). Questionnaires, rectal barostat test, and colonoscopy with mucosal biopsy were conducted. Fecal microbiota transplantation (FMT) was performed using samples from HC or IBS-D patients, and interventions with Akkermansia muciniphila or Fusobacterium varium were carried out on colon- or dorsal root ganglion (DRG)- Piezo2 knockdown pseudo-germ-free mice. Visceral sensitivity and intestinal motility were assessed. Piezo2 levels were detected using western blot and immunofluorescence. Fecal 16S rRNA sequencing and cecum untargeted metabolomics analysis, followed by molecular docking predictions of Piezo2, were also performed. The ratio of Piezo2[+]/5-HT[+] cells was lower in IBS-D patients, positively correlated with visceral sensation and intestinal dysbiosis. The mice that received FMT from IBS-D patients exhibited colonic dysmotility and visceral hypersensitivity, along with elevated Piezo2 protein levels in the colon and DRG. Knockdown of Piezo2 in the colon or DRG ameliorated the FMT-induced colonic dysmotility and visceral hypersensitivity. Fecal 16S rRNA sequencing revealed distinct microbiota composition. Notably, Fusobacterium varium, but not Akkermansia muciniphila, induced gut dysmotility and visceral hypersensitivity, effects that could be alleviated by colon or DRG Piezo2 knockdown. Additionally, Fusobacterium varium lead to increased Piezo2 protein levels, as well as elevated levels of indole-3-acetic acid and indole-3-acrylic acid, which were predicted to bind to Piezo2, causing disturbances. Piezo2 can be regulated by gut microbiota and involved in visceral hypersensitivity and colonic dysmotility, with Fusobacterium varium playing a crucial role.},
}

*Gastrointestinal Microbiome/physiology
Animals
Humans
Mice
*Irritable Bowel Syndrome/microbiology/physiopathology/metabolism/therapy
*Ion Channels/metabolism/genetics
Male
Female
Fecal Microbiota Transplantation
*Gastrointestinal Motility
Adult
Middle Aged
Colon/metabolism
Mice, Inbred C57BL
Feces/microbiology
Fusobacterium/physiology
Dysbiosis/microbiology
Disease Models, Animal
Ganglia, Spinal/metabolism
Akkermansia

@article {pmid40295906,
year = {2025},
author = {Ahmadi, A and Shokoohizadeh, L and Sheikhesmaili, F and Mirzaei, MK and Mohammadi, A and Nikkhoo, B and Khodaei, H and Alikhani, MY and Yousefimashouf, R},
title = {Gut microbiomes and treatment-resistant ulcerative colitis: a case-control study using qPCR.},
journal = {BMC microbiology},
volume = {25},
number = {1},
pages = {254},
pmid = {40295906},
issn = {1471-2180},
mesh = {Humans ; *Colitis, Ulcerative/microbiology/drug therapy ; Case-Control Studies ; *Gastrointestinal Microbiome/genetics ; Male ; Adult ; Female ; Feces/microbiology ; Middle Aged ; Real-Time Polymerase Chain Reaction ; *Bacteria/genetics/classification/isolation & purification ; Young Adult ; },
abstract = {BACKGROUND: The gut microbiome has been identified as a pivotal factor in ulcerative colitis (UC), given its role as the main reservoir of microbes in the body. This community of microorganisms, present in variable concentrations in the digestive tract, makes a wide range of beneficial roles for the host. However, the role of the gut microbiome in patients with refractory UC is still significant, so this study aimed to further investigate the role of these bacteria in patients with refractory UC.

METHODS: This case-control study was conducted on stool samples from four distinct groups: the first group comprised new patients diagnosed with ulcerative colitis (all of them had responded to treatment after follow-up) (N = 24); the second group consisted of patients with treatment-resistant ulcerative colitis (N = 23); the third group included first-degree relatives of group 1 patients (N = 24); and the fourth group consisted of first-degree relatives of group 2 patients (N = 23). The research tools employed in this study included a questionnaire, quantitative real-time PCR (qPCR) test, and culture on stool samples.

RESULT: The mean age of patients in groups 1 and 2 was 45.88 ± 18.51 and 41.30 ± 13.01 years, while the mean age of controls in groups 3 and 4 was 37.29 ± 9.62 and 40.96 ± 13.01 years, respectively. Stool culture results for pathogenic bacteria were negative in all four groups. The of history of consuming dairy products containing probiotics was highest in Group 1, with 22 (91.67%) subjects, while the lowest was observed in Group 3, with 16 (66.67%). The highest history of self-administered antibiotic use was observed in Group 2, with 13 cases (56.52%), while the lowest was noted in Group 3, with 4 cases (16.67%). The findings indicated a statistically significant relationship (P < 0.05) between Groups 2 and 4 with respect to the E. coli and Bifidobacterium ssp. microbial population. Additionally, a significant relationship was identified between the Lactobacillus ssp., Bifidobacterium ssp., and Bacteroides ssp. microbial community between groups 1 and 2 (P < 0.05).

CONCLUSION: The findings of this study demonstrated that several intestinal microbiomes have a substantial impact on the management of ulcerative colitis. The results of this study suggest that by comparing the gut microbiome of treatment-resistant and individuals newly diagnosed with ulcerative colitis, we can gain a better understanding of microbiome differences that may influence treatment outcomes. The results of this study may also lead to the identification of new therapeutic strategies that are based on regulating the gut microbiome. These strategies could include the use of fecal microbiome transplantation (FMT), probiotics, prebiotics, or specific bacteria-based therapies.},
}

Humans
*Colitis, Ulcerative/microbiology/drug therapy
Case-Control Studies
*Gastrointestinal Microbiome/genetics
Male
Adult
Female
Feces/microbiology
Middle Aged
Real-Time Polymerase Chain Reaction
*Bacteria/genetics/classification/isolation & purification
Young Adult

@article {pmid40295607,
year = {2025},
author = {Mohammadi, M and Rahimi, K and Rezaie, A and Tabandeh, MR},
title = {The role of fecal microbiota transplantation on the NLRP3-Caspase 1 pathway and anxiety like behavioral in the ulcerative colitis model in rats.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {14831},
pmid = {40295607},
issn = {2045-2322},
mesh = {Animals ; *Caspase 1/metabolism/genetics ; *Fecal Microbiota Transplantation/methods ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Anxiety/therapy/metabolism/etiology ; Rats ; Signal Transduction ; Male ; *Colitis, Ulcerative/therapy/chemically induced/metabolism ; Disease Models, Animal ; Hippocampus/metabolism ; Behavior, Animal ; Colon/metabolism/pathology ; Acetic Acid ; Interleukin-18/metabolism ; },
abstract = {The purpose of this study was to investigate the function of the NLRP3-Caspase 1 signaling pathway in the colon during fecal microbiota transplantation (FMT) in colitis induced by acetic acid. Additionally, the study aimed to determine the impact of FMT on anxiety behaviors by analyzing the function of the NLRP3-Caspase 1 signaling pathway in the hippocampus. A total of twenty-four rats were selected randomly for the study and divided into two groups, a control group, and an acid acetic-induced colitis group. The acid acetic-induced colitis group further consisted of three subgroups: untreated acid acetic-induced colitis group, mesalazine 0.3 gr/kg group, and FMT group. After 6 days, the colon was evaluated for macroscopic and microscopic damage, and the signaling pathway NLRP3-Caspase1-related genes in the colon and hippocampus were analyzed. Additionally, anxiety-related behaviors of the rats were observed. FMT decreased colonic mRNA expression levels of NLRP3, NF-кB, and Caspase1 and pro-inflammatory cytokines (IL-1β and IL-18). Also, FMT reduced the expression of NLRP3, NF-κB, and Caspase1 protein levels as well as pro-inflammatory cytokines IL-1β and IL-18 in the hippocampus, resulting in a reduction of anxiety behaviors in the open field and elevated plus maze tests in the colitis model. FMT may improve acetic acid-induced colitis by regulating the NLRP3-Caspase1 signaling pathway in the colon. It also reduced colitis-induced anxiety behavior by regulating the expression of proteins related to the NLRP3-Caspase 1 pathway in the hippocampus.},
}

Animals
*Caspase 1/metabolism/genetics
*Fecal Microbiota Transplantation/methods
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics
*Anxiety/therapy/metabolism/etiology
Rats
Signal Transduction
Male
*Colitis, Ulcerative/therapy/chemically induced/metabolism
Disease Models, Animal
Hippocampus/metabolism
Behavior, Animal
Colon/metabolism/pathology
Acetic Acid
Interleukin-18/metabolism

@article {pmid40295196,
year = {2025},
author = {Sun, J and Shi, L and Xu, F and Sun, H and Liu, Y and Sun, J and Zhou, Q},
title = {Naringenin Inhibits Colorectal Cancer associated with a High-Fat Diet through Modulation of Gut Microbiota and IL-6/STAT3 Pathway.},
journal = {Journal of microbiology and biotechnology},
volume = {35},
number = {},
pages = {e2412029},
doi = {10.4014/jmb.2412.12029},
pmid = {40295196},
issn = {1738-8872},
mesh = {*Flavanones/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Colorectal Neoplasms/drug therapy/microbiology/prevention & control/etiology/metabolism ; *STAT3 Transcription Factor/metabolism ; *Diet, High-Fat/adverse effects ; Animals ; *Interleukin-6/metabolism ; Mice ; Male ; Signal Transduction/drug effects ; Fecal Microbiota Transplantation ; Humans ; Mice, Inbred C57BL ; Bacteria/drug effects/classification/genetics ; },
abstract = {Colorectal cancer (CRC) is a worldwide health issue. It causes illness and death in millions of people each year. A positive correlation has been observed between the intake of dietary fat and the development of CRC. The composition of gut microbiota exhibits a significant correlation with pathophysiologic processes in intestine. Clinical treatment remains inadequate due to the complex pathogenic mechanisms of CRC triggered by a high-fat diet (HFD). Naringenin, a flavonoid from grapefruit, has anti-cancer activity. Our findings suggest that naringenin enhances gut microbiota diversity by increasing the abundance of beneficial bacterial species while reducing opportunistic pathogenic bacteria. The fecal microbiota transplantation assay (FMT) demonstrated that the anti-HFD-CRC activity of naringenin depended on the gut microbiota. Furthermore, naringenin antagonized the IL-6/STAT3 pathway. These results suggest that naringenin may be a potential treatment for HFD-CRC.},
}

*Flavanones/pharmacology
*Gastrointestinal Microbiome/drug effects
*Colorectal Neoplasms/drug therapy/microbiology/prevention & control/etiology/metabolism
*STAT3 Transcription Factor/metabolism
*Diet, High-Fat/adverse effects
Animals
*Interleukin-6/metabolism
Mice
Male
Signal Transduction/drug effects
Fecal Microbiota Transplantation
Humans
Mice, Inbred C57BL
Bacteria/drug effects/classification/genetics

@article {pmid40294087,
year = {2025},
author = {Duarte, L and Magne, F and Gotteland, M},
title = {Gut microbiota in patients with metabolic, dysfunction-associated steatotic liver disease.},
journal = {Current opinion in clinical nutrition and metabolic care},
volume = {},
number = {},
pages = {},
pmid = {40294087},
issn = {1473-6519},
abstract = {PURPOSE OF REVIEW: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent condition that can progress to fibrosis, steatohepatitis, and hepatocellular carcinoma. This review examines recent advances concerning the role of gut microbiota in MASLD and microbiota-focused interventions to positively impact disease outcome.

RECENT FINDINGS: Dysbiotic microbiota and a compromised gut barrier facilitate the translocation of microbial-associated molecular patterns and harmful metabolites into the portal circulation and liver, where they exacerbate inflammatory and fibrogenic processes. Conversely, other bacterial metabolites have protective effects in the liver. Therefore, microbiota homeostasis is essential for maintaining liver health.

SUMMARY: Levels of harmful bacterial metabolites including ethanol, NH3, trimethylamine-L-oxide, 2-oleylglycerol, and litocholic acid are often increased in patients with MASLD. Conversely, short-chain fatty acids, indole derivatives, histidine, and the acids taurodeoxycholic, 3-succinylcholic, and hyodeoxycholic are decreased. The main aim of current interventions/treatments is to reduce harmful metabolites and increase beneficial ones. These interventions include drugs (pemafibrate, metformin, obeticholic acid), natural compounds (silymarin, lupeol, dietary fiber, peptides), exogenous bacteria (probiotics, gut symbionts), special diets (Mediterranean diet, time-restricted feeding), as well as microbiota transplantation, and phage therapy. Most improve gut permeability, liver inflammation, and fibrosis through microbiota regulation, and are promising alternatives for MASLFD management. However, most results come from animal studies, while clinical trials in MASLD patients are lacking. Further research is therefore needed in this area.},
}

@article {pmid40292220,
year = {2025},
author = {Ma, P and Wang, R and Chen, H and Zheng, J and Yang, W and Meng, B and Liu, Y and Lu, Y and Zhao, J and Gao, H},
title = {Fecal microbiota transplantation alleviates lipopolysaccharide-induced osteoporosis by modulating gut microbiota and long non-coding RNA TUG1 expression.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1535666},
pmid = {40292220},
issn = {2235-2988},
mesh = {Animals ; *RNA, Long Noncoding/genetics/metabolism ; *Gastrointestinal Microbiome/genetics ; *Osteoporosis/therapy/chemically induced/microbiology ; *Fecal Microbiota Transplantation/methods ; *Lipopolysaccharides/adverse effects ; Mice, Inbred C57BL ; Mice ; Disease Models, Animal ; RNA, Ribosomal, 16S/genetics ; Femur/pathology/diagnostic imaging ; Core Binding Factor Alpha 1 Subunit/metabolism ; X-Ray Microtomography ; Male ; },
abstract = {PURPOSE: To study whether fecal microbiota transplantation (FMT) can alleviate lipopolysaccharide (LPS)-induced osteoporosis (OP) by regulating the composition and abundance of gut microbiota and the expression level of long non-coding RNA (lncRNA) TUG1.

METHODS: Twenty C57BL/6 mice were selected. Two mice were randomly designated as fecal donors, while the remaining mice were randomly divided into control group, LPS group, and LPS + FMT group. Each group consisted of 6 mice. The mice in the LPS and LPS + FMT groups were intraperitoneally injected with LPS to establish the OP model, and the mice in the LPS + FMT group were treated with donor feces by gavage. Micro-CT was used to scan the femur specimens of mice, and the bone structural parameters of the control and LPS groups were compared to verify the effectiveness of the OP model. HE staining was used to compare the microstructure of femurs in the 3 groups. 16S rRNA gene sequencing was used to analyze the composition and abundance of gut microbiota in mice. Immunofluorescence staining was used to compare the expression levels of Runt-related transcription factor 2 (RUNX2) in the femur of the 3 groups. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to compare the expression levels of lncRNA TUG1 in the intestines and serum of mice in the 3 groups.

RESULTS: Micro-CT showed that compared with the control group, the mice in the LPS group had more bone loss. The bone mineral density, trabecular number, and trabecular thickness of the control group was higher, and the trabecular separation was smaller. The models were validated effectively. HE staining showed that compared with the control group, the bone trabeculae in the LPS group were thinner and sparse, while that in the LPS + FMT group were dense and clear. The 16s rRNA sequencing showed that the abundance of Bacteroides and Lactobacillus in LPS+FMT group was significantly higher than that in LPS group. Immunofluorescence staining showed that the RUNX2 level in the control group and LPS + FMT group was similar, and both were higher than that in the LPS group. The qRT-PCR results showed that the TUG1 mRNA level in the control group and LPS + FMT group was similar and significantly higher than that in the LPS group.

CONCLUSION: FMT can enhance osteoblast levels and improve bone structure by modulating the abundance of gut microbiota in OP mice (such as increasing Bacteroides and Lactobacillus populations) and promoting the expression of lncRNA TUG1, thereby alleviating LPS-induced OP.},
}

Animals
*RNA, Long Noncoding/genetics/metabolism
*Gastrointestinal Microbiome/genetics
*Osteoporosis/therapy/chemically induced/microbiology
*Fecal Microbiota Transplantation/methods
*Lipopolysaccharides/adverse effects
Mice, Inbred C57BL
Mice
Disease Models, Animal
RNA, Ribosomal, 16S/genetics
Femur/pathology/diagnostic imaging
Core Binding Factor Alpha 1 Subunit/metabolism
X-Ray Microtomography
Male

@article {pmid40292216,
year = {2025},
author = {Bu, F and Chen, K and Chen, S and Jiang, Y},
title = {Gut microbiota and intestinal immunity interaction in ulcerative colitis and its application in treatment.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1565082},
pmid = {40292216},
issn = {2235-2988},
mesh = {Humans ; *Colitis, Ulcerative/immunology/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/immunology ; *Immunity, Mucosal ; Intestinal Mucosa/immunology/microbiology ; Animals ; },
abstract = {Ulcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease characterized by inflammation and injury of the colonic mucosa, exhibiting an increasing global incidence. Although research into UC pathogenesis is ongoing, the precise mechanisms remain to be fully elucidated. Studies indicate that UC development results from a complex interplay of factors, including genetic predisposition, environmental exposures, gut microbial dysbiosis, and immune dysregulation. Specifically, UC pathogenesis involves aberrant immune responses triggered by interactions between the host and gut microbiota. A complex, dynamic relationship exists between the microbial community and the host immune system throughout UC pathogenesis. Accumulating evidence suggests that changes in microbiota composition significantly impact gut immunity. This review will examine the intricate balance between the gut microbiota and mucosal immunity in UC progression and discuss potential therapeutic applications, providing a reference for further clinical treatment of this patient population.},
}

Humans
*Colitis, Ulcerative/immunology/therapy/microbiology
*Gastrointestinal Microbiome/immunology
Dysbiosis/immunology
*Immunity, Mucosal
Intestinal Mucosa/immunology/microbiology
Animals

@article {pmid40291934,
year = {2025},
author = {Mattar, L and Thalib, HI and Alnuwaimi, M and Alsaadi, H and Allouji, HA and Alyafei, J and Alshowiman, L and Alsobyani, N and Hassan, FES},
title = {Challenges of concurrent HIV infection in the course and management of Crohn's disease.},
journal = {Journal of medicine and life},
volume = {18},
number = {3},
pages = {171-178},
pmid = {40291934},
issn = {1844-3117},
mesh = {Humans ; *Crohn Disease/therapy/complications/immunology ; *HIV Infections/complications/immunology ; Disease Progression ; Probiotics/therapeutic use ; Gastrointestinal Microbiome ; },
abstract = {Crohn's disease (CD) is a chronic transmural bowel inflammation with a multifactorial etiology involving genetic predisposition and immune dysregulation in response to environmental triggers. In patients with human immunodeficiency virus (HIV), an already compromised immune system further complicates the progression and management of CD, creating unique therapeutic challenges. Probiotics have recently gained attention as a potential therapeutic option for CD, especially due to their role in modulating the gut microbiota. However, their effectiveness in patients with HIV, especially in enhancing and maintaining remissions, remains underexplored. This review aimed to examine how HIV infection influences the course of inflammatory bowel disease (IBD) and its impact on CD management strategies. A systematic literature search was conducted using Google Scholar, PubMed, Springer, and Web of Science to identify studies on patients with HIV and CD. HIV infection significantly alters the progression and management of CD due to its impact on the immune system. The immunosuppressed state of patients with HIV can complicate both the diagnosis and treatment of CD, often requiring adjustments in therapeutic approaches, necessitating a careful, tailored approach.},
}

Humans
*Crohn Disease/therapy/complications/immunology
*HIV Infections/complications/immunology
Disease Progression
Probiotics/therapeutic use
Gastrointestinal Microbiome

@article {pmid40289872,
year = {2025},
author = {Gao, L and Zhang, Y and Hu, Z and Chen, S and Wang, Q and Zeng, Y and Yin, H and Zhao, J and Zhan, Y and Gao, C and Xin, Y and Chen, B and van der Veen, S and Zhao, M and Fang, D and Lu, Q},
title = {Microbiota-Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e2409837},
doi = {10.1002/advs.202409837},
pmid = {40289872},
issn = {2198-3844},
support = {2022YFC3601800//National Key R&D Program of China/ ; 32141004//Special Program of National Natural Science Foundation of China/ ; 2021-I2M-1-059//CAMS Innovation Fund for Medical Sciences (CIFMS) No/ ; 2024-I2M-ZH-020//CAMS Innovation Fund for Medical Sciences (CIFMS) No/ ; 2020-RC320-003//Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; NO.82430102//Key Program of the National Natural Science Foundation of China/ ; 82404154//National Natural Science Foundation of China/ ; },
abstract = {The role of gut microbiota dysbiosis in systemic lupus erythematosus (SLE) pathogenesis remains elusive. Here, it is shown that fecal microbiota transplantation (FMT) from healthy mice to lupus mice ameliorates lupus-like symptoms. Microbiota reconstitution effectively reduces systemic class switch recombination (CSR) and elevates immunoglobulin heavy chain (IGH) naïve isotype. Microbiota profiling reveals an enrichment of Lactobacillus johnsonii post-FMT, with a significant correlation to purine metabolites. Importantly, the L. johnsonii-derived inosine, an intermediate metabolite in purine metabolism, effectively alleviates lupus pathogenesis in mice. Inosine inhibits B cell differentiation and reduces renal B cell infiltration to protect mice from lupus. At the molecular level, inosine reprograms B cells through the eDDxtracellular signal-regulated kinase (ERK)-hypoxia-inducible factor-1alpha (HIF-1α) signaling pathway. Therefore, this study highlights the discovery of a novel microbial metabolite modulating autoimmunity and suggests its potential for innovative microbiome-based therapeutic approaches.},
}

@article {pmid40289678,
year = {2025},
author = {Xu, Z and Li, L and Cheng, L and Gu, Z and Hong, Y},
title = {Maternal obesity and offspring metabolism: revisiting dietary interventions.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d4fo06233g},
pmid = {40289678},
issn = {2042-650X},
abstract = {Maternal obesity increases the risk of metabolic disorders in offspring. Understanding the mechanisms underlying the transgenerational transmission of metabolic diseases is important for the metabolic health of future generations. More research is needed to elucidate the mechanisms underlying the associated risks and their clinical implications because of the inherently complex nature of transgenerational metabolic disease transmission. Diet is a well-recognized risk factor for the development of obesity and other metabolic diseases, and rational dietary interventions are potential therapeutic strategies for their prevention. Despite extensive research on the physiological effects of diet on health and its associated mechanisms, little work has been devoted to understanding the effects of early-life dietary interventions on the metabolic health of offspring. In addition, existing dietary interventions are insufficient to meet clinical needs. Here, we discuss the literature on the effects of maternal obesity on the metabolic health of offspring, focusing on the mechanisms underlying the transgenerational transmission of metabolic diseases. We revisit current dietary interventions and describe their strengths and weaknesses in ameliorating maternal obesity-induced metabolism-related disorders in offspring. We also propose innovative strategies, such as the use of precision nutrition and fecal microbiota transplantation, which may limit the vicious cycle of intergenerational metabolic disease transmission.},
}

@article {pmid40289444,
year = {2025},
author = {Grimstad, T and Carlsen, A and Kvaløy, JT and Bolstad, N and Warren, DJ and Aabakken, L and Lundin, KEA and Karlsen, L and Steinsbø, Ø and Omdal, R},
title = {Fatigue in Inflammatory Bowel Disease: No Effect of Serum Concentrations of Infliximab, Adalimumab or Anti-Drug Antibodies During Maintenance Therapy.},
journal = {Scandinavian journal of immunology},
volume = {101},
number = {5},
pages = {e70029},
doi = {10.1111/sji.70029},
pmid = {40289444},
issn = {1365-3083},
mesh = {Humans ; *Adalimumab/therapeutic use/blood/immunology ; *Infliximab/blood/therapeutic use/immunology ; Male ; Female ; Adult ; Cross-Sectional Studies ; Middle Aged ; *Fatigue/drug therapy/etiology/blood ; C-Reactive Protein/metabolism ; Leukocyte L1 Antigen Complex/metabolism ; *Inflammatory Bowel Diseases/drug therapy/complications ; *Crohn Disease/drug therapy ; Severity of Illness Index ; Antibodies/blood ; *Colitis, Ulcerative/drug therapy ; Feces/chemistry ; Aged ; },
abstract = {Several studies have shown that infliximab and adalimumab ameliorate fatigue in inflammatory bowel disease. We investigated whether serum levels of these agents above or below a selected threshold influence fatigue severity. In this cross-sectional study, we measured serum concentrations (s-) of infliximab and adalimumab and corresponding anti-drug antibody levels. Therapeutic thresholds were defined as s-infliximab ≥ 5.0 mg/L and s-adalimumab ≥ 7.0 mg/L. Disease activity was assessed using the Harvey-Bradshaw Index for Crohn's disease, Partial Mayo Score for ulcerative colitis, and C-reactive protein (CRP) and faecal calprotectin levels for both conditions. Fatigue was assessed with the Fatigue Visual Analog Scale and Fatigue Severity Scale, and depression was evaluated with the Hospital Anxiety and Depression Scale, Depression subscale. Of 171 included patients (112 with Crohn's disease, 59 with ulcerative colitis), 66 (38.6%) were on infliximab and 105 (61.4%) were on adalimumab. Scores on the two fatigue scales were similar for serum values above versus below therapeutic thresholds for both drugs and did not differ with versus without anti-drug antibodies against either drug. CRP was numerically higher with infliximab levels below versus above the threshold (p = 0.06), whereas both CRP and faecal calprotectin were increased with adalimumab below versus above the threshold (p = 0.022, p = 0.0242). In patients with inflammatory bowel disease on maintenance therapy, s-infliximab and s-adalimumab levels below or above therapeutic thresholds or the presence of anti-drug antibodies did not affect fatigue severity. Trial Registration: ClinicalTrials.gov identifier: NCT02134054.},
}

Humans
*Adalimumab/therapeutic use/blood/immunology
*Infliximab/blood/therapeutic use/immunology
Male
Female
Adult
Cross-Sectional Studies
Middle Aged
*Fatigue/drug therapy/etiology/blood
C-Reactive Protein/metabolism
Leukocyte L1 Antigen Complex/metabolism
*Inflammatory Bowel Diseases/drug therapy/complications
*Crohn Disease/drug therapy
Severity of Illness Index
Antibodies/blood
*Colitis, Ulcerative/drug therapy
Feces/chemistry
Aged

@article {pmid40288637,
year = {2025},
author = {La Rosa, F and Guzzardi, MA and Pardo-Tendero, M and Barone, M and Ruocco, C and Conti, G and Panetta, D and Riabitch, D and Bernardi, S and Giorgetti, A and Campani, D and Monleon, D and Nisoli, E and Brigidi, P and Iozzo, P},
title = {Effects of Children's Microbiota on Adipose and Intestinal Development in Sex-Matched Mice Persist into Adulthood Following a Single Fecal Microbiota Transplantation.},
journal = {Molecular metabolism},
volume = {},
number = {},
pages = {102157},
doi = {10.1016/j.molmet.2025.102157},
pmid = {40288637},
issn = {2212-8778},
abstract = {BACKGROUND: The global prevalence of obesity and type 2 diabetes, particularly among children, is rising, yet the long-term impacts of early-life fecal microbiota transplantation (FMT) on metabolic health remain poorly understood.

OBJECTIVE: To investigate how early-life FMT from children to young, sex-matched mice influences metabolic outcomes and adipose tissue function in later, adult life.

METHODS: Germ-free mice were colonized with fecal microbiota from either lean children or children with obesity. The impacts on brown adipose tissue (BAT), white adipose tissue (WAT), glucose metabolism, and gut health were analyzed in male and female mice. Microbial communities and metabolite profiles were characterized using sequencing and metabolomics.

RESULTS: Male mice receiving FMT from obese donors exhibited marked BAT whitening and impaired amino acid and glucose metabolism. In contrast, female recipients developed hyperglycemia, accompanied by gut barrier dysfunction and WAT impairment. Distinct microbial and metabolite profiles were associated with these phenotypes: Collinsella and trimethylamine in females; and Paraprevotella, Collinsella, Lachnospiraceae NK4A136, Bacteroides, Coprobacillus, and multiple metabolites in males. These phenotypic effects persisted despite changes in host environment and diet.

CONCLUSION: Early-life FMT induced long-lasting effects on the metabolic landscape, profoundly affecting adipose tissue function and systemic glucose homeostasis in adulthood. Donor dietary habits correlated with the fecal microbial profiles observed in recipient mice. These findings highlight the critical need for identifying and leveraging beneficial exposures during early development to combat obesity and diabetes.},
}

@article {pmid40288317,
year = {2025},
author = {Banerjee, A and Mal, S and Roy, P and Chatterji, U},
title = {Regulating environmental arsenic-mediated gut-brain toxicity using chitosan-conjugated luteolin gold nanoparticles.},
journal = {Ecotoxicology and environmental safety},
volume = {297},
number = {},
pages = {118250},
doi = {10.1016/j.ecoenv.2025.118250},
pmid = {40288317},
issn = {1090-2414},
abstract = {Anxiety and depression are two major contributors to global disease burden. Amongst various causal factors, exposure to even low doses of environmental heavy metals, like arsenic, can induce anxiety and depression-like behaviour in mammals. Ingestion of arsenic, primarily through contaminated drinking water, severely disrupts the gut microbes, thereby inducing structural and functional abnormalities in the brain. Fecal microbiota transplantation (FMT) from arsenic-exposed mice to recipient healthy mice (As-FMT) enriched LPS-secreting Gram-negative bacteria and upregulated the expression of TLR4 in intestinal epithelial cells. Consequently, inflammation, oxidative stress and compromised barrier integrity in the gut facilitated LPS translocation into the bloodstream and promoted systemic inflammation. The secretomes eventually affected the brain by activating microglia, altering neurotransmitter levels and reducing the glucocorticoid receptor (GR) expression, contributing to appearance of pyknotic nuclei in dentate gyrus of hippocampus and emergence of anxiety- and depression-like behaviour. Luteolin, a flavonoid, devoid of any apparent side-effects, yet known for its anti-inflammatory and antioxidant properties, showed potential in alleviating the gut-brain toxic effects. However, its limited solubility and bioavailability pose challenges for its effectiveness, for which chitosan-conjugated luteolin gold nanoparticles (CH-LuAuNPs) were synthesized. Interestingly, where FMT from arsenic-treated mice to healthy mice showed deleterious effects in the transplanted mice, FMT from arsenic-treated mice co-administered with CH-LuAuNP attenuated As-FMT-mediated disruption of the gut-brain axis. This study highlighted the critical contribution of healthy gut microbiota in preserving neurobehavioural physiology, as well as underscored the potential therapeutic benefits of luteolin nanoparticles in ameliorating arsenic-induced gut dysbiosis and consequent mental disorders.},
}

@article {pmid40287572,
year = {2025},
author = {Zou, T and Tang, X and Wang, H and Shang, X and Liang, X and Ma, X},
title = {Nanocrystalline cellulose-geniposide complex enhances gut-brain axis modulation for depression treatment.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {667},
pmid = {40287572},
issn = {2399-3642},
mesh = {Animals ; *Cellulose/chemistry/pharmacology ; Mice ; *Depression/drug therapy ; *Iridoids/pharmacology/chemistry ; *Nanoparticles/chemistry ; Gastrointestinal Microbiome/drug effects ; *Antidepressive Agents/pharmacology ; Male ; Fecal Microbiota Transplantation ; *Brain/drug effects/metabolism ; Mice, Inbred C57BL ; *Brain-Gut Axis/drug effects ; Disease Models, Animal ; },
abstract = {Depression, a major global health issue, is closely associated with imbalances in gut microbiota and altered intestinal functions. This study investigates the antidepressant potential of a composite of Geniposide (GP) and Nanocrystalline Cellulose (NCC), focusing on its effects on the gut-brain axis. Utilizing network pharmacology, GP was identified as a key compound targeting the BCL2 gene in depression management. Experimental approaches, including a chronic unpredictable mild stress (CUMS) model in mice, cellular assays, and fecal microbiota transplantation (FMT), were used to evaluate the composite's effectiveness. Results indicate that GP activates the adenosine monophosphate-activated protein kinase (AMPK) pathway by upregulating BCL2, enhancing intestinal barrier integrity, and balancing gut flora. These mechanisms contribute to its positive effects on hippocampal function and depressive-like behaviors in mice, suggesting that the GP-NCC composite could be a promising avenue for developing depression therapies that target gut health.},
}

Animals
*Cellulose/chemistry/pharmacology
Mice
*Depression/drug therapy
*Iridoids/pharmacology/chemistry
*Nanoparticles/chemistry
Gastrointestinal Microbiome/drug effects
*Antidepressive Agents/pharmacology
Male
Fecal Microbiota Transplantation
*Brain/drug effects/metabolism
Mice, Inbred C57BL
*Brain-Gut Axis/drug effects
Disease Models, Animal

@article {pmid40286751,
year = {2025},
author = {Ji, H and Dong, Z and Yang, Y and Cui, W and Han, J and Hu, Y and Chen, H and Qiao, C and Li, Q and Li, H and Wu, S},
title = {Neixiao-ruanmai decoction No 2 improves carotid atherosclerosis by modulating gut microbiota and inhibiting TLR4/NF-κB pathway activation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {142},
number = {},
pages = {156775},
doi = {10.1016/j.phymed.2025.156775},
pmid = {40286751},
issn = {1618-095X},
abstract = {BACKGROUND: Carotid atherosclerosis(CAs) plaques are challenging to reverse. Neixiao-Ruanmai Decoction No 2(NXRMT No 2), a Traditional Chinese Medicine (TCM) decoction, has shown potential in treating CAs. However, while preliminary clinical trials have confirmed the efficacy of NXRMT No 2 in improving CAs, the comparative effectiveness of long-term versus short-term treatment courses remains unclear, and the underlying mechanisms of this decoction are not yet fully understood.

METHODS: We conducted clinical trials, animal studies, 16S rRNA sequencing, metabolomics and fecal microbiota transplantation.

RESULT: Clinical research results indicate that NXRMT No 2(24 weeks of treatment) reduced total plaque area by 22.02%, maximum plaque thickness by 7.91%, and maximum plaque area by 21.29%. NXRMT No 2 improves patients'serum inflammatory levels, with a 24-week treatment course demonstrated superior efficacy compared to the 12-week treatment. Animal experiments demonstrated that NXRMT No 2 improved CAs progression, modulated the gut microbiota, inhibited the intestinal Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway and activated the expression of intestinal tight junction proteins.

CONCLUSION: NXRMT No 2 significantly attenuates CAs progression, with its primary mechanism likely related to modulating the gut microbiota to counteract the TLR4/NF-κB pathway and protect the intestinal barrier. This study provides evidence-based support for the use of NXRMT No 2 in treating CAs, offers guidance on optimal treatment duration for patients, and contributes to the development of traditional Chinese medicine formulations that improve CAs by modulating the gut microbiota-a significant advance in the prevention and treatment of CAs.},
}

@article {pmid40285477,
year = {2025},
author = {Hansen, SH and Maseng, MG and Grännö, O and Vestergaard, MV and Bang, C and Olsen, BC and Lund, C and Olbjørn, C and Løvlund, EE and Vikskjold, FB and Huppertz-Hauss, G and Perminow, G and Yassin, H and Valeur, J and Aass Holten, KI and Henriksen, M and Bengtson, MB and Ricanek, P and Opheim, R and Boyar, R and Torp, R and Frigstad, SO and Aabrekk, TB and Detlie, TE and Kristensen, VA and Strande, V and Hovde, Ø and Asak, Ø and Jess, T and Franke, A and Halfvarsson, J and Høivik, ML and Hov, JR},
title = {Fecal Microbiome Reflects Disease State and Prognosis in Inflammatory Bowel Disease in an Adult Population-Based Inception Cohort.},
journal = {Inflammatory bowel diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/ibd/izaf060},
pmid = {40285477},
issn = {1536-4844},
support = {//Pfizer/ ; //Tillotts Pharma/ ; //Dam Foundation/ ; //Norwegian South-Eastern Health Authorities/ ; 2020066//Regional Health Authorities South-Eastern Norway/ ; 327634//Research Council of Norway/ ; //Bio-Me AS/ ; //DFG Excellence Cluster 2167/ ; //DFG Research Unit/ ; DNRF148//National Research Foundation/ ; },
abstract = {INTRODUCTION: We aimed to determine the diagnostic and prognostic potential of baseline microbiome profiling in inflammatory bowel disease (IBD).

METHODS: Participants with ulcerative colitis (UC), Crohn's disease (CD), suspected IBD, and non-IBD symptomatic controls were included in the prospective population-based cohort Inflammatory Bowel Disease in South-Eastern Norway III (third iteration) based on suspicion of IBD. The participants donated fecal samples that were analyzed with 16S rRNA sequencing. Disease course severity was evaluated at the 1-year follow-up. A stringent statistical consensus approach for differential abundance analysis with 3 different tools was applied, together with machine learning modeling.

RESULTS: A total of 1404 individuals were included, where n = 1229 samples from adults were used in the main analyses (n = 658 UC, n = 324 CD, n = 36 IBD-U, n = 67 suspected IBD, and n = 144 non-IBD symptomatic controls). Microbiome profiles were compared with biochemical markers in machine learning models to differentiate IBD from non-IBD symptomatic controls (area under the receiver operating curve [AUC] 0.75-0.79). For UC vs controls, integrating microbiome data with biochemical markers like fecal calprotectin mildly improved classification (AUC 0.83 to 0.86, P < .0001). Extensive differences in microbiome composition between UC and CD were identified, which could be quantified as an index of differentially abundant genera. This index was validated across published datasets from 3 continents. The UC-CD index discriminated between ileal and colonic CD (linear regression, P = .008) and between colonic CD and UC (P = .005), suggesting a location-dependent gradient. Microbiome profiles outperformed biochemical markers in predicting a severe disease course in UC (AUC 0.72 vs 0.65, P < .0001), even in those with a mild disease at baseline (AUC 0.66 vs 0.59, P < .0001).

CONCLUSIONS: Fecal microbiome profiling at baseline held limited potential to diagnose IBD from non-IBD compared with standard-of-care. However, microbiome shows promise for predicting future disease courses in UC.},
}

@article {pmid40284630,
year = {2025},
author = {Zhang, Y and Wang, L and Peng, L},
title = {The Role of Intestinal Fungi in the Pathogenesis and Treatment of Ulcerative Colitis.},
journal = {Microorganisms},
volume = {13},
number = {4},
pages = {},
pmid = {40284630},
issn = {2076-2607},
abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely associated with dysbiosis of the gut microbiome, encompassing not only bacterial communities but also fungal populations. Despite the growing recognition of the gut microbiome's role in UC pathogenesis, the contribution of intestinal fungi has only recently garnered significant attention. In this review, we comprehensively examine the characteristics of intestinal fungi in both healthy individuals and UC patients, elucidating their role in disease pathogenesis and their interactions with bacterial communities. Additionally, we explore the impact of intestinal fungi on disease severity and therapeutic responses in UC. Furthermore, we evaluate the therapeutic potential of antifungal agents, probiotics, and fecal microbiota transplantation (FMT) in UC management, emphasizing the critical role of fungi in these treatment modalities. Future research should prioritize elucidating the multifunctional roles of fungi in UC pathogenesis and their implications for treatment strategies. Moreover, the identification of fungal biomarkers associated with FMT efficacy could pave the way for precision medicine approaches in FMT, offering novel insights into personalized therapeutic interventions for UC.},
}

@article {pmid40284188,
year = {2025},
author = {Bonomo, MG and D'Angelo, S and Picerno, V and Carriero, A and Salzano, G},
title = {Recent Advances in Gut Microbiota in Psoriatic Arthritis.},
journal = {Nutrients},
volume = {17},
number = {8},
pages = {},
pmid = {40284188},
issn = {2072-6643},
mesh = {Humans ; *Arthritis, Psoriatic/microbiology/therapy/immunology ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; },
abstract = {Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by joint inflammation and skin lesions. Recent research has underscored the critical role of gut microbiota-comprising bacteria, fungi, viruses, and archaea-in the pathogenesis and progression of PsA. This narrative review synthesizes the latest findings on the influence of gut microbiota on PsA, focusing on mechanisms such as immune modulation, microbial dysbiosis, the gut-joint axis, and its impact on treatment. Advances in high-throughput sequencing and metagenomics have revealed distinct microbial profiles associated with PsA. Studies show that individuals with PsA have a unique gut microbiota composition, differing significantly from healthy controls. Alterations in the abundance of specific bacterial taxa, including a decrease in beneficial bacteria and an increase in potentially pathogenic microbes, contribute to systemic inflammation by affecting the intestinal barrier and promoting immune responses. This review explores the impact of various factors on gut microbiota composition, including age, hygiene, comorbidities, and medication use. Additionally, it highlights the role of diet, probiotics, and fecal microbiota transplantation as promising strategies to modulate gut microbiota and alleviate PsA symptoms. The gut-skin-joint axis concept illustrates how gut microbiota influences not only gastrointestinal health but also skin and joint inflammation. Understanding the complex interplay between gut microbiota and PsA could lead to novel, microbiome-based therapeutic approaches. These insights offer hope for improved patient outcomes through targeted manipulation of the gut microbiota, enhancing both diagnosis and treatment strategies for PsA.},
}

Humans
*Arthritis, Psoriatic/microbiology/therapy/immunology
*Gastrointestinal Microbiome
Dysbiosis/microbiology
Probiotics/therapeutic use
Fecal Microbiota Transplantation

@article {pmid40283508,
year = {2025},
author = {Boicean, A and Ichim, C and Sasu, SM and Todor, SB},
title = {Key Insights into Gut Alterations in Metabolic Syndrome.},
journal = {Journal of clinical medicine},
volume = {14},
number = {8},
pages = {},
pmid = {40283508},
issn = {2077-0383},
abstract = {Over time, extensive research has underscored the pivotal role of gut microbiota in the onset and progression of various diseases, with a particular focus on fecal microbiota transplantation (FMT) as a potential therapeutic approach. The practice of transferring fecal matter from a healthy donor to a patient provides valuable insights into how alterations in gut microbiota can impact disease development and how rectifying dysbiosis may offer therapeutic benefits. Re-establishing a balanced symbiotic relationship in the gastrointestinal tract has shown positive results in managing both intestinal and systemic conditions. Currently, one of the most pressing global health issues is metabolic syndrome-a cluster of conditions that includes insulin resistance, lipid imbalances, central obesity and hypertension. In this context, FMT has emerged as a promising strategy for addressing key components of metabolic syndrome, such as improving insulin sensitivity, body weight and lipid profiles. However, further well-structured studies are needed to refine treatment protocols and establish the long-term safety and efficacy of this intervention.},
}

@article {pmid40283148,
year = {2025},
author = {Marano, G and Rossi, S and Sfratta, G and Traversi, G and Lisci, FM and Anesini, MB and Pola, R and Gasbarrini, A and Gaetani, E and Mazza, M},
title = {Gut Microbiota: A New Challenge in Mood Disorder Research.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {4},
pages = {},
pmid = {40283148},
issn = {2075-1729},
abstract = {The gut microbiome has emerged as a novel and intriguing focus in mood disorder research. Emerging evidence demonstrates the significant role of the gut microbiome in influencing mental health, suggesting a bidirectional communication between the gut and the brain. This review examines the latest findings on the gut-microbiota-brain axis and elucidates how alterations in gut microbiota composition can influence this axis, leading to changes in brain function and behavior. Although dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation have yielded encouraging results, significant advances are needed to establish next-generation approaches that precisely target the neurobiological mechanisms of mood disorders. Future research must focus on developing personalized treatments, facilitated by innovative therapies and technological progress, which account for individual variables such as age, sex, drug history, and lifestyle. Highlighting the potential therapeutic implications of targeting the gut microbiota, this review emphasizes the importance of integrating microbiota research into psychiatric studies to develop more effective and personalized treatment strategies for mood disorders.},
}

@article {pmid40282300,
year = {2025},
author = {Nemati, MH and Yazdanpanah, E and Kazemi, R and Orooji, N and Dadfar, S and Oksenych, V and Haghmorad, D},
title = {Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential.},
journal = {Biology},
volume = {14},
number = {4},
pages = {},
pmid = {40282300},
issn = {2079-7737},
abstract = {Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the commensal microbiota, or dysbiosis, have been shown to affect immune homeostasis, leading to elevated levels of pro-inflammatory cytokines and disruption of the gut-brain axis. In this review, we provide a comprehensive overview of interactions between the gut microbiota and MS, especially focusing on the immunomodulatory actions of microbiota, such as influencing T-cell balance and control of metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., Prevotella and Faecalibacterium) were suggested to lay protective roles, whereas Akkermansia muciniphila was associated with disease aggravation. Interventions focusing on microbiota, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary therapies to normalize gut microbial homeostasis, suppress inflammation and are proven to improve clinical benefits in MS patients. Alterations in gut microbiota represent opportunities for identifying biomarkers for early diagnosis, disease progression and treatment response monitoring. Further studies need to be conducted to potentially address the interplay between genetic predispositions, environmental cues, and microbiota composition to get the precise mechanisms of the gut-brain axis in MS. In conclusion, the gut microbiota plays a central role in MS pathogenesis and offers potential for novel therapeutic approaches, providing a promising avenue for improving clinical outcomes in MS management.},
}

@article {pmid40281872,
year = {2025},
author = {Dipasquale, V and Romano, C},
title = {New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {8},
pages = {},
pmid = {40281872},
issn = {2227-9032},
abstract = {Pediatric gastroenterology is entering a pivotal phase marked by significant challenges and emerging opportunities in treating conditions like celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH) pose significant clinical hurdles, but new therapeutic avenues are emerging. Advances in precision medicine, particularly proteomics, are reshaping care by tailoring treatments to individual patient characteristics. For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent. Immunotherapy and microbiota modulation, including probiotics and fecal microbiota transplantation (FMT), are also under exploration, with potential benefits in symptom management. Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated. These therapies require more pediatric-specific research to optimize their use. For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments. New medications for individuals with refractory or steroid-dependent AIH have been explored. Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric IBD management. This narrative review explores recent breakthroughs in treating CeD, EoE, IBD, and AIH, with a focus on pediatric studies when available, and discusses the growing role of proteomics in advancing personalized gastroenterological care.},
}

@article {pmid40280962,
year = {2025},
author = {Wissel, EF and Chien, HY and Wei, KH and Lee, YC and Ullah, K and Hsieh, PCH},
title = {Microbial metabolites associated in stool and left ventricle of heart failure patients revealed by meta-analysis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {14576},
pmid = {40280962},
issn = {2045-2322},
support = {110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; },
mesh = {Humans ; *Heart Failure/microbiology/metabolism ; *Feces/microbiology ; *Heart Ventricles/metabolism/microbiology ; Metabolomics/methods ; *Gastrointestinal Microbiome ; Metabolome ; },
abstract = {Heart Failure (HF) impacts approximately 64 million people globally. While overall incidence of HF is relatively stable across countries, the overall number of HF patients is increasing due to aging populations. Many articles examine the microbiome in HF, however, studies from humans have not been analyzed systematically. The aim of this meta-analysis is to bridge this gap by analyzing previously published data on human HF patients with untargeted metabolomics to understand whether microbially-mediated metabolites are consistently important for HF status. A systematic survey of the literature identified 708 articles discussing HF, the microbiome, and metabolomics. Of these, 82 were primary studies of HF patients, 61 studied human adults, 23 included an untargeted metabolomics measure, and 3 studies had data that was usable and publicly accessible. These studies include a GCMS study from stool, NMR of saliva and exhaled breath condensate, and LCMS from left ventricle of HF patients undergoing transplantation and unused donor hearts. Significant differences were observed from PCA between HF and controls for stool and left ventricle, but not saliva or EBC samples. OPLS-DA was conducted for stool and ventricle samples, and further revealed significant group differences. Univariate testing with FDR correction revealed 8 significant microbially-relevant metabolites (p < 0.005 after correction), most notably asparagine from left ventricle and 2-methylbutyryl carnitine from stool. Though there is much discussion of the microbiome in health outcomes in HF, there is limited research from human populations. Some microbial co-metabolites from both stool and heart were significantly associated with HF.},
}

Humans
*Heart Failure/microbiology/metabolism
*Feces/microbiology
*Heart Ventricles/metabolism/microbiology
Metabolomics/methods
*Gastrointestinal Microbiome
Metabolome

@article {pmid40280130,
year = {2025},
author = {Wellens, J and Vissers, E and Dumoulin, A and Hoekx, S and Vanderstappen, J and Verbeke, J and Vangoitsenhoven, R and Derrien, M and Verstockt, B and Ferrante, M and Matthys, C and Raes, J and Verbeke, K and Vermeire, S and Sabino, J},
title = {Cooking methods affect advanced glycation end products and lipid profiles: A randomized cross-over study in healthy subjects.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {102091},
doi = {10.1016/j.xcrm.2025.102091},
pmid = {40280130},
issn = {2666-3791},
abstract = {Thermal treatments used in ultra-processed foods (UPFs) lead to advanced glycation end products (AGEs). UPFs and serum AGEs are associated with cardiometabolic disease. We explore differential cooking methods as a mechanistic link between UPFs and detrimental health outcomes through a randomized cross-over cooking method trial in healthy subjects using identical ingredients and a deep profiling analysis. We show that low-AGE-generating cooking methods such as boiling and steaming decrease serum AGEs, improve lipid profiles, and increase serum protein 4E-BP1. In contrast, high-AGE-generating cooking methods such as grilling and baking increase fecal butyrate. In sum, this suggests that low-AGE-generating cooking methods should be considered in cardiovascular risk prevention. Since current dietary guidelines focus on ingredients, but not cooking methods, our results suggest that culinary techniques should be considered as an important factor in cardiometabolic preventive strategies and future dietary trial design. This study was registered at ClinicalTrials.gov (NCT06547190).},
}

@article {pmid40280127,
year = {2025},
author = {Cai, W and Haddad, M and Haddad, R and Kesten, I and Hoffman, T and Laan, R and Westfall, S and Defaye, M and Abdullah, NS and Wong, C and Brown, N and Tansley, S and Lister, KC and Hooshmandi, M and Wang, F and Lorenzo, LE and Hovhannisyan, V and Ho-Tieng, D and Kumar, V and Sharif, B and Thurairajah, B and Fan, J and Sahar, T and Clayton, C and Wu, N and Zhang, J and Bar-Yoseph, H and Pitashny, M and Krock, E and Mogil, JS and Prager-Khoutorsky, M and Séguéla, P and Altier, C and King, IL and De Koninck, Y and Brereton, NJB and Gonzalez, E and Shir, Y and Minerbi, A and Khoutorsky, A},
title = {The gut microbiota promotes pain in fibromyalgia.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2025.03.032},
pmid = {40280127},
issn = {1097-4199},
abstract = {Fibromyalgia is a prevalent syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome is unknown. Here, we show that fecal microbiota transplantation from fibromyalgia patients, but not from healthy controls, into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations. Replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. An open-label trial in women with fibromyalgia (Registry MOH_2021-11-04_010374) showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. We conclude that altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.},
}

@article {pmid40279964,
year = {2025},
author = {Zheng, Z and Du, Y and Jiang, H and Shi, Z and Zhou, H and Jiao, L and Liu, P and Gong, Y},
title = {KAJF alleviated colorectal cancer liver metastasis by reshaping the gut microbiota and inhibiting M2-like macrophage polarization.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {142},
number = {},
pages = {156766},
doi = {10.1016/j.phymed.2025.156766},
pmid = {40279964},
issn = {1618-095X},
abstract = {BACKGROUND: Colorectal cancer liver metastasis (CRLM) represents one of the most severe complications of colorectal cancer (CRC), often associated with unfavorable prognosis. The herbal formulation Kang-Ai-Jing-Fang (KAJF) has been employed clinically against CRC for several decades, although its precise mechanism of action remains elusive.

PURPOSE: This study investigates the anti-metastatic potential of KAJF in CRLM, focusing on its modulatory effects on gut microbiota and inhibition of M2-like macrophage activation.

METHODS: KAJF was administered orally to CRLM model mice established through intrasplenic injection of murine CRC cells. To elucidate the role of gut microbiota reshaped by KAJF, fecal microbiota transplantation (FMT) was utilized to assess its impact on CRLM inhibition. Core targets and active compounds were identified through network pharmacology and molecular docking. To characterize microbiota composition, metabolite profiles, and gene expression variations, 16S rRNA sequencing, untargeted liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics, and transcriptomics analyses were performed.

RESULTS: KAJF demonstrated significant inhibitory effects on CRLM and ameliorated gut microbiota dysbiosis by enhancing the abundance of butyrate-producing bacteria (Lactobacillus, Bacteroides, Bifidobacterium). The therapeutic efficacy of KAJF-induced bacterial alterations in delaying CRLM and promoting butyrate-producing microbiota enrichment was further substantiated by FMT. Network pharmacology identified active ingredients in KAJF, including asperulosidic acid, polyphyllin II, ganoderenic acid B, calycosin, and ganoderic acid C, which exhibit substantial interactions with TLR4, PPARγ, SIRT1, PTGS2, and TNF. Molecular dynamics simulations and surface plasmon resonance (SPR) analysis demonstrated that ganoderic acid C2 exhibits a strong binding affinity for PPARγ. Moreover, KAJF administration led to a marked reduction in F4/80[+] CD206[+] macrophages and their associated cytokines (CCL17, CCL22, IL10, IL4, TGF), accompanied by a decrease in CD4[+] T cells and myeloid-derived suppressor cells (MDSCs), while increasing CD8[+] T cell populations.

CONCLUSIONS: This study demonstrates that KAJF mitigates CRLM, primarily through the regulation of gut microbiota and microbial metabolites, alongside inhibition of M2-like macrophage polarization. By integrating metabolomics, transcriptomics, and network pharmacology, this research elucidates the molecular mechanisms underpinning KAJF's therapeutic effects against CRLM, offering a promising approach for clinical intervention.},
}

@article {pmid40279942,
year = {2025},
author = {Zhang, S and Qian, Y and Li, N and Zhu, Q and Zhang, S and Wen, P and Xiao, Y and Yan, C and Lin, Z and Zhong, J and Ma, J and Wu, X and Zhuang, G and Zhang, K},
title = {Specific MSI2 deletion maintains intestinal barrier integrity by down-regulating ILC3s-derived IL-17 a in mice with colitis.},
journal = {International immunopharmacology},
volume = {156},
number = {},
pages = {114717},
doi = {10.1016/j.intimp.2025.114717},
pmid = {40279942},
issn = {1878-1705},
abstract = {BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease with an unknown cause. Previous studies have shown that Group 3 innate lymphoid cells (ILC3s) are crucial for maintaining intestinal mucosal immune homeostasis by producing key cytokines such as IL-22 and IL-17 A. While the RNA-binding protein Musashi-2 (MSI2) is recognized as essential for promoting intestinal epithelial regeneration post-injury, its impact on immune regulation remains unclear. Therefore, we aim to investigate the protective mechanisms associated with ILC3s-specific MSI2 deletion in a mouse model of ulcerative colitis.

METHODS: Dextran sulfate sodium (DSS) was used to induce a mouse colitis model. Colitis severity was evaluated through weight loss, diarrhea, fecal traits, colon length, and pathological scoring. Transcriptome sequencing was utilized to identify differentially expressed genes in colon tissues. Flow cytometry was employed to measure the quantity and functionality of ILC3s. Western blot was conducted to analyze protein expression, while real-time polymerase chain reaction and enzyme-linked immunosorbent assay were employed to quantify inflammatory factors. Additionally, immunofluorescence, AB-PAS staining, and immunohistochemistry were employed to evaluate the integrity of the intestinal barrier.

RESULTS: Following DSS treatment, colon damage was milder in Msi2[∆Rorc] mice than in Msi2[fl/fl] mice. Transcriptomic analysis revealed the down-regulation of cytokines and pro-inflammatory factors in the colon tissue of Msi2[∆Rorc] mice. Flow cytometry showed that specific deletion of MSI2 reduced the infiltration of ILC3s in the intestinal lamina propria of Msi2[∆Rorc] mice and decreased IL-17 A production. The reduction of IL-17 A-mediated immune responses lessened inflammatory damage to the intestinal barrier, thereby reducing colitis severity.

CONCLUSIONS: Specific deletion of MSI2 alleviates DSS-induced colitis in mice by reducing ILC3s infiltration and IL-17 A secretion in the lamina propria of the colon. This decrease in inflammatory mediators and cell infiltration dampens the inflammatory response in the intestinal mucosa, helping to maintain the integrity of the intestinal barrier in mice with colitis. These findings enhance our understanding of UC pathogenesis and offer novel avenues for clinical diagnosis and treatment.},
}

@article {pmid40278398,
year = {2025},
author = {Zheng, F and Yang, Y and Lu, G and Tan, JS and Mageswary, U and Zhan, Y and Ayad, ME and Lee, YY and Xie, D},
title = {Metabolomics Insights into Gut Microbiota and Functional Constipation.},
journal = {Metabolites},
volume = {15},
number = {4},
pages = {},
pmid = {40278398},
issn = {2218-1989},
support = {2024ZYD0149//Sichuan Science and Technology Program/ ; TB2024017//Special Research Foundation for the Postdoctoral Program of Sichuan Province/ ; 2024SZY004, 2024SZY016//Key Research and Development Project of Deyang Science and Technology Bureau/ ; 2022067//Chengdu Medical Research Project/ ; 2024JDKPO1117//Sichuan Science and Technology Program/ ; FHS202503//Projects of Deyang People's Hospital/ ; },
abstract = {Background: The composition and metabolic activity of the gut microbiota play a crucial role in various health conditions, including the occurrence and development of chronic constipation. Recent metabolomic advances reveal that gut microbiota-derived metabolites-such as SCFAs, bile acids, neurotransmitters, and microbial gases-play critical roles in regulating intestinal function. Methods: We systematically analyzed the current literature on microbial metabolomics in chronic constipation. This review consolidates findings from high-throughput metabolomic techniques (GC-MS, LC-MS, NMR) comparing metabolic profiles of constipated patients with healthy individuals. It also examines diagnostic improvements and personalized treatments, including fecal microbiota transplantation and neuromodulation, guided by these metabolomic insights. Results: This review shows that reduced SCFA levels impair intestinal motility and promote inflammation. An altered bile acid metabolism-with decreased secondary bile acids like deoxycholic acid-disrupts receptor-mediated signaling, further affecting motility. Additionally, imbalances in amino acid metabolism and neurotransmitter production contribute to neuromuscular dysfunction, while variations in microbial gas production (e.g., methane vs. hydrogen) further modulate gut transit. Conclusions: Integrating metabolomics with gut microbiota research clarifies how specific microbial metabolites regulate gut function. These insights offer promising directions for precision diagnostics and targeted therapies to restore microbial balance and improve intestinal motility.},
}

@article {pmid40274530,
year = {2025},
author = {Ji, ZH and Xie, WY and Wu, HY and Yuan, B},
title = {Coix Seed Polysaccharide Mitigates Ulcerative Colitis in Mice through the Modulation of Gut Microbiota and Improvement of Intestinal Metabolism Balance.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c02458},
pmid = {40274530},
issn = {1520-5118},
abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a rising incidence globally, whereas existing treatments exhibit significant limitations. Coix seed polysaccharide (CSP), a component of traditional Chinese medicine known for its immunomodulatory and antioxidant properties, has not been thoroughly investigated for its role in UC. In this study, CSP was prepared via water extraction and ethanol precipitation, and its protective effects and mechanisms were evaluated using a dextran sulfate sodium salt (DSS)-induced UC mouse model. The results demonstrated that CSP significantly ameliorated DSS-induced UC symptoms, including weight loss, an elevated Disease Activity Index, colon shortening, increased levels of inflammatory cytokines, and intestinal barrier damage. Moreover, CSP reshaped the DSS-induced gut microbiota dysbiosis by increasing gut microbial diversity and regulating the abundance of specific genera, such as increasing Anaerotruncus. Metabolomic analysis revealed that CSP significantly modulated the levels of 116 metabolites, particularly enhancing the beneficial metabolite 3-hydroxybutyrate. Importantly, the preventive effect of CSP on UC was dependent on the gut microbiota and could be transferred via fecal microbiota transplantation. This study demonstrates that CSP, a microecology-regulating polysaccharide, effectively modulates gut microbiota and alleviates symptoms of UC. These findings support the potential of CSP as a dietary supplement for UC prevention and underscore its value in the development of medicinal foods and functional food applications.},
}

@article {pmid40274437,
year = {2025},
author = {Chang, Z and Zhu, Y and Wang, P and Du, L and Wu, M and Wang, X and Kong, C and Huang, D and Xie, R and Ji, G and Wang, C and Cheng, L and Yan, X and Wei, Q and Qin, H},
title = {Multi-omic analyses of the development of obesity-related depression linked to the gut microbe Anaerotruncus colihominis and its metabolite glutamate.},
journal = {Science bulletin},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.scib.2025.04.010},
pmid = {40274437},
issn = {2095-9281},
abstract = {Emerging evidence implicates gut microbiota in the pathogenesis of obesity-related depression (OD); however, the underlying molecular mechanisms remain inadequately explored. This study compared the microbial and transcriptional profiles between patients with OD and healthy individuals. The results revealed an enrichment of Anaerotruncus colihominis (A. colihominis) and glutamate metabolism-related genes in the OD group. Fecal microbiota transplantation (FMT) from patients with OD induced weight gain, compromised barrier function, and intensified depression-like behaviors in high-fat diet (HFD) mice. Microbial analysis in the mice feces corroborated the clinical findings. Single-cell RNA sequencing highlighted the pivotal role of the Efnb2-Ephb2 interaction in cell communication among colon epithelial and hippocampal neuron subtypes in OD mice. Notably, A. colihominis correlated with glutamate levels in the OD mice and patients. It produced glutamate through a glutamic acid metabolism-related DNA sequence, verified in an engineered Escherichia coli MG1655 strain. Both A. colihominis and glutamate reduced barrier proteins in colon epithelial cells and modulated cognitive proteins in neurons. Finally, A. colihominis treatment induced the Efnb2-Ephb2 interaction, exacerbating depression-like behaviors in germ-free HFD mice. Collectively, these findings reveal that A. colihominis and glutamate are potential intervention targets for OD treatment.},
}

@article {pmid40272913,
year = {2025},
author = {Bohm, MS and Joseph, SC and Sipe, LM and Kim, M and Leathem, CT and Mims, TS and Willis, NB and Tanveer, UA and Elasy, JH and Grey, EW and Pye, ME and Mustafa, ZT and Harper, BA and McGrath, LG and Daria, D and Landvoigt Schmitt, B and Myers, JA and Pantoja Newman, P and Pence, BD and Van der Merwe, M and Davis, MJ and Pierre, JF and Makowski, L},
title = {The gut microbiome enhances breast cancer immunotherapy following bariatric surgery.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.187683},
pmid = {40272913},
issn = {2379-3708},
abstract = {Bariatric surgery is associated with improved breast cancer (BC) outcomes, including greater immunotherapy effectiveness in a pre-clinical BC model. A potential mechanism of bariatric surgery-associated protection is the gut microbiota. Here, we demonstrate the dependency of improved immunotherapy response on the post-bariatric surgery gut microbiome via fecal microbial transplant (FMT). Response to αPD-1 immunotherapy was significantly improved following FMT from formerly obese bariatric surgery-treated mice. When stool from post-bariatric surgery patients was transplanted into recipient mice and compared to the patients' pre-surgery transplants, post-surgery microbes significantly reduced tumor burden and doubled immunotherapy effectiveness. Microbes impact tumor burden through microbially derived metabolites, including branched chain amino acids (BCAA). Circulating BCAAs correlated significantly with natural killer T (NKT) cell content in the tumor microenvironment in donor mice after bariatric surgery and FMT recipients of donor cecal content after bariatric surgery compared to obese controls. BCAA supplementation replicated improved αPD-1 effectiveness in two BC models, supporting the role of BCAAs in increased immunotherapy effectiveness after bariatric surgery. Ex vivo exposure increased primary NKT cell expression of anti-tumor cytokines, demonstrating direct activation of NKT cells by BCAAs. Together, findings suggest that reinvigorating anti-tumor immunity may depend upon bariatric surgery-associated microbially derived metabolites, namely BCAAs.},
}

@article {pmid40272874,
year = {2025},
author = {Ubsdell, D and Maddox, NL and Sheridan, R},
title = {Management of severe and fulminant Clostridioides difficile infection in adults.},
journal = {Journal of medical microbiology},
volume = {74},
number = {4},
pages = {},
pmid = {40272874},
issn = {1473-5644},
mesh = {Humans ; *Clostridium Infections/therapy/microbiology/drug therapy ; *Clostridioides difficile/drug effects ; *Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Adult ; Metronidazole/therapeutic use ; },
abstract = {Clostridioides difficile (formerly known as Clostridium difficile) is a significant cause of healthcare-associated infection with symptoms ranging from diarrhoea and abdominal pain to pseudomembranous colitis and toxic megacolon. Severe disease can pose a significant morbidity and mortality risk and is to be considered a medical emergency. The emergence of a new C. difficile ribotype with an estimated mortality rate of 20% (ribotype 995) has prompted a re-review of the evidence and guidelines around managing severe C. difficile infections (CDI). International guidance on the management of CDI varies regarding first-line antibiotic choice. Metronidazole is no longer favoured as first line due to concerns around resistance, and vancomycin and fidaxomicin are now recommended as first line options. Antibiotic therapy should be used in conjunction with good supportive measures and early consideration of surgical management. Faecal microbiota transplant can be utilized in recurrent CDI and may be useful in severe disease. Severe CDI is a significant ongoing threat to public health, and further research into effective management is essential to ensure the best possible outcomes for patients.},
}

Humans
*Clostridium Infections/therapy/microbiology/drug therapy
*Clostridioides difficile/drug effects
*Anti-Bacterial Agents/therapeutic use
Fecal Microbiota Transplantation
Adult
Metronidazole/therapeutic use

@article {pmid40272147,
year = {2025},
author = {Dai, X and Cao, Y and Li, L and Gao, Y-X and Wang, J-X and Liu, Y-J and Ma, T-T and Zheng, J-M and Zhan, P-P and Shen, Z-Y},
title = {Gut microbiome and metabolome profiles in renal allograft rejection from multiomics integration.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0162624},
doi = {10.1128/msystems.01626-24},
pmid = {40272147},
issn = {2379-5077},
abstract = {UNLABELLED: The gut microbiome and metabolome play crucial roles in renal allograft rejection progression. Integrated multiomics analyses may provide a comprehensive understanding of specific underlying mechanisms, which remain elusive. This study aimed to identify new approaches for clinical renal allograft rejection diagnosis and treatment. Thirty-five patients were divided into three groups: the rejection (n = 16), dysfunction (n = 7), and control (n = 12) groups. Metagenomic sequencing and nontargeted metabolomics were used to analyze stool and plasma samples. Significant microbiota, metabolites, and signaling pathways were identified. LASSO regression was used to construct a diagnostic model, and its diagnostic value was assessed via receiver operating characteristic curves. The microbiota composition and the related genes in the rejection group significantly differed from that in the dysfunction and control groups at the phylum, genus, and species levels (P < 0.001). The core species in the rejection group networks were Escherichia coli and Ruminococcus gnavus, while core species in the dysfunction group networks were Faecalibacterium prausnitzii and Bacteroides ovatus. The balance of specific microbial species was associated with kidney function in rejection patients. Spearman analysis revealed that specific differential species like Agathobaculum butyriciproducens and Gemmiger qucibialis were closely linked to the levels of serum 4-pyridoxic acid, 4-acetamidobutanoate, and fecal tryptamine from specific differential pathways. Finally, we constructed four clinical models to distinguish the rejection and dysfunction groups, and the model had excellent diagnostic performance. Altered gut microbiota may contribute to changes in metabolic pathway activity and metabolite abundance in rejection and dysfunction patients, which are strongly correlated with host immunological rejection. The diagnostic model, developed based on the gut microbiota and metabolites, has high clinical value for diagnosing renal rejection.

IMPORTANCE: This study aimed to screen new markers for non-invasive diagnosis by the gut microbiome and metabolome analysis, providing new insights into rejection mechanisms and identifying new approaches for clinical renal allograft rejection diagnosis.},
}

@article {pmid40270478,
year = {2025},
author = {Schoultz, I and Claesson, MJ and Dominguez-Bello, MG and Fåk Hållenius, F and Konturek, P and Korpela, K and Laursen, MF and Penders, J and Roager, H and Vatanen, T and Öhman, L and Jenmalm, MC},
title = {Gut microbiota development across the lifespan: Disease links and health-promoting interventions.},
journal = {Journal of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1111/joim.20089},
pmid = {40270478},
issn = {1365-2796},
abstract = {The gut microbiota plays a pivotal role in human life and undergoes dynamic changes throughout the human lifespan, from infancy to old age. During our life, the gut microbiota influences health and disease across life stages. This review summarizes the discussions and presentations from the symposium "Gut microbiota development from infancy to old age" held in collaboration with the Journal of Internal Medicine. In early infancy, microbial colonization is shaped by factors such as mode of delivery, antibiotic exposure, and milk-feeding practices, laying the foundation for subsequent increased microbial diversity and maturation. Throughout childhood and adolescence, microbial maturation continues, influencing immune development and metabolic health. In adulthood, the gut microbiota reaches a relatively stable state, influenced by genetics, diet, and lifestyle. Notably, disruptions in gut microbiota composition have been implicated in various inflammatory diseases-including inflammatory bowel disease, Type 1 diabetes, and allergies. Furthermore, emerging evidence suggests a connection between gut dysbiosis and neurodegenerative disorders such as Alzheimer's disease. Understanding the role of the gut microbiota in disease pathogenesis across life stages provides insights into potential therapeutic interventions. Probiotics, prebiotics, and dietary modifications, as well as fecal microbiota transplantation, are being explored as promising strategies to promote a healthy gut microbiota and mitigate disease risks. This review focuses on the gut microbiota's role in infancy, adulthood, and aging, addressing its development, stability, and alterations linked to health and disease across these critical life stages. It outlines future research directions aimed at optimizing the gut microbiota composition to improve health.},
}

@article {pmid40265594,
year = {2025},
author = {Zhang, D and Zhang, Z and Liao, L and Dong, B and Xiong, X and Qin, X and Fan, X},
title = {Impact of fecal microbiota transplantation on lung function and gut microbiome in an ARDS rat model: A multi-omics analysis including 16S rRNA sequencing, metabolomics, and transcriptomics.},
journal = {International journal of immunopathology and pharmacology},
volume = {39},
number = {},
pages = {3946320251333982},
doi = {10.1177/03946320251333982},
pmid = {40265594},
issn = {2058-7384},
mesh = {Animals ; *Gastrointestinal Microbiome ; Rats, Sprague-Dawley ; *Fecal Microbiota Transplantation/methods ; *Respiratory Distress Syndrome/therapy/microbiology/metabolism/physiopathology/genetics ; *Lung/metabolism/physiopathology/microbiology ; *RNA, Ribosomal, 16S/genetics ; Metabolomics/methods ; Disease Models, Animal ; Rats ; Male ; *Transcriptome ; Multiomics ; },
abstract = {OBJECTIVE: Acute respiratory distress syndrome (ARDS) is a severe pulmonary condition characterized by inflammation and lung damage, frequently resulting in poor clinical outcomes. Recent studies suggest that the gut-lung axis, mediated by gut microbiota, is critical in ARDS progression. This study investigates the therapeutic potential of fecal microbiota transplantation (FMT) in an ARDS rat model (n = 6).

INTRODUCTION: The pathogenesis of ARDS involves complex interactions between the lungs and gut, with microbiota playing a key role. Understanding the effects of FMT on lung function and gut microbiota may provide new therapeutic strategies for ARDS management.

METHODS: Sprague-Dawley rats were pre-treated with a broad-spectrum antibiotic cocktail to create a germ-free state and subsequently exposed to intranasal lipopolysaccharide to induce ARDS. The rats then received FMT treatment. Lung samples were analyzed using histopathology and transcriptomics. Fecal samples were analyzed using 16S rRNA sequencing and metabolomics.

RESULTS: FMT treatment significantly reduced lung injury and improved pulmonary function, as evidenced by increased partial pressure of arterial oxygen (PaO2) and decreased partial pressure of arterial carbon dioxide (PaCO2). FMT also significantly altered in gut microbiota composition by regulating the gut microbiota composition of Akkermansia and Lactobacillus, restoring the abundance of genera such as Muribaculaceae, Clostridia_UCG-014, Prevotella, and Adlercreutzia, while reducing Romboutsia. FMT restored key metabolic pathways involved in lipid metabolism, amino acid biosynthesis, and immune regulation, including the modulation of immune pathways like mTOR signaling. These alterations contribute to reduced lung injury and improved pulmonary function.

CONCLUSION: These findings indicate that FMT may exert its beneficial effects in ARDS by modulating the gut microbiota and enhancing metabolic and immune responses. However, given that this study remains in the preclinical stage, further validation in clinical studies is necessary before considering clinical application.},
}

Animals
*Gastrointestinal Microbiome
Rats, Sprague-Dawley
*Fecal Microbiota Transplantation/methods
*Respiratory Distress Syndrome/therapy/microbiology/metabolism/physiopathology/genetics
*Lung/metabolism/physiopathology/microbiology
*RNA, Ribosomal, 16S/genetics
Metabolomics/methods
Disease Models, Animal
Rats
Male
*Transcriptome
Multiomics

@article {pmid40263850,
year = {2025},
author = {He, G and Zhang, B and Chen, T and Shen, C and Wang, N and Yang, J and Chang, F and Sui, Y and Yin, X and Wang, Y and Wang, S and Li, Y and Zong, J and Luo, Y and Meng, Y and Li, C and Zhou, X},
title = {Effects of chitosan on restoring spermatogenesis in mice: Insights from gut microbiota and multi-omics analysis.},
journal = {Food research international (Ottawa, Ont.)},
volume = {208},
number = {},
pages = {116218},
doi = {10.1016/j.foodres.2025.116218},
pmid = {40263850},
issn = {1873-7145},
mesh = {Animals ; Male ; *Spermatogenesis/drug effects ; *Gastrointestinal Microbiome/drug effects ; *Chitosan/pharmacology ; Mice ; Metabolomics ; Testis/drug effects/metabolism ; Busulfan ; Docosahexaenoic Acids/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Prebiotics ; Multiomics ; },
abstract = {Chitosan, is a natural bio-based polymer with known prebiotic properties. However, its potential in the management of spermatogenic disorders remains largely unexplored. By utilizing a busulfan-treated mouse model and integrated multi-omics analysis, this study explored the potential mechanisms through which chitosan improves impaired spermatogenesis. The results showed that chitosan treatment can improve testicular function and significantly reshape the gut microbiota composition in busulfan-treated mice. Metabolomics revealed that docosahexaenoic acid (DHA) transport was significantly dysregulated in busulfan-treated mice, but chitosan reversed this dysfunction by modulating tight junction proteins and fatty acid transporters in the intestine. Fecal microbiota transplantation experiments further highlighted the critical role of gut microbiota in DHA transport and spermatogenesis. Additionally, DHA supplementation alleviated busulfan-induced ferroptosis in testicular tissues. Hence, owing to its prebiotic effects chitosan could serve as a novel therapeutic strategy for improving busulfan-induced spermatogenic disorders by restoring the homeostasis of the gut-testis axis.},
}

Animals
Male
*Spermatogenesis/drug effects
*Gastrointestinal Microbiome/drug effects
*Chitosan/pharmacology
Mice
Metabolomics
Testis/drug effects/metabolism
Busulfan
Docosahexaenoic Acids/metabolism
Mice, Inbred C57BL
Fecal Microbiota Transplantation
Prebiotics
Multiomics

@article {pmid40263438,
year = {2025},
author = {Kumpunya, S and Kawang, K and Pollapong, K and Nilaratanakul, V},
title = {The effects of repeated fecal transplantation and activated charcoal treatment on gut dysbiosis induced by concurrent ceftriaxone administration in mice.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {13908},
pmid = {40263438},
issn = {2045-2322},
support = {RA-MF-52/64//Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University/ ; HEA_FF_68_079_3000_013//Thailand Science Research and Innovation Fund Chulalongkorn University/ ; },
mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Charcoal/pharmacology ; *Dysbiosis/chemically induced/therapy/microbiology ; *Ceftriaxone/adverse effects/administration & dosage ; *Gastrointestinal Microbiome/drug effects ; Mice ; Mice, Inbred C57BL ; *Anti-Bacterial Agents/adverse effects/administration & dosage ; RNA, Ribosomal, 16S/genetics ; Male ; Intestinal Mucosa/pathology/microbiology/drug effects ; },
abstract = {BACKGROUND: Antibiotic treatment contributes to gut microbiota dysbiosis. Previous studies have shown that fecal microbiota transplantation (FMT), fecal filtrate (FF), and activated charcoal (AC) treatments can prevent gut microbiota disturbances caused by antibiotics or Clostridioides difficile infection. However, these treatments have typically been limited to restoring gut microbiota after dysbiosis, and antibiotics must be discontinued beforehand. Here, we investigated the protective effects of these treatments on gut microbiota to prevent dysbiosis during concurrent systemic ceftriaxone administration.

METHODS: C57BL/6 mice that received intraperitoneal ceftriaxone for seven consecutive days were concomitantly treated with AC, FMT, FMT + AC, FF, or FF + AC via oral gavage. Gut microbiomes were analyzed using 16 S rRNA gene sequencing, and intestinal mucosal pathology was evaluated through H&E staining.

RESULTS: Systemic ceftriaxone administration significantly altered gut microbiota diversity and composition but did not affect intestinal mucosal histology. Alpha and beta diversity analyses showed that microbiota diversity decreased in all ceftriaxone-treated groups, with the ceftriaxone + FF + AC group retaining the highest diversity. The ceftriaxone + AC group had higher Enterococcus but lower Muribaculaceae relative abundances than the control (no ceftriaxone), ceftriaxone only, and ceftriaxone + FF + AC groups.

CONCLUSIONS: These results show that fecal filtrate transplantation combined with activated charcoal treatment may help balance gut microbiota diversity and reduce the presence of resistant bacteria during ceftriaxone exposure.},
}

Animals
*Fecal Microbiota Transplantation/methods
*Charcoal/pharmacology
*Dysbiosis/chemically induced/therapy/microbiology
*Ceftriaxone/adverse effects/administration & dosage
*Gastrointestinal Microbiome/drug effects
Mice
Mice, Inbred C57BL
*Anti-Bacterial Agents/adverse effects/administration & dosage
RNA, Ribosomal, 16S/genetics
Male
Intestinal Mucosa/pathology/microbiology/drug effects

@article {pmid40263148,
year = {2025},
author = {Chi, Q and Tang, J and Ji, C and Chen, S and Chen, Q and Zeng, M and Cao, J and Sun, S and Herr, DR and Zhang, QG and Wang, Z and Huang, CM},
title = {Profiling electric signals of electrogenic probiotic bacteria using self-attention analysis.},
journal = {Applied microbiology and biotechnology},
volume = {109},
number = {1},
pages = {100},
pmid = {40263148},
issn = {1432-0614},
mesh = {*Probiotics/metabolism ; Animals ; Mice ; *Lactococcus lactis/metabolism/physiology ; Chorioallantoic Membrane/microbiology ; Glucose/metabolism ; *Electricity ; Chickens ; Intestines/microbiology ; },
abstract = {We fabricated a self-assembled electric circuit to detect the electrical signals produced by two electrogenic probiotic bacteria [Leuconostoc mesenteroides (L. mesenteroides) and Lactococcus lactis (L. lactis)] on chicken egg chorioallantoic membranes as well as in the intestine lumen of mice. Inoculation of L. mesenteroides or L. lactis plus glucose onto a ferrozine assay triggered the reduction of ferric ions to ferrous ions and the formation of ferrozine complexes, indicating the bacterial electron production. In the presence of glucose, L. lactis yielded higher electricity, measured by voltage changes, than L. mesenteroides in vitro. The spectra of the electrical signals generated by these two probiotic bacteria were highly distinguishable. We evaluated the importance of these differences with the application of a self-attention mechanism, a deep learning-based module, revealing several unique signals in the electrical spectra of L. mesenteroides as well as L. lactis bacteria. The specific electrical spectrum for each probiotic bacterium provided a dynamic signature for evaluation of the efficacy of various therapies using probiotics, antibiotics, and fecal microbiota transplantation in the future. KEY POINTS: • The electrical signals produced by probiotic bacteria L. mesenteroides and L. lactis on chicken egg chorioallantoic membranes and in the mouse intestine lumen were detectable. • In the presence of glucose, L. lactis yielded higher electricity than L. mesenteroides in vitro. Furthermore, the electrical spectra generated by these two bacteria were different. • The importance of these differences with the application of a self-attention mechanism revealed several unique signals in the electrical spectra.},
}

*Probiotics/metabolism
Animals
Mice
*Lactococcus lactis/metabolism/physiology
Chorioallantoic Membrane/microbiology
Glucose/metabolism
*Electricity
Chickens
Intestines/microbiology

@article {pmid40262063,
year = {2025},
author = {Elkrief, A and Routy, B and Derosa, L and Bolte, L and Wargo, JA and McQuade, JL and Zitvogel, L},
title = {Gut Microbiota in Immuno-Oncology: A Practical Guide for Medical Oncologists With a Focus on Antibiotics Stewardship.},
journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting},
volume = {45},
number = {3},
pages = {e472902},
doi = {10.1200/EDBK-25-472902},
pmid = {40262063},
issn = {1548-8756},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Antimicrobial Stewardship ; *Neoplasms/microbiology/immunology ; *Anti-Bacterial Agents/therapeutic use ; Immune Checkpoint Inhibitors/therapeutic use ; *Medical Oncology ; Oncologists ; },
abstract = {The gut microbiota has emerged as a critical determinant of immune checkpoint inhibitor (ICI) efficacy, resistance, and toxicity. Retrospective and prospective studies profiling the taxonomic composition of intestinal microbes of patients treated with ICI have revealed specific gut microbial signatures associated with response. By contrast, dysbiosis, which can be caused by chronic inflammatory processes (such as cancer) or comedications, is a risk factor of resistance to ICI. Recent large-scale meta-analyses have confirmed that antibiotic (ATB) use before or during ICI therapy alters the microbiota repertoire and significantly shortens overall survival, even after adjusting for prognostic factors. These results underscore the importance of implementing ATB stewardship recommendations in routine oncology practice. Microbiota-centered interventions are now being explored to treat gut dysbiosis and optimize ICI responses. Early-phase clinical trials evaluating fecal microbiota transplantation (FMT) from ICI responders or healthy donors have shown that this approach is safe and provided preliminary data on potential efficacy to overcome both primary and secondary resistance to ICI in melanoma, non-small cell lung cancer, and renal cell carcinoma. More targeted interventions including live bacterial products including Clostridium butyricum and Akkermansia massiliensis represent novel microbiome-based adjunct therapies. Likewise, dietary interventions, such as high-fiber diets, have shown promise in enhancing ICI activity. In this ASCO Educational Book, we summarize the current state-of-the-evidence of the clinical relevance of the intestinal microbiota in cancer immunotherapy and provide a practical guide for ATB stewardship.},
}

Humans
*Gastrointestinal Microbiome/drug effects/immunology
*Antimicrobial Stewardship
*Neoplasms/microbiology/immunology
*Anti-Bacterial Agents/therapeutic use
Immune Checkpoint Inhibitors/therapeutic use
*Medical Oncology
Oncologists

@article {pmid40261509,
year = {2025},
author = {Mahgoup, EM},
title = {"Gut Microbiota as a Therapeutic Target for Hypertension: Challenges and Insights for Future Clinical Applications" "Gut Microbiota and Hypertension Therapy".},
journal = {Current hypertension reports},
volume = {27},
number = {1},
pages = {14},
pmid = {40261509},
issn = {1534-3111},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Hypertension/therapy/microbiology/physiopathology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Antihypertensive Agents/therapeutic use ; Blood Pressure/physiology ; Dysbiosis ; Prebiotics ; },
abstract = {PURPOSE OF REVIEW: Systemic hypertension is a major risk factor for cardiovascular disease and remains challenging to manage despite the widespread use of antihypertensive medications and lifestyle modifications. This review explores the role of gut microbiota in hypertension development and regulation, highlighting key mechanisms such as inflammation, gut-brain axis modulation, and bioactive metabolite production. We also assess the potential of microbiota-targeted therapies for hypertension management.

RECENT FINDINGS: Emerging evidence indicates that microbial dysbiosis, high-salt diets, and gut-derived metabolites such as short-chain fatty acids (SCFAs) and bile acids significantly influence blood pressure regulation. Preclinical and early clinical studies suggest that interventions targeting gut microbiota, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), and dietary modifications, may help modulate hypertension. However, variability in gut microbiota composition among individuals and limited human trial data pose challenges to translating these findings into clinical practice. While microbiota-based therapies show promise for hypertension management, further research is needed to establish their efficacy and long-term effects. Large-scale, standardized clinical trials are crucial for understanding the therapeutic potential and limitations of gut microbiota interventions. A deeper understanding of the gut-hypertension axis could lead to novel, personalized treatment strategies for hypertension.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Hypertension/therapy/microbiology/physiopathology
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Antihypertensive Agents/therapeutic use
Blood Pressure/physiology
Dysbiosis
Prebiotics

@article {pmid40260582,
year = {2025},
author = {Shaukat, A and Drekonja, DM and Huang, Y and Zhang, JH and Davis-Karim, A and Kyriakides, TC},
title = {Efficacy and Safety of Fecal Microbiota Transplant for Prevention of Recurrent Clostridioides difficile Infection.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf142},
pmid = {40260582},
issn = {1537-6591},
}

@article {pmid40260552,
year = {2025},
author = {Davido, B and Kharkhordine, M and Moine, P},
title = {Fecal Microbiota Transplantation in Clostridioides Difficile Infections: Rethinking the Approach by Patient Profile in Light of New Evidence.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf143},
pmid = {40260552},
issn = {1537-6591},
}

@article {pmid40260548,
year = {2025},
author = {Khoruts, A and Staley, C},
title = {FMT for Recurrent Clostridioides difficile Infection.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf138},
pmid = {40260548},
issn = {1537-6591},
}

@article {pmid40260536,
year = {2025},
author = {Paaske, SE and Baunwall, SMD and Ianiro, G and Iqbal, T and Keller, J and Kupciskas, J and Link, A and Mullish, BH and Vehreshild, MJGT and Dahlerup, JF and Hvas, CL},
title = {Clostridioides difficile: Treating Sustained Antibiotic Responders With Fecal Microbiota Transplantation Does Not Improve Efficacy.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf141},
pmid = {40260536},
issn = {1537-6591},
support = {//the National Institute of Health Research (NIHR) Imperial Biomedical Research Centre (BRC)/ ; //Imperial College London/ ; //Imperial College Healthcare NHS Trust/ ; MR/Z504002/1/MRC_/Medical Research Council/United Kingdom ; },
}

@article {pmid39607629,
year = {2025},
author = {Chua, HC and Pham, S and Lombardi, DA and Hot, E and Mody, L},
title = {Patient Satisfaction Scale Following a Laxative for Antibiotic Washout Prior to Oral Microbiome Therapy.},
journal = {Advances in therapy},
volume = {42},
number = {1},
pages = {490-499},
pmid = {39607629},
issn = {1865-8652},
mesh = {Humans ; *Patient Satisfaction ; *Laxatives/administration & dosage/therapeutic use ; Male ; Female ; Middle Aged ; *Anti-Bacterial Agents/administration & dosage/therapeutic use ; Aged ; Adult ; Psychometrics ; Reproducibility of Results ; Administration, Oral ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/prevention & control ; Surveys and Questionnaires ; },
abstract = {INTRODUCTION: Administration of fecal microbiota spores, live-brpk [Vowst Oral Spores (VOS)], an oral microbiome therapeutic approved for prevention of recurrent Clostridioides difficile infection in adults, requires antibiotic washout using a laxative prior to administration. Patient acceptability of the prerequisite laxative is important. This study assessed psychometric properties of the Antibiotic Washout Patient Satisfaction Scale (AWPSS) which was minimally modified from a previously validated patient satisfaction scale for bowel preparation prior to colonoscopy.

METHODS: Patients from the ECOSPOR IV trial who received a laxative preparation prior to oral administration of VOS and were administered the AWPSS were included. Reliability and construct validity of the AWPSS were evaluated.

RESULTS: AWPSS data were available for 110 patients; all completed all 6 items of the AWPSS, supporting its acceptability. Domain 1 mean/median transformed total scores of 105.9/100 [range (best-worst), 0-300] suggested that patients were satisfied with the laxative preparation; a Cronbach's alpha of 0.81 showed acceptable reliability. Almost all patients (97.3%) reported they were able to consume the entire laxative solution as instructed and would take it again if needed (95.5%). Higher satisfaction with the laxative preparation predicted higher acceptability of future use if needed (lower score) with mean/median of 101.7/100 and 195.0/200.00 for those who were willing or not willing to accept, respectively (P = 0.008).

CONCLUSIONS: AWPSS is a valid and reliable 6-item patient-reported outcome measure for use in patients requiring a laxative prior to oral microbiome therapy. AWPSS showed antibiotic washout was well tolerated and predicted that patients would be willing to consume the laxative in the future if needed.},
}

Humans
*Patient Satisfaction
*Laxatives/administration & dosage/therapeutic use
Male
Female
Middle Aged
*Anti-Bacterial Agents/administration & dosage/therapeutic use
Aged
Adult
Psychometrics
Reproducibility of Results
Administration, Oral
*Fecal Microbiota Transplantation/methods
*Clostridium Infections/prevention & control
Surveys and Questionnaires

@article {pmid40259408,
year = {2025},
author = {Cuisiniere, T and Hajjar, R and Oliero, M and Calvé, A and Fragoso, G and Rendos, HV and Gerkins, C and Taleb, N and Gagnon-Konamna, M and Dagbert, F and Loungnarath, R and Sebajang, H and Schwenter, F and Wassef, R and Ratelle, R and De Broux, É and Richard, C and Santos, MM},
title = {Initial gut microbiota composition is a determining factor in the promotion of colorectal cancer by oral iron supplementation: evidence from a murine model.},
journal = {Microbiome},
volume = {13},
number = {1},
pages = {100},
pmid = {40259408},
issn = {2049-2618},
support = {PJT-159775/CAPMC/CIHR/Canada ; RGPIN-2024-05660//Natural Sciences and Engineering Research Council of Canada/ ; },
mesh = {Animals ; *Colorectal Neoplasms/microbiology/pathology/etiology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Iron/adverse effects/administration & dosage ; Humans ; Disease Models, Animal ; *Dietary Supplements/adverse effects ; Fecal Microbiota Transplantation ; Male ; Female ; Administration, Oral ; Feces/microbiology ; Bacteria/classification/isolation & purification/genetics ; Carcinogenesis/drug effects ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Colorectal cancer (CRC) development is influenced by both iron and gut microbiota composition. While iron supplementation is routinely used to manage anemia in CRC patients, it may also impact gut microbiota and promote tumorigenesis. In this study, we investigated the impact of initial gut microbiota composition on iron-promoted tumorigenesis. We performed fecal microbiota transplantation (FMT) in Apc[Min/+] mice using samples from healthy controls, CRC patients, and mice, followed by exposure to iron sufficient or iron excess diets.

RESULTS: We found that iron supplementation promoted CRC and resulted in distinct gut microbiota changes in Apc[Min/+] mice receiving FMT from CRC patients (FMT-CRC), but not from healthy controls or mice. Oral treatment with identified bacterial strains, namely Faecalibaculum rodentium, Holdemanella biformis, Bifidobacterium pseudolongum, and Alistipes inops, protected FMT-CRC mice against iron-promoted tumorigenesis.

CONCLUSIONS: Our findings suggest that microbiota-targeted interventions may mitigate tumorigenic effects of iron supplementation in anemic patients with CRC.},
}

Animals
*Colorectal Neoplasms/microbiology/pathology/etiology
*Gastrointestinal Microbiome/drug effects
Mice
*Iron/adverse effects/administration & dosage
Humans
Disease Models, Animal
*Dietary Supplements/adverse effects
Fecal Microbiota Transplantation
Male
Female
Administration, Oral
Feces/microbiology
Bacteria/classification/isolation & purification/genetics
Carcinogenesis/drug effects
Mice, Inbred C57BL

@article {pmid40259351,
year = {2025},
author = {Kamlárová, A and Kvaková, M and Ambro, Ľ and Link, R and Bertková, I and Hertelyová, Z and Janíčko, M and Hijová, E and Štofilová, J},
title = {Improvement of the inflammation-damaged intestinal barrier and modulation of the gut microbiota in ulcerative colitis after FMT in the SHIME® model.},
journal = {BMC complementary medicine and therapies},
volume = {25},
number = {1},
pages = {145},
pmid = {40259351},
issn = {2662-7671},
support = {APVV-23-0031//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-23-0031//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-23-0031//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-23-0031//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-23-0031//Agentúra na Podporu Výskumu a Vývoja/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; },
mesh = {*Colitis, Ulcerative/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Caco-2 Cells ; Inflammation ; HT29 Cells ; Male ; Female ; Intestinal Mucosa/microbiology ; Adult ; },
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) seems to be a promising approach in ulcerative colitis (UC) management with the aim of repopulating a patient's dysbiotic microbiota with beneficial bacteria and restore its metabolic activity to its healthy characteristics. Metabolites present after FMT may improve the function and integrity of the intestinal barrier, reduce inflammation, and thus induce remission in an UC patient. In this study we evaluated whether the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) model may be a suitable non-invasive alternative for studying and modifying the dysbiotic microbiota in UC by FMT application.

METHODS: SHIME® model was used to investigate microbial and metabolic changes in the gut microbiota of UC patient induced by FMT application. FMT-modified metabolites from SHIME® were applied to an in vitro model of the intestinal barrier (differentiated Caco-2 and HT-29-MTX-E12 cell lines) compromised by pro-inflammatory cytokines to study the effect of FMT on the intestinal barrier.

RESULTS: Qualitative and quantitative microbial analyses showed that FMT increased the diversity and variability of the microbiota in UC patient associated with a significant increase in total bacteria, Bacteroidota and Lactobacillus, as well as an increase in butyrate levels. In addition, an increase in the relative abundance of some important species such as Faecalibacterium prausnitzii and Bifidobacterium longum was observed, and there was also an enrichment of the microbiota with new species such as Blautia obeum, Roseburia faecis, Bifidobacterium adolescentis, Fusicatenibacter saccharivorans and Eubacterium rectale. Furthermore, microbial metabolites modulated by FMT from the SHIME® model prevented intestinal barrier damage and inhibited interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) secretion when cell barriers were pretreated with FMT medium for 24 h. In summary, this study confirmed that a single dose of FMT beneficially modulated the composition and metabolic activity of the UC microbiota in the SHIME® model.

CONCLUSIONS: FMT favorably modulates the gut microbiota of UC patient cultured in the SHIME® model. FMT-modulated SHIME-derived microbial metabolites improve intact and inflamed intestinal barrier properties in vitro. Repeated applications are necessary to maintain the beneficial effect of FMT in SHIME® model.},
}

*Colitis, Ulcerative/therapy/microbiology
Humans
*Gastrointestinal Microbiome
*Fecal Microbiota Transplantation
Caco-2 Cells
Inflammation
HT29 Cells
Male
Female
Intestinal Mucosa/microbiology
Adult

@article {pmid40258046,
year = {2025},
author = {Lund, AJ and Metzger, ME and Kramer, VL and Kjemtrup, AM},
title = {Low risk for locally acquired Chagas disease in California: A review of human cases and triatomine submissions, 2013-2023.},
journal = {PLoS neglected tropical diseases},
volume = {19},
number = {4},
pages = {e0013036},
doi = {10.1371/journal.pntd.0013036},
pmid = {40258046},
issn = {1935-2735},
abstract = {Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi, which is carried in the guts of triatomine insects. Transmission typically occurs when infective trypomastigotes in triatomine feces encounter mucous membranes or bite wounds, though it is also possible by food-borne, transplant- and transfusion-mediated, and congenital routes. Most transmission occurs in rural and peri-urban parts of continental Latin America where triatomines often inhabit human dwellings. Triatomines infected with T. cruzi are also present across the southern United States, yet relatively few locally acquired infections have been documented. Rather, most reported cases have plausible exposure in Latin America. In California, the widespread distribution of T. cruzi-infected triatomines suggests a potential risk of local transmission. Here, we summarize triatomine submissions and human case reports made to the California Department of Public Health between 2013 and 2023. Of 226 triatomines tested, 63 (28%) were positive for T. cruzi via PCR; none were linked to any of the 40 human T. cruzi cases reported in the same period. Human cases were assessed for likelihood of local transmission. Country of birth, travel history, and location of primary residence suggested non-local transmission for 31 (78%) cases. Local transmission could not be ruled out for the remaining nine (22%) cases. Information on country of birth and travel history were missing from these case reports and prevented full assessment of local transmission criteria, though most of these patients resided within 400 meters of potential triatomine habitat. Despite the presence of triatomines, T. cruzi, and human cases in California, statewide data indicates the risk for locally acquired Chagas disease is low.},
}

@article {pmid40257861,
year = {2025},
author = {Hu, M and Zhu, X and Huang, X and Hua, L and Lin, X and Zhang, H and Hu, Y and Tong, T and Li, L and Xuan, B and Zhao, Y and Zhou, Y and Ding, J and Ma, Y and Jiang, Y and Ning, L and Zhang, Y and Wang, Z and Fang, JY and Zhang, Y and Xiao, X and Hong, J and Chen, H and Li, J and Chen, H},
title = {Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype.},
journal = {Cell reports},
volume = {44},
number = {5},
pages = {115589},
doi = {10.1016/j.celrep.2025.115589},
pmid = {40257861},
issn = {2211-1247},
abstract = {Immunotherapy has revolutionized cancer treatment, but response variability remains a challenge. The gut microbiome's role in therapeutic efficacy is well established, but the impact of the gut mycobiome is less understood. Using unsupervised clustering, we identify two gut mycobiome-based enterotypes, favorable type and unfavorable type, characterized by distinct microbial compositions linked to immunotherapy outcomes. Favorable-type enterotypes exhibit higher fungal and bacterial alpha diversity, enriched butyrate-producing bacteria, and metabolic pathways related to butyric acid and sugar/starch metabolism. External validation confirms their predictive value in assessing immunotherapy efficacy. Multi-omics analysis reveals increased CD8[+] T cell infiltration in the tumor microenvironment of favorable-type patients. Fecal microbiota transplantation (FMT) from favorable-type donors enhances anti-PD-1 sensitivity, promotes CD8[+] T cell infiltration, and boosts butyrate production in vivo. These findings highlight the gut mycobiome's role in immunotherapy response and support FMT from favorable-type donors as a potential strategy for improving treatment outcomes and patient stratification.},
}

@article {pmid40257672,
year = {2025},
author = {Bénard, MV and de Bruijn, CMA and Matamoros, S and Wentink-Bonnema, EMS and Benninga, MA and Ponsioen, CY and Zonneveld, R},
title = {Transient colonization with Blastocystis spp. after transmission via fecal microbiota transplantation.},
journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology},
volume = {},
number = {},
pages = {},
pmid = {40257672},
issn = {1435-4373},
abstract = {BACKGROUND: The pathogenicity of Blastocystis spp. is still debated. Guidelines for feces donor screening differ in their advice to screen for Blastocystis spp., but when tested, its presence is a common reason for exclusion. Blastocystis spp. are correlated to increased bacterial alpha-diversity and distinct bacterial groups and therefore its presence may indicate favorable efficacy of fecal microbiota transplantation (FMT). The latest European consensus report no longer advices rejecting feces donors testing positive for Blastocystis spp. Only one paper has been published on human transmission of Blastocystis spp. via frozen FMT.

OBJECTIVE: To investigate the transmission and long-term effects of Blastocystis-positive FMT, prepared with fresh (i.e., unfrozen) feces.

METHODS: In a trial (NCT03074227) on FMT for refractory Irritable Bowel Syndrome (IBS), adolescents (age 16-20 years) received two administrations - at baseline and after 6 weeks - of fresh allogeneic FMT from a Blastocystis-positive donor via nasoduodenal tube. The follow-up was 48 weeks. Blastocystis spp. presence, viability and subtyping were determined using microscopy, culture, PCR and sequencing.

RESULTS: Three recipients received FMT from one donor colonized with Blastocystis subtype 3 (ST3). At baseline, two recipients were negative for Blastocystis spp. and one recipient carried ST2. Culturing revealed viable Blastocystis spp. in fresh donor feces but not in frozen samples. After FMT with fresh feces, the two prior-negative recipients tested positive for the donor's ST3 at 12 weeks, but had lost this subtype by week 24 and 48. The recipient initially colonized with ST2 remained colonized with ST2 and did not acquire ST3. Transient adverse events occurred, but did not differ from patients treated with Blastocystis-negative FMT. No FMT-related serious adverse events emerged.

CONCLUSION: We present the first long-term data on viable Blastocystis spp. transmission via fresh FMT in three cases. Transient colonization with Blastocystis spp. was observed, without serious FMT-related adverse events.},
}

@article {pmid40257135,
year = {2025},
author = {Deepti, I and Chettri, B and Mehra, A and Pinheiro, AM and Ravi, R},
title = {Faecal microbiota transplantation for recurrent Clostridiodes difficile infection & its global regulatory landscape.},
journal = {The Indian journal of medical research},
volume = {161},
number = {2},
pages = {113-119},
pmid = {40257135},
issn = {0971-5916},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/therapy/microbiology ; *Clostridioides difficile/pathogenicity ; Recurrence ; Feces/microbiology ; Gastrointestinal Microbiome ; },
abstract = {For recurrent Clostridioides difficile infection (rCDI), faecal microbiota transplantation (FMT) is a known and useful treatment that involves introducing faeces from a healthy individual into the digestive tract of a diseased person. Clostridioides difficile is a substantial global health burden due to its high death rate in elderly populations and its ability to produce colitis and diarrhoea. Despite being used since millennia, FMT has recently become more well-known and two FMT products, namely Vowst and Rebyota also received FDA approval. Different nations address regulation in different ways. For instance, FMT is regulated as a drug in the US but is classified as a medicinal product in the UK. The regulatory frameworks among various European countries also vary; a working group, citing FMT as a transplant product, has requested for complete regulation. There are other classifications as well; in Australia, FMT is categorised as a biologic by the Therapeutic Goods Administration. Research indicates that FMT is beneficial in various illnesses, apart from CDI, due to its impact on the gut flora. Challenges include insufficient FMT product characterisation, ethical concerns, and limited hospital accessibility. There are still issues with data accessibility, security, and privacy, especially considering FMT's commercialisation. The official FMT recommendation for recurrent CDI is emphasised from the perspective of public health, with the argument that early implementation could limit antibiotic overuse and prevent antibiotic resistance. Initiatives like the Universal Stool Bank concept aim to streamline donor selection and distribution procedures to minimise operational restrictions.},
}

Humans
*Fecal Microbiota Transplantation/methods
*Clostridium Infections/therapy/microbiology
*Clostridioides difficile/pathogenicity
Recurrence
Feces/microbiology
Gastrointestinal Microbiome

@article {pmid40256591,
year = {2024},
author = {Abedi, B and Karimian, R and Bahari, Z and Iman, M},
title = {Absorbents therapy, as a conservative option, can improve kidney function in chronic kidney disease.},
journal = {Archives of Razi Institute},
volume = {79},
number = {4},
pages = {695-700},
pmid = {40256591},
issn = {2008-9872},
mesh = {Humans ; *Renal Insufficiency, Chronic/therapy/physiopathology ; *Renal Dialysis/methods ; *Conservative Treatment/methods ; },
abstract = {Chronic kidney disease (CKD), also called chronic kidney failure, is increasingly recognized as a global public health problem in the entire world. It is characterized by slow, progressive, and irreversible loss in kidney physiology. Today, the prevalence of CKD is increasing dramatically. CKD can affect almost every organ system, including the cardiovascular system. Many treatments have been attempted for CKD, such as renal transplantation, hemodialysis (HD), and peritoneal dialysis (PD). At the end stage of CKD, HD is the most widely used therapy throughout the world. However, these options can decrease volume expansion and uremic solute retention and also increase patient survival. Furthermore, there are certain complications associated with the use of these methods. Previous studies have reported that the main side effects are headaches, muscle cramps, abdominal pain, hypotension, hypertension, vomiting, and constipation. Therefore, the investigation for better and more convenient dialysis techniques should continue, as well as the search for a better material to enhance the clearance of nitrogenous waste products from the body. The intestine has a significant effect on the clearance of nitrogenous waste products from the body, making it a potentially appropriate site for CKD management. The potential mechanism of the intestinal dialysis technique is that it can absorb excess fluids, uremic toxins, and electrolytes within the gastrointestinal (GI) tract and exert them in the feces before they can be absorbed into the blood. In the present review, we will focus on different absorbents as a conservative treatment to remove uremic waste metabolites from the GI tract for the improvement of kidney function in CKD.},
}

Humans
*Renal Insufficiency, Chronic/therapy/physiopathology
*Renal Dialysis/methods
*Conservative Treatment/methods

@article {pmid40161742,
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 = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40161742},
issn = {2692-8205},
support = {UM1 CA186644/CA/NCI NIH HHS/United States ; },
abstract = {Composition and function of the gut microbiome is 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 to recapitulate 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 were more similar in gut composition to other mice than their respective human donors, with taxa including Akkermansia muciniphila and Bacteroides species 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 datasets 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 were more like other mice than their human donor. Our data suggest that HMA mice are limited models to assess 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 overwhelm ecological effects of treatment in humans that HMA models aim to recapitulate.},
}

@article {pmid39395412,
year = {2025},
author = {Talwar, C and Davuluri, GVN and Kamal, AHM and Coarfa, C and Han, SJ and Veeraragavan, S and Parsawar, K and Putluri, N and Hoffman, K and Jimenez, P and Biest, S and Kommagani, R},
title = {Identification of distinct stool metabolites in women with endometriosis for non-invasive diagnosis and potential for microbiota-based therapies.},
journal = {Med (New York, N.Y.)},
volume = {6},
number = {2},
pages = {100517},
pmid = {39395412},
issn = {2666-6340},
support = {R01 CA220297/CA/NCI NIH HHS/United States ; R01 HD104813/HD/NICHD NIH HHS/United States ; U54 HG006348/HG/NHGRI NIH HHS/United States ; R01 CA216426/CA/NCI NIH HHS/United States ; P50 HD103555/HD/NICHD NIH HHS/United States ; P30 ES030285/ES/NIEHS NIH HHS/United States ; R01 HD102680/HD/NICHD NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Endometriosis/diagnosis/microbiology/metabolism/therapy ; *Feces/microbiology/chemistry ; Animals ; Mice ; *Gastrointestinal Microbiome ; Metabolomics ; Metabolome ; Indoles/metabolism ; Adult ; Fecal Microbiota Transplantation ; Disease Models, Animal ; },
abstract = {BACKGROUND: Endometriosis, a poorly studied gynecological condition, is characterized by the presence of ectopic endometrial lesions resulting in pelvic pain, inflammation, and infertility. These associated symptoms contribute to a significant burden, often exacerbated by delayed diagnosis. Current diagnostic methods involve invasive procedures, and existing treatments provide no cure.

METHODS: Microbiome-metabolome signatures in stool samples from individuals with and without endometriosis were determined using unbiased metabolomics and 16S bacteria sequencing. Functional studies for selected microbiota-derived metabolites were conducted in vitro using patient-derived cells and in vivo by employing murine and human xenograft pre-clinical disease models.

FINDINGS: We discovered a unique bacteria-derived metabolite signature intricately linked to endometriosis. The altered fecal metabolite profile exhibits a strong correlation with that observed in inflammatory bowel disease (IBD), revealing intriguing connections between these two conditions. Notably, we validated 4-hydroxyindole, a gut-bacteria-derived metabolite that is lower in stool samples of endometriosis. Extensive in vivo studies found that 4-hydroxyindole suppressed the initiation and progression of endometriosis-associated inflammation and hyperalgesia in heterologous mouse and in pre-clinical models of the disease.

CONCLUSIONS: Our findings are the first to provide a distinct stool metabolite signature in women with endometriosis, which could serve as stool-based non-invasive diagnostics. Further, the gut-microbiota-derived 4-hydroxyindole poses as a therapeutic candidate for ameliorating endometriosis.

FUNDING: This work was funded by the NIH/NICHD grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society to R.K.},
}

Humans
Female
*Endometriosis/diagnosis/microbiology/metabolism/therapy
*Feces/microbiology/chemistry
Animals
Mice
*Gastrointestinal Microbiome
Metabolomics
Metabolome
Indoles/metabolism
Adult
Fecal Microbiota Transplantation
Disease Models, Animal

@article {pmid40255763,
year = {2025},
author = {Rathore, K and Shukla, N and Naik, S and Sambhav, K and Dange, K and Bhuyan, D and Imranul Haq, QM},
title = {The Bidirectional Relationship Between the Gut Microbiome and Mental Health: A Comprehensive Review.},
journal = {Cureus},
volume = {17},
number = {3},
pages = {e80810},
pmid = {40255763},
issn = {2168-8184},
abstract = {The gut microbiome plays a fundamental role in mental health, influencing mood, cognition, and emotional regulation through the gut-brain axis. This bidirectional communication system connects the gastrointestinal and CNS, facilitated by microbial metabolites, neurotransmitters, and immune interactions. Recent research highlights the association between gut dysbiosis and psychiatric disorders, including anxiety, depression, and stress-related conditions. Key findings indicate that altered microbial diversity, decreased short-chain fatty acid (SCFA) production, and increased neuroinflammation contribute to mental health disturbances. This paper explores the mechanism linking the gut microbiome to brain function, including microbial neurotransmitter synthesis, vagus nerve signaling, and hypothalamic-pituitary-adrenal (HPA) axis modulation. Additionally, it evaluates the potential of microbiome-targeted interventions, such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation (FMT), in alleviating psychiatric symptoms. Microbiome sequencing and bioinformatics advances further support the development of personalized microbiome-based mental health interventions. Despite promising evidence, challenges such as inter-individual variability, methodological inconsistencies, and the need for longitudinal studies remain. Future research should focus on standardizing microbiome assessment techniques and optimizing therapeutic applications. Integrating precision psychiatry with microbiome-based diagnostics holds immense potential in transforming mental health treatment.},
}

@article {pmid40254304,
year = {2025},
author = {Fehily, SR and Wright, EK and Basnayake, C and Wilson-O'Brien, AL and Stanley, A and Marks, EP and Russell, EE and Hamilton, AL and Bryant, RV and Costello, SP and Kamm, MA},
title = {Faecal microbiota transplantation in Crohn's disease: an Australian randomised placebo-controlled trial protocol.},
journal = {BMJ open},
volume = {15},
number = {4},
pages = {e094714},
pmid = {40254304},
issn = {2044-6055},
mesh = {Humans ; *Crohn Disease/therapy ; *Fecal Microbiota Transplantation/methods ; Australia ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Remission Induction ; Adult ; Male ; Gastrointestinal Microbiome ; Female ; Multicenter Studies as Topic ; },
abstract = {INTRODUCTION: The enteric microbiota drives inflammation in Crohn's disease. Yet, there are no placebo controlled trials evaluating the efficacy and safety of faecal microbiota transplantation (FMT) in inducing and maintaining remission in patients with active Crohn's disease. The Microbial Restoration (MIRO) study aims to establish this evidence.

METHODS AND ANALYSIS: At two specialist inflammatory bowel disease centres, 120 enrolled patients will have a 3-week period of diet optimisation (removal of ultra-processed foods) together with a 7-day course of antibiotics (to facilitate subsequent FMT engraftment). Patients will then be stratified to upper gut (for disease proximal to the splenic flexure) or lower gut (distal to the splenic flexure) disease. Patients will then be randomised in a 2:1 ratio to receive anaerobically prepared stool or placebo for 8 weeks either by gastroscopy, or colonoscopy and enemas. Clinical response at 8 weeks (Crohn's Disease Activity Index (CDAI) reduction ≥100 points or to <150 points) is the primary outcome measure. Non-responders to placebo and partial responders to FMT (CDAI decrease <100 but >70) receive FMT for weeks 8-16.Patients achieving clinical response from FMT after 8 or 16 weeks will be randomised in a 1:1 ratio to either a 44-week maintenance phase of FMT or placebo. Patients will receive FMT from one donor throughout the study.The MIRO study will establish whether FMT is an effective and safe therapy to induce and maintain remission in patients with active Crohn's disease.

ETHICS AND DISSEMINATION: Ethical approval has been received by the St Vincent's Hospital Melbourne Human Research Ethics Committee (HREC-A 084/21). The results will be disseminated in peer-reviewed journals and presented at international conferences.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT04970446; Registered on 20 July 2021.},
}

Humans
*Crohn Disease/therapy
*Fecal Microbiota Transplantation/methods
Australia
Randomized Controlled Trials as Topic
Treatment Outcome
Remission Induction
Adult
Male
Gastrointestinal Microbiome
Female
Multicenter Studies as Topic

@article {pmid40253186,
year = {2025},
author = {Hao, Y and Wang, C and Wang, L and Hu, L and Duan, T and Zhang, R and Yang, X and Li, T},
title = {Nondigestible stachyose alleviates cyclophosphamide-induced small intestinal mucosal injury in mice by regulating intestinal exosomal miRNAs, independently of the gut microbiota.},
journal = {Food research international (Ottawa, Ont.)},
volume = {209},
number = {},
pages = {116258},
doi = {10.1016/j.foodres.2025.116258},
pmid = {40253186},
issn = {1873-7145},
mesh = {Animals ; *Cyclophosphamide/adverse effects/toxicity ; *Gastrointestinal Microbiome/drug effects ; *MicroRNAs/metabolism/genetics ; *Intestinal Mucosa/drug effects/pathology/metabolism ; *Oligosaccharides/pharmacology ; Mice ; *Intestine, Small/drug effects/pathology/metabolism ; *Exosomes/metabolism/drug effects/genetics ; Male ; Oxidative Stress/drug effects ; Mice, Inbred C57BL ; Cytokines/metabolism ; Prebiotics ; Permeability ; Germ-Free Life ; Tight Junction Proteins/metabolism ; },
abstract = {Stachyose has traditionally been considered to exert prebiotic effects primarily through its interaction with gut microbiota. However, this study reveals a novel mechanism by which stachyose alleviates cyclophosphamide (CY)-induced small intestinal mucosa disruption by regulating the intestinal exosomal miRNAs, without relying on the gut microbiota. Specifically, stachyose significantly mitigates CY-caused damage to the intestinal permeability, oxidative stress, and the structure of intestinal villi and crypts in pseudo-germ-free (PGF) mice. The immunofluorescence staining and qPCR analyses show that stachyose treatment restores CY-caused abnormal changes on the levels of tight junction proteins including MUC2, Occludin, Claudin-1, and ZO-1, and pro-inflammatory cytokines including TNF-α, IL-1β, and IL-2. Furthermore, by conducting fecal miRNA transplantation experiment, we further demonstrated that, similar to stachyose, stachyose-shaped intestinal miRNAs protect against CY-induced intestinal mucosal damage in PGF mice. In summary, this study provides new scientific evidence for the direct interaction between nondigestible stachyose and the proximal small intestine. It also opens new avenues for further investigation into the systemic nutritional functions of stachyose, particularly the health benefits of stachyose in the upper gastrointestinal tract.},
}

Animals
*Cyclophosphamide/adverse effects/toxicity
*Gastrointestinal Microbiome/drug effects
*MicroRNAs/metabolism/genetics
*Intestinal Mucosa/drug effects/pathology/metabolism
*Oligosaccharides/pharmacology
Mice
*Intestine, Small/drug effects/pathology/metabolism
*Exosomes/metabolism/drug effects/genetics
Male
Oxidative Stress/drug effects
Mice, Inbred C57BL
Cytokines/metabolism
Prebiotics
Permeability
Germ-Free Life
Tight Junction Proteins/metabolism

@article {pmid40253185,
year = {2025},
author = {Yang, H and Zhao, Y and Zhang, R and Zhao, L and Yang, H and Liao, X},
title = {CiLi (Rosa roxburghii Tratt.) polyphenols improve colitis via gut microbiota-lipid mediator-immunity axis.},
journal = {Food research international (Ottawa, Ont.)},
volume = {209},
number = {},
pages = {116257},
doi = {10.1016/j.foodres.2025.116257},
pmid = {40253185},
issn = {1873-7145},
mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Polyphenols/pharmacology ; *Colitis/drug therapy/chemically induced/microbiology/immunology ; Mice ; Mice, Inbred C57BL ; Oxidative Stress/drug effects ; Dextran Sulfate ; Dysbiosis ; Male ; Lipid Metabolism/drug effects ; Disease Models, Animal ; Colon/drug effects ; Fatty Acids, Volatile ; },
abstract = {Dysbiosis of gut microbiome is one of the most important factors leading to inflammatory bowel disease (IBD). Intake of phytochemicals from fruits and vegetables is an effective way to improve IBD, but how these bioactivators regulate gut microbiota to exert healthy effects remains unclear. Here, we found that pretreatment with CiLi juice, particularly its polyphenol component, alleviated dextran sulfate sodium (DSS)-induced colitis while preserving intestinal barrier integrity. CiLi polyphenols (CL_PP) reduced inflammation and oxidative stress in colon tissue and enriched fecal short-chain fatty acids. Importantly, CL_PP significantly regulated the gut microbiome diversity, increasing beneficial bacteria (e.g., Clostridia_UCG-014, f_Muribaculaceae and Ileibacterium_valens) while decreasing harmful bacteria (Escherichia-Shigella and Romboutsia). Multiomics analysis revealed that CL_PP upregulated bioactive lipid metabolites, particularly those derived from polyunsaturated fatty acids (e.g., resolvin D2, prostaglandin A1, and glycerophosphocholine) related gene expressions (Pltp, Alox15 and Pld4). Additionally, CL-PP downregulated the oxidative stress markers (oxidized glutathione and glutathione peroxidase 3), and immune cell markers (CD8 and CD68). Fecal microbiota transplantation confirmed that the fecal microbiota from CL_PP-treated mice exhibited anti-colitis effects. These effects were diminished in antibiotic-treated mice, underscoring the importance of the gut microbiota in mediating the CL_PP's anti-inflammatory benefits. This study suggests that CL_PP is a potential modulator of gut microbiome dysbiosis for the prevention and treatment of colitis.},
}

*Gastrointestinal Microbiome/drug effects
Animals
*Polyphenols/pharmacology
*Colitis/drug therapy/chemically induced/microbiology/immunology
Mice
Mice, Inbred C57BL
Oxidative Stress/drug effects
Dextran Sulfate
Dysbiosis
Male
Lipid Metabolism/drug effects
Disease Models, Animal
Colon/drug effects
Fatty Acids, Volatile

@article {pmid40253128,
year = {2025},
author = {Zuo, G and Li, M and Guo, X and Wang, L and Yao, Y and Huang, JA and Liu, Z and Lin, Y},
title = {Fu brick tea supplementation ameliorates non-alcoholic fatty liver disease and associated endotoxemia via maintaining intestinal homeostasis and remodeling hepatic immune microenvironment.},
journal = {Food research international (Ottawa, Ont.)},
volume = {209},
number = {},
pages = {116207},
doi = {10.1016/j.foodres.2025.116207},
pmid = {40253128},
issn = {1873-7145},
mesh = {*Non-alcoholic Fatty Liver Disease/immunology ; Animals ; *Endotoxemia ; Gastrointestinal Microbiome/drug effects ; Male ; Humans ; Homeostasis/drug effects ; *Tea/chemistry ; *Liver/immunology/drug effects/metabolism ; Rats ; Diet, High-Fat/adverse effects ; Caco-2 Cells ; Dysbiosis ; Rats, Sprague-Dawley ; *Dietary Supplements ; Intestines ; },
abstract = {Non-alcoholic fatty liver disease (NAFLD) is a prevalent disorder of excessive fat accumulation and inflammation in the liver that currently lacks effective therapeutic interventions. Fu brick tea (FBT) has been shown to ameliorate liver damage and modulate gut microbiota dysbiosis in NAFLD, but the potential mechanisms have not been comprehensively elucidated, especailly whether its hepatoprotective effects are determined to depend on the homeostasis of gut microbiota, intestinal barrier function and hepatic immune microenvironment. In this study, our results further demonstrated that FBT not only alleviated NAFLD symptoms and related endotoxemia in high-fat diet (HFD)-fed rats, but also attenuated intestinal barrier dysfunction and associated inflammation, also confirmed in Caco-2 cell experiment. Meanwhile, FBT intervention significantly relieved HFD-induced gut microbiota dysbiosis, characterized by increased diversity and composition, particularly facilitating beneficial microbes, including short chain fatty acids (SCFAs) and bile acids producers, such as Blautia and Fusicatenibacter, and inhibiting Gram-negative bacteria, such as Prevotella_9 and Phascolarctobacterium. Also, the gut microbiota-dependent hepatoprotective effects of FBT were verified by fecal microbiota transplantation (FMT) experiment. Thus, the beneficial moulation of gut microbiota altered by FBT in levels of SCFAs, bile acids and lipopolysaccharides, intestinal barrier function and TLR4/NF-κB pathway contributed to alleviate liver steatosis and inflammation. Additionally, the hepatoprotective effects of FBT was further demonstrated by suppressing Kupffer cell activation and regulating lipid metabolism using an ex vivo model of liver organoid. Therefore, FBT supplementation can maintain intenstinal homeostasis and remodel hepatic immune microenvironment to prevent NAFLD and associated endotoxemia.},
}

*Non-alcoholic Fatty Liver Disease/immunology
Animals
*Endotoxemia
Gastrointestinal Microbiome/drug effects
Male
Humans
Homeostasis/drug effects
*Tea/chemistry
*Liver/immunology/drug effects/metabolism
Rats
Diet, High-Fat/adverse effects
Caco-2 Cells
Dysbiosis
Rats, Sprague-Dawley
*Dietary Supplements
Intestines

@article {pmid40252900,
year = {2025},
author = {Sahebi, K and Arianejad, M and Azadi, S and Hosseinpour-Soleimani, F and Kazemi, R and Tajbakhsh, A and Negahdaripour, M},
title = {The Interplay between Gut Microbiome, Epigenetics, and Substance Use Disorders: from Molecular to Clinical Perspectives.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {177630},
doi = {10.1016/j.ejphar.2025.177630},
pmid = {40252900},
issn = {1879-0712},
abstract = {Substance use disorders (SUDs) involve a complex series of central and peripheral pathologies, leading to impairments in cognitive, behavioral, and physiological processes. Emerging evidence indicates a more significant role for the microbiome-gut-brain axis (MGBA) in SUDs than previously recognized. The MGBA is interconnected with various body systems by producing numerous metabolites, most importantly short-chain fatty acids (SCFAs), cytokines, and neurotransmitters. These mediators influence the human body's epigenome and transcriptome. While numerous epigenetic alterations in different brain regions have been reported in SUD models, the intricate relationship between SUDs and the MGBA suggests that the gut microbiome may partially contribute to the underlying mechanisms of SUDs. Promising results have been observed with gut microbiome-directed interventions in patients with SUDs, including prebiotics, probiotics, antibiotics, and fecal transplantation. Nonetheless, the long-term epigenetic effects of these interventions remain unexplored. Moreover, various confounding factors and study limitations have hindered the identification of molecular mechanisms and clinical applications of gut microbiome interventions in SUDs. In the present review, we will (i) provide a comprehensive discussion on how the gut microbiome influences SUDs, with an emphasis on epigenetic alterations; (ii) discuss the current evidence on the bidirectional relationship of gut microbiome and SUDs, highlighting potential targets for intervention; and (iii) review recent advances in gut microbiome-directed therapies, along with their limitations and future directions.},
}

@article {pmid40252828,
year = {2025},
author = {Zhao, Y and Zhao, W and Chai, X and Sun, P and Huang, J and Guo, X and Zhang, L and Ren, D and Yi, C and Zhu, X and Zhao, S},
title = {Reshaping the gut microbiota: A novel oppinion of Eucommiae cortex polysaccharide alleviate learning and memory impairments in Alzheimer's disease.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2025.04.025},
pmid = {40252828},
issn = {2090-1224},
abstract = {BACKGROUND: Alzheimer's disease (AD), which is a chronic neurodegenerative disorder, is marked by the progressive deteriorations in learning and memory capabilities. The microbiota-gut-brain axis has come to be regarded as a crucial element in relation to the pathogenesis as well as the treatment of AD. Eucommiae cortex polysaccharides (EPs), being among the most plentiful substances present in the Eucommiae cortex, show the potential to exert immunomodulatory and neuroprotective function. However, whether EPs are protective against AD and their mechanism of action remain to be investigated OBJECTIVES: We hypothesize that EPs can regulate brain glutamine metabolism through gut microbiota and the butyric acid metabolized by them, improve oxidative stress and autophagy in the brain, and thus alleviate AD.

METHODS: In the present study, we used EPs (0.25 % w/w in food) and fecal microbiota transplantation, as well as butyrate supplementation (0.1 M in water), to intervene in AD mice. Multi-omics were used to determine the mechanism by which EPs improve AD-related learning and memory impairments.

RESULTS: Our results suggest that EPs, functioning as a prebiotic, alleviated learning and memory impairments in AD mice. Mechanistically, EPs are able to reshape the gut microbiota, promote the growth of gut microbiota involved in short-chain fatty acid metabolism, particularly butyrate-producing microbes. The butyrate produced by these microbes improves the brain microenvironment by modulating oxidative stress and autophagy mediated by brain glutamate metabolism, improving learning and memory impairments in AD mice, and inhibiting the formation and deposition of beta-amyloid proteins. Fecal microbiota transplantation (FMT) and butyrate supplementation further confirm this conclusion.

CONCLUSIONS: Our results highlighted that EPs can alleviate learning and memory impairments in AD with a gut microbiota-dependent manner and that butyric acid metabolized by butyric acid-metabolizing bacteria in the gut plays a central role in regulating brain glutamine metabolism to improve brain microenvironmental homeostasis. Meanwhile, the present study provides new insights into the treatment of AD with natural products.},
}

@article {pmid40252432,
year = {2025},
author = {Wang, R and Gan, C and Gong, B and Huang, J and Lou, Z and Wang, D and Yan, R and Li, G and Xiong, T and Guo, J},
title = {Tongfu Xingshen capsule alleviates stroke-associated pneumonia-induced multiple organ injuries by modulating the gut microbiota and sphingolipid metabolism.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {142},
number = {},
pages = {156756},
doi = {10.1016/j.phymed.2025.156756},
pmid = {40252432},
issn = {1618-095X},
abstract = {BACKGROUND: Stroke-associated pneumonia (SAP) represents a major complication and cause of death in patients suffering from intracerebral haemorrhage (ICH). It's urgent to develop more effective therapeutic strategies. Tongfu Xingshen capsule (TFXS) is a traditional Chinese medicine that has been utilised in clinical studies for the treatment of ICH and SAP, but the underlying mechanisms remain to be fully elucidated.

PURPOSE: This study aims to explore the therapeutic effects and mechanisms of TFXS on SAP using an aspiration-induced Klebsiella pneumoniae infection-complicating ICH rat model and an intratracheal injection of lipopolysaccharide (LPS)-induced acute lung injury-complicating ICH rat model.

METHODS: The chemical components of TFXS are characterised using ULPLC-Q Exactive-Orbitrap-MS. The therapeutic effects of TFXS are evaluated through neurological scoring, histopathology analysis, magnetic resonance imaging, immunofluorescence, Alcian blue-nuclear fast red staining, myeloperoxidase activity assessment, leukocyte counting, and ELISA. To investigate the underlying mechanisms, faecal microbiota transplantation, 16S rRNA sequencing, untargeted metabolomics, and Spearman correlation analyses are performed.

RESULTS: A total of 60 compounds are identified in TFXS. Pharmacological analysis reveals that TFXS significantly mitigates neurological deficits, enhances haematoma absorption, attenuates brain damage and neuroinflammation, and improves pneumonia and pulmonary injury by reducing the infiltration of leukocytes and lymphocytes, as well as suppressing the infiltration and overactivation of neutrophils. TFXS also alleviates intestinal lesions and barrier damage by increasing acidic mucins and the expression of the tight junction protein zonula occludens-1 (ZO-1). Mechanistically, TFXS ameliorates pneumonia and pulmonary injury in a gut microbiota-dependent manner. It reverses sphingolipid metabolism disorders and ceramide accumulation by modulating SAP-induced gut microbiota dysbiosis and enhancing the abundance of probiotics, including Lactobacillus, Allobaculum and Enterococcus.

CONCLUSION: TFXS exerts anti-inflammatory and protective effects on the brain, lung, and gut by alleviating gut microbiota dysbiosis and sphingolipid metabolism disorders. These findings highlight TFXS as a promising therapeutic candidate for the treatment of SAP.},
}

@article {pmid40252102,
year = {2025},
author = {Vassallo, GA and Dionisi, T and De Vita, V and Augello, G and Gasbarrini, A and Pitocco, D and Addolorato, G},
title = {The role of fecal microbiota transplantation in diabetes.},
journal = {Acta diabetologica},
volume = {},
number = {},
pages = {},
pmid = {40252102},
issn = {1432-5233},
abstract = {Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy for modulating gut dysbiosis in diabetes mellitus. This review critically evaluates preclinical and clinical evidence on FMT in type 1 (T1D) and type 2 diabetes (T2D). Studies suggest that FMT can restore microbial diversity, improve glycemic control, and modulate immune responses, with varying effects across diabetes subtypes. In T1D, preclinical models demonstrate that FMT influences regulatory T-cell expansion and β-cell preservation, though clinical translation remains limited. In T2D, FMT has shown transient improvements in insulin sensitivity, with sustained effects observed only in patients with specific microbiome signatures. However, heterogeneity in patient responses, donor variability, and methodological limitations complicate its clinical application. This review highlights the interplay between FMT, immune modulation, and microbial metabolism, advocating for phenotype-stratified trials and multi-omics integration to enhance therapeutic precision.},
}

@article {pmid40251524,
year = {2025},
author = {Pan, Q and Guo, F and Chen, J and Huang, H and Huang, Y and Liao, S and Xiao, Z and Wang, X and You, L and Yang, L and Huang, X and Xiao, H and Liu, HF and Pan, Q},
title = {Exploring the role of gut microbiota modulation in the long-term therapeutic benefits of early MSC transplantation in MRL/lpr mice.},
journal = {Cellular & molecular biology letters},
volume = {30},
number = {1},
pages = {49},
pmid = {40251524},
issn = {1689-1392},
support = {82070757//National Natural Science Foundation of China/ ; 82270770//National Natural Science Foundation of China/ ; 82400841//National Natural Science Foundation of China/ ; 2022B1212030003//Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases/ ; 2022A1515220028//Guangdong Basic and Applied Basic Research Foundation Enterprise Joint Fund/ ; 2021A05060//Zhanjiang Science and Technology Project (Competitive)/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome ; Mice, Inbred MRL lpr ; *Mesenchymal Stem Cell Transplantation/methods ; *Lupus Erythematosus, Systemic/therapy/microbiology ; Mice ; Fecal Microbiota Transplantation ; Humans ; Mesenchymal Stem Cells/cytology/metabolism ; Female ; Disease Models, Animal ; Receptors, Aryl Hydrocarbon/metabolism ; Cytokines/metabolism ; },
abstract = {BACKGROUND: Systemic lupus erythematosus (SLE), influenced by gut microbiota dysbiosis, is characterized by autoimmune and inflammatory responses. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation is an effective and safe treatment for refractory or severe SLE; however, the long-term efficacy and mechanisms of early hUC-MSC therapeutic benefits in SLE need further investigation.

METHODS: Here, lupus-prone MRL/MpJ-Fas[lpr] (MRL/lpr) mice were divided into three groups: the control (Ctrl) group received saline injections, while the MSC and MSC-fecal microbiota transplantation (FMT) groups received early hUC-MSC transplants at weeks 6, 8, and 10. The MSC-FMT group also underwent FMT from the Ctrl group between weeks 9 and 13.

RESULTS: Our results showed that early MSC treatment extended therapeutic effects up to 12 weeks, reducing autoantibodies, proinflammatory cytokines, B cells, and improving lupus nephritis. It also modulated the gut microbiota, increasing the abundance of beneficial bacteria, such as Lactobacillus johnsonii and Romboutsia ilealis, which led to higher levels of plasma tryptophan and butyrate metabolites. These metabolites activate the aryl hydrocarbon receptor (AHR), upregulate the Cyp1a1 and Cyp1b1 gene, enhance the zonula occludens 1 (ZO-1) protein, promote intestinal repair, and mitigate SLE progression. Notably, FMT from lupus mice significantly reversed hUC-MSC benefits, suggesting that the modulation of the gut microbiota plays a crucial role in the therapeutic response observed in MRL/lpr mice.

CONCLUSIONS: This research innovatively explores the early therapeutic window for MSCs in SLE, highlighting the partial mechanisms through which hUC-MSCs modulate the gut microbiota-tryptophan-AHR axis, thereby ameliorating SLE symptoms.},
}

Animals
*Gastrointestinal Microbiome
Mice, Inbred MRL lpr
*Mesenchymal Stem Cell Transplantation/methods
*Lupus Erythematosus, Systemic/therapy/microbiology
Mice
Fecal Microbiota Transplantation
Humans
Mesenchymal Stem Cells/cytology/metabolism
Female
Disease Models, Animal
Receptors, Aryl Hydrocarbon/metabolism
Cytokines/metabolism