@article {pmid40447159,
year = {2025},
author = {Jeong, SH and Vasavada, SP and Lashner, B and Werneburg, GT},
title = {Fecal microbiota transplant is associated with resolution of recurrent urinary tract infection.},
journal = {Urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.urology.2025.05.052},
pmid = {40447159},
issn = {1527-9995},
abstract = {OBJECTIVE: To investigate the association of fecal microbiota transplant (FMT) therapy, an effective treatment for recurrent C. difficile colitis, with resolution of recurrent UTI (rUTI).

METHODS: A prospectively accrued database of patients who underwent FMT for recurrent Clostridoides difficile colitis was retrospectively reviewed for individuals with rUTI in the two years prior to FMT. Recurrent UTI status (defined as two UTI episodes in six months or three UTI episodes in one year) and UTI frequency in the two years prior to the FMT were compared to those in the two year follow up period after FMT using the two-tailed Wilcoxin matched pairs signed rank test. A p-value <0.05 was considered statistically significant.

RESULTS: Of 11 patients who had rUTI in the two years preceding FMT, no patient had rUTI over the follow up period following FMT (p=0.001). The average number of UTIs in the two years prior to FMT was 3.7 (range 2-6), and the average number of UTIs in the follow up period was 0.27 (range 0-1) (p=0.001). The Kaplan-Meier estimate, the median time to UTI recurrence, was 19.6 months (95% CI: 15.2 - 23.9). There was no marked difference in antibiotic susceptibility profiles before and after FMT.

CONCLUSIONS: FMT was associated with resolution of rUTI and reduction in UTI frequency in this cohort. The results of this study support the hypothesis that modulation of the gut microbiome may reduce rUTI risk, and support a clinical trial to further assess the safety and efficacy of FMT for rUTI.},
}

@article {pmid40446472,
year = {2025},
author = {Chen, L and Ahmad, M and Li, J and Li, J and Yang, Z and Hu, C},
title = {Gut microbiota manipulation to mitigate the toxicities of environmental pollutants.},
journal = {Aquatic toxicology (Amsterdam, Netherlands)},
volume = {285},
number = {},
pages = {107425},
doi = {10.1016/j.aquatox.2025.107425},
pmid = {40446472},
issn = {1879-1514},
abstract = {The gut microbiome, commonly termed as a "super organ", plays a crucial role in the modulation of various biological functions associated with metabolism, endocrinology, immunology, and neurology. However, gut microbiome is extremely susceptible to the risks of environmental pollutants, which will drive gut microbial community to dysbiosis. Simultaneously, restoring healthy gut microbiome can protect the hosts from the health hazards of pollutants. It is increasingly verified that probiotics, prebiotics, and fecal microbiota transplantation (FMT) are efficacious measures to manipulate and remediate gut microecosystem. Among various probiotic strains, lactic acid bacteria are the most extensively applied in toxicity mitigation, which is characterized by shaping gut microbiota structure and metabolism, increasing gut epithelial barrier integrity, promoting fecal elimination of pollutants, suppressing inflammation symptoms, and then improving host systemic physiology. Prebiotics are dietary fibers that cannot be digested by the host, but can be fermented by specific gut bacteria to produce short chain fatty acids, which are identified as the key effect molecules in the manifestation of prebiotic toxicity mitigation actions. In addition, by transplanting the entire community of healthy gut microbiota, FMT also shows effective performances in counteracting the adverse effects of environmental pollutants and recovering host animal health. Intriguingly, FMT from young donors is even found to inhibit the toxic disturbances in healthy aging progression. Based on current evidence, this review summarized the findings about using probiotics, prebiotics, and FMT to manipulate gut microbiota and alleviate the health impairment of environmental pollutants. Key mechanistic insights into the interactive behaviors were underlined. Furthermore, the challenges and future directions in harnessing gut microbiota manipulation as a novel therapeutic approach to mitigate pollutant-induced toxicities were postulated. This review is expected to advocate comprehensive scientific research and literally favor the application of health intervention strategies.},
}

@article {pmid40446358,
year = {2025},
author = {Porcari, S and Ng, SC and Zitvogel, L and Sokol, H and Weersma, RK and Elinav, E and Gasbarrini, A and Cammarota, G and Tilg, H and Ianiro, G},
title = {The microbiome for clinicians.},
journal = {Cell},
volume = {188},
number = {11},
pages = {2836-2844},
doi = {10.1016/j.cell.2025.04.016},
pmid = {40446358},
issn = {1097-4172},
mesh = {Humans ; *Microbiota ; Clinical Trials as Topic ; },
abstract = {Despite promising evidence in diagnostics and therapeutics, microbiome research is not yet implemented into clinical medicine. Several initiatives, including the standardization of microbiome research, the refinement of microbiome clinical trial design, and the development of communication between microbiome researchers and clinicians, are crucial to move microbiome science toward clinical practice.},
}

Humans
*Microbiota
Clinical Trials as Topic

@article {pmid40444969,
year = {2025},
author = {Xie, J and Kim, T and Liu, Z and Panier, H and Bokoliya, S and Xu, M and Zhou, Y},
title = {Young gut microbiota transplantation improves the metabolic health of old mice.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0160124},
doi = {10.1128/msystems.01601-24},
pmid = {40444969},
issn = {2379-5077},
abstract = {UNLABELLED: The gut microbiota evolves over a lifetime and significantly impacts the aging process. Targeting the gut microbiota represents a novel avenue to delay aging and aging-related physical and mental decline. However, the underlying mechanism by which the microbiota modulates the aging process, particularly age-related physical and behavioral changes is not completely understood. We conducted fecal microbiota transplantation (FMT) from young or old male donor mice to the old male recipients. Old recipients with young microbiota had a higher alpha diversity than the old recipients with old microbiota. Compared to FMT with old microbiota, FMT with young microbiota reduced body weight and prevented fat accumulation in the old recipients. FMT with young microbiota also lowered frailty, increased grip strength, and alleviated depression and anxiety-like behavior in the old recipients. Consistent with observed physical changes, untargeted metabolomic analysis of serum and stools revealed that FMT with young microbiota lowered age-related long-chain fatty acid levels and increased amino acid levels in the old recipients. Bulk RNAseq analysis of the amygdala of the brain showed that FMT with young microbiota downregulated inflammatory pathways and upregulated oxidative phosphorylation in the old recipients. Our results demonstrate that FMT with young microbiota has substantial positive influences on age-related body composition, frailty, and psychological behaviors. These effects are associated with changes in host lipid and amino acid metabolism in the periphery and transcriptional regulation of neuroinflammation and energy utilization in the brain.

IMPORTANCE: The gut microbiome is a key hallmark of aging. Fecal microbiota transplantation (FMT) using young microbiota represents a novel rejuvenation strategy to delay aging. Our study provides compelling evidence that transplanting microbiota from young mice significantly improved grip strength, frailty, and body composition in aged recipient mice. At the molecular level, FMT improved aging-related metabolic markers in the gut and circulation. Additionally, FMT from young microbiota rejuvenated the amygdala of the aged brain by downregulating inflammatory pathways. This study highlights the importance of metabolic reprogramming via young microbiota FMT in improving physical and metabolic health in elderly recipients.},
}

@article {pmid40443229,
year = {2025},
author = {Lee, MA and Slead, T and Suchodolski, J and Tolbert, MK and Marsilio, S},
title = {Adverse events after fecal microbiota transplantation in nine cats: a case series.},
journal = {Journal of feline medicine and surgery},
volume = {27},
number = {5},
pages = {1098612X251337274},
doi = {10.1177/1098612X251337274},
pmid = {40443229},
issn = {1532-2750},
mesh = {Animals ; Cats ; *Cat Diseases/therapy ; *Fecal Microbiota Transplantation/veterinary/adverse effects ; Female ; Male ; Diarrhea/veterinary/therapy ; },
abstract = {This case series describes nine cases of fecal microbiota transplantation in cats and associated adverse events (AEs) from two tertiary referral hospitals. AEs were graded according to criteria established by the Veterinary Cooperative Oncology Group's Common Terminology Criteria for Adverse Events (VCOG-CTCAE v2) for clinical trials. Cats received 5-6 g/kg donor feces 2-6 times for chronic enteropathy (n = 4) or therapy-resistant diarrhea (n = 5). AEs included lethargy (n = 7), vomiting (n = 5), diarrhea (n = 5), weight loss (n = 5), inappetence (n = 5), dehydration (n = 5), abdominal pain (n = 2), gastroenterocolitis based on ultrasound (n = 2) and anorexia (n = 1). Temperatures of up to 103.4°F were noted but did not meet the criteria for AEs (>103.5°F). Cats responded to antimicrobials (metronidazole, marbofloxacin), anthelmintics (fenbendazole), supportive care with fluids, ondansetron and mirtazapine (n = 5), gabapentin (n = 2), pradofloxacin (n = 1) or self-resolved (n = 1). Positive response to fecal microbiota transplantation for the presenting complaint was seen in eight cats (seven complete, one partial and transient).Relevance and novel informationFecal microbiota transplantation is increasing in usage among companion animals. Fecal microbiota transplantations in cats have been rarely described in the literature as have AEs after administration. This case series represents the first description of AEs after fecal microbiota transplantation in cats.},
}

Animals
Cats
*Cat Diseases/therapy
*Fecal Microbiota Transplantation/veterinary/adverse effects
Female
Male
Diarrhea/veterinary/therapy

@article {pmid40443227,
year = {2025},
author = {Green, GBH and Cox-Holmes, AN and Marlow, GH and Potier, ACE and Wang, Y and Zhou, L and Chen, D and Morrow, CD and McFarland, BC},
title = {Human microbiota influence the immune cell composition and gene expression in the tumor environment of a murine model of glioma.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2508432},
doi = {10.1080/19490976.2025.2508432},
pmid = {40443227},
issn = {1949-0984},
mesh = {Animals ; *Glioma/immunology/microbiology/genetics ; Mice ; Humans ; *Gastrointestinal Microbiome/immunology ; Disease Models, Animal ; *Tumor Microenvironment/immunology/genetics ; *Brain Neoplasms/immunology/microbiology/genetics ; Cell Line, Tumor ; Feces/microbiology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; RNA, Ribosomal, 16S/genetics ; Bacteria/classification/genetics/isolation & purification ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Immunotherapy has shown success against other cancers but not glioblastoma. Previous data has revealed that microbiota influences anti-PD-1 efficacy. We have previously found that, when using gnotobiotic mice transplanted with human fecal microbiota, the gut microbial composition influenced the response to anti-PD-1 in a mouse model of glioma. However, the role of the human microbiota in influencing the mouse immune cells in the glioma microenvironment and anti-PD-1 response was largely unknown. Using two distinct humanized microbiome (HuM) lines, we used single-cell RNA sequencing (scRNA-seq) to determine how gut microbiota affect immune infiltration and gene expression in a murine glioma model.

METHODS: 16S rRNA sequencing was performed on fecal samples from HuM1 (H1) and HuM2 (H2) mice. Mice were intracranially injected with murine glioma cells (GL261), and on day 13 treated with one dose of isotype control or anti-PD1. Mice were euthanized on day 14 for analysis of all immune cells in the tumors by scRNA-seq.

RESULTS: HuM1 and HuM2 mice had different microbial populations, with HuM1 being primarily dominated via Alistipes, and HuM2 being primarily composed of Odoribacter. Sc-RNA-seq of the tumor immune cells revealed 21 clusters with significant differences between H1 and H2 samples with a larger population of M1 type macrophages in H1 samples. Gene expression analysis revealed higher expression of inflammatory markers in the M1 population in H2 mice treated with anti-PD-1.

CONCLUSIONS: Microbial gut communities influence the presence and gene activation patterns of immune cells in the brain tumors of mice both under control (isotype) and following anti-PD-1 treatment.},
}

Animals
*Glioma/immunology/microbiology/genetics
Mice
Humans
*Gastrointestinal Microbiome/immunology
Disease Models, Animal
*Tumor Microenvironment/immunology/genetics
*Brain Neoplasms/immunology/microbiology/genetics
Cell Line, Tumor
Feces/microbiology
Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology
RNA, Ribosomal, 16S/genetics
Bacteria/classification/genetics/isolation & purification
Mice, Inbred C57BL

@article {pmid40441587,
year = {2025},
author = {Luo, M and Du, Y and Liu, X and Zhang, S and Zhu, W and Liu, K and Ren, X and Zhang, N},
title = {Fecal Microbiota Transplantation Alleviates Cirrhotic Portal Hypertension in Rats via Butyrate-Mediated HDAC3 Inhibition and PI3K/Akt/eNOS Signaling Regulation.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {177781},
doi = {10.1016/j.ejphar.2025.177781},
pmid = {40441587},
issn = {1879-0712},
abstract = {BACKGROUND: Portal hypertension (PHT) is a severe complication of liver cirrhosis, with limited therapeutic options. Despite emerging evidence linking gut microbiota dysbiosis to PHT progression, the mechanisms by which microbial metabolites modulate liver sinusoidal endothelial cells (LSECs) dysfunction and the therapeutic efficacy of fecal microbiota transplantation (FMT) remain poorly understood. This study investigated the potential of FMT to alleviate PHT in cirrhotic rats, exploring the underlying mechanisms involving butyrate-mediated HDAC3 inhibition and PI3K/Akt/eNOS signaling regulation in LSECs.

METHODS: Cirrhosis with PHT was induced in Sprague-Dawley rats via intraperitoneal carbon tetrachloride injection, followed by FMT or butyrate supplementation via oral gavage. Analyses included portal hemodynamic measurements, gut microbiota sequencing, serum SCFA metabolomics profiling, HDAC3 activity assays, NO level quantification, and assessments of liver fibrosis, liver function, and LSEC ultrastructure. LSECs were isolated for PI3K/Akt/eNOS signaling analysis via qRT-PCR, Western blotting, and immunofluorescence staining.

RESULTS: A two-week FMT intervention in cirrhotic rats with PHT enriched butyrate-producing bacteria and increased serum butyrate levels, which were associated with reduced portal pressure and intrahepatic vascular resistance, without affecting liver fibrosis, function, or LSEC ultrastructure. FMT reduced HDAC3 activity by 2.17-fold and increased Akt and eNOS phosphorylation in primary LSECs by 1.69-fold and 1.25-fold, respectively, elevating plasma NO levels by 1.66-fold compared to untreated controls. In vitro experiments with primary LSECs confirmed these butyrate-mediated effects.

CONCLUSION: FMT alleviates cirrhotic PHT through butyrate-mediated HDAC3 inhibition and subsequent PI3K/Akt/eNOS signaling activation in LSECs, highlighting the therapeutic potential of targeting the gut-liver axis via microbial metabolites for PHT management.},
}

@article {pmid40441086,
year = {2025},
author = {Sharma, P and Das, S and Rituraj, R and Bhagyashree, B},
title = {Understanding oncobiosis in ovarian cancer: Emerging concepts in tumor progression.},
journal = {Pathology, research and practice},
volume = {271},
number = {},
pages = {156026},
doi = {10.1016/j.prp.2025.156026},
pmid = {40441086},
issn = {1618-0631},
abstract = {Ovarian cancer is a leading cause of gynecologic cancer mortality and has recently been linked to microbial dysbiosis or oncobiosis. Tumorigenesis is a highly complex process, and recent research has revealed numerous new mechanisms showing how tumors interact with their surrounding microenvironment. The inclusion of microbiome studies has significantly advanced this field revealing the important role microbes play, not only in maintaining normal physiological functions of the human body but also in influencing oncogenic pathways. This expanding knowledge is deepening our understanding of tumor pathophysiology and is helping to create new diagnostic, prognostic, therapeutic and preventive strategies for specific cancers. This review explores the role of the microbiome in ovarian carcinogenesis, focusing on its interaction with the tumor microenvironment (TME) and its influence on inflammation, immune regulation and metabolic signaling. This review studied dysbiosis in several anatomical compartments such as the gut, oral cavity, lower and upper genital tracts and ovarian tissues, in relation to ovarian oncobiosis. Emerging clinical implications of these studies include the use of microbial profiles as diagnostic or prognostic biomarkers. Therapeutic strategies such as fecal microbiota transplantation and probiotics are also discussed for their ability to restore microbial balance and enhance treatment efficacy. This review highlights the importance of continued research to explore causal relationships between the microbiome and tumorigenesis, positioning microbiome studies as promising tools in ovarian cancer management and improving patient care.},
}

@article {pmid40438840,
year = {2025},
author = {Saleem, MM and Masood, S and Rahmatullah, MM and Ayesha Imdad, I and Mohammed Aslam Sange, A and Nasr, D},
title = {Gut Microbiota Dysbiosis and Its Role in the Development of Irritable Bowel Syndrome.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e83084},
pmid = {40438840},
issn = {2168-8184},
abstract = {The gut microbiota refers to the diverse community of symbiotic and pathogenic microorganisms inhabiting the host digestive tract. This microbiome plays a vital role in maintaining the integrity of the digestive system. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) characterized by chronic abdominal pain and altered bowel habits. Although the pathophysiology of IBS remains unclear, recent studies suggest that the disruption of the gut microbiota (dysbiosis) may play a significant role. This study aims to examine the role of the gut microbiota in the development of IBS, analyze factors influencing the gut microbiome, and explore the potential for microbiota-targeted therapies. Relevant literature published from 2014 until 2024 was sourced from Google Scholar, PubMed, and Scopus using the keywords "microbiome", "irritable bowel syndrome", "dysbiosis", "faecal transplantation", and "probiotics". This review revealed consistent evidence of gut microbiota dysbiosis in individuals with IBS, characterized by altered microbial diversity, composition, and metabolic function. Contributing factors included a reduced abundance of beneficial commensals, overgrowth of potentially pathogenic species, and disrupted host-microbiota interactions. This dysbiosis was also frequently associated with symptom severity and specific IBS subtypes. Emerging evidence further highlights the role of diet, stress, and genetic factors in modulating gut microbiota and influencing IBS development. The growing body of research supports a strong link between dysbiosis and the pathogenesis and symptomatology of IBS. Understanding the microbial underpinnings of IBS opens avenues for potential diagnostic biomarkers and innovative therapeutic interventions aimed at restoring a balanced gut microbiota. However, further research is needed to elucidate the underlying mechanisms and translate these insights into effective clinical strategies for the management of IBS. This review underscores the significance of gut microbiota in IBS and its potential as a target for future therapeutic interventions.},
}

@article {pmid40438215,
year = {2025},
author = {Hanna, A and Abbas, H and Yassine, F and AlBush, A and Bilen, M},
title = {Systematic review of gut microbiota composition, metabolic alterations, and the effects of treatments on PCOS and gut microbiota across human and animal studies.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1549499},
pmid = {40438215},
issn = {1664-302X},
abstract = {INTRODUCTION: Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting around 12% of women globally, associated with infertility and various comorbidities. Emerging evidence suggests a crucial role of gut microbiota in PCOS pathophysiology, prompting research to investigate alterations in gut microbial composition in patients with PCOS.

METHODS: This systematic review aims to analyze human and animal studies that compare gut microbiota composition, gut-derived metabolites, and treatment interventions in PCOS patients versus healthy controls. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, yielding studies examining gut microbiota, metabolomic shifts, and treatment responses in PCOS models and human populations.

RESULTS: Our analysis revealed decreases in alpha diversity in PCOS patients, with more pronounced changes in beta diversity in animal models. Specific bacterial taxa, such as Bacteroides vulgatus, Escherichia-Shigella and Lactobacillus, showed implication in PCOS pathogenesis, suggesting potential microbial markers. Furthermore, discrepancies between human and animal studies show the need for humanized mouse models to bridge this gap. Interventions like probiotics and fecal microbiota transplantation (FMT) showed varying levels of efficacy, with FMT emerging as a more promising but invasive option, offering live bacteriotherapy as a potential therapeutic alternative. Alterations in gut-derived metabolites, including short-chain fatty acids and bile acids, highlighted the multifaceted nature of PCOS, with implications extending to metabolic, hormonal, and gut-brain axis disruptions.

DISCUSSION: In conclusion, PCOS exhibits complex interactions between gut microbiota and metabolic pathways, necessitating further research with standardized methods and larger sample sizes to elucidate the microbiome's role in PCOS.},
}

@article {pmid40437401,
year = {2025},
author = {Unrug-Bielawska, K and Sandowska-Markiewicz, Z and Pyśniak, K and Piątkowska, M and Czarnowski, P and Goryca, K and Mróz, A and Żeber-Lubecka, N and Wójcik-Trechcińska, U and Bałabas, A and Dąbrowska, M and Surynt, P and Radkiewicz, M and Mikula, M and Ostrowski, J},
title = {Western Diet and fecal microbiota transplantation alter phenotypic, liver fatty acids, and gut metagenomics and metabolomics in Mtarc2 knockout mice.},
journal = {Genes & nutrition},
volume = {20},
number = {1},
pages = {13},
pmid = {40437401},
issn = {1555-8932},
support = {2018/29/B/NZ7/00809//Narodowe Centrum Nauki/ ; },
}

@article {pmid40436727,
year = {2025},
author = {Qingsong, L},
title = {Comment on "Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection".},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2025.05.033},
pmid = {40436727},
issn = {0929-6646},
}

@article {pmid40433559,
year = {2025},
author = {Zhang, J and Chen, K and Chen, F},
title = {Exploring the impact of the liver-intestine-brain axis on brain function in non-alcoholic fatty liver disease.},
journal = {Journal of pharmaceutical analysis},
volume = {15},
number = {5},
pages = {101077},
pmid = {40433559},
issn = {2214-0883},
abstract = {This study investigates the molecular complexities of non-alcoholic fatty liver disease (NAFLD)-induced brain dysfunction, with a focus on the liver-intestine-brain axis and potential therapeutic interventions. The main objectives include understanding critical microbiota shifts in NAFLD, exploring altered metabolites, and identifying key regulatory molecules influencing brain function. The methods employed encompassed 16S ribosomal RNA (rRNA) sequencing to scrutinize stool microbiota in NAFLD patients and healthy individuals, non-targeted metabolomics using LC-MS to uncover elevated levels of deoxycholic acid (DCA) in NAFLD mice, and single-cell RNA sequencing (scRNA-seq) to pinpoint the pivotal gene Hpgd in microglial cells and its downstream Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Behavioral changes and brain function were assessed in NAFLD mice with and without Fecal microbiota transplantation (FMT) treatment, utilizing various assays and analyses. The results revealed significant differences in microbiota composition, with increased levels of Bacteroides in NAFLD patients. Additionally, elevated DCA levels were observed in NAFLD mice, and FMT treatment demonstrated efficacy in ameliorating liver function and brain dysfunction. Hpgd inhibition by DCA activated the JAK2/STAT3 pathway in microglial cells, leading to inflammatory activation, inhibition of mitochondrial autophagy, induction of neuronal apoptosis, and reduction in neuronal action potentials. This study elucidates the intricate molecular mechanisms underlying the liver-gut-brain axis in NAFLD, and the identification of increased DCA and the impact of JAK2/STAT3 signaling on microglial cells highlight potential therapeutic targets for addressing NAFLD-induced brain dysfunction.},
}

@article {pmid40431274,
year = {2025},
author = {Schiavone, N and Isoldi, G and Calcagno, S and Rovida, E and Antiga, E and De Almeida, CV and Lulli, M},
title = {Exploring the Gut Microbiota-Retina Axis: Implications for Health and Disease.},
journal = {Microorganisms},
volume = {13},
number = {5},
pages = {},
doi = {10.3390/microorganisms13051101},
pmid = {40431274},
issn = {2076-2607},
abstract = {The gut microbiota represents a rich and adaptive microbial network inhabiting the gastrointestinal tract, performing key functions in nutrient processing, immune response modulation, intestinal wall protection, and microbial defense. Its composition remains highly personalized and responsive to external influences, including lifestyle patterns, physical activity, body composition, and nutritional intake. The interactions of the gut microbiota with bodily systems are conventionally interpreted as broad systemic impacts on organ balance. Yet, emerging research-exemplified by the gut microbiota-brain axis-suggests the potential existence of more targeted and direct communication mechanisms. Dysbiosis, characterized by microbial ecosystem disturbance, generates multiple metabolic compounds capable of entering systemic circulation and reaching distant tissues, notably including ocular structures. This microbial imbalance has been associated with both systemic and localized conditions linked to eye disorders. Accumulating scientific evidence now supports the concept of a gut-retina axis, underscoring the significant role of microbiota disruption in generating various retinal pathologies. This review comprehensively investigates gut microbiota composition, functional dynamics, and dysbiosis-induced alterations, with specific focus on retinal interactions in age-related macular degeneration, diabetic retinopathy, glaucoma, and retinal artery occlusion. Moreover, the review explores microbiota-targeted therapeutic strategies, including precision nutritional interventions and microbial transplantation, as potential modulators of retinal disease progression.},
}

@article {pmid40431196,
year = {2025},
author = {Harder, JW and Ma, J and Collins, J and Alard, P and Jala, VR and Bodduluri, H and Kosiewicz, MM},
title = {Characterization of Sex-Based Differences in Gut Microbiota That Correlate with Suppression of Lupus in Female BWF1 Mice.},
journal = {Microorganisms},
volume = {13},
number = {5},
pages = {},
doi = {10.3390/microorganisms13051023},
pmid = {40431196},
issn = {2076-2607},
support = {Target Identification in Lupus Grant//Alliance for Lupus Research/ ; R01AR067188/NH/NIH HHS/United States ; },
abstract = {Systemic lupus erythematosus (SLE) is more prevalent in female mice and humans and is associated with microbiota dysbiosis. We analyzed the fecal microbiota composition in female and male NZBxNZWF1 (BWF1) mice, a model of SLE, using 16S RNA gene sequencing. Composition of gut microbiota differed between adult disease-prone female (pre-disease) and disease-resistant male mice. Transfer of male cecal contents by gavage into female mice suppressed kidney disease (decreased proteinuria) and improved survival. After our mouse colony was moved to a new barrier facility with similar housing, male cecal transplants failed to suppress disease in female recipients. After two years, the protective phenotype reemerged: male cecal transplants once again suppressed disease in female mice. We compared the gut microbiota composition in female and male BWF1 mice for the three different periods, during which the male microbiota either protected or failed to protect female recipients. In female vs. male mice and in female mice receiving male cecal transplants, we found Bacteroides was high, Clostridium was low (high Bacteroides/Clostridium ratio), and Alistipes was present during periods when male cecal transplants suppressed disease. These data suggest that specific bacterial populations may have opposing effects on disease suppression in a model of microbiota transplantation.},
}

@article {pmid40431182,
year = {2025},
author = {Matsumoto, H and Gu, T and Yo, S and Sasahira, M and Monden, S and Ninomiya, T and Osawa, M and Handa, O and Umegaki, E and Shiotani, A},
title = {Fecal Microbiota Transplantation Using Donor Stool Obtained from Exercised Mice Suppresses Colonic Tumor Development Induced by Azoxymethane in High-Fat Diet-Induced Obese Mice.},
journal = {Microorganisms},
volume = {13},
number = {5},
pages = {},
doi = {10.3390/microorganisms13051009},
pmid = {40431182},
issn = {2076-2607},
support = {JP 19K11484//Japanese Grant-in-Aid Scientific Reserach/ ; },
abstract = {The gut microbiota plays an important role in the development of colorectal tumors. However, the underlying mechanisms remain unclear. In this study, we examined the effects of fecal microbiota transplantation (FMT) on azoxymethane (AOM)-induced colorectal tumors in obese mice. We divided the study subjects into the following five groups: high-fat diet (HFD), normal diet (ND), ND+exercise (Ex), HFD+FMT from ND-alone donor (HFD+FMT(ND alone)), and HFD+FMT from ND+Ex donor (HFD+FMT(ND+Ex)). The Ex group performed treadmill exercise for 15 weeks. Thereafter, fecal and colonic mucus samples were extracted for microbiome analysis. The deoxyribonucleic acid sample was collected from the feces and colonic mucosa, and V3-V4 amplicon sequencing analysis of the 16S rRNA gene was performed using MiSeq. The number of polyps was significantly lower in the ND (6.0 ± 1.6) and ND+Ex (1.8 ± 1.3) groups than in the HFD group (11.4 ± 1.5). The ND+Ex group had significantly fewer polyps than the ND group. The HFD+FMT(ND alone) (5.2 ± 0.8) and HFD+FMT(ND+Ex) (2.8 ± 2.6) groups also had significantly fewer polyps than the HFD group. The IL-15 mRNA levels in the colonic tissues were significantly higher in the HFD+FMT(ND alone) group than in the ND group. Fecal ω-muricholic acid concentrations were significantly higher in the HFD+FMT(ND alone) group than in the ND group and in the HFD+FMT(ND+Ex) group than in the ND+Ex group. The ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of Lacyobacillaceae than the HFD group. In the FMT group, Erysipelotrichaceae and Tannerellaceae were significantly less abundant. Compared with the HFD group, the ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of Muribaculaceae and a significantly higher abundance of Lactobacillaceae and Rikenellaceae in common among the ND and ND+Ex groups. The common and significantly less common species were Bacteroidaceae in the FMT group and Lactobacillaceae and Rikenellaceae in the ND alone and ND+Ex groups. Bacteroidaceae and Lachnospiraceae were significantly less common in the FMT group. We found that FMT inhibited AOM-induced colorectal tumorigenesis in obese mice. Furthermore, the fecal concentrations of short-chain fatty acids, bile acids, microbiota, and mucosa-associated microbiota differed between the FMT and diet/EX groups, suggesting that the inhibitory effect of FMT on colorectal tumorigenesis may be due to mechanisms different from those of ND alone and ND+Ex.},
}

@article {pmid40430481,
year = {2025},
author = {Zhou, Q and Yang, C and Jia, M and Qu, Q and Peng, X and Ren, W and Li, G and Xie, Y and Li, B and Shi, X},
title = {Gut Microbiota-Targeted Intervention of Hyperlipidemia Using Monascus-Fermented Ginseng.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {5},
pages = {},
doi = {10.3390/ph18050661},
pmid = {40430481},
issn = {1424-8247},
support = {82174093//National Natural Science Foundation of China/ ; },
abstract = {Background/Objectives: Hyperlipidemia (HLP) encompasses a spectrum of poorly understood lipid metabolism disorders that are frequently overlooked or misdiagnosed, potentially leading to multiple complications. While the gut microbiota has been implicated in HLP pathogenesis, the causal relationships and molecular mechanisms remain elusive. This study aimed to investigate the therapeutic mechanisms of Monascus-fermented ginseng (MFG) on HLP through gut microbiota modulation and explore treatment potential via fecal microbiota transplantation (FMT). Methods: The MFG-modulated gut microbiota was transplanted into HLP mice. Systemic evaluations, including serum biochemical parameter detection, histopathological section analysis, 16S rRNA sequencing, and fecal metabolomics, were conducted to assess therapeutic efficacy and identify associated metabolic pathways. Results: FMT significantly improved lipid profiles, reduced body weight, and attenuated hepatic lipid accumulation in HLP mice. Mechanistically, it enhanced cholesterol excretion and fatty acid β-oxidation while suppressing lipogenic regulators, concurrently promoting primary-to-secondary bile acid conversion. Gut microbiota analysis revealed that the MFG intervention effectively normalized the Firmicutes/Bacteroidetes ratio and enriched beneficial microbiota. Conclusions: These findings demonstrate FMT's therapeutic value in HLP management and provide new perspectives on utilizing fermented herbal medicines for metabolic disorders via gut microbiota reprogramming.},
}

@article {pmid40428769,
year = {2025},
author = {Datkhayeva, Z and Iskakova, A and Mireeva, A and Seitaliyeva, A and Skakova, R and Kulniyazova, G and Shayakhmetova, A and Koshkimbayeva, G and Sarmuldayeva, C and Nurseitova, L and Koshenova, L and Imanbekova, G and Maxutova, D and Yerkenova, S and Shukirbayeva, A and Pernebekova, U and Dushimova, Z and Amirkhanova, A},
title = {The Multifactorial Pathogenesis of Endometriosis: A Narrative Review Integrating Hormonal, Immune, and Microbiome Aspects.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {5},
pages = {},
doi = {10.3390/medicina61050811},
pmid = {40428769},
issn = {1648-9144},
mesh = {Humans ; *Endometriosis/physiopathology/microbiology/immunology/etiology ; Female ; *Gastrointestinal Microbiome/physiology/immunology ; Estrogens/metabolism ; Dysbiosis/complications ; Inflammation ; },
abstract = {Endometriosis (EM) is a common estrogen-dependent chronic inflammatory disorder affecting reproductive-aged women, yet its pathogenesis remains incompletely understood. Recent evidence suggests that the gut microbiota significantly influence immune responses, estrogen metabolism, and systemic inflammation, potentially contributing to EM progression. This narrative review explores the relationship between the gut microbiota and EM, emphasizing microbial dysbiosis, inflammation, estrogen regulation, and potential microbiome-targeted therapies. Studies published within the last 30 years were included, focusing on the microbiota composition, immune modulation, estrogen metabolism, and therapeutic interventions in EM. The selection criteria prioritized peer-reviewed articles, clinical trials, meta-analyses, and narrative reviews investigating the gut microbiota's role in EM pathophysiology and treatment. Microbial dysbiosis in EM is characterized by a reduced abundance of beneficial bacteria (Lactobacillus, Bifidobacterium, and Ruminococcaceae) and an increased prevalence of pro-inflammatory taxa (Escherichia/Shigella, Streptococcus, and Bacteroides). The gut microbiota modulate estrogen metabolism via the estrobolome, contributing to increased systemic estrogen levels and lesion proliferation. Additionally, lipopolysaccharides (LPS) from Gram-negative bacteria activate the TLR4/NF-κB signaling pathway, exacerbating inflammation and EM symptoms. The interaction between the gut microbiota, immune dysregulation, and estrogen metabolism suggests a critical role in EM pathogenesis. While microbiota-targeted interventions offer potential therapeutic benefits, further large-scale, multi-center studies are needed to validate microbial biomarkers and optimize microbiome-based therapies for EM. Integrating microbiome research with precision medicine may enhance the diagnostic accuracy and improve the EM treatment efficacy.},
}

Humans
*Endometriosis/physiopathology/microbiology/immunology/etiology
Female
*Gastrointestinal Microbiome/physiology/immunology
Estrogens/metabolism
Dysbiosis/complications
Inflammation

@article {pmid40427529,
year = {2025},
author = {Daude, N and Machado, I and Arce, L and Yang, J and Westaway, D},
title = {Microbial Composition, Disease Trajectory and Genetic Background in a Slow Onset Model of Frontotemporal Lobar Degeneration.},
journal = {Biomolecules},
volume = {15},
number = {5},
pages = {},
doi = {10.3390/biom15050636},
pmid = {40427529},
issn = {2218-273X},
support = {N/A//Nanostring AD panel/ ; N/A//SynAD ADRD/ ; 16308/CAPMC/CIHR/Canada ; 173286/CAPMC/CIHR/Canada ; NIF 21633//Canada Foundation for Innovation/ ; NIF 39588//Canada Foundation for Innovation/ ; N/A//Campus Alberta Neuroscience/ ; APRIIEP201600033//Alberta Prion Research Institute/ ; N/A//Hope for Tomorrow/ ; },
mesh = {Animals ; Mice ; Mice, Transgenic ; Disease Models, Animal ; tau Proteins/metabolism/genetics ; *Frontotemporal Lobar Degeneration/genetics/microbiology/pathology/metabolism ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome/genetics ; Genetic Background ; Humans ; Male ; },
abstract = {Slow-onset neurodegenerative disease in a low-expresser 2N4R P301L transgenic (Tg) mouse model is marked by neuroinflammation and by differing patterns of CNS deposition and accumulation of tau conformers, with such heterogeneities present even within inbred backgrounds. Gut microbial genotypes were notably divergent within C57BL6/Tac or 129SvEv/Tac congenic (Cg) sublines of TgTau[P301L] mice, and these sublines differed when challenged with antibiotic treatment and fecal microbial transplantation. Whereas aged, transplanted Cg 129SvEv/Tac TgTau[P301L] mice had neuroanatomical deposition of tau resembling controls, transplanted Cg C57BL6/Tac TgTau[P301L] mice had different proportions of rostral versus caudal tau accumulation (p = 0.0001). These data indicate the potential for environmental influences on tau neuropathology in this model. Furthermore, Cg C57BL6/Tac TgTau[P301L] cohorts differed from 129SvEv/Tac counterparts by showing 28% versus 9% net intercurrent loss (p = 0.0027). While the origin of this phenomenon is not established, it offers a parallel to differing patterns of frailty observed in C57BL6 versus 129 SvEv Tg mice expressing the 695 amino acid isoform of human amyloid precursor protein. We infer that generalized responses to protein aggregation might account for similar reductions in viability even when expressing different human proteins in the same inbred strain background.},
}

Animals
Mice
Mice, Transgenic
Disease Models, Animal
tau Proteins/metabolism/genetics
*Frontotemporal Lobar Degeneration/genetics/microbiology/pathology/metabolism
Mice, Inbred C57BL
*Gastrointestinal Microbiome/genetics
Genetic Background
Humans
Male

@article {pmid40427424,
year = {2025},
author = {Golenia, A and Olejnik, P},
title = {The Role of Oxidative Stress in Ischaemic Stroke and the Influence of Gut Microbiota.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {5},
pages = {},
doi = {10.3390/antiox14050542},
pmid = {40427424},
issn = {2076-3921},
abstract = {Ischaemic stroke is the most prevalent stroke subtype, accounting for 80-90% of all cases worldwide, and remains a leading cause of morbidity and mortality. Its pathophysiology involves complex molecular cascades, with oxidative stress playing a central role. During cerebral ischaemia, reduced blood flow deprives neurons of essential oxygen and nutrients, triggering excitotoxicity, mitochondrial dysfunction, and excessive production of reactive oxygen and nitrogen species (RONS). Not only do these species damage cellular components, but they also activate inflammatory pathways, particularly those mediated by the transcription factor nuclear factor kappa-B (NF-κB). The pro-inflammatory milieu intensifies neuronal damage, compromises blood-brain barrier integrity, and exacerbates reperfusion-induced damage. Recent findings highlight the importance of the gut microbiota in modulating stroke outcomes, primarily through metabolic and immunological interactions along the gut-brain axis. Dysbiosis, characterised by reduced microbial diversity and an imbalance between beneficial and harmful strains, has been linked to increased systemic inflammation, oxidative stress, and worse prognoses. Specific gut-derived metabolites, including short-chain fatty acids (SCFAs) and trimethylamine N-oxide (TMAO), appear to either mitigate or intensify neuronal injury. SCFAs may strengthen the blood-brain barrier and temper inflammatory responses, whereas elevated TMAO levels may increase thrombotic risk. This narrative review consolidates both experimental and clinical data demonstrating the central role of oxidative stress in ischaemic stroke pathophysiology and explores the gut microbiota's ability to modulate these damaging processes. Therapeutic strategies targeting oxidative pathways or rebalancing gut microbial composition, such as antioxidant supplementation, dietary modulation, probiotics, and faecal microbiota transplantation, present promising paradigms for stroke intervention. However, their widespread clinical implementation is hindered by a lack of large-scale, randomised trials. Future efforts should employ a multidisciplinary approach to elucidate the intricate mechanisms linking oxidative stress and gut dysbiosis to ischaemic stroke, thereby paving the way for novel, mechanism-based therapies for improved patient outcomes.},
}

@article {pmid40426604,
year = {2025},
author = {Xia, YM and Zhang, MX and Ma, XY and Tan, LL and Li, T and Wu, J and Li, MA and Zhao, WJ and Qiao, CM and Jia, XB and Shen, YQ and Cui, C},
title = {Intranasal Transplantation of Microbiota Derived from Parkinson's Disease Mice Induced Astrocyte Activation and Neurodegenerative Pathology from Nose to Brain.},
journal = {Brain sciences},
volume = {15},
number = {5},
pages = {},
doi = {10.3390/brainsci15050433},
pmid = {40426604},
issn = {2076-3425},
support = {82171429//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Parkinson's disease (PD) is characterized by early-onset olfactory dysfunction preceding motor symptoms, yet its mechanisms remain elusive. Based on the studies on microbiota-gut-brain axis, the microbiota-nose-brain axis might be involved in the pathogenesis of PD. However relative studies are rare.

METHODS: By consecutive 14-days intranasally transplanting bacteria, we established mice models exhibiting nasal microbiota dysbiosis (NMD), including animal group received intranasal drops of fecal bacterial suspension from normal mice (NB group) and animal group received intranasal drops of fecal bacterial suspension from PD mice (PB group), with animals that only received anesthesia used as the control group. Then we analyzed the nasal microbiota composition via 16S rRNA sequencing, evaluated the olfactory and motor functions through behavioral experiments, including buried food test, open field test, pole descent test, and traction test. The neuropathology in olfactory-related and PD-related brain regions, including olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum, was also detected by western blotting, immunofluorescence and immunohistochemical experiments using the antibodies of NeuN, TH and GFAP.

RESULTS: 16S rRNA sequencing revealed that PB mice were primarily characterized by an increase in bacteria associated with inflammation and PD. Behavioral assessments revealed that mice with NMD demonstrated impairments in the buried food test and pole descent test, indicative of olfactory and motor dysfunction. By detecting NeuN and GFAP expression, we identified neuronal loss and astrocytes activation in olfactory-related brain regions and adjacent structures, including the olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum of both NMD groups, which may contribute to the observed functional disorders. Notably, animals exposed to PD-derived bacteria exhibited more pronounced changes in nasal bacteria, with more severe neuropathology.

CONCLUSIONS: We present evidence supporting the microbiota-nose-brain axis, and the NMD-induced astrocyte activation and neurodegenerative pathology along the olfactory pathway may serve as a link between nose and brain.},
}

@article {pmid40424882,
year = {2025},
author = {Huang, YY and Qin, SM and Nguyen, MT and Chen, W and Si, XM and Huang, YQ and Zhang, HY},
title = {The protective effects of dietary resistant starch against post-antibiotic bone loss in meat ducks associated with the recovery of caecal microbiota dysbiosis.},
journal = {Poultry science},
volume = {104},
number = {8},
pages = {105238},
doi = {10.1016/j.psj.2025.105238},
pmid = {40424882},
issn = {1525-3171},
abstract = {Compromised bone quality increases the risk of fractures in domesticate birds, resulting in pain and altered behaviour. Although dietary resistant starch (RS) supplementation show promise for improving inferior bone mass, the diet-mediated gut microbiota alterations as a potential mechanism underlying RS positive roles in bone remains uncertain. With a post-antibiotic model and faecal microbiota transplantation (FMT), this study investigated the effects of a RS diet on antibiotic-induced bone loss and gut microbial composition in meat ducks. Ducklings were assigned to 4 treatments with 6 replicate pens until 21 d, including the control group (Ctrl, feeding a basal diet) and the RS-fed group, and post-antibiotic treatment following the gavage of phosphate-buffered saline (Post-anti-PBS) or faecal microbiota transplantation (Post-anti-FMT). The RS diet increased the proportion of Firmicutes, improved intestinal integrity, and reduced inflammation-induced bone resorption, all of which contributed to an increase in tibial bone volume (P < 0.05). Post-antibiotic treatment was found to reduce tibial quality by stimulating bone resorption and inhibiting bone formation, accompanied by gut microbiota dysbiosis, increased intestinal permeability (P = 0.059), and inflammatory flare compared to control birds. FMT from RS-fed ducks into the antibiotic-treated birds reversed bone loss by primarily blocking osteoclastic frequency and activity. Furthermore, FMT increased the ratio of Firmicutes to Bacteroidetes (P < 0.05) and suppressed the release of pro-osteoclastogenic cytokines such as tumour necrosis factor-α (P = 0.062) and interleukin-1β (P < 0.05) in the bone marrow. These results demonstrated the involvement of gut microbiota in improving bone quality of meat ducks by RS, and FMT of RS-fed birds corrected the imbalance of ceca microbiota and attenuated bone loss in meat ducks with enhanced bone resorption.},
}

@article {pmid40335381,
year = {2025},
author = {Vuyk, W and Bobholz, M and Emmen, I and Lail, A and Minor, N and Bhimalli, P and Eickhoff, JC and Ries, HJ and Machkovech, H and Wei, W and Weiler, A and Richardson, A and DePagter, C and VanSleet, G and Bhasin, M and Kamal, S and Wolf, S and Virdi, A and Bradley, T and Gifford, A and Benito, M and Shipe, A and Mohamed, R and Smith, J and Wilson, N and Friedrich, TC and O'Connor, DH and Garonzik-Wang, J},
title = {Longitudinal Assessment of Solid Organ Transplant Recipients With SARS-CoV-2 Infection.},
journal = {Transplantation proceedings},
volume = {57},
number = {5},
pages = {922-930},
doi = {10.1016/j.transproceed.2025.04.004},
pmid = {40335381},
issn = {1873-2623},
mesh = {Humans ; *COVID-19/diagnosis/virology/epidemiology/immunology ; Middle Aged ; *SARS-CoV-2/genetics/isolation & purification ; Male ; *Organ Transplantation/adverse effects ; *Immunocompromised Host ; Female ; Virus Shedding ; *Transplant Recipients ; Prospective Studies ; Adult ; RNA, Viral ; Longitudinal Studies ; Viral Load ; Aged ; Feces/virology ; },
abstract = {BACKGROUND: Compared with immunocompetent individuals, those who are immunocompromised, including solid organ transplant (SOT) recipients, have higher SARS-CoV-2-related morbidity and mortality. We determined the duration of SARS-CoV-2 RNA positivity to evaluate viral persistence in SOT recipients.

METHODS: This study prospectively followed SOT recipients who recently tested positive for SARS-CoV-2. The duration of viral RNA shedding in nasal swabs and stool samples was tracked, and viral genome sequencing was performed where possible. Persistent infection was defined as a positive nucleic acid amplification test (NAAT) for SARS-CoV-2 at 28 days or later after initial infection. This duration was chosen based on the U.S. Centers for Disease Control and Prevention (CDC) recommendation that immunocompromised individuals isolate for at least 20 days [1], compared with 10 days for non-immunocompromised individuals.

RESULTS: Of 30 SOT recipients, 12 (40%) had positive SARS-CoV-2 RNA in nasal swabs or stool (cycle threshold [Ct] < 40) at 28 or more days after the first positive SARS-CoV-2 test. Immunocompromised (IC) subject 015 had high viral loads (Ct < 30) at 28 days, with continued detection for 54 days.

CONCLUSIONS: In 12 of 30 SOT subjects, SARS-CoV-2 RNA was detected at or beyond 28 days post-detection (dpd), despite vaccination and antibody and/or antiviral treatment in most participants. Three subjects tested positive for SARS-CoV-2 RNA past 50 dpd. Viral persistence in the setting of host immune suppression, coupled with exposure to antiviral treatments, raises concern about the selection of unusual viral variants.},
}

Humans
*COVID-19/diagnosis/virology/epidemiology/immunology
Middle Aged
*SARS-CoV-2/genetics/isolation & purification
Male
*Organ Transplantation/adverse effects
*Immunocompromised Host
Female
Virus Shedding
*Transplant Recipients
Prospective Studies
Adult
RNA, Viral
Longitudinal Studies
Viral Load
Aged
Feces/virology

@article {pmid40422666,
year = {2025},
author = {Gaspar, BS and Roşu, OA and Enache, RM and Manciulea Profir, M and Pavelescu, LA and Creţoiu, SM},
title = {Gut Mycobiome: Latest Findings and Current Knowledge Regarding Its Significance in Human Health and Disease.},
journal = {Journal of fungi (Basel, Switzerland)},
volume = {11},
number = {5},
pages = {},
doi = {10.3390/jof11050333},
pmid = {40422666},
issn = {2309-608X},
abstract = {The gut mycobiome, the fungal component of the gut microbiota, plays a crucial role in health and disease. Although fungi represent a small fraction of the gut ecosystem, they influence immune responses, gut homeostasis, and disease progression. The mycobiome's composition varies with age, diet, and host factors, and its imbalance has been linked to conditions such as inflammatory bowel disease (IBD) and metabolic disorders. Advances in sequencing have expanded our understanding of gut fungi, but challenges remain due to methodological limitations and high variability between individuals. Emerging therapeutic strategies, including antifungals, probiotics, fecal microbiota transplantation, and dietary interventions, show promise but require further study. This review highlights recent discoveries on the gut mycobiome, its interactions with bacteria, its role in disease, and potential clinical applications. A deeper understanding of fungal contributions to gut health will help develop targeted microbiome-based therapies.},
}

@article {pmid40421334,
year = {2025},
author = {Ponce Alencastro, JA and Salinas Lucero, DA and Solis, RP and Herrera Giron, CG and Estrella López, AS and Anda Suárez, PX},
title = {Molecular Mechanisms and Emerging Precision Therapeutics in the Gut Microbiota-Cardiovascular Axis.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e83022},
pmid = {40421334},
issn = {2168-8184},
abstract = {A microbiome in the gut plays a significant role in cardiovascular health and disease. Dysbiosis is an imbalance in the gut microbiome, leading to multiple cardiovascular diseases (CVD) such as atherosclerosis, hypertension, and heart failure. Gut microbe-derived metabolites such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs) are important mediators of the gut-heart axis. Evaluation of the relationship between the gut microbiome and host biomarkers with CVD requires the integration of metagenomics and metabolomics with meta-omics approaches. The literature review found that microbes and metabolic signatures are associated with the risk and progression of CVD. The development of precision therapeutic approaches for targeting gut microbiota includes preventing adverse microbial effects using probiotics, prebiotics, and the drug-as-bug approach to inhibit harmful metabolites of microbiomes, and fecal microbiota transplantation (FMT). However, the implication and practice of these findings in clinical settings face challenges due to the heterogeneity of study designs, difficulty in the determination of causality, and the impact of confounding factors such as diet, medication, and potential inter-individual gut microbiome variability. Future researchers are recommended to conduct longitudinal studies to further establish both gut microbiome associations with CVD and develop successful precision therapeutics approaches based on the microbiome for the treatment of CVD.},
}

@article {pmid40420583,
year = {2025},
author = {He, X and Luthuli, S and Wen, Q and Wang, C and Ding, J and Cui, B and Zhang, F},
title = {Washed microbiota transplantation for ribotype 027 Clostridioides difficile infection in a pregnant woman with two-year follow-up: a case report.},
journal = {Journal of biomedical research},
volume = {},
number = {},
pages = {1-4},
doi = {10.7555/JBR.39.20250063},
pmid = {40420583},
issn = {1674-8301},
abstract = {Clostridioides difficile (C. difficile) is one of the major causes of nosocomial infections. The pregnant women, who were considered at low risk for C. difficile infection (CDI), have attracted attention with increasing reports. Oral vancomycin, the only first-line treatment for the pregnant women infected with C. difficile, came with the problem of increasing strains resistance that was associated with decreased efficacy. Fecal microbiota transplantation (FMT) is recommended for severe, fulminant and recurrent CDI, while it is avoided in the pregnant women due to safety concerns. We reported a pregnant woman case with primary ribotype 027 CDI, who got a successful outcome with washed microbiota transplantation (WMT), an improved FMT, via enema. The specific strain of ribotype 027 was related to severe outcomes but was not reported in the pregnant women. The follow-up lasted two years, the patient's diarrhea was fully alleviated without recurrence. The baby had normal growth and development and no adverse events were recorded in both of them. This case provides evidence for the efficacy and safety of WMT in the pregnant women infected with C. difficile, indicating that WMT via enema may be a strategy for this population in treating CDI.},
}

@article {pmid40419682,
year = {2025},
author = {Nishinarita, Y and Miyoshi, J and Kuronuma, S and Wada, H and Oguri, N and Hibi, N and Takeuchi, O and Akimoto, Y and Lee, STM and Matsuura, M and Kobayashi, T and Hibi, T and Hisamatsu, T},
title = {Characteristic gene expression profile of intestinal mucosa early in life promotes bacterial colonization leading to healthy development of the intestinal environment.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {18437},
pmid = {40419682},
issn = {2045-2322},
support = {19K23977//Japan Society for the Promotion of Science/ ; 21K07900//Japan Society for the Promotion of Science/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome/genetics ; Mice ; *Intestinal Mucosa/microbiology/metabolism ; Fecal Microbiota Transplantation ; *Bacteria/genetics/growth & development/classification ; Germ-Free Life ; *Transcriptome ; Male ; Gene Expression Profiling ; Female ; Feces/microbiology ; Mice, Inbred C57BL ; },
abstract = {The gut microbiome early in life plays a crucial role in development of the host and affects health throughout life. The definition of a healthy microbiome early in life has not been established, and the underlying mechanism of how a young host selects appropriate microbes for colonization remains unclear. Understanding the mechanism may provide insights into novel preventive and therapeutic strategies by correcting dysbiosis early in life. We employed germ-free mice early in life (4 weeks of age) and later in life (10 weeks of age) for fecal microbiota transfer (FMT) from specific pathogen-free mice. We performed age-unmatched FMT between recipients early in life and donors early or later in life, in addition to common age-matched FMT. Age-matched FMT resulted in significantly different bacterial compositions between recipients early vs. later in life. When the gut microbiome from donors early or later in life was transferred to recipients early in life, bacterial compositions of recipients from donors later in life were similar to those of recipients from donors early in life. This finding suggests that the host early in life has mechanisms to select microbes appropriate for age from the exposed microbiome. We hypothesized that the age-specific intestinal environment promotes age-appropriate intestinal microbiome colonization and examined gene expression in the intestinal mucosa of germ-free mice. We observed that gene expression profiles were different between early vs. later in life. Correlation analysis demonstrated that genera Lachnospiraceae NK4A136 group and Roseburia were positively correlated to genes expressed predominantly early in life, but negatively with genes expressed predominantly later in life. We confirmed that the relative abundance of these genera was significantly higher in specific pathogen-free mice early in life compared with mice later in life. The characteristic gene expression of the intestinal mucosa early in life might play roles in selecting specific bacteria in the intestinal microbiome early in life.},
}

Animals
*Gastrointestinal Microbiome/genetics
Mice
*Intestinal Mucosa/microbiology/metabolism
Fecal Microbiota Transplantation
*Bacteria/genetics/growth & development/classification
Germ-Free Life
*Transcriptome
Male
Gene Expression Profiling
Female
Feces/microbiology
Mice, Inbred C57BL

@article {pmid40419041,
year = {2025},
author = {Chen, L and Zhao, S and Chen, Q and Luo, P and Li, X and Song, Y and Pan, S and Wu, Q and Zhang, Y and Shen, X and Chen, Y},
title = {Poria cocos polysaccharides ameliorate AOM/DSS-induced colorectal cancer in mice by remodeling intestinal microbiota composition and enhancing intestinal barrier function.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {144477},
doi = {10.1016/j.ijbiomac.2025.144477},
pmid = {40419041},
issn = {1879-0003},
abstract = {Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the development of novel therapeutic strategies. Poria cocos polysaccharides (PCP), bioactive components of the traditional medicinal fungus Poria cocos, exhibit significant anticancer potential. This study investigates the protective effects of PCP against azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC in mice, with a focus on its impact on intestinal microbiota composition, intestinal barrier integrity, and inflammatory responses. PCP treatment significantly reduced tumor incidence, tumor size, and tumor burden while improving histopathological features and inhibiting Ki67-positive cell proliferation. Mechanistically, PCP enhanced intestinal barrier function by restoring tight junction proteins (E-cadherin, ZO-1, Claudin-3) and mucin secretion (MUC2), thereby reducing intestinal permeability and systemic lipopolysaccharide (LPS) levels. Furthermore, PCP exhibited potent anti-inflammatory effects by downregulating pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and upregulating the anti-inflammatory cytokine IL-10. 16S rRNA sequencing results revealed that PCP modulated the intestinal microbiota, decreasing pathogenic bacteria such as Helicobacter and Eisenbergiella while promoting beneficial taxa including Limosilactobacillus, Paraprevotella, and Muribaculum. Fecal microbiota transplantation (FMT) further confirmed the microbiota-mediated protective effects of PCP, as FMT from PCP-treated donors significantly suppressed tumorigenesis, restored intestinal barrier integrity, and alleviated inflammation in CRC mice. Additionally, PCP demonstrated a favorable safety profile, with no adverse effects on major organs. These findings highlight PCP as promising natural agents for CRC prevention and therapy, acting through modulation of the intestinal microbiota, enhancement of intestinal barrier function, and suppression of inflammation.},
}

@article {pmid40415934,
year = {2025},
author = {Liu, L and Zhao, W and Zhang, H and Shang, Y and Huang, W and Cheng, Q},
title = {Relationship between pediatric asthma and respiratory microbiota, intestinal microbiota: a narrative review.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1550783},
pmid = {40415934},
issn = {1664-302X},
abstract = {Pediatric asthma is a common chronic airway inflammatory disease that begins in childhood and its impact persists throughout all age stages of patients. With the continuous progress of detection technologies, numerous studies have firmly demonstrated that gut microbiota and respiratory microbiota are closely related to the occurrence and development of asthma, and related research is increasing day by day. This article elaborates in detail on the characteristics, composition of normal gut microbiota and lung microbiota at different ages and in different sites, as well as the connection of the gut-lung axis. Subsequently, it deeply analyzes various factors influencing microbiota colonization, including host factor, delivery mode, maternal dietary and infant feeding patterns, environmental microbial exposure and pollutants, and the use of antibiotics in early life. These factors are highly likely to play a crucial role in the onset process and disease progression of asthma. Research shows that obvious changes have occurred in the respiratory and gut microbiota of asthma patients, and these microbiomes exhibit different characteristics according to the phenotypes and endotypes of asthma. Finally, the article summarizes the microbiota-related treatment approaches for asthma carried out in recent years, including the application of probiotics, nutritional interventions, and fecal microbiota transplantation. These treatment modalities are expected to become new directions for future asthma treatment and bring new hope for solving the problem of childhood asthma.},
}

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

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

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

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

@article {pmid40414934,
year = {2025},
author = {Jan, A and Bayle, P and Mohellibi, N and Lemoine, C and Pepke, F and Béguet-Crespel, F and Jouanin, I and Tremblay-Franco, M and Laroche, B and Serror, P and Rigottier-Gois, L},
title = {A consortium of seven commensal bacteria promotes gut microbiota recovery and strengthens ecological barrier against vancomycin-resistant enterococci.},
journal = {Microbiome},
volume = {13},
number = {1},
pages = {129},
pmid = {40414934},
issn = {2049-2618},
support = {COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; PhD scholarship AJ (2020-2023)//INRAE Metaprogram HOLOFLUX and doctoral school ABIES at University Paris-Saclay/ ; Travel grants from Graduate schools Life sciences and Health (LSH) and Biosphera from University Paris-Saclay//France 2030 program "ANR-11-IDEX-0003"/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; Key action MIND (2017)//INRAE Metaprogram MEM/ ; Key action MIND (2017)//INRAE Metaprogram MEM/ ; Key action MIND (2017)//INRAE Metaprogram MEM/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome ; *Vancomycin-Resistant Enterococci/growth & development ; Mice ; Symbiosis ; Dysbiosis/microbiology/chemically induced ; Anti-Bacterial Agents ; *Gram-Positive Bacterial Infections/microbiology ; Feces/microbiology ; *Bacteria/classification/genetics/isolation & purification ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Vancomycin-resistant enterococci (VRE) often originate from the gastrointestinal tract, where their proliferation precedes dissemination into the bloodstream, and can lead to systemic infection. Uncovering the actors and mechanisms reducing the intestinal colonisation by VRE is essential to control infection. We aimed to identify commensal bacteria that interfere with VRE gut colonisation or act as an ecological barrier.

RESULTS: We performed a 3-week longitudinal analysis of the gut microbiota composition and VRE carriage levels during microbiota recovery in mice colonised with VRE after antibiotic-induced dysbiosis. By combining biological data and mathematical modelling, we identified 15 molecular species (OTUs) that negatively correlated with VRE overgrowth. Six strains representative of these OTUs were collected, cultivated and used in mixture with a seventh strain (Mix7) in two different mouse lines challenged with VRE. Of the seven strains, three belonged to Lachnospiraceae, one to Muribaculaceae, one to Ruminococcaceae and two to Lactobacillaceae. We found that Mix7 led to a better recovery of the gut microbiota composition and reduced VRE carriage. Differences in the effect of Mix7 were observed between responder and non-responder mice. These differences were associated with variations in the composition of the initial microbiota and during recovery and represent potential biomarkers for predicting response to Mix7. In a mouse model of alternative stable state of dysbiosis, response to Mix7 was associated with higher concentrations of short-chain fatty acids (acetate, propionate, butyrate) and a range of metabolites including bile acids, reflecting the recovery of the microbiota back to initial state. Furthermore, Muribaculum intestinale strain was required to obtain the Mix7 effect on VRE reduction in vivo, but the presence of at least one of the other six strains was needed. None of the supernatant of the seven strains, alone or in combination, inhibited VRE growth in vitro. Interestingly, five strains belong to species shared among humans and mice, and the other two have human functional equivalents.

CONCLUSIONS: An innovative approach based on mathematical modelling of the microbiota composition permitted to identify a mixture of commensal bacterial strains, which improves the ecological barrier effect against VRE. The mechanisms are dependent on the recovery and initial composition of the microbiota. Ultimately, this work will enable a move towards a personalised medicine by targeting predisposed patients presenting a risk of infection, such as neutropenic or bone-marrow transplant patients, and likely to respond to supplementation with commensal strains, providing new live biotherapeutic products and biomarkers to predict response to supplementation. Video Abstract.},
}

Animals
*Gastrointestinal Microbiome
*Vancomycin-Resistant Enterococci/growth & development
Mice
Symbiosis
Dysbiosis/microbiology/chemically induced
Anti-Bacterial Agents
*Gram-Positive Bacterial Infections/microbiology
Feces/microbiology
*Bacteria/classification/genetics/isolation & purification
Mice, Inbred C57BL

@article {pmid40414635,
year = {2025},
author = {Kumar, R and Kumar, R},
title = {Intestinal dysbiosis leads to the reduction in neurochemical production in Parkinson's disease (PD).},
journal = {International review of neurobiology},
volume = {180},
number = {},
pages = {25-56},
doi = {10.1016/bs.irn.2025.03.004},
pmid = {40414635},
issn = {2162-5514},
mesh = {Humans ; *Dysbiosis/metabolism/therapy ; *Parkinson Disease/metabolism/therapy/physiopathology/microbiology ; *Gastrointestinal Microbiome/physiology ; Animals ; },
abstract = {Parkinson's Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, with emerging research suggesting a critical link between intestinal dysbiosis and PD progression. This review explores the pathophysiological mechanisms underlying PD, such as alpha-synuclein aggregation, mitochondrial dysfunction, neuroinflammation, and oxidative stress, while focusing on the impact of gut dysbiosis on intestinal barrier function and its role in reduced neurochemical production. The clinical features of PD, including dopamine, serotonin, and GABA deficiencies, are examined, with a focus on how dysbiosis contributes to neurotransmitter depletion. Current treatments of PD, such as levodopa and dopamine agonists, are discussed alongside gut health therapies such as probiotics, prebiotics, and Fecal Microbiota Transplantation (FMT). Future therapeutic directions, including synbiotics, engineered microbes, phage therapy, and the integration of machine learning (ML) and artificial intelligence (AI), are explored. The chapter also considers preventive strategies, such as lifestyle adjustments and early gut health monitoring using modern diagnostic tools and biosensors. Furthermore, a strong need for continued research into the gut-brain axis (GBA) to develop more effective, gut-targeted therapies for managing PD is discussed.},
}

Humans
*Dysbiosis/metabolism/therapy
*Parkinson Disease/metabolism/therapy/physiopathology/microbiology
*Gastrointestinal Microbiome/physiology
Animals

@article {pmid40414634,
year = {2025},
author = {Singh, S and Saini, V and Jha, HC},
title = {The role of secondary genomes in neurodevelopment and co-evolutionary dynamics.},
journal = {International review of neurobiology},
volume = {180},
number = {},
pages = {245-297},
doi = {10.1016/bs.irn.2025.03.008},
pmid = {40414634},
issn = {2162-5514},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodevelopmental Disorders/genetics/microbiology ; *Biological Evolution ; Animals ; *Brain/growth & development ; },
abstract = {This chapter examines how human biology and microbial "secondary genomes" have co-evolved to shape neurodevelopment through the gut-brain axis. Microbial communities generate metabolites that cross blood-brain and placental barriers, influencing synaptogenesis, immune responses, and neural circuit formation. Simultaneously, Human Accelerated Regions (HARs) and Endogenous Retroviruses (ERVs) modulate gene expression and immune pathways, determining which microbes thrive in the gut and impacting brain maturation. These factors converge to form a dynamic host-microbe dialogue with significant consequences for neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia. Building on evolutionary perspectives, the chapter elucidates how genetic and immune mechanisms orchestrate beneficial and pathological host-microbe interactions in early brain development. It then explores therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation, and CRISPR-driven microbial engineering, targeting gut dysbiosis to mitigate or prevent neurodevelopmental dysfunctions. Furthermore, innovative organ-on-chip models reveal mechanistic insights under physiologically relevant conditions, offering a translational bridge between in vitro experiments and clinical applications. As the field continues to evolve, this work underscores the translational potential of manipulating the microbiome to optimize neurological outcomes. It enriches our understanding of the intricate evolutionary interplay between host genomes and the microbial world.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Neurodevelopmental Disorders/genetics/microbiology
*Biological Evolution
Animals
*Brain/growth & development

@article {pmid40414573,
year = {2025},
author = {Yu, F and Ji, JL and Wang, Y and Liu, YD and Lian, YM and Wang, MZ and Cai, ZX},
title = {Anti-epileptic and Gut-protective Effects of Trioctanoin and the Critical Role of Gut Microbiota in a Mouse Model of Epilepsy.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111401},
doi = {10.1016/j.brainresbull.2025.111401},
pmid = {40414573},
issn = {1873-2747},
abstract = {Gut microbiota structure and function affect metabolism, gut health, and behavioral responses and are regulated by dietary factors. Recent research suggests the association of the gut-brain axis with epilepsy pathogenesis, thus offering potential new therapeutic targets. This study evaluated the anti-epileptic effect of trioctanoin and explored the potential role of the gut microbiota in a chronic pentylentetrazol (PTZ)-induced seizure mouse model. Behavioral assessments, electroencephalogram monitoring, immunofluorescence staining, neurotransmitter detection, gut microbiota sequencing, intestinal barrier function tests, and Fecal Microbiota Transplantation (FMT) were performed to systematically study the anti-epileptic effects of trioctanoin and the potential role of microbiota. Trioctanoin significantly restored glial cell proliferation to normal levels in chronic PTZ mice. Moreover, trioctanoin reduced elevated glutamate levels in the hippocampus of PTZ mice and improved gut microbiota imbalance and gut health by restoring the abundance of Dubosiella and Faecalibaculum genera, upregulating tight junction protein expression in the colon, and decreasing elevated levels of the inflammatory markers. Antibiotics(Abx) pre-treatment abolished the anticonvulsant protective effect of Trioctanoin. Although the FMT experiment did not transfer the anticonvulsant protection to the Abx+PTZ group mice, the results suggest that FMT still partially restored the gut microbiota imbalance in the chronic PTZ-induced epilepsy mouse model. These results provide new insights into dietary and gut microbiota-based therapeutic strategies for epilepsy.},
}

@article {pmid40413728,
year = {2025},
author = {Kousgaard, SJ and Dall, SM and Albertsen, M and Nielsen, HL and Thorlacius-Ussing, O},
title = {Fecal microbiota transplantation from a healthy pouch donor for chronic pouchitis: a proof-of-concept study.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2510464},
doi = {10.1080/19490976.2025.2510464},
pmid = {40413728},
issn = {1949-0984},
mesh = {Humans ; *Pouchitis/therapy/microbiology ; *Fecal Microbiota Transplantation/adverse effects/methods ; Male ; Female ; Adult ; Middle Aged ; Feces/microbiology ; Quality of Life ; Chronic Disease/therapy ; Gastrointestinal Microbiome ; Proof of Concept Study ; Treatment Outcome ; Tissue Donors ; Denmark ; },
abstract = {Chronic pouchitis is a common complication after ileal pouch-anal anastomosis (IPAA) with limited treatment options. In this case series, we aimed to investigate clinical and microbiome changes, as well as adverse events, associated with using fecal microbiota transplantation (FMT) from a donor with a normal functioning IPAA to induce remission in patients with chronic pouchitis. Methods The study was a case-series including a 4-week intervention period and 12-month follow-up. Patients with chronic pouchitis who met the inclusion criteria were recruited from the Department of Gastrointestinal Surgery at Aalborg University Hospital, Denmark. Participants received FMT derived from a donor with a normal functioning IPAA. Treatment was administered by enema daily for two weeks, then every other day for two more weeks. Disease severity and quality of life (QoL) were accessed at baseline and 30-day follow-up. Clinical remission was defined as Pouchitis Disease Activity Index (PDAI) <7. Fecal samples from participants, healthy donors, and the IPAA donor were analyzed using shotgun metagenomic sequencing. Results Three patients with chronic pouchitis were included and completed the treatment protocol and follow-up visits. At the 30-day follow-up, all participants achieved clinical remission with reduced endoscopic inflammation. The median total PDAI score decreased from 8 (range 10-8) at baseline to 6 (range 6-5) at 30 days. Two participants reported improved QoL, while one reported no change. Few mild, self-limited adverse events were reported by all participants during treatment, with no serious events. Principal component analysis of fecal samples distinguished two clusters: healthy donors and the IPAA donor, with participant samples forming a separate cluster Conclusion We observed that all participants achieved clinical remission with reduced endoscopic inflammation following a 4-week FMT intervention. Adverse events were mild and self-limited. Metagenomic analysis revealed distinct microbiome clusters between IPAA donor and recipients, both of which differed from those of healthy donors.},
}

Humans
*Pouchitis/therapy/microbiology
*Fecal Microbiota Transplantation/adverse effects/methods
Male
Female
Adult
Middle Aged
Feces/microbiology
Quality of Life
Chronic Disease/therapy
Gastrointestinal Microbiome
Proof of Concept Study
Treatment Outcome
Tissue Donors
Denmark

@article {pmid40413726,
year = {2025},
author = {Zhang, DY and Li, D and Chen, SJ and Zhang, LJ and Zhu, XL and Chen, FD and Chen, C and Wang, Q and Du, Y and Xiong, JX and Huang, SM and Zhang, XD and Lv, YT and Zeng, F and Chen, RX and Huang, X and Mao, F and Zhou, S and Yao, Q and Huang, Y and Chen, R and Mo, Y and Xie, Y and Jiang, YH and Chen, Z and Mo, CY and Chen, JJ and Bai, FH},
title = {Bacteroides uniformis-generated hexadecanedioic acid ameliorates metabolic-associated fatty liver disease.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2508433},
doi = {10.1080/19490976.2025.2508433},
pmid = {40413726},
issn = {1949-0984},
mesh = {Humans ; Gastrointestinal Microbiome ; Animals ; *Bacteroides/metabolism/genetics ; Mice ; Male ; Female ; Middle Aged ; Feces/microbiology ; Liver/metabolism ; *Fatty Liver/microbiology/metabolism ; Fecal Microbiota Transplantation ; Prospective Studies ; Adult ; Metabolomics ; Mice, Inbred C57BL ; },
abstract = {Gut microbiota exerts a pivotal influence on the development of Metabolic Associated Fatty Liver Disease (MAFLD), although the specific contributions of individual bacterial strains and their metabolites remain poorly defined. We conducted stool shotgun metagenomic sequencing and plasma untargeted metabolomics in a large prospective cohort comprising 120 MAFLD patients and 120 matched healthy controls. The mechanisms and microbial-derived metabolites involved in MAFLD were further investigated through multi-omics analyses in vitro and in vivo. Distinct differences were identified in both the microbial community structure and metabolomic profiles between MAFLD patients and healthy controls. Bacteroides uniformis (B. uniformis) was the most significantly depleted species in MAFLD and negatively correlated with hepatic steatosis and BMI. MAFLD was characterized by marked disruptions in fatty acid and amino acid metabolism. Combined analysis of metabolomic and metagenomic data achieved high diagnostic accuracy for MAFLD and hepatic steatosis severity (AUC = 0.93). Transplantation of fecal microbiota from MAFLD subjects into ABX mice led to the onset of MAFLD-like symptoms, whereas B. uniformis administration alleviate disease progression by inhibiting intestinal fat absorption, FFA from eWAT influx into liver via the gut-liver axis, and IRE1α-XBP1s-mediated flipogenesis and ferroptosis, as confirmed by hepatic transcriptomic and proteomic analyses. Hexadecanedioic acid (HDA), potentially identified as a key metabolite produced by B. uniformis, ameliorated MAFLD symptoms. Mechanistically, B. uniformis-derived HDA also inhibited fat absorption and transported, and entered the liver via the portal vein to suppress IRE1α-XBP1s-mediated flipogenesis and ferroptosis. B. uniformis and its potential putative metabolite HDA may contribute to MAFLD progression modulation, through regulation of the IRE1α-XBP1s axis. This study provides new insights into the gut-liver axis in MAFLD and offers promising therapeutic targets based on specific microbes and their metabolites.},
}

Humans
Gastrointestinal Microbiome
Animals
*Bacteroides/metabolism/genetics
Mice
Male
Female
Middle Aged
Feces/microbiology
Liver/metabolism
*Fatty Liver/microbiology/metabolism
Fecal Microbiota Transplantation
Prospective Studies
Adult
Metabolomics
Mice, Inbred C57BL

@article {pmid40412060,
year = {2025},
author = {Lin, Z and Wang, J and Luo, H and Huang, L and Pan, Z and Yang, S and Zhong, C and Shan, NC and Ye, Z and Tan, H and Yang, X and Zhang, B and Huang, C and Zhang, H},
title = {Changdiqing decoction (CDQD) ameliorates colitis via suppressing inflammatory macrophage activation and modulating gut microbiota.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {143},
number = {},
pages = {156856},
doi = {10.1016/j.phymed.2025.156856},
pmid = {40412060},
issn = {1618-095X},
abstract = {BACKGROUND: Ulcerative colitis (UC) is a non-specific inflammatory bowel disease. Unlike any single form of cell death reported previously, macrophage PANoptosis, a unique programmed cell death characterized by inflammation and necrosis, plays a crucial role in the pathogenesis of colitis. Changdiqing Decoction (CDQD), an empirical hospital prescription enema, has been used to treat UC for decades. This study aimed to investigate the multi-target anti-colitic effects of CDQD by examining its impact on intestinal homeostasis and its anti-inflammatory properties.

METHODS: A dextran sulfate sodium (DSS)-induced mouse model of acute colitis was employed. Interferon-gamma (IFN-γ) and KPT-330 were used to induce macrophage PANoptosis. Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLCHRMS) was utilized to identify the chemical constituents of CDQD. Multi-omics analysis and fecal microbiota transplantation (FMT) were used to explore the therapeutic targets and gut microbiota alterations induced by CDQD.

RESULTS: CDQD treatment significantly alleviated colitis symptoms in mice, with a dose-dependent therapeutic effect. The decoction mitigated PANoptosis in colon tissues and bone marrow-derived macrophages (BMDMs). 16S rRNA sequencing analysis and metabonomics revealed that CDQD administration significantly altered the gut microbiota composition and metabolite profiles. Notably, CDQD-modulated gut microbiota exhibited anti-colitic effects through FMT. Integrated transcriptomics and network pharmacology analysis revealed that CDQD significantly downregulated the PI3K/Akt signaling pathway in colitis. This finding was further validated using the inhibitors LY294002 and MK2206.

CONCLUSIONS: CDQD alleviates colitis by suppressing inflammatory macrophage activation and modulating the gut microbiota. Our research provides a novel traditional Chinese medicine strategy for the treatment of UC via enema administration.},
}

@article {pmid40411710,
year = {2025},
author = {Chen, L and Chen, C and Bai, Y and Li, C and Wei, C and Wei, R and Luo, R and Li, R and Ma, Q and Geng, Y},
title = {Evaluation of the effects of different formulations of protectants on the preservation of the microbiota in fecal microbiota transplantation.},
journal = {International microbiology : the official journal of the Spanish Society for Microbiology},
volume = {},
number = {},
pages = {},
pmid = {40411710},
issn = {1618-1905},
abstract = {BACKGROUND: With the increasing indications for fecal microbiota transplantation for the treatment of diseases, there is a growing demand for the preparation of frozen or lyophilized fecal microbiota products that are viable and can stably colonize the recipient. The addition of protective agents plays an important role in the preparation. However, there has been no systematic evaluation of the protective agents used in fecal microbiota sample transplantation preparation for transplantation.

METHODS: We were used the donor bacterial flora containing 10 different formulations of protective agents were frozen, lyophilized, and stored. Plate counting, CCK8 assay, flow cytometry after LIVE/DEAD staining, and fluorescence intensity were used to assess viable bacteria in vitro. In addition, the donor bacterial flora samples containing different formulations protective agents were transplanted into antibiotic-treated SPF mice, with 3 mice in each group and a total of 5 groups. Fecal samples were collected for metagenomic sequencing to observe the colonization of the bacterial flora in the recipient mice.

RESULTS: The preliminary screening results showed that the survival rate of bacteria in the 5% trehalose (T) groups, and 5% sucrose, 5% inulin, and 1% cysteine hydrochloride (SI) groups was slightly higher than that in the other groups. SI groups tended to be more protective against anaerobes than T groups. The donor gut microbiota containing the SI groups protective agent exhibited the best colonization of the recipient mice. The protective effects of different formulations of protective agents on the colonized probiotic strains and the metabolic function of the bacterial flora in recipient mice were found to be species specific.

CONCLUSIONS: SI groups can not only better protect the activity of anaerobic bacteria in the intestine, but also effectively promote the effective colonization of donor intestinal bacteria in the recipient mice, and the effect of frozen storage method is less, and can be used at the same time as frozen and freeze-dried preparation. It can be used as a reference for the selection of protective agents in the preparation of fecal microbiota transplantation samples.},
}

@article {pmid39581509,
year = {2025},
author = {Chen, S and Wen, Q and Zhang, F},
title = {An Unusual Cause of Diarrhea and Hematochezia.},
journal = {Gastroenterology},
volume = {168},
number = {6},
pages = {1066-1070},
doi = {10.1053/j.gastro.2024.11.007},
pmid = {39581509},
issn = {1528-0012},
}

@article {pmid40411629,
year = {2025},
author = {Nezhadi, J and Lahouty, M and Rezaee, MA and Fadaee, M},
title = {Clostridium difficile as a potent trigger of colorectal carcinogenesis.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {910},
pmid = {40411629},
issn = {2730-6011},
abstract = {Clostridium difficile, traditionally recognized as a cause of antibiotic-associated colitis, has emerged as a potential oncogenic factor in colorectal cancer (CRC). This article explores the mechanisms by which C. difficile toxins, TcdA and TcdB, contribute to CRC pathogenesis through epithelial barrier disruption, DNA damage, and chronic inflammation via NF-κB and STAT3 activation. Dysbiosis further exacerbates tumorigenesis by altering microbial metabolites. Understanding these interactions highlights potential therapeutic strategies, including toxin-neutralizing antibodies, fecal microbiota transplantation, and anti-inflammatory interventions, to mitigate CRC risk associated with C. difficile.},
}

@article {pmid40410854,
year = {2025},
author = {Fan, L and Chen, J and Zhang, Q and Ren, J and Chen, Y and Yang, J and Wang, L and Guo, Z and Bu, P and Zhu, B and Zhao, Y and Wang, Y and Liu, X and Wang, W and Chen, Z and Gao, Q and Zheng, L and Cai, J},
title = {Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial.},
journal = {Microbiome},
volume = {13},
number = {1},
pages = {133},
pmid = {40410854},
issn = {2049-2618},
support = {82300564//National Natural Science Foundation of China/ ; 81630014//National Natural Science Foundation of China/ ; BRWEP2024W012060100//Beijing Research Ward Excellence Program/ ; BRWEP2024W012060100//Beijing Research Ward Excellence Program/ ; 2024ZD0526804//National Science and Technology Major Project for the Prevention and Treatment of Cancer, Cardiovascular and Cerebrovascular Diseases, Respiratory Diseases and Metabolic Diseases/ ; 2024ZD0526800//National Science and Technology Major Project for the Prevention and Treatment of Cancer, Cardiovascular and Cerebrovascular Diseases, Respiratory Diseases and Metabolic Diseases/ ; BRWEP2024W012060105//Beijing Research Ward Excellence Program，BRWEP/ ; CIFMS, 2021-I2M-1-007//CAMS Innovation Fund for Medical Sciences/ ; 81825002//National Outstanding Youth Science Fund Project of National Natural Science Foundation of China/ ; BJJWZYJH01201910023029//Beijing Outstanding Young Scientist Program/ ; Z231100004623009//Beijing Municipal Science & Technology Commission/ ; CI2021A00920//Key project of Science and Technology Innovation Project of China Academy of Chinese Medical Sciences/ ; ZLRK202511//Beijing Hospitals Authority Clinical medicine Development of special funding support/ ; L248105//Beijing Natural Science Foundation/ ; },
mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; Male ; Female ; *Hypertension/therapy/microbiology ; Adult ; *Gastrointestinal Microbiome/physiology ; Middle Aged ; Feces/microbiology ; Blood Pressure ; China ; Treatment Outcome ; },
abstract = {BACKGROUND: On the basis of the contribution of the gut microbiota to hypertension development, a novel strategy involving fecal microbiota transplantation (FMT) has been proposed to treat hypertension, but its efficacy has not been investigated in the clinic.

METHODS: In a randomized, blinded, placebo-controlled clinical trial (2021/03-2021/12, ClinicalTrials.gov, NCT04406129), hypertensive patients were recruited from seven centers in China, and received FMT or placebo capsules orally at three visits. The patients were randomized at a 1:1 ratio in blocks of four and stratified by center by an independent statistician. The intention-to-treat principle was implemented, as all randomized participants who received at least one intervention were included. The primary outcome was the decrease in office systolic blood pressure (SBP) from baseline to the day 30 visit. Adverse events (AEs) were recorded through the 3-month follow-up to assess safety measures. Alterations in BP, the fecal microbiome, and the plasma metabolome were assessed via exploratory analyses.

RESULTS: This study included 124 patients (mean age 43 years, 73.4% men) who received FMT (n = 63) or placebo (n = 61) capsules. The numbers of participants who experienced AEs (13 (20.6%) vs. 9 (14.8%), p = 0.39) and the primary outcome (6.28 (11.83) vs. 5.77 (10.06) mmHg, p = 0.62) were comparable between the groups. The FMT group presented a decrease in SBP after 1 week of FMT, with a between-arm difference of - 4.34 (95% CI, - 8.1 to - 0.58; p = 0.024) mmHg, but this difference did not persist even after repeated intervention. After FMT, shifts in microbial richness and structure were identified and the abundance of the phyla Firmicutes and Bacteroidetes was altered. Decreases in the abundances of Eggerthella lenta, Erysipelatoclostridium ramosum, Anaerostipes hadrus, Gemella haemolysans, and Streptococcus vestibularis and increases in the abundances of Parabacteroides merdae, Prevotella copri, Bacteroides galacturonicus, Eubacterium sp. CAG 180, Desulfovibrio piger, Megamonas hypermegale, Collinsella stercoris, Coprococcus catus, and Allisonella histaminiformans were identified and correlated with office SBP. Those species were also correlated with responding and inversely office SBP-associated metabolites including tyrosine, glutamine, aspartate, phenylalanine, methionine, serine, sarcosine, and/or asparagine.

CONCLUSIONS: Safety but unsustainable BP reduction was observed in the first trial of the effects of FMT on hypertension. Additional intervention studies on specific microbes with metabolite-targeting and BP-modulating features are needed. Video Abstract.},
}

Humans
*Fecal Microbiota Transplantation/methods/adverse effects
Male
Female
*Hypertension/therapy/microbiology
Adult
*Gastrointestinal Microbiome/physiology
Middle Aged
Feces/microbiology
Blood Pressure
China
Treatment Outcome

@article {pmid40409520,
year = {2025},
author = {Sen, U},
title = {Gut microbiota and well-being: a comprehensive summary of the special issue.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {107791},
doi = {10.1016/j.phrs.2025.107791},
pmid = {40409520},
issn = {1096-1186},
abstract = {Gut microbes play an immense role in digesting ingested food, providing nutrients to the host, and producing several bioactive metabolites that not only help maintain health but can also elicit disease during dysbiotic conditions. The bioactive compounds derived from gut microbiota metabolites include trimethylamine-N-oxide (TMAO), uremic toxins, short chain fatty acids (SCFAs), phytoestrogens, anthocyanins, bile acids, lipopolysaccharide - to name a few. Once these compounds enter the host cells, tissues, and organs they can cause diseases such as epigenetic, metabolic, neurodegenerative, psychiatric, cardiovascular, hypertension, respiratory, gastrointestinal, kidney, bone, cancer, and others. Regulating healthy gut microbiota thus provides a potential option for the prevention, reversal, or even treatment of these diseases. Towards this end, various interventional strategies are postulated in this field of emerged and rapidly expanding health research arena that includes fecal microbiota transplantation, prebiotics, and probiotics, and to introduce the concept that correcting gut dysbiosis can ameliorate disease symptoms, thus offering a new approach towards dysbiosis-related disease mitigation and treatment. In the special issue of Pharmacological Research titled "Gut Microbiota and Well-Being," several outstanding research findings and review articles are published, covering a broad spectrum of topics related to the influence of gut microbiota on health and disease. This editorial summarizes each of these contributions, prioritizing research findings before discussing the review articles. The summaries are restructured abstracts of relevant articles focusing on major findings or thematic topics.},
}

@article {pmid40409481,
year = {2025},
author = {Chen, E and Zhou, W},
title = {Immunotherapy in Microsatellite-Stable Colorectal Cancer: Strategies to Overcome Resistance.},
journal = {Critical reviews in oncology/hematology},
volume = {},
number = {},
pages = {104775},
doi = {10.1016/j.critrevonc.2025.104775},
pmid = {40409481},
issn = {1879-0461},
abstract = {Colorectal cancer (CRC) is among the foremost causes of cancer-related mortality worldwide; however, individuals with microsatellite-stable (MSS) disease-who constitute most CRC diagnoses-derive limited benefit from existing immunotherapeutic approaches. Here, we outline emerging methods designed to address the inherent resistance of MSS CRC to immune checkpoint inhibitors (ICIs). Recent findings emphasize how the immunosuppressive tumor microenvironment (TME) in MSS CRC, marked by diminished immunogenicity and high levels of regulatory T cells and myeloid-derived suppressor cells, restricts effective antitumor immune activity. Combination regimens that merge ICIs with chemotherapy, anti-angiogenic agents, or targeted blockade of pathways such as TGF-β and VEGF have shown encouraging early outcomes, including enhanced antigen presentation and T-cell penetration. Novel immunomodulatory platforms-such as epigenetic modifiers, oncolytic viruses, and engineered probiotic vaccines-are under assessment to further reprogram the TME and boost therapeutic efficacy. Concurrently, progress in adoptive cell therapies (for example, chimeric antigen receptor (CAR) T cells) and the development of cancer vaccines targeting tumor-associated and neoantigens promise to extend immune control over MSS CRC. In parallel, improving patient selection through predictive biomarkers-from circulating tumor DNA (ctDNA) to gene expression signatures and specific molecular subtypes-could refine individualized treatment strategies. Finally, interventions that alter the gut microbiome, including probiotics and fecal transplantation, serve as complementary tools to strengthen ICI responses. Taken together, these insights and combined treatment strategies lay the foundation for more successful immunotherapeutic interventions in MSS CRC, ultimately aiming to provide sustained clinical benefits to a broader spectrum of patients.},
}

@article {pmid40406094,
year = {2025},
author = {Eslami, M and Naderian, R and Bahar, A and Babaeizad, A and Rezanavaz Gheshlagh, S and Oksenych, V and Tahmasebi, H},
title = {Microbiota as diagnostic biomarkers: advancing early cancer detection and personalized therapeutic approaches through microbiome profiling.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1559480},
pmid = {40406094},
issn = {1664-3224},
mesh = {Humans ; Precision Medicine/methods ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/diagnosis/therapy/microbiology ; *Early Detection of Cancer/methods ; *Biomarkers, Tumor ; Animals ; Fecal Microbiota Transplantation ; },
abstract = {The important function of microbiota as therapeutic modulators and diagnostic biomarkers in cancer has been shown by recent developments in microbiome research. The intricate interplay between the gut microbiota and the development of cancer, especially in colorectal and breast cancers, emphasizes how microbial profiling may be used for precision treatment and early diagnosis. Important microbial signatures, including Bacteroides fragilis and Fusobacterium nucleatum, have been linked to the development and progression of cancer, providing important information on the processes behind carcinogenesis. Additionally, the influence of microbiota on the effectiveness of treatments such as immunotherapy and chemotherapy highlights its dual function in improving treatment outcomes and reducing side effects. To optimize treatment results, strategies including dietary changes and fecal microbiota transplantation (FMT) are being investigated. Despite these developments, there are still issues, such as individual variations in microbial composition, a lack of standardized procedures, and the requirement for reliable biomarkers. Integrating microbiome-based diagnostics with conventional approaches, such as liquid biopsies and machine learning algorithms, could revolutionize cancer detection and management. This review provides an overview of the current understanding of the host-microbe immunological axis and discusses emerging therapeutic strategies centered on microbiota modulation to support human health. Further research is essential to overcome existing challenges and fully realize the promise of microbiota-driven innovations in oncology.},
}

Humans
Precision Medicine/methods
*Gastrointestinal Microbiome/immunology
*Neoplasms/diagnosis/therapy/microbiology
*Early Detection of Cancer/methods
*Biomarkers, Tumor
Animals
Fecal Microbiota Transplantation

@article {pmid40402463,
year = {2025},
author = {Li, L and Hu, M and Zhu, X and Huang, X and Chen, H},
title = {Microbiota Transplantation in Tumor Immunology Studies.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2930},
number = {},
pages = {295-306},
pmid = {40402463},
issn = {1940-6029},
mesh = {*Neoplasms/immunology/therapy/microbiology/pathology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; Animals ; Humans ; Mice ; Feces/microbiology ; },
abstract = {This protocol outlines the standardized procedures for utilizing fecal microbiota transplantation (FMT) in tumor immunology studies. FMT, the process of transferring gut microbiota from a healthy donor to a recipient, has shown potential in modulating the immune response against tumors. This protocol details the selection criteria for donors and recipients, preparation and processing of fecal material, and the administration routes for transplantation. Additionally, it describes the pre- and posttransplantation monitoring of microbiota composition, immune parameters, and tumor progression. By following this protocol, researchers can systematically investigate the impact of microbiota on tumor growth and immune modulation, contributing to the development of microbiota-based therapeutic strategies in oncology.},
}

*Neoplasms/immunology/therapy/microbiology/pathology
*Fecal Microbiota Transplantation/methods
*Gastrointestinal Microbiome/immunology
Animals
Humans
Mice
Feces/microbiology

@article {pmid40401951,
year = {2025},
author = {Huang, J and Qiao, H and Li, Q and Zhang, Y and Zhang, C and Su, H and Sun, X},
title = {Osteopontin protects from ovalbumin-induced asthma by preserving the microbiome and the intestinal barrier function.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0038925},
doi = {10.1128/msystems.00389-25},
pmid = {40401951},
issn = {2379-5077},
abstract = {UNLABELLED: The gut and lung microbiota are associated with asthma. Osteopontin (OPN) is an important cytokine associated with several inflammatory diseases. The potential role of OPN in the asthma-associated microbiome remains poorly understood. Here, we investigated whether OPN could moderate asthma by affecting the gut and lung microbiota. Our results showed that compared with wild-type (WT) mice, Spp1[-/-] mice exhibited immune cell infiltration in the lung, OVA-specific IgG1, increased levels of Th2- and Th17-related inflammatory factors, and decreased levels of Th1-related inflammatory factors and forkhead box P3 (FOXP3) expression, resulting in a Th1/Th2 and Th17/Treg imbalance. In addition, gut structure was impaired, and expression of tight junction-related proteins was reduced in Spp1[-/-] mice, which disrupted gut barrier function. Importantly, OPN-deficient significantly aggravated gut and lung microbiota dysbiosis in OVA-induced asthmatic mice. The results of high-throughput 16S rRNA sequencing demonstrated that OPN-deficient mice showed a substantial reduction in beneficial gut and lung bacteria (Bacteroidetes, Lactobacillus, Allobaculum), and an OVA-induced increase in the abundance of bacteria associated with potentially pathogenic gut and lung (Epsilonbacteraeota, Helicobacter, Desulfovibrio, Oscillibacter)-associated bacteria was elevated in abundance. Allobaculum was negatively correlated with interleukin-4 and GATA-3 and was positively correlated with interferon gamma and FOXP3. Moreover, through fecal microbiota transplantation, we found that OVA-induced IgE and IgG1 levels were reduced in OPN-deficient asthmatic mice, Th1/Th2 and Th17/Treg balance was maintained, gut barrier function was improved, and microbiome changes in OPN-deficient mice were compensated for, with an elevated abundance of Allobaculum and reduced abundance of Desulfovibrio and Oscillibacter. We further discovered that OPN deficiency reduces FOXP3 expression and decreases Lactobacillus colonization through activation of the PD-1/PD-L1 pathway in the intestine and lung. The present study suggests that OPN may moderate OVA-induced asthma by modulating the gut and lung microbiota.

IMPORTANCE: Osteopontin deficiency exacerbated asthmatic airway inflammation, an effect associated with microbiota dysbiosis, impaired intestinal barrier function, and increased PD-1/PD-L1 expression and thus decreased Treg cell function. The study provides clinicians with new insights into asthma mechanisms and can also lead to new ideas for asthma treatment.},
}

@article {pmid40401932,
year = {2025},
author = {McMullen, BN and Chen See, J and Baker, S and Wright, JR and Anderson, SLC and Yochum, G and Koltun, W and Portolese, A and Jeganathan, NA and Lamendella, R},
title = {Metatranscriptomic analysis of colonic mucosal samples exploring the functional role of active microbial consortia in complicated diverticulitis.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0243124},
doi = {10.1128/spectrum.02431-24},
pmid = {40401932},
issn = {2165-0497},
abstract = {In this study, we investigated complicated diverticulitis, an inflammatory condition associated with abscesses, fistulas, intestinal obstructions, perforations, and primarily affects adults over the age of 60. Although the exact etiology remains unclear, the gut microbiome has been suggested as a contributing factor. Previous studies have used 16S rRNA gene analysis from patient fecal samples, which is limited to identifying the bacterial communities present. Herein, we employed shotgun metatranscriptomics on 40 patient-matched samples of diseased and adjacent normal colonic mucosal tissues from 20 patients with complicated diverticulitis to gain a more comprehensive understanding of active microbial taxa and gene expression patterns that may be involved in this disease state. Our findings revealed distinct beta diversity and a conglomerate of pathogenic microbiota in the diseased tissues, including Staphylococcus cohnii, Corynebacterium jeikeium, Kineococcus, Talaromyces rugulosus, Campylobacteraceae, and Ottowia, among others. The adjacent normal tissues were a stark contrast, harboring anti-inflammatory taxa such as Streptococcus salivarius and housekeeping genes and pathways such as the ABC-2 type transport system ATP-binding protein. These results align with previous amplicon sequencing studies and provide novel functional insights that may be crucial for understanding the etiology of complicated diverticulitis.IMPORTANCEComplicated diverticulitis is a virulent condition with no clear cause other than the association with colonic diverticulosis. We assessed the microbial gene expression in complicated diverticulitis patients using colonic tissue samples, revealing microbes in the diseased tissue known to exacerbate the diverticular condition and to live in extreme places, and microbes in patients' normal tissue known to maintain normal bodily functions. This functional information is therefore important for understanding what microbial taxa are present and what they are doing. It is possible clinicians could someday harness this information to more effectively treat complicated diverticulitis symptoms. For example, clinicians may suggest dietary changes and prescribe probiotics to increase beneficial bacteria. Clinicians may also prescribe targeted antibiotics or consider the emerging treatment option of fecal transplants in complicated diverticulitis patients. While not curing complicated diverticulitis, each potential treatment option mentioned addresses balancing out dysbiosis of the gut microbiome, therefore alleviating associated symptoms.},
}

@article {pmid40400677,
year = {2025},
author = {Men, J and Cui, C and Li, H and Li, Z and Zhang, Y and Liu, Z and Wang, Q and Liu, P and Zou, S and Yu, Z and Zhang, Y and Wu, S and Zhu, G and Wang, P and Huang, X},
title = {Cold water swimming reshapes gut microbiome to improve high-fat diet-induced obesity.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1589902},
pmid = {40400677},
issn = {1664-302X},
abstract = {Hypothermia and swimming have been shown to alleviate high-fat diet (HFD)-induced obesity, with effects linked to the gut microbiota (GM). However, whether the effects of cold water swimming (CWS) on GM can be effectively transferred through fecal microbiota transplantation (FMT) has not been investigated. This study established mice models of obesity, CWS and FMT to investigate the mechanism by which CWS reshapes GM to improve HFD-induced obesity. Additionally, we analyzed the relationship between obesity phenotypes, GM composition, gene expression and CWS. The study found that HFD induced obesity phenotypes and GM dysbiosis in mice, while CWS produced opposite effects. The FMT results confirmed that CWS effectively alleviated HFD-induced lipid accumulation, metabolic disorders, and chronic inflammatory responses, which are associated with increased GM diversity, enrichment of beneficial bacteria, and the repair of intestinal barrier damage. Furthermore, these beneficial effects can be effectively transferred via FMT. The evidence from this study suggests that GM plays a critical role in the anti-obesity effects of CWS, with intestinal barrier repair emerging as a potential therapeutic target. This also provides scientific evidence for the feasibility of FMT as a strategy to combat obesity.},
}

@article {pmid40399878,
year = {2025},
author = {Qian, S and Su, Z and Lin, J and Hou, Q and Wang, X and Li, Y and Wang, J and Huang, C and Wang, Z and Cubero, FJ and Wang, X and Liao, L},
title = {Inhibition of Farnesoid-x-receptor signaling during abdominal sepsis by dysbiosis exacerbates gut barrier dysfunction.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {236},
pmid = {40399878},
issn = {1478-811X},
support = {81971814//the National Natural Science Foundation of China/ ; 81971814//the National Natural Science Foundation of China/ ; 81971814//the National Natural Science Foundation of China/ ; 81971814//the National Natural Science Foundation of China/ ; 20192BAB205013//the Natural Science Foundation of Jiangxi Province/ ; 20192BAB205013//the Natural Science Foundation of Jiangxi Province/ ; 20192BAB205013//the Natural Science Foundation of Jiangxi Province/ ; PWRd2020-06//Academic medicine leader's training Program in health systems of Pudong New Area/ ; PWYgf2021-03//Shanghai Pudong New Area Summit (emergency medicine and critical care) construction project/ ; 23Y11908300//Medical Innovation Research Special Project of Shanghai 2023 Science and Technology Innovation Action Plan/ ; 2020PJD050//Shanghai Pujiang Program/ ; },
mesh = {Animals ; *Receptors, Cytoplasmic and Nuclear/metabolism/agonists ; *Sepsis/metabolism/pathology/microbiology ; *Signal Transduction ; *Dysbiosis/metabolism/pathology ; Mice ; Myeloid Differentiation Factor 88/metabolism ; Fibroblast Growth Factors/metabolism ; Mice, Inbred C57BL ; Gastrointestinal Microbiome ; Male ; *Intestinal Mucosa/metabolism ; Liver/metabolism ; Bile Acids and Salts/metabolism ; },
abstract = {BACKGROUND AND AIMS: Bacterial translocation and intestinal dysbiosis due to gut barrier dysfunction are widely recognized as major causes of the initiation and development of intra-abdominal sepsis. Systemic bacterial translocation and hepatic activation of the myeloid differentiation primary response gene 88 (Myd88) can disturb bile acids (BAs) metabolism, further exacerbating intestinal dysbiosis. The farnesoid X receptor (FXR) and fibroblast growth factor (FGF) 15/19 are well known to be involved in the control of BAs synthesis and enterohepatic circulation. However, the influence of intestinal microbiota on intestinal Myd88 signaling, the FXR/FGF15 axis, as well as gut-liver crosstalk during sepsis remains unclear. The present study aims to decipher the role of intestinal Myd88 in abdominal sepsis, its impact on intestinal FXR signaling and FGF15-mediated gut-liver crosstalk.

METHODS: Expression levels of FXR and FGF15 in the liver and intestines, alongside assessments of gut barrier function, were evaluated in septic wild-type (WT) mice 24 h post-cecal ligation and puncture (CLP) surgery. Subsequently, the FXR agonist INT-747 was administered to explore the relationship between FXR activation and gut barrier function. Further investigations involved Myd88-deficient mice with specific deletion of Myd88 in intestinal epithelial cells (Myd88[△IEC]), subjected to CLP to examine the interplay among intestinal Myd88, FXR, gut barrier function, microbiota, and BA composition. Additionally, fecal microbiota transplantation (FMT) from septic mice to Myd88[△IEC] mice was conducted to study the impact of dysbiosis on intestinal Myd88 expression during sepsis, using floxed (Myd88[fl/fl]) mice as controls. Finally, the effects of the probiotic intervention on gut barrier function and sepsis outcomes in CLP mice were investigated.

RESULTS: Induction of sepsis via CLP led to hepatic cholestasis, suppressed FXR-FGF15 signaling, altered gut microbiota composition, and compromised gut barrier function. Administration of INT-747 increased intestinal FXR and FGF15 expression, strengthened gut barrier function, and enhanced barrier integrity. Interestingly, Myd88[△IEC] mice exhibited partial reversal of sepsis-induced changes in FXR signaling, BA metabolism, and intestinal function, suggesting enhanced FXR expression upon Myd88 knockdown. Moreover, FMT from septic mice activated intestinal Myd88, subsequently suppressing FXR-FGF15 signaling, exacerbating cholestasis, and ultimately compromising gut barrier function. Probiotic treatment during abdominal sepsis mitigated flora disturbances, reduced Myd88 activation in the intestinal epithelium, increased FXR expression, alleviated cholestasis, and consequently reduced barrier damage.

CONCLUSIONS: This study highlights the critical role of Myd88/FXR signaling in intestinal epithelial cells as a pivotal mediator of the detrimental effects induced by sepsis-related intestinal dysbiosis on barrier function and bile acid metabolism. In summary, disordered intestinal flora in septic mice specifically triggers intestinal epithelial Myd88 activation, inhibit the FXR-FGF15 axis, and then worsen intestinal barrier function impairment.},
}

Animals
*Receptors, Cytoplasmic and Nuclear/metabolism/agonists
*Sepsis/metabolism/pathology/microbiology
*Signal Transduction
*Dysbiosis/metabolism/pathology
Mice
Myeloid Differentiation Factor 88/metabolism
Fibroblast Growth Factors/metabolism
Mice, Inbred C57BL
Gastrointestinal Microbiome
Male
*Intestinal Mucosa/metabolism
Liver/metabolism
Bile Acids and Salts/metabolism

@article {pmid40339798,
year = {2025},
author = {Gîlcă-Blanariu, GE and Pakpour, S and Kao, D},
title = {More questions than answers? Predicting faecal microbiota transplantation outcomes for recurrent Clostridioides difficile infection.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmi.2025.04.036},
pmid = {40339798},
issn = {1469-0691},
}

@article {pmid40398680,
year = {2025},
author = {Zhou, Y and Komnick, MR and Sepulveda, F and Liu, G and Nieves-Ortiz, E and Meador, K and Ndatabaye, O and Fatkhullina, A and Bozicevich, A and Juengel, B and Wu-Woods, NJ and Naydenkov, PM and Kent, J and Christiansen, N and Madariaga, ML and Witkowski, P and Ismagilov, RF and Esterházy, D},
title = {Inducible, but not constitutive, pancreatic REG/Reg isoforms are regulated by intestinal microbiota and pancreatic diseases.},
journal = {Mucosal immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.mucimm.2025.05.003},
pmid = {40398680},
issn = {1935-3456},
abstract = {The REG/Reg gene locus encodes a conserved family of potent antimicrobial but also pancreatitis-associated proteins. Here we investigated whether REG/Reg family members differ in their baseline expression levels and abilities to be regulated in the pancreas and gut upon perturbations. We found, in humans and mice, the pancreas and gut differed in REG/Reg isoform levels and preferences, with the duodenum most resembling the pancreas. Pancreatic acinar cells and intestinal enterocytes were the dominant REG producers. Intestinal symbiotic microbes regulated the expression of the same, select Reg members in gut and pancreas. These Reg members had the most STAT3-binding sites close to the transcription start sites and were partially IL-22 dependent. We thus categorized them as "inducible" and others as "constitutive". Indeed, in pancreatic ductal adenocarcinoma and pancreatitis models, only inducible Reg members were upregulated in the pancreas. While intestinal Reg expression remained unchanged upon pancreatic perturbation, pancreatitis altered the microbial composition of the duodenum and feces shortly after disease onset. Our study reveals differential usage and regulation of REG/Reg isoforms as a mechanism for tissue-specific innate immunity, highlights the intimate connection of pancreas and duodenum, and implies a gut-to-pancreas communication axis resulting in a coordinated Reg response.},
}

@article {pmid40398524,
year = {2025},
author = {He, X and Wei, X and He, Z and Yao, C and Nie, M and Ma, X and Chen, Q and Guo, DA},
title = {Biotransformation of artemisinin by human intestinal fungi and cytotoxicity against breast cancer cells of its metabolites.},
journal = {Phytochemistry},
volume = {},
number = {},
pages = {114551},
doi = {10.1016/j.phytochem.2025.114551},
pmid = {40398524},
issn = {1873-3700},
abstract = {Artemisinin widely exists in the Artemisia annua L. and is the front-line of antimalarial drugs. In this study, microbial transformation of artemisinin was performed based on seventeen human intestinal fungal species. Our findings revealed that isomerization and deoxygenation were the most prevalent metabolic pathways in fungi. Incubation of artemisinin with Rhizopus microspores (PT2906) and Candida boidinii (M7017B) afforded three new compounds (P3, P5 and P6) along with seven known metabolites which were elucidated by extensive spectroscopic data analysis. All metabolites were evaluated for their cytotoxicity against MCF-7 cells, and the results showed that 3β-hydroxydeoxyartemisinin (P5) suppressed the growth of MCF-7 cells better than artemisinin. In addition, ten artemisinin isomers were found in the feces of antibiotic-treated mice after M7017B transplantation, demonstrating that human intestinal fungi have the potential to participate in the in vivo intestinal transformation of artemisinin.},
}

@article {pmid40398303,
year = {2025},
author = {Xu, Y and Chen, K and Huang, Y and Yan, Y and Zhang, W and Tian, J and Zhang, D and Liu, M and Nie, Q},
title = {Fecal microbiota transplantation improves growth performance of chickens by increasing the intestinal Lactobacillus and glutamine.},
journal = {Poultry science},
volume = {104},
number = {8},
pages = {105243},
doi = {10.1016/j.psj.2025.105243},
pmid = {40398303},
issn = {1525-3171},
abstract = {Chicken meat is an essential source of high-quality animal protein, mainly derived from slow-growth chicken (SC) and fast-growth chicken (FC) breeds. Skeletal muscle is a highly adaptable tissue that is influenced by breed differences and the gut microbiome. Investigation whether remodeling the gut microbiota by fecal microbiota transplantation (FMT) improves chicken growth is an interesting question. We compared the gut microbial composition of eight breeds of SC (Xinghua chicken, Yangshan chicken, Zhongshan Salan chicken, Qingyuan Partridge chicken, Huiyang Bearded chicken and Huaixiang chicken) and FC (Xiaobai chicken and White rock chicken). Fecal microbiota from donor FC (Xiaobai chickens) with superior growth performance were transferred to SC (Xinghua chickens). The effects of FMT on growth performance, metabolic profile and gut microbiome of recipient chickens were evaluated. We found significant differences in gut microbial composition, with a higher abundance of Bacteroidetes in SC and a higher abundance of Firmicutes in FC. Xiaobai chickens with better growth performance and abundant Lactobacillus, and FMT significantly enhanced growth performance, the expression of mRNA (MYOG, MYF5, MYF6 and IGF1) related to breast and leg muscle development and improved the villus/crypt ratio in the jejunum. FMT altered the microbiota in the duodenum, jejunum, and ileum, increased Lactobacillus abundance, decreased the relative mRNA expression of the intestinal inflammatory factors (IL-1β, IL-6 and TNF-α), increased glutamine levels in the host, including in muscle tissues and intestinal contents, and Spearman correlation analysis indicated that the relative abundance of Lactobacillus was positively correlated with glutamine levels. Additionally, antibiotic treatment reduces glutamine levels in the intestines, blood, and muscle tissues of chickens. Glutamine can increase the expression of cyclinD1, cyclinD2, cyclinB2, MYOG, MYF5, MYF6 and IGF1 mRNA to promote chicken myoblasts proliferation and differentiation. This study found that the SC and FC gut microbes were significantly different, and the FC chicken gut microbes were able to reshape the FC gut microbiota through FMT, i.e., higher Lactobacillus, promoted chicken myoblasts proliferation and differentiation and growth performance by increasing glutamine levels.},
}

@article {pmid40395920,
year = {2025},
author = {Ishikawa, D and Zhang, X and Nagahara, A},
title = {Current Applications and Future Prospects of Fecal Microbiota Transplantation.},
journal = {Juntendo medical journal},
volume = {71},
number = {2},
pages = {68-75},
pmid = {40395920},
issn = {2759-7504},
abstract = {In recent years, the impact of gut microbiota on human health has gained increasing recognition, highlighting the potential benefits of regulating gut microbiota for patient care. Consequently, fecal microbiota transplantation (FMT) has emerged as a novel treatment for improving dysbiosis. It is necessary to summarize and discuss the current research and future development possibilities. This advanced microbial therapy restores the gut microbiome by introducing a diverse array of microorganisms from healthy donors, thereby correcting dysbiosis and re-establishing a fully functional ecosystem. Ongoing research on FMT is actively conducted in various fields worldwide. This study provides an overview of the progress of clinical research on the effects of FMT in gastrointestinal diseases, immune checkpoint inhibitors, allergic diseases, and central nervous system diseases, as well as the results of our ongoing clinical study on "FMT combined with antibiotics for ulcerative colitis."},
}

@article {pmid40395507,
year = {2025},
author = {Shabani, M and Ghoshehy, A and Mottaghi, AM and Chegini, Z and Kerami, A and Shariati, A and Taati Moghadam, M},
title = {The relationship between gut microbiome and human diseases: mechanisms, predisposing factors and potential intervention.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1516010},
pmid = {40395507},
issn = {2235-2988},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Probiotics ; Prebiotics ; Metabolic Diseases/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/microbiology ; Nervous System Diseases/microbiology ; Disease Susceptibility ; Diet ; Diabetes Mellitus, Type 2/microbiology ; },
abstract = {The complex interrelation of gut microbiota with human health underlines the profound influence this microbial ecosystem has on mechanisms of disease and wellness. The gut microbiome profoundly impacts various human diseases, encompassing gastrointestinal disorders, metabolic disorders, neurological disorders, and immune-related diseases. Gastrointestinal disorders are closely linked to microbial imbalances in the gut. Metabolic disorders, including obesity and type 2 diabetes, are influenced by the gut microbiota's role in energy regulation and glucose metabolism. Furthermore, the gut-brain axis highlights the correlation between gut microbiota and neurological conditions such as Alzheimer's and Parkinson's. Moreover, the gut microbiome assumes a pivotal function in regulating the immune system, whereby dysbiosis is implicated in developing immunological-related ailments, including allergies and autoimmune disorders. Predisposing factors, including diet, medicines, lifestyle, and environmental influences, are described as having an important role in the composition of the gut microbiome. By understanding these factors, we can get valuable insights into how to intervene to reduce the chances of a disease. Current interventions, including probiotics, prebiotics, fecal microbiota transplants, and lifestyle modification, show promise, but there are still challenges and unanswered questions in this evolving field that may lead to improvements. This review interrelates the complicated gut microbiome with various human diseases, mechanisms, predisposing factors, and potential interventions.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Dysbiosis/microbiology
Probiotics
Prebiotics
Metabolic Diseases/microbiology
Fecal Microbiota Transplantation
Gastrointestinal Diseases/microbiology
Nervous System Diseases/microbiology
Disease Susceptibility
Diet
Diabetes Mellitus, Type 2/microbiology

@article {pmid40394204,
year = {2025},
author = {Oliver, PJ and Civitelli, L and Hu, MT},
title = {The gut-brain axis in early Parkinson's disease: from prodrome to prevention.},
journal = {Journal of neurology},
volume = {272},
number = {6},
pages = {413},
pmid = {40394204},
issn = {1432-1459},
mesh = {Humans ; *Parkinson Disease/prevention & control/metabolism/microbiology/physiopathology ; *Gastrointestinal Microbiome/physiology ; alpha-Synuclein/metabolism ; *Prodromal Symptoms ; *Brain-Gut Axis/physiology ; *Brain/metabolism ; Dysbiosis ; Animals ; },
abstract = {Parkinson's disease is the second most common neurodegenerative disorder and fastest growing neurological condition worldwide, yet its etiology and progression remain poorly understood. This disorder is characterized pathologically by the prion-like spread of misfolded neuronal alpha-synuclein proteins in specific brain regions leading to Lewy body formation, neurodegeneration, and progressive neurological impairment. It is unclear what triggers Parkinson's and where α-synuclein protein aggregation begins, although proposed induction sites include the olfactory bulb and dorsal motor nucleus of the vagus nerve. Within the last 20 years, there has been increasing evidence that Parkinson's could be triggered by early microbiome changes and α-synuclein accumulation in the gastrointestinal system. Gut microbiota dysbiosis that alters gastrointestinal motility, permeability, and inflammation could enable prion-like spread of α-synuclein from the gut-to-brain via the enteric nervous system. Individuals with isolated rapid eye movement sleep behavior disorder have a high likelihood of developing Parkinson's and might represent a prodromal 'gut-first' subtype of the condition. The gut-first model of Parkinson's offers novel gut-based therapeutic avenues, such as anti-, pre-, and pro-biotic preparations and fecal microbiota transplants. Crucially, gut-based interventions offer an avenue to treat Parkinson's at early prodromal stages with the aim of mitigating evolution to clinically recognizable Parkinson's disease characterized by motor impairment.},
}

Humans
*Parkinson Disease/prevention & control/metabolism/microbiology/physiopathology
*Gastrointestinal Microbiome/physiology
alpha-Synuclein/metabolism
*Prodromal Symptoms
*Brain-Gut Axis/physiology
*Brain/metabolism
Dysbiosis
Animals

@article {pmid40300608,
year = {2025},
author = {Wirbel, J and Andermann, TM and Brooks, EF and Evans, L and Groth, A and Dvorak, M and Chakraborty, M and Palushaj, B and Reynolds, GZM and Porter, IE and Al Malki, M and Rezvani, A and Gooptu, M and Elmariah, H and Runaas, L and Fei, T and Martens, MJ and Bolaños-Meade, J and Hamadani, M and Holtan, S and Jenq, R and Peled, JU and Horowitz, MM and Poston, KL and Saber, W and Kean, LS and Perales, MA and Bhatt, AS},
title = {Accurate prediction of absolute prokaryotic abundance from DNA concentration.},
journal = {Cell reports methods},
volume = {5},
number = {5},
pages = {101030},
doi = {10.1016/j.crmeth.2025.101030},
pmid = {40300608},
issn = {2667-2375},
mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; *DNA, Bacterial/genetics/analysis ; Machine Learning ; *Prokaryotic Cells ; Male ; Parkinson Disease/microbiology ; },
abstract = {Quantification of the absolute microbial abundance in a human stool sample is crucial for a comprehensive understanding of the microbial ecosystem, but this information is lost upon metagenomic sequencing. While several methods exist to measure absolute microbial abundance, they are technically challenging and costly, presenting an opportunity for machine learning. Here, we observe a strong correlation between DNA concentration and the absolute number of 16S ribosomal RNA copies as measured by digital droplet PCR in clinical stool samples from individuals undergoing hematopoietic cell transplantation (BMT CTN 1801). Based on this correlation and additional measurements, we trained an accurate yet simple machine learning model for the prediction of absolute prokaryotic load, which showed exceptional prediction accuracy on an external cohort that includes people living with Parkinson's disease and healthy controls. We propose that, with further validation, this model has the potential to enable accurate absolute abundance estimation based on readily available sample measurements.},
}

Humans
RNA, Ribosomal, 16S/genetics
Feces/microbiology
*DNA, Bacterial/genetics/analysis
Machine Learning
*Prokaryotic Cells
Male
Parkinson Disease/microbiology

@article {pmid40393939,
year = {2025},
author = {Zhang, X and He, Q and Zhang, C and Ji, Z and Yang, D and Wang, X and Liu, C and Zhang, C and Yuan, J and Xu, N and Chu, J},
title = {Gegen Qinlian Decoction protects kidney in diabetic rats by improving intestinal barrier and regulating intestinal microbiota.},
journal = {The Journal of pharmacy and pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jpp/rgaf030},
pmid = {40393939},
issn = {2042-7158},
support = {82204707//National Natural Science Foundation of China/ ; },
abstract = {OBJECTIVES: To investigate the renoprotective effects of Gegen Qinlian Decoction (GQD) in Diabetes mellitus (DM) rats via the intestinal barrier and microbiota.

METHODS: GQD was analyzed by UPLC. STZ-induced DM rat models and antibiotic-induced sterile DM rat models were established, and fecal microbiota transplantation was performed in the latter. Renal function, oxidative stress, serum inflammatory factors, and pathological alterations were assessed. Intestinal cells and tight junction were observed by transmission electron microscopy. Inflammatory factors in the colon and tight junction protein expression were evaluated. The gut microbiota and its abundance were assessed by 16sRNA sequencing.

KEY FINDINGS: Four components were determined in the GQD, including puerarin, baicalin, berberine, and liquiritin. After GQD treatment, Scr and BUN were reduced, renal pathological changes were attenuated, intestinal cell swelling was reduced, intestinal tight junctions were improved, and GQD modulated the intestinal microbiota. Furthermore, a fecal bacterial solution containing GQD reduced renal lesions, improved intestinal tight junctions, and regulated intestinal microbiota in DM rats.

CONCLUSIONS: GQD regulated the intestinal microbiota of DM rats, reduced intestinal inflammation, and repaired the intestinal barrier, thus reducing the burden on the kidneys, and exerting a protective effect on the kidneys of DM rats.},
}

@article {pmid40393246,
year = {2025},
author = {Liu, X and Li, Y and Yuan, C and Zhao, Y and Zhou, L and Yan, Y and Ren, J and Liu, Q},
title = {Sophocarpine suppresses MAPK-mediated inflammation by restoring gut microbiota in colorectal cancer.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {143},
number = {},
pages = {156833},
doi = {10.1016/j.phymed.2025.156833},
pmid = {40393246},
issn = {1618-095X},
abstract = {BACKGROUND: Colorectal cancer (CRC), as one of the most common cancers globally, poses a significant challenge to public health due to its high incidence and mortality rates. This underscores the need for continuous exploration of new therapeutic targets and effective drugs. Sophocarpine (SC), a natural compound derived from traditional Chinese medicine, holds considerable therapeutic potential in the treatment of CRC, however, the relevant mechanisms remains unclear.

PURPOSE: This study aims to explore the anti-tumor effects of SC against CRC by modulating gut microbiota, and uncover potential mechanisms linking SC's therapeutic effects to gut microbiota regulation by analyzing the impact of SC on microbiota composition and CRC progression.

MATERIAL: This study explores the impact of SC on the gut microbiota in CRC by constructing subcutaneous xenograft tumors of CRC and integrating 16S rRNA sequencing and RNA transcriptomic sequencing. The fecal microbiota transplantation (FMT) mouse model was used to validate the biological function of SC in correcting gut microbiota dysbiosis to treat CRC. Subsequently, we conducted in vitro studies on the molecular mechanisms by which SC regulates the gut microbiota as an effective hallmark of CRC treatment, using lipopolysaccharide (LPS) to simulate an inflammatory gut microbiota environment and P38 MAPK knockdown cell line.

RESULTS: SC significantly inhibited CRC cell proliferation with IC50 values of 2.547±0.256 μM for HCT116 and 2.851±0.332 μM for LoVo cells. In vivo experiments demonstrated that SC effectively suppressed tumor growth in xenograft models. 16S rRNA sequencing revealed that SC modulated gut microbiota composition, particularly affecting Bacteroides and Alistipes populations. SC significantly reduced the levels of inflammatory factors and inhibited the MAPK signaling pathway, as evidenced by decreased p-JNK, p-p38 MAPK, and p-NF-κB p65 expression.

CONCLUSIONS: Current clinical practice still lacks effective therapeutic agents targeting CRC through gut microbiota modulation. This study presents the first evidence that SC, a natural compound, exhibits dual-action therapeutic efficacy against CRC progression by simultaneously modulating gut microbial composition and suppressing MAPK pathway-mediated inflammatory responses. These findings highlight SC's novel therapeutic potential as a promising microbiota-regulating candidate for CRC intervention, offering an innovative approach that bridges microbial ecology with cancer signaling pathways.},
}

@article {pmid40392289,
year = {2025},
author = {Piteková, B and Hric, I and Baranovičová, E and Zieg, J and Planet, PJ and Bielik, V},
title = {The effect of fecal microbial transplantation in a pediatric patient after 28 episodes of febrile urinary tract infection.},
journal = {Pediatric nephrology (Berlin, Germany)},
volume = {},
number = {},
pages = {},
pmid = {40392289},
issn = {1432-198X},
support = {VEGA 1/0313/25//Ministerstvo školstva, vedy, výskumu a športu Slovenskej republiky/ ; VEGA 1/0022/26//Ministerstvo školstva, vedy, výskumu a športu Slovenskej republiky/ ; APVV-22-0047//Agentúra Ministerstva Školstva, Vedy, Výskumu a Športu SR/ ; },
abstract = {Recurrent febrile urinary tract infections (fUTIs) in children can lead to serious complications such as renal scarring and progressive chronic kidney disease (CKD), with growing evidence indicating that gut microbiome dysbiosis may play a key role in their development. Fecal microbial transplantation (FMT) is an established therapeutic approach for restoring gut microbial balance; however, its use in patients with recurrent fUTIs remains limited and underexplored. This case study describes a 10-year-old boy with recurrent fUTIs and CKD secondary to a posterior urethral valve (PUV) anomaly. The patient was administered a total of seven doses of FMT. FMT reduced pathogenic Enterobacteriaceae, increased beneficial short-chain fatty acid (SCFA)-producing genera, and correspondingly raised SCFA levels, indicating restoration of gut microbiota balance. FMT presents an innovative therapeutic option for pediatric patients with recurrent fUTIs, demonstrating outstanding clinical outcomes.},
}

@article {pmid40391506,
year = {2025},
author = {Ai, R and Jin, Y and Zhang, F and Cui, B and Ji, G},
title = {Washed microbiota transplantation effectively treats a case of acute severe ulcerative colitis combined with viral myocarditis.},
journal = {Journal of biomedical research},
volume = {},
number = {},
pages = {1-5},
doi = {10.7555/JBR.39.20250036},
pmid = {40391506},
issn = {1674-8301},
abstract = {Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis (UC). Management of myocarditis is primarily supportive, as there are currently no established targeted therapies. Recent studies have increasingly demonstrated the association between gut microbiota and myocarditis. Here, we report a case of acute severe UC complicated by cytomegalovirus (CMV) and Epstein-Barr virus (EBV) co-infections leading to viral myocarditis. The patient experienced rapid remission of both intestinal and cardiac symptoms following washed microbiota transplantation (WMT), suggesting WMT as a potential alternative treatment for these life-threatening conditions.},
}

@article {pmid40390988,
year = {2025},
author = {Abdulaal, R and Tlaiss, Y and Jammal, F and Moussbah, TH and Tarchichi, A and Hteit, A and Tlais, M and Nassif, D},
title = {The role of microbiome dysbiosis in cardiovascular disease: Mechanisms and therapeutic implications.},
journal = {Global cardiology science & practice},
volume = {2025},
number = {1},
pages = {e202503},
pmid = {40390988},
issn = {2305-7823},
abstract = {The gut microbiome plays a critical role in cardiovascular disease (CVD) pathogenesis through systemic inflammation, disrupted lipid metabolism, and proatherogenic metabolites like trimethylamine-N-oxide (TMAO). Dysbiosis contributes to increased intestinal permeability, platelet hyperreactivity, and reduced short-chain fatty acids (SCFAs), exacerbating cardiovascular risk. Emerging microbiome-targeted therapies, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary interventions, show promise in mitigating CVD. However, challenges remain in translating these findings into clinical practice due to strain-specific effects and interindividual variability. The gut-heart axis represents a transformative avenue for CVD prevention and management, warranting further research to optimize long-term efficacy and safety.},
}

@article {pmid40390224,
year = {2025},
author = {Adedayo, SI and Riethmacher, E},
title = {Emerging New Treatments for Colon Cancer.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673372776250505155945},
pmid = {40390224},
issn = {1875-533X},
abstract = {Colorectal cancer includes cancer of the rectum and colon. It is the primary cause of cancer-related deaths among men under 50 years of age. In 2022, over 1.9 million cases of CRC were reported, resulting in approximately 904,000 deaths worldwide. Factors like smoking, alcohol consumption, obesity, familial history, and inflammation significantly contribute to the risk of CRC development. Additionally, bacterial infections from organisms like Bacteroides fragilis, Fusobacterium nucleatum, and Helicobacter pylori also play a role in increasing this risk. Conventional treatment methods for CRC typically involve surgery/polypectomy, chemotherapy, and radiotherapy. Because of limitations like lack of target specificity, the risk of tumor relapse, and the potential for tumor resistance, there is a growing necessity for more individually tailored treatment strategies to improve the outcomes of patients with CRC. As such, emerging treatments like cancer vaccine, (CAR) T-cells, CAR-NK cells, macrophages, and stem cell engineering (particularly mesenchymal stem cells), dendritic vaccine, siRNA, and miRNA, hold significant promise in enhancing outcomes for CRC patients. Moreover, specific gut microbiomes like Bacteroides fragilis, Streptococcus gallolyticus, Enterococcus faecalis, and Escherichia coli, linked to CRC development, have been identified. Hence, modulating the gut microbiome to potentially enhance responses to CRC in high- -risk populations could be a new line of treatment. This modulation can be accomplished through dietary interventions, prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT). This review summarizes the most promising new emerging treatments in the fight against colon cancer.},
}

@article {pmid40390189,
year = {2025},
author = {Krynicka, P and Koulaouzidis, G and Marlicz, W and Koulaouzidis, A},
title = {Innovations in the Diagnosis, treatment, and management of disorders of gut-brain interaction (DGBI).},
journal = {Expert review of gastroenterology & hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1080/17474124.2025.2508967},
pmid = {40390189},
issn = {1747-4132},
abstract = {INTRODUCTION: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are the most prevalent disorders of gut-brain interaction (DGBI), frequently overlapping and associated with complex pathophysiological mechanisms. Increasing evidence implicates gut microbiota alterations in driving symptoms via immune activation, altered motility, gut vascular barrier and gut-brain axis disruption.

AREAS COVERED: This review explores the role of gut microbiota in FD and IBS pathogenesis and symptomatology. A comprehensive literature search was conducted using PubMed, EMBASE, and Google Scholar databases, including studies published between January 2013 and March 2025. Particular focus is given to microbiota-targeted therapies such as prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). The review also discusses multidimensional treatment strategies combining dietary and lifestyle modification, cognitive-behavioral therapy, and pharmacological neuromodulation. Recent advances in diagnostic methods, including capsule-based microbiota sampling and digital tools for remote psychogastroenterology care, are highlighted.

EXPERT OPINION: Despite scientific progress, current DGBI management remains insufficiently personalized. Future approaches should integrate individualized microbiota profiling with targeted interventions and utilize innovative diagnostic and digital health technologies to enhance clinical outcomes in FD and IBS.},
}

@article {pmid40390033,
year = {2025},
author = {Teng, T and Huang, F and Xu, M and Li, X and Zhang, L and Yin, B and Cai, Y and Chen, F and Zhang, L and Zhang, J and Geng, A and Chen, C and Yu, X and Sui, J and Zhu, ZJ and Guo, K and Zhang, C and Zhou, X},
title = {Microbiota alterations leading to amino acid deficiency contribute to depression in children and adolescents.},
journal = {Microbiome},
volume = {13},
number = {1},
pages = {128},
pmid = {40390033},
issn = {2049-2618},
support = {82301714//the National Natural Science Foundation of China/ ; 22425404//the National Natural Science Foundation of China/ ; 82271565//the National Natural Science Foundation of China/ ; 2023TQ0398//the China Postdoctoral Science Foundation/ ; CSTB2023NSCQ-BHX0106//Natural Science Foundation of Chongqing, China/ ; 2208013341918508//Postdoctoral Innovation Talents Support Program of Chongqing, China/ ; 2022YFC3400702//National Key R&D Program of China/ ; 2024YFC2707800//National Key R&D Program of China/ ; 2022ZD0212900//STI2030-Major Projects/ ; },
mesh = {Humans ; Adolescent ; Child ; *Gastrointestinal Microbiome/physiology ; Male ; *Depressive Disorder, Major/microbiology/metabolism ; Female ; *Amino Acids/deficiency/blood/metabolism ; Magnetic Resonance Imaging ; Animals ; Rats ; Brain/diagnostic imaging/metabolism ; Feces/microbiology ; Metagenomics/methods ; Metabolomics/methods ; *Depression/microbiology ; },
abstract = {BACKGROUND: Major depressive disorder (MDD) in children and adolescents is a growing global public health concern. Metabolic alterations in the microbiota-gut-brain (MGB) axis have been implicated in MDD pathophysiology, but their specific role in pediatric populations remains unclear.

RESULTS: We conducted a multi-omics study on 256 MDD patients and 307 healthy controls in children and adolescents, integrating plasma metabolomics, fecal metagenomics, and resting-state functional magnetic resonance imaging (rs-fMRI) of the brain. KEGG enrichment analysis of 360 differential expressed metabolites (DEMs) indicated significant plasma amino acid (AA) metabolism deficiencies (p-value < 0.0001). We identified 58 MDD-enriched and 46 MDD-depleted strains, as well as 6 altered modules in amino acid metabolism in fecal metagenomics. Procrustes analysis revealed the association between the altered gut microbiome and circulating AA metabolism (p-value = 0.001, M[2] = 0.932). Causal analyses suggested that plasma AAs might mediate the impact of altered gut microbiota on depressive and anxious symptoms. Additionally, rs-fMRI revealed that connectivity deficits in the frontal lobe are associated with depression and 22 DEMs in AA metabolism. Furthermore, transplantation of fecal microbiota from MDD patients to adolescent rats induced depressive-like behaviors and 14 amino acids deficiency in the prefrontal cortex (PFC). Moreover, the dietary lysine restriction increased depression susceptibility in adolescent rats by reducing the expression of excitatory amino acid transporters in the PFC.

CONCLUSIONS: Our findings highlight that gut microbiota alterations contribute to AAs deficiency, particularly lysine, which plays a crucial role in MDD pathogenesis in children and adolescents. Targeting AA metabolism may offer novel therapeutic strategies for pediatric depression. Video Abstract.},
}

Humans
Adolescent
Child
*Gastrointestinal Microbiome/physiology
Male
*Depressive Disorder, Major/microbiology/metabolism
Female
*Amino Acids/deficiency/blood/metabolism
Magnetic Resonance Imaging
Animals
Rats
Brain/diagnostic imaging/metabolism
Feces/microbiology
Metagenomics/methods
Metabolomics/methods
*Depression/microbiology

@article {pmid40390010,
year = {2025},
author = {Han, J and Meng, X and Kong, H and Li, X and Chen, P and Zhang, XA},
title = {Links between short-chain fatty acids and osteoarthritis from pathology to clinic via gut-joint axis.},
journal = {Stem cell research & therapy},
volume = {16},
number = {1},
pages = {251},
pmid = {40390010},
issn = {1757-6512},
support = {Grant No. 32371184//National Natural Science Foundation of China/ ; No. 2023JH2/101300072//the Liaoning Province Applied Basic Research Program/ ; LJKQZ20222425//the basic scientific research project of higher education institutions of Liaoning Province/ ; },
abstract = {Short-chain fatty acids (SCFAs), the primary metabolites produced by the microbial fermentation of dietary fibers in the gut, have a key role in protecting gut health. Increasing evidence indicates SCFAs can exert effects on distant tissues and organs beyond the gut via blood circulation. Osteoarthritis (OA) is a chronic inflammatory joint disease that severely diminishes the physical function and quality of life. However, effective clinical treatments for OA remain elusive. Recent studies have shown that SCFAs can exert beneficial effects on damaged joints in OA. SCFAs can mitigate OA progression by preserving intestinal barrier function and maintaining the integrity of cartilage and subchondral bone, suggesting that they have substantial potential to be the adjunctive treatment strategy for OA. This review described the SCFAs in the human body and their cellular signaling mechanism, and summarized the multiple effects of SCFAs (especially butyrate, propionate, and acetate) on the prevention and treatment of OA by regulating the gut-joint axis, providing novel insights into their promising clinical applications.},
}

@article {pmid40388727,
year = {2025},
author = {Kong, J and Han, X and Wei, C},
title = {Causal relationship between metabolic dysfunction-associated fatty liver disease and endotoxin biomarkers: A Mendelian randomization study.},
journal = {Medicine},
volume = {104},
number = {20},
pages = {e42311},
doi = {10.1097/MD.0000000000042311},
pmid = {40388727},
issn = {1536-5964},
support = {[No. (2022)4].//Shandong Provincial Key Laboratory of Traditional Chinese Medicine/ ; },
mesh = {Humans ; Mendelian Randomization Analysis ; *Non-alcoholic Fatty Liver Disease/genetics/blood ; Biomarkers/blood ; *Lipopolysaccharides/blood ; Genome-Wide Association Study ; Acute-Phase Proteins/genetics ; Obesity ; Carrier Proteins/blood ; Membrane Glycoproteins/blood ; *Metabolic Syndrome/genetics ; Risk Factors ; Triglycerides/blood ; Cholesterol, HDL/blood ; *Endotoxins/blood ; },
abstract = {Although the relationship among lipopolysaccharides (LPS), LPS-binding proteins, and metabolic dysfunction-associated fatty liver disease (MAFLD) is widely studied, no conclusive evidence is available. In this study, we used mendelian randomization (MR) to study the causal relationship of LPS, LPS-binding proteins, and MAFLD. Using bidirectional two-sample MR method, we evaluated data from the genome wide association study; for this analysis, nonalcoholic fatty liver disease (NAFLD), liver fat percentage, and other metabolic syndromes were employed as outcomes. Furthermore, MR analysis mainly involved the inverse variance weighted method. Heterogeneity and pleiotropy tests were also conducted. LPS was found to have a causal relationship with NAFLD, obesity, high density lipoprotein cholesterol, and TG levels. Furthermore, TG levels and LBP had significant causal relationships. This study mainly concluded that LPS is a risk factor for NAFLD, obesity, high density lipoprotein cholesterol, and TG, corroborating it's the LPS role in MAFLD pathogenesis. Hence, optimizing the gut microbiota using proper diet, probiotics, or fecal microbiota transplantation may help to reduce inflammation and (IR), thereby improving lipid and glucose metabolism disorders. Although a causal relationship between TG and LBP was observed, further studies are required to determine a specific mechanism.},
}

Humans
Mendelian Randomization Analysis
*Non-alcoholic Fatty Liver Disease/genetics/blood
Biomarkers/blood
*Lipopolysaccharides/blood
Genome-Wide Association Study
Acute-Phase Proteins/genetics
Obesity
Carrier Proteins/blood
Membrane Glycoproteins/blood
*Metabolic Syndrome/genetics
Risk Factors
Triglycerides/blood
Cholesterol, HDL/blood
*Endotoxins/blood

@article {pmid40388258,
year = {2025},
author = {Ebadpour, N and Abavisani, M and Sahebkar, A},
title = {Microbiome-driven precision medicine: Advancing drug development with pharmacomicrobiomics.},
journal = {Journal of drug targeting},
volume = {},
number = {},
pages = {1-27},
doi = {10.1080/1061186X.2025.2509283},
pmid = {40388258},
issn = {1029-2330},
abstract = {Pharmacomicrobiomics investigates the complicated relationship between the gut microbiome and medications, highlighting how the microbiome affects drug absorption, metabolism, and overall treatment outcomes. The interaction between pharmaceutical agents and the host microbiota is inherently bidirectional and complex. While the administration of various drugs can alter the composition and diversity of the gut microbial community, the intestinal microbiota, in turn, plays a crucial role in modulating fundamental pharmacokinetic and pharmacodynamic processes, which in turn affect the efficacy and safety of drugs. Microbial communities can influence the metabolism and efficacy of many medications in two primary ways: directly and indirectly. Direct mechanisms typically entail the induction of biochemical alterations and multiple transformations directly on the drug, whereas indirect mechanisms encompass modifications in host metabolism, alterations in the gut microbial community, the synthesis of various metabolites, and interactions with the host immune system, which indirectly influence the drug's metabolism, absorption, and efficacy. For instance, microbial communities play an important part in activating prodrugs like sulfasalazine, improving the outcomes of immunotherapy, and minimizing toxicity through specific interventions. Nonetheless, barriers can also emerge from the microbial breakdown of medications, reducing their therapeutic efficacy, along with adverse reactions mediated by microbiota. Innovations like probiotics, fecal microbiota transplantation, and microbiota profiling have shown promise in enhancing these interactions. Utilizing the distinct microbiota composition of individuals, pharmacomicrobiomics offers a route to personalized, precise, and safer therapies, signaling an important evolution in drug development and clinical practice. This study aims to provide a comprehensive overview of microbiome-drug interactions, with a particular focus on the influence of gut microbiota on drug efficacy, and to highlight their potential to revolutionize precision medicine.},
}

@article {pmid40387516,
year = {2025},
author = {Kochkarian, T and Nagy, HI and Li, Q},
title = {Gut-Heart Axis: Cardiac Remodeling and Heart Failure in the Context of Inflammatory Bowel Disease and Dysbiosis.},
journal = {American journal of physiology. Gastrointestinal and liver physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpgi.00016.2025},
pmid = {40387516},
issn = {1522-1547},
support = {R01 HL152683/HL/NHLBI NIH HHS/United States ; },
abstract = {Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are debilitating and complex chronic gastrointestinal disorders that affect not only the gut but also extraintestinal organs, including the heart. The gut-heart crosstalk has garnered increasing attention in recent years; however, the molecular mechanisms underlying this complex interplay remain poorly understood. This review explores the gut-heart axis, focusing on how IBD disrupts gut microbiota homeostasis and promotes cardiac remodeling through systemic inflammation and various mediators, ultimately contributing to the onset or progression of heart failure. IBD compromises the integrity of the intestinal barrier, allowing microbial metabolites such as trimethylamine N-oxide and phenylacetylglutamine, along with inflammatory cytokines and microRNAs (miRNA) (e.g., miR-155, miR-21, let-7a), to enter the circulation and contribute to cardiac remodeling and heart failure. We identify dysfunction of nucleotide-binding oligomerization domain-containing protein 2 as a critical link between gut immunity and cardiovascular pathology. Additionally, we discuss emerging microbiome-based therapeutic strategies, including fecal microbiota transplantation and IL-23 inhibitors, aimed at restoring gut homeostasis and mitigating cardiovascular risk. By integrating molecular mechanisms, clinical evidence, and therapeutic approaches, this review underscores the pivotal role of gut dysbiosis in cardiac dysfunction and offers new perspectives for managing cardiac dysfunction in patients with IBD.},
}

@article {pmid40386180,
year = {2025},
author = {Fang, Y and Min, S and Wu, Y and Xu, F and Chen, H and Li, Y and Lu, Y and Hu, J and Zhu, L and Shen, H},
title = {Integration of Multi-Omics and Network Pharmacology Analysis Reveals the Mechanism of Qingchang Huashi Jianpi Bushen Formula in Repairing the Epithelial Barrier of Ulcerative Colitis.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {6167-6189},
pmid = {40386180},
issn = {1178-7031},
abstract = {PURPOSE: Derivation of Qingchang Huashi formula, named Qingchang Huashi Jianpi Bushen (QCHS_JPBS) formula, has shown significant therapeutic effect on patients with ulcerative colitis (UC). In this study, the potential mechanism of QCHS_JPBS formula in repairing mucosal damage was explored from the perspective of intestinal stem cell (ISCs) differentiation, and potential targets of the QCHS_JPBS formula to improve UC were predicted using network pharmacology analysis.

METHODS: The therapeutic efficacy of QCHS_JPBS formula was evaluated in a mouse model of 2.5% dextran sulfate sodium (DSS) induced colitis. The effect of this formula on the ISC differentiation was evaluated using tissue transmission electron microscopy, immunofluorescence, and RT-qPCR. The cecal contents were subjected to 16s RNA sequencing analysis and non-target metabolomics analysis using LC-MS/MS. The fecal microbiota transplantation method verified the essential role of gut microbiota in promoting ISC differentiation and repairing mucosal damage.

RESULTS: The results indicated that QCHS_JPBS formula suppressed the inflammatory response and repaired the damaged intestinal epithelial barrier in DSS-induced colitis mice. QCHS_JPBS formula promoted ISC differentiation, particularly in the direction of goblet cells. QCHS_JPBS formula restored gut dysbiosis and regulated metabolic disorders in DSS-induced colitis mice. And then, the results of fecal microbiota transplantation indicated that QCHS_JPBS formula promoted differentiation of intestinal stem cells to repair mucosal damage through gut microbiota. Finally, a total of 79 active ingredients of QCHS_JPBS formula were identified based on LC-MS analysis and EGFR, STAT3, SRC, AKT1, and HSP90AA1 were considered as potential therapeutic UC targets of QCHS_JPBS formula based on network pharmacology analysis.

CONCLUSION: The present study demonstrated that QCHS_JPBS formula promoted the differentiation of ISCs through gut microbiota to repair the damaged intestinal epithelial barrier in UC mice.},
}

@article {pmid40385744,
year = {2025},
author = {Truong, MH and Ngo, T and Nguyen, QT and Le, H},
title = {Diagnosis and Treatment Outcomes of Fournier's Gangrene at a Tertiary Hospital.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e82344},
pmid = {40385744},
issn = {2168-8184},
abstract = {Introduction Fournier's gangrene (FG) is a severe necrotizing fasciitis caused by polymicrobial agents. This study aims to evaluate the clinical and paraclinical characteristics, treatment outcomes, and factors related to mortality in patients with FG at People's Hospital 115, Vietnam. Methods A retrospective cohort study was conducted on all adult patients diagnosed with FG at People's Hospital 115 from January 2018 to October 2024. Variables, including sociodemographic, clinical features, laboratory tests, and treatment outcomes, were collected. Data analysis was performed using SPSS version 26.0 (IBM Corp, Armonk, NY, USA). Results A total of 60 patients (47 males and 13 females) were enrolled; the mean age was 58.2 ± 12.6 years. The most common infection origins were from skin infections (36.7%), followed by the gastrointestinal tract (31.7%) and the genitourinary tract (30%). Most patients presented with symptoms such as perineal pain (98.3%), perianal swelling (91.7%), fever (48.3%), lower abdominal fluid collection (43.3%), and purulent discharge or perineal necrosis (31.7%). The most prevalent risk factor was diabetes mellitus (61.8%). Pathogenic bacteria that were commonly Escherichia coli, Klebsiella, and Proteus species could be isolated. Treatment involved both medical management (resuscitation, broad-spectrum antibiotics, and wound care) and surgical interventions (debridement, necrotic tissue excision, and fecal and urinary diversion). The overall mortality rate was 18.3%. Factors significantly associated with mortality included advanced age, female sex, a history of long-term corticosteroid use, high severity index scores, and septic shock. Conclusion FG is an uncommon urological emergency that is a rapidly progressing disease with a high mortality rate. Early detection and aggressive treatment approaches to achieve better outcomes.},
}

@article {pmid40383915,
year = {2025},
author = {Kim, YJ and Lee, J and Lee, E and Park, SJ and Kim, JH},
title = {Impact of stool transplantation and metformin on polyp reduction and inflammation in an APC Min mouse model.},
journal = {Intestinal research},
volume = {},
number = {},
pages = {},
doi = {10.5217/ir.2025.00011},
pmid = {40383915},
issn = {1598-9100},
abstract = {BACKGROUND/AIMS: Familial adenomatous polyposis is a hereditary condition characterized by numerous adenomatous polyps in the colon and rectum, significantly increasing colorectal cancer risk. Current management strategies, such as prophylactic colectomy, are invasive and have long-term consequences, highlighting the need for alternative therapies. This study aimed to evaluate whether stool transplantation and metformin therapy synergistically reduce polyp formation and inflammation.

METHODS: APC Min mice were divided into 4 groups: control, anti-control (antibiotic pretreatment), stool (stool transplantation), and stool+metformin. Polyp burden, bacterial abundance, inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, IL-10), and tumorigenic markers (NF-κB, Cox2, c-myc, β-catenin) were assessed using messenger RNA (mRNA) and protein analyses of intestinal tissues, along with serum and fecal microbiota evaluations.

RESULTS: Stool transplantation combined with metformin significantly reduced bacterial abundance and polyp burden. The anti-control group showed similar reductions, suggesting suppression of gut microbiota re-establishment. TNF-α and IL-10 levels remained unchanged, but a significant increase in IL-6 was observed in the stool+metformin group's intestinal tissues, indicating localized immune activation. Intestinal Cox2 mRNA expression was reduced in the combination group, correlating with polyp suppression. Protein levels of NF-κB, Cox2, and β-catenin showed no significant changes in vivo, while in vitro experiments revealed a decrease in NF-κB and an increase in Cox2, suggesting complex regulation of inflammation-related pathways.

CONCLUSIONS: Stool transplantation combined with metformin reduces polyp burden in APC Min mice through gut microbiota modulation and localized immune activation. These findings support the therapeutic potential of this combination treatment for familial adenomatous polyposis.},
}

@article {pmid40383790,
year = {2025},
author = {Chen, J and Feng, R and Gong, BB and Wu, WK and Dai, BS and Tan, R and Xu, WL and Meng, T and Wang, XB and Xiao, YZ and Yang, C and Zhang, L and Liang, CZ},
title = {High-salt-driven gut microbiota dysfunction aggravates prostatitis by promoting AHR/SGK1/FOXO1 axis-mediated Th17 cell differentiation.},
journal = {Military Medical Research},
volume = {12},
number = {1},
pages = {21},
pmid = {40383790},
issn = {2054-9369},
support = {82300872//National Natural Science Foundation of China/ ; 82170787//National Natural Science Foundation of China/ ; T000529//Supporting Projects for Innovative Leading Talents/ ; 2021-108-10//Distinguished Young Scholar of Anhui Colleges/ ; 2022AH020073//Science Foundation for Outstanding Young Scholar of Anhui Colleges/ ; SZSM20210300//Sanming Project of Medicine in Shenzhen Nanshan/ ; 2408085Y038//Anhui Provincial Natural Science Foundation/ ; },
mesh = {Male ; Animals ; Mice ; *Prostatitis/physiopathology/etiology ; *Gastrointestinal Microbiome/drug effects/physiology ; *Th17 Cells/metabolism/drug effects ; Receptors, Aryl Hydrocarbon/metabolism ; Humans ; Cell Differentiation/drug effects ; Protein Serine-Threonine Kinases/metabolism ; Immediate-Early Proteins/metabolism ; Sodium Chloride, Dietary/adverse effects ; Disease Models, Animal ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a frequently encountered disorder characterized by voiding symptoms and pelvic or perineal pain. Proinflammatory T helper 17 (Th17) cells are essential for triggering the development of CP/CPPS. High-salt diet (HSD) consumption has been found to cause an accumulation of sodium chloride in peripheral organs, inducing autoimmune responses via the Th17 cell axis. It is currently unknown whether HSD affects the etiology and course of CP/CPPS.

METHODS: Patients diagnosed with CP/CPPS were evaluated with the National Institutes of Health Chronic Prostatitis Symptom Index scoring system, and the correlation between the symptoms of CP/CPPS with HSD was analyzed. The experimental autoimmune prostatitis (EAP) mouse was established and the mice were fed either a normal-salt diet (NSD) or HSD for 6 weeks to investigate the impact of HSD on CP/CPPS. Then, 16S ribosomal RNA sequencing and untargeted metabolomics were introduced to detect the differences in the gut microflora composition and metabolite profiles between NSD-fed and HSD-fed mice, followed by fecal microbiota transplantation, 5-hydroxyindole acetic acid (5-HIAA) supplementation, aryl hydrocarbon receptor (AHR) inhibition, and in vitro Th17 differentiation experiments, which were performed to explore the mechanisms underlying HSD-aggravated CP/CPPS. Finally, chromatin immunoprecipitation assay and quantitative polymerase chain reaction were conducted to validate whether AHR can serve as a transcription factor by interacting with the serum and glucocorticoid-regulated kinase 1 (Sgk1) promoter in CD4[+] T cells.

RESULTS: Increased salt consumption had a positive correlation with symptom scores of CP/CPPS patients, which was validated by feeding EAP mice with HSD, and HSD worsened the prostate inflammation and tactile allodynia in EAP mice through promoting the differentiation of CD4[+] T cells to Th17 cells. HSD exacerbated EAP by significantly reducing the relative abundance of beneficial gut microflora, such as Lactobacillaceae, and gut microbiota metabolite 5-HIAA, which is related to tryptophan metabolism. The prostate inflammation, tactile allodynia, and proportion of Th17 cells in mice that received fecal suspensions from the EAP + HSD group were significantly more severe or higher than those in mice that received fecal suspensions from the EAP + NSD group. However, 5-HIAA supplementation ameliorated the symptoms of EAP caused by HSD through inhibiting the differentiation of CD4[+] T cells to Th17 cells, while AHR inhibition abrogated the protective effects of 5-HIAA supplementation on EAP mice fed a HSD through promoting the differentiation of CD4[+] T cells to Th17 cells. Mechanistically, it has been revealed that the SGK1/forkhead box protein O1 (FOXO1) pathway was significantly activated during cytokine-induced Th17 cell differentiation, and AHR has been shown to inhibit SGK1 transcription by interacting with the Sgk1 promoter in CD4[+] T cells to inhibit FOXO1 phosphorylation, consequently restoring the equilibrium of Th17 cell differentiation.

CONCLUSION: Our findings indicated that high salt intake represented a risk factor for the development of CP/CPPS as it promoted the differentiation of CD4[+] T cells to Th17 cells through the 5-HIAA/AHR/SGK1/FOXO1 axis, which might be a potential therapeutic target for CP/CPPS.},
}

Male
Animals
Mice
*Prostatitis/physiopathology/etiology
*Gastrointestinal Microbiome/drug effects/physiology
*Th17 Cells/metabolism/drug effects
Receptors, Aryl Hydrocarbon/metabolism
Humans
Cell Differentiation/drug effects
Protein Serine-Threonine Kinases/metabolism
Immediate-Early Proteins/metabolism
Sodium Chloride, Dietary/adverse effects
Disease Models, Animal
Mice, Inbred C57BL

@article {pmid40383397,
year = {2025},
author = {Merrick, B and Prossomariti, D and Allen, E and Bisnauthsing, K and Kertanegara, M and Sergaki, C and Le Guennec, AD and Delord, M and Bell, JT and Conte, MR and Moyes, DL and Shankar-Hari, M and Douiri, A and Goodman, AL and Shawcross, DL and Goldenberg, SD},
title = {Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic-Resistant Organisms (FERARO): a feasibility randomised controlled trial.},
journal = {The Journal of infection},
volume = {},
number = {},
pages = {106504},
doi = {10.1016/j.jinf.2025.106504},
pmid = {40383397},
issn = {1532-2742},
abstract = {OBJECTIVES: The gastrointestinal tract (GIT) is a reservoir of multidrug-resistant organisms (MDRO). Colonisation with MDRO precedes invasive infections which can be challenging to treat with excess morbidity and mortality compared to antimicrobial susceptible infections. Currently, there are no effective GIT decolonisation strategies. Whilst Faecal Microbiota Transplant (FMT) has emerged as a potential therapeutic, there remains uncertainty about its feasibility, safety and efficacy.

METHODS: Population: Patients with invasive infection with Extended-spectrum Beta-Lactamase (ESBL-) or Carbapenem-resistant Enterobacterales (CRE) and persistent GIT carriage.

INTERVENTION: Three doses of encapsulated lyophilised FMT.

COMPARATOR: Matched placebo capsules.

OUTCOMES: Primary outcome was participant consent rate as a proportion of those approached to be screened for GIT carriage of ESBL-E/CRE. Secondary outcomes were additional feasibility, safety and tolerability, and efficacy metrics. Exploratory outcomes included stool metagenomic analysis.

RESULTS: Of 460 approached individuals, 124 (27%) consented. 53/124 participants (43%) fulfilled all eligibility criteria. 44/53 (83%) of those eligible were randomised and 41/44 (93%) received investigational medicinal product (IMP): 20 FMT and 21 placebo. 39/41 (95%) completed IMP dosing. Abdominal bloating and skin and subcutaneous tissue disorders were more common following FMT but there were no unanticipated harms. MDRO carriage decreased over time across arms but was lower at all time points in the FMT arm. FMT increased microbiome diversity and microbiome-based health measures. FMT recipients' samples clustered into two groups with those with more dissimilar community composition to donors more likely to decolonise post-FMT (3/5 vs. 0/12, p=0.01). Patients that decolonised exhibited a trend towards increased proportional representation of donor-derived strains in their post-FMT samples (p=0.05) and change in strain dominance within MDRO at species-level.

CONCLUSIONS: Progression to a substantive trial is feasible with modifications to the existing FERARO protocol. FMT was safe, well tolerated, and acceptable to patients colonised with MDRO. Microbiome analysis infers that greater donor-recipient microbiome dissimilarity at baseline and higher rates of donor-derived strain engraftment favour MDRO decolonisation, which in turn maybe facilitated by conspecific strain replacement.},
}

@article {pmid40383206,
year = {2025},
author = {Stensvold, CR and Tomiak, J and Seyoum, Y and Nielsen, HV and van der Giezen, M},
title = {Letter to the Editor: Comment to "Assessment of Dientamoeba fragilis interhuman transmission by fecal microbiota transplantation" by Moreno-Sabater et al. (2025).},
journal = {International journal of antimicrobial agents},
volume = {},
number = {},
pages = {107541},
doi = {10.1016/j.ijantimicag.2025.107541},
pmid = {40383206},
issn = {1872-7913},
}

@article {pmid40381961,
year = {2025},
author = {Zhao, X and Lei, C and Wang, Y and Zhang, L and Tang, W and Li, Z and Jiang, L and Li, X},
title = {Impact of TLR5 Overexpression on Gut Microbiota and Metabolites: Insights into Salmonella Infection Outcomes.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {107708},
doi = {10.1016/j.micpath.2025.107708},
pmid = {40381961},
issn = {1096-1208},
abstract = {BACKGROUND: The gut microbiome and the host immune system work together to maintain intestinal health and protect against infections. Toll-like receptor 5 (TLR5) recognizes bacterial flagellin and plays a crucial role in this network. However, the precise role of TLR5 in regulating gut microbiota and resistance to infection remains unclear. This study utilized a TLR5 intestine-specific overexpression mouse model to explore these interactions and their impact on Salmonella infection.

METHODS: TLR5 intestine-specific overexpression mice (TLR5+/+) and wild-type (WT) mice were infected with Salmonella to assess TLR5's protective role. Survival time, fecal Salmonella load, and intestinal tissue integrity were evaluated. Subsequently, 16S rRNA sequencing and LC-MS-based metabolomics were performed to analyze gut microbiota composition and fecal metabolites. Fecal microbiota transplantation (FMT) and metabolite transplantation experiments were conducted to evaluate the functional impact of microbiota and metabolites on resistance to infection.

RESULTS: TLR5 overexpression significantly improved survival time and reduced fecal Salmonella load, demonstrating its protective role against infection. 16S rRNA sequencing revealed enrichment of beneficial taxa, while metabolomic analysis identified altered metabolites in TLR5+/+ mice. Although fecal microbiota and metabolite transplantation did not fully replicate the protective effects, these experiments highlighted the important roles of microbiota and metabolites in infection outcomes, with limitations in transplantation likely affecting the results. These findings underscore the significance of microbiota and metabolites in TLR5-mediated gut immunity.

CONCLUSION: TLR5 overexpression significantly alters gut microbiota and metabolite profiles, contributing to improved infection outcomes. These findings highlight the critical roles of microbiota and metabolites in TLR5-mediated immunity and provide a foundation for exploring targeted strategies to enhance resistance against enteric pathogens.},
}

@article {pmid40381958,
year = {2025},
author = {Bolte, LA and Björk, JR and Gacesa, R and Weersma, RK},
title = {Pharmacomicrobiomics: The role of the gut microbiome in immunomodulation and cancer therapy.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2025.04.025},
pmid = {40381958},
issn = {1528-0012},
abstract = {There is a large heterogeneity among individuals in their therapeutic responses to the same drug and in the occurrence of adverse events. A key factor increasingly recognized to contribute to this variability is the gut microbiome. The gut microbiome can be regarded as a second genome, holding significant metabolic capacity. Consequently, the field of pharmacomicrobiomics has emerged as a natural extension of pharmacogenomics for studying variations in drug responses. Pharmacomicrobiomics explores the interaction of microbiome variation with drug response and disposition. The interaction between microbes and drugs is, however, complex and bidirectional. While drugs can directly alter microbial growth or influence gut microbiome composition and functionality, the gut microbiome also modulates drug responses directly through enzymatic activities and indirectly via host-mediated immune and metabolic mechanisms. Here we review recent studies that demonstrate the interaction between drugs and the gut microbiome, focusing on cancer immunotherapy and immunomodulation in the context of inflammatory bowel disease and solid organ transplantation. Since the gut microbiome is modifiable, pharmacomicrobiomics presents promising opportunities for optimizing therapeutic outcomes, with recent clinical trials highlighting fecal microbiota transplantation as a strategy to enhance the efficacy of immune checkpoint blockade. We also shed light on the future perspectives for patients arising from this field. While multiple lines of evidence already demonstrate that the gut microbiome interacts with drugs, and vice versa, thereby affecting treatment efficacy and safety, well-designed clinical studies and integrated in vivo and ex vivo models are necessary to obtain consistent results, improve clinical translation and further unlock the gut microbiome's potential to improve drug responses.},
}

@article {pmid40381872,
year = {2025},
author = {Barlowe, TS and Desai, S and Sanderford, AE and Holowka, T and Peery, AF and McGill, SK},
title = {Fulminant Clostridioides difficile Infection Following Fecal Microbiota Spores compared to Fecal Microbiota Transplant.},
journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cgh.2025.03.027},
pmid = {40381872},
issn = {1542-7714},
}

@article {pmid40381501,
year = {2025},
author = {Jia, Y and Liu, X and Gao, X and Yin, S and Wu, K and Meng, X and Ren, H and Liu, J and Liu, Z and Li, H and Jiang, Y},
title = {Plantamajoside alleviates DSS-induced ulcerative colitis by modulating gut microbiota, upregulating CBS, and inhibiting NF-κB.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {143},
number = {},
pages = {156827},
doi = {10.1016/j.phymed.2025.156827},
pmid = {40381501},
issn = {1618-095X},
abstract = {BACKGROUND: Plantamajoside (PMS) is a natural bioactive compound derived from medicinal, food homologous plants of the genus Plantago.

PURPOSE AND METHODS: This study aimed to investigate the protective effects of PMS on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and explore the associated mechanisms.

RESULTS: We found that PMS treatment significantly alleviated UC symptoms in mice by preventing body weight loss, increasing colon length, and reducing disease activity index scores. Moreover, PMS alleviated colonic lesions, increased the number of goblet cells, upregulated the expression of intestinal barrier proteins (ZO-1, occludin, and claudin-3), and decreased the levels of pro-inflammatory factors. PMS treatment modulated the gut microbiota by increasing the relative abundance of Bacteroidota and Verrucomicrobiota and decreasing that of Firmicutes and Proteobacteria at the phylum level. At the genus level, PMS suppressed the abundance of pathogenic bacteria, such as Turicibacter and upregulated the abundance of [Eubacterium]_xylanophilum_group. Fecal microbiota transplantation experiments further confirmed that PMS treatment alleviated UC by modulating the gut microbiota. Transcriptomic analysis of colon tissues, coupled with reverse transcription-quantitative polymerase chain reaction and western blotting, showed that PMS treatment upregulated cystathionine beta-synthase (CBS) expression and inhibited NF-κB pathway activation. In a lipopolysaccharide-induced inflammation model in RAW264.7 cells, PMS treatment inhibited the secretion of pro-inflammatory cytokines, upregulated CBS expression, and prevented NF-κB pathway activation.

CONCLUSION: PMS protects against UC in mice via multiple mechanisms, including modulating the gut microbiota, increasing the expression levels of CBS, and inhibiting the NF-κB pathway.},
}

@article {pmid40380157,
year = {2025},
author = {Deng, M and Li, X and Wu, H and Xue, D and Wang, Y and Guo, R and Cui, Y and Jin, C and Luo, F and Li, H},
title = {The current status and prospects of gut microbiota combined with PD-1/PD-L1 inhibitors in the treatment of colorectal cancer: a review.},
journal = {BMC gastroenterology},
volume = {25},
number = {1},
pages = {380},
pmid = {40380157},
issn = {1471-230X},
support = {2021XM22//Key Research and Development (R&D) Projects of Shanxi Province/ ; 202103021224346//Fundamental Research Program of Shanxi Province/ ; },
mesh = {*Colorectal Neoplasms/therapy/microbiology/genetics ; *Gastrointestinal Microbiome ; Humans ; *Immune Checkpoint Inhibitors/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; B7-H1 Antigen/antagonists & inhibitors ; Microsatellite Instability ; },
abstract = {BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor. Immune checkpoint inhibitors (ICIs), particularly those targeting programmed cell death protein 1(PD-1) and programmed cell death ligand 1(PD-L1), have shown promising potential in the treatment of CRC. Specific gut microbiota can modulate the efficacy of ICIs through immune or metabolic pathways. This review summarizes recent advances in the combined application of gut microbiota and PD-1/PD-L1 inhibitors in the treatment of CRC, aiming to provide insights for expanding clinical treatment options for CRC.

MATERIALS AND METHODS: We employed a systematic search strategy to screen relevant literature from databases such as PubMed, EMBASE, Medline, Cochrane Library, and Clinical Trial registries, with the search period covering from the inception of each database to October 2024. This study includes animal models and human trial subjects. Data extraction and literature screening were strictly carried out by two independent researchers.

RESULTS: A total of 8 animal studies and 5 clinical trials were included to evaluate the effects of gut microbiota combined with PD-1/PD-L1 inhibitors in CRC. Tumor types included Microsatellite Stability(MSS), Microsatellite Instability-Low(MSI-L), and MSI-H CRC. Main outcomes were tumor volume, weight, and incidence; one study reported survival. Study durations ranged from 20 days to 26 weeks. Two studies used human fecal microbiota transplantation(FMT), and six applied experimental microbial interventions. The 5 clinical trials used ORR as the primary endpoint.Some also reported DCR, PFS, and OS. Two studies targeted Microsatellite Instability-High(MSI-H)/Deficient Mismatch Repair(dMMR), two MSS/Proficient Mismatch Repair(pMMR), and one lacked molecular subtype specification. All trials used full microbiota transplantation; one has released preliminary data.

CONCLUSION: The treatment regimen combining gut microbiota with PD-1/PD-L1 inhibitors has shown promising therapeutic prospects in both animal studies and clinical research, although most clinical trials are data remain limited. Future studies should focus on: (1) gene-edited probiotic strains with targeted modifications; (2) the synergistic effects of multiple probiotics; and (3) conducting high-quality, multicenter clinical trials.},
}

*Colorectal Neoplasms/therapy/microbiology/genetics
*Gastrointestinal Microbiome
Humans
*Immune Checkpoint Inhibitors/therapeutic use
Animals
Fecal Microbiota Transplantation
Programmed Cell Death 1 Receptor/antagonists & inhibitors
B7-H1 Antigen/antagonists & inhibitors
Microsatellite Instability

@article {pmid40376856,
year = {2025},
author = {Takyi, E and Nirmalkar, K and Adams, J and Krajmalnik-Brown, R},
title = {Interventions targeting the gut microbiota and their possible effect on gastrointestinal and neurobehavioral symptoms in autism spectrum disorder.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2499580},
doi = {10.1080/19490976.2025.2499580},
pmid = {40376856},
issn = {1949-0984},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Autism Spectrum Disorder/therapy/microbiology ; Probiotics/therapeutic use/administration & dosage ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; *Gastrointestinal Diseases/therapy/microbiology ; Gastrointestinal Tract/microbiology ; Child ; Anti-Bacterial Agents/therapeutic use ; },
abstract = {Autism spectrum disorder (ASD) is a developmental disorder that is characterized by deficits in social communication and restricted, repetitive, and stereotyped behaviors. In addition to neurobehavioral symptoms, children with ASD often have gastrointestinal symptoms (e.g. constipation, diarrhea, gas, abdominal pain, reflux). Several studies have proposed the role of gut microbiota and metabolic disorders in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients; these results offer promising avenues for novel treatments of this disorder. Interventions targeting the gut microbiota - such as fecal microbiota transplant (FMT), microbiota transplant therapy (MTT), probiotics, prebiotics, synbiotics, antibiotics, antifungals, and diet - promise to improve gut health and can potentially improve neurological symptoms. The modulation of the gut microbiota using MTT in ASD has shown beneficial and long-term effects on GI symptoms and core symptoms of autism. Also, the modulation of the gut microbiota to resemble that of typically developing individuals seems to be the most promising intervention. As most of the studies carried out with MTT are open-label studies, more extensive double-blinded randomized control trials are needed to confirm the efficacy of MTT as a therapeutic option for ASD. This review examines the current clinical research evidence for the use of interventions that target the microbiome - such as antibiotics, antifungals, probiotics/prebiotics, synbiotics, and MTT - and their effectiveness in changing the gut microbiota and improving gastrointestinal and neurobehavioral symptoms in ASD.},
}

Humans
*Gastrointestinal Microbiome/drug effects
*Autism Spectrum Disorder/therapy/microbiology
Probiotics/therapeutic use/administration & dosage
Fecal Microbiota Transplantation
Prebiotics/administration & dosage
*Gastrointestinal Diseases/therapy/microbiology
Gastrointestinal Tract/microbiology
Child
Anti-Bacterial Agents/therapeutic use

@article {pmid40375906,
year = {2025},
author = {Finotto, T and Chevenet, C and Fayard, A},
title = {Fecal Microbiota Transplantation as a Salvage Therapy for Concomitant Resistant Digestive Graft Versus Host Disease and Cryptosporidiosis in a Patient Post Hematopoietic Stem Cell Transplant: about a Case.},
journal = {Mediterranean journal of hematology and infectious diseases},
volume = {17},
number = {1},
pages = {e2025035},
pmid = {40375906},
issn = {2035-3006},
}

@article {pmid40375326,
year = {2025},
author = {Liu, J and Zhang, D and Zhou, Y and Wu, J and Feng, W and Peng, C},
title = {Fuzi alleviates cold-related rheumatoid arthritis via regulating gut microbiota and microbial bile acid metabolism.},
journal = {Chinese medicine},
volume = {20},
number = {1},
pages = {64},
pmid = {40375326},
issn = {1749-8546},
support = {82104409//National Natural Science Foundation of China/ ; 82304850//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Rheumatoid arthritis (RA) with cold pattern is an important type of RA according to the theory of traditional Chinese medicine. Fuzi (also known as the lateral roots of Aconitum carmichaelii Debx.) represents a typical traditional Chinese medicine that has been clinically used for treatment of the RA especially cold-related RA for thousands of years, yet its mechanism remains unknown.

PURPOSE: The purpose of the research was to study the therapeutic effects of Fuzi on cold-related RA, and to investigate the mechanism of its action.

METHODS: Here, we investigated the pharmacological effects of Fuzi on cold-related RA using micro-CT, histopathological analysis, and inflammatory cytokine test. Then, a gut microbiota composition analysis in combination with fecal microbiota transplantation were used to confirm the role of gut microbiota in the therapeutic effects of Fuzi. Further, targeted bile acid metabolomics was used to screen the possible differential microbial bile acids involved in the mechanism of Fuzi. In vitro bioactivity analysis of differential bile acids was used to assess their anti-inflammation activity. Finally, western blot was used to investigate the signaling pathways of Fuzi in reducing the inflammation of cold-related RA.

RESULTS: The results showed that Fuzi alleviates cold-related RA by improving arthritis index, paw swelling, bone damage, and inflammatory cytokines. In addition, the ameliorative effect of Fuzi is dependent on gut microbiota such as the taxa Lachnospiraceae and Ruminococcaceae. Targeted analysis of fecal and serum bile acids showed that TCA and THDCA were the main differential metabolites. In vitro, TCA and THDCA showed anti-inflammation effects on RAW264.7 cells. Western blot showed that Fuzi regulates TGR5-cAMP-PKA signaling and NLRP3 inflammasome to reduce cold-related arthritis.

CONCLUSION: Overall, our results demonstrated that Fuzi could regulate gut microbiota and microbial bile acid metabolism, the microbial metabolite THDCA acts on TGR5-cAMP-PKA signaling pathway and NLRP3 inflammasome to reduce cold-related arthritis. Our study suggests that supplementation of Fuzi or THDCA can be of great value for the prevention and clinical treatment of cold-related RA.},
}

@article {pmid40375187,
year = {2025},
author = {Bai, XJ and Mei, YC and Zhao, JT and Chen, ZR and Yang, CX and Dong, XJ and Yu, JW and Xiang, LB and Zhou, EZ and Chen, Y and Hao, JY and Zhang, ZJ and Liuyang, YX and Ren, L and Yao, YM and Zhang, L and Lv, Y and Lu, Q},
title = {Changes in microbiome composition after fecal microbiota transplantation via oral gavage and magnetic navigation technology-assisted proximal colon/cecum enema in antibiotic knock-down rats: a comparative experimental study.},
journal = {BMC microbiology},
volume = {25},
number = {1},
pages = {295},
pmid = {40375187},
issn = {1471-2180},
support = {92048202//Major Research Plan of the National Natural Science Foundation of China/ ; 2021GXLH-Z-047//Key R&D Plan of Shaanxi Province/ ; },
mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Rats ; Feces/microbiology ; *Gastrointestinal Microbiome ; Rats, Sprague-Dawley ; *Colon/microbiology ; *Enema/methods ; Male ; *Cecum/microbiology ; Anti-Bacterial Agents ; *Bacteria/classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Administration, Oral ; },
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) transfers fecal matter from a donor into the gastrointestinal tract of a recipient to induce changes to the gut microbiota for therapeutic benefit; however, differences in the composition of gut microbiota after FMT via different donor material delivery routes are poorly understood. In this study, we first developed a novel technique for FMT, magnetic navigation technology(MAT)-assisted proximal colon enemas, in healthy Sprague-Dawley rats. Besides, the difference in fecal microbiota composition after FMT via oral gavage and proximal colon/cecum enemas was determined in antibiotic knock-down rats, in addition to the impact on intestinal barrier function.

METHODS: A device consisting of an external magnet and a magnet-tipped 6 Fr tube was used in the MAT group (n = 6), and the control group (n = 6) where fecal matter was delivered without magnetic navigation. The feasibility and safety of this method were assessed by angiography and histology. Next, the fecal microbiota of donor rats was transplanted into antibiotic knock-down rats via oral gavage (n = 6) and MAT-assisted proximal colon/cecum enema (n = 6) for a week. Analysis of fecal 16 S rRNA was conducted to determine differences in the composition of gut microbiota between different groups. The rat intestinal barrier integrity were evaulated by H&E and ZO-1/MUC2 immunofluorescence staining.

RESULTS: The end of the fecal tube could be placed in the cecum or proximal colon of rats in MAT group; however, this was rarely achieved in the control group. No colon perforation or bleeding was detected in either group. After fecal microbiota transplantation, the microbiota α-diversity and β-diversity were comparable among the different delivery routes.At the family level, the relative abundances of Muribaculaceae, Oscillospiraceae, and Erysipelotrichaceae were higher in the gavage treatment group, whereas Lactobacillaceae and Saccharimonadaceae were higher in the enema treatment group (all p < 0.05). FMT by enema was superior to gavage in maintaining the integrity of the rat intestinal barrier, as assessed by an elevation in the density of goblet cells and increased expression of mucin-2.

CONCLUSIONS: Fecal microbiota tube placement using magnetic navigation was safe and feasible in rats.Different delivery route for FMT affects the gut microbiota composition and the integrity of the rat intestinal barrier. Future experimental designs should consider the colonization outcomes of critical microbial taxa to determine the optimal FMT delivery routes in scientific research as well as clinical practise.},
}

Animals
*Fecal Microbiota Transplantation/methods
Rats
Feces/microbiology
*Gastrointestinal Microbiome
Rats, Sprague-Dawley
*Colon/microbiology
*Enema/methods
Male
*Cecum/microbiology
Anti-Bacterial Agents
*Bacteria/classification/genetics/isolation & purification
RNA, Ribosomal, 16S/genetics
Administration, Oral

@article {pmid40373043,
year = {2025},
author = {Cassir, N and Benech, N and Galperine, T and Alric, L and Scanzi, J and Bleibtreu, A and Kapel, N and Sokol, H},
title = {A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection: The Failure of a Procedure, not of a Therapy.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf249},
pmid = {40373043},
issn = {1537-6591},
}

@article {pmid40371968,
year = {2025},
author = {Jansen, D and Deleu, S and Caenepeel, C and Marcelis, T and Simsek, C and Falony, G and Machiels, K and Sabino, J and Raes, J and Vermeire, S and Matthijnssens, J},
title = {Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2499575},
doi = {10.1080/19490976.2025.2499575},
pmid = {40371968},
issn = {1949-0984},
mesh = {Humans ; *Fecal Microbiota Transplantation ; *Colitis, Ulcerative/therapy/virology/microbiology ; *Virome ; Male ; Female ; Feces/virology ; Adult ; Gastrointestinal Microbiome ; Middle Aged ; *Bacteriophages/genetics/isolation & purification/classification ; Young Adult ; },
abstract = {Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent colonic inflammation. Standard treatments focus on controlling inflammation but remain ineffective for one-third of patients. This underscores the need for alternative approaches, such as fecal microbiota transplantation (FMT), which transfers healthy donor microbiota to patients. The role of viruses in this process, however, remains underexplored. To address this, we analyzed the gut virome using metagenomic sequencing of enriched viral particles from 320 longitudinal fecal samples of 44 patients enrolled in the RESTORE-UC FMT trial. Patients were treated with FMTs from healthy donors (allogenic, treatment) or themselves (autologous, control). We found that colonic inflammation, both its presence and location, had a greater impact on the gut virome than FMT itself. In autologous FMT patients, the virome was unstable and showed rapid divergence over time, a phenomenon we termed virome drift. In allogenic FMT patients, the virome temporarily shifted toward the healthy donor, lasting up to 5 weeks and primarily driven by microviruses. Notably, two distinct virome configurations were identified and linked to either healthy donors or patients. In conclusion, inflammation strongly affects the gut virome in UC patients, which may lead to instability and obstruct the engraftment of allogeneic FMT.},
}

Humans
*Fecal Microbiota Transplantation
*Colitis, Ulcerative/therapy/virology/microbiology
*Virome
Male
Female
Feces/virology
Adult
Gastrointestinal Microbiome
Middle Aged
*Bacteriophages/genetics/isolation & purification/classification
Young Adult

@article {pmid40371237,
year = {2025},
author = {Singh, A and Young, E and Maurya, A and Rajagopalan, A},
title = {Nasogastric Delivery of Fecal Microbiota Transplantation for the Treatment of Fulminant Clostridioides difficile Infection: A Case Report.},
journal = {JGH open : an open access journal of gastroenterology and hepatology},
volume = {9},
number = {5},
pages = {e70177},
pmid = {40371237},
issn = {2397-9070},
abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) is a significant cause of antibiotic-associated diarrhea with high morbidity and mortality, particularly in cases of fulminant disease. Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating severe and refractory CDI, typically administered via colonoscopy. However, in cases complicated by toxic megacolon, alternative methods of FMT delivery may be necessary.

CASE REPORT: This case report describes a 46-year-old female with cirrhosis and fulminant CDI complicated by toxic megacolon. Due to the patient's hemodynamic instability and contraindications to endoscopic FMT delivery, a novel approach of nasogastric FMT administration was utilized. The patient received a combination of enema-delivered and nasogastric FMT alongside standard antibiotic therapy. This approach resulted in rapid clinical improvement, with resolution of toxic megacolon, normalization of inflammatory markers, and avoidance of colectomy.

DISCUSSION: This report highlights the successful use of nasogastric FMT in a patient with fulminant CDI, offering a potential alternative delivery route when colonoscopic administration is contraindicated. To our knowledge, this is the first reported case of nasogastric FMT successfully resolving C. difficile-associated toxic megacolon.},
}

@article {pmid40370465,
year = {2025},
author = {Cui, X and Li, C and Zhong, J and Liu, Y and Xiao, P and Liu, C and Zhao, M and Yang, W},
title = {Gut microbiota - bidirectional modulator: role in inflammatory bowel disease and colorectal cancer.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1523584},
pmid = {40370465},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Colorectal Neoplasms/microbiology/immunology/therapy/etiology ; *Inflammatory Bowel Diseases/microbiology/immunology/therapy/etiology ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; },
abstract = {The gut microbiota is a diverse ecosystem that significantly impacts human health and disease. This article focuses on how the gut microbiota interacts with inflammatory bowel diseases and colorectal tumors, especially through immune regulation. The gut microbiota plays a role in immune system development and regulation, while the body's immune status can also affect the composition of the microbiota. These microorganisms exert pathogenic effects or correct disease states in gastrointestinal diseases through the actions of toxins and secretions, inhibition of immune responses, DNA damage, regulation of gene expression, and protein synthesis. The microbiota and its metabolites are essential in the development and progression of inflammatory bowel diseases and colorectal tumors. The complexity and bidirectionality of this connection with tumors and inflammation might render it a new therapeutic target. Hence, we explore therapeutic strategies for the gut microbiota, highlighting the potential of probiotics and fecal microbiota transplantation to restore or adjust the microbial community. Additionally, we address the challenges and future research directions in this area concerning inflammatory bowel diseases and colorectal tumors.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Colorectal Neoplasms/microbiology/immunology/therapy/etiology
*Inflammatory Bowel Diseases/microbiology/immunology/therapy/etiology
Animals
Fecal Microbiota Transplantation
Probiotics/therapeutic use

@article {pmid40369623,
year = {2025},
author = {Hu, J and Liu, D and Liao, G and Guo, Y and Li, M and Liao, J and Chen, H and Zhou, S and Yang, S and Li, S and Liu, Y and Zhao, M},
title = {Fecal microbiota transplantation alleviates immunosuppressant-associated diarrhea and recurrent urinary tract infection in kidney transplant recipients: a retrospective analysis.},
journal = {Gut pathogens},
volume = {17},
number = {1},
pages = {28},
pmid = {40369623},
issn = {1757-4749},
abstract = {BACKGROUND: Immunosuppressant administration subsequent to organ transplantation exerts a substantial influence on gut microbiota composition, thereby affecting patients' prognosis and quality of life.

METHODS AND RESULTS: We conducted a retrospective analysis involving 18 patients who experienced severe diarrhea or recurrent urinary tract infection (rUTI) due to prolonged immunosuppressant usage after kidney transplantation. Following episodes of severe diarrhea or rUTI, these individuals underwent fecal microbiota transplantation (FMT), resulting in notable alleviation of clinical symptoms. No unexpected adverse or serious adverse events were reported. In comparison to the pre-FMT period, the α-diversity of the intestinal microbiota in patients did not exhibit a significant difference following FMT; however, there was a notable distinction in the β-diversity and analysis of similarity (ANOSIM). In addition, our findings indicated a significant decline in the relative abundance of the bacterial genera Veillonella, Enterococcus, and Oribacterium, whereas a marked elevation was observed in the relative abundance of Faecalibacterium, Roseburia, Sutterella, Parasutterella, and Ruminiclostridium 5 after FMT in patients. Furthermore, there was a notable alteration in the metabolic pathway of gut microbiota in patients following FMT, with a significant enrichment observed in pathways such as Flavone and flavonol biosynthesis, Cytoskeleton proteins, Chromosome-related processes, NOD-like receptor signaling pathway, Progesterone-mediated oocyte maturation, and Antigen processing and presentation.

CONCLUSION: FMT exhibited an effective approach for managing rUTI and diarrhea arising from postoperative immunosuppressant exposure in kidney transplant recipients.},
}

@article {pmid40155609,
year = {2025},
author = {Rodriguez, J and Cordaillat-Simmons, M and Pot, B and Druart, C},
title = {The regulatory framework for microbiome-based therapies: insights into European regulatory developments.},
journal = {NPJ biofilms and microbiomes},
volume = {11},
number = {1},
pages = {53},
pmid = {40155609},
issn = {2055-5008},
mesh = {Humans ; *Microbiota ; Europe ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; *Biological Therapy/methods ; },
abstract = {The emergence of a broad spectrum of microbiome-based therapies has triggered changes in European regulatory frameworks. The first part of the review describes these innovative therapies. The second part provides an overview of the current framework and key changes introduced by the Regulation on substances of human origin (SoHO) for the development of microbiome-based therapies, highlighting the need of microbiome regulatory science to unlock the full potential of microbiome-based therapies.},
}

Humans
*Microbiota
Europe
Probiotics/therapeutic use
Fecal Microbiota Transplantation
*Biological Therapy/methods

@article {pmid40369317,
year = {2025},
author = {Gao, YQ and Tan, YJ and Fang, JY},
title = {Roles of the gut microbiota in immune-related adverse events: mechanisms and therapeutic intervention.},
journal = {Nature reviews. Clinical oncology},
volume = {},
number = {},
pages = {},
pmid = {40369317},
issn = {1759-4782},
abstract = {Immune checkpoint inhibitors (ICIs) constitute a major breakthrough in the field of cancer therapy; their use has resulted in improved outcomes across various tumour types. However, ICIs can cause a diverse range of immune-related adverse events (irAEs) that present a considerable challenge to the efficacy and safety of these treatments. The gut microbiota has been demonstrated to have a crucial role in modulating the tumour immune microenvironment and thus influences the effectiveness of ICIs. Accumulating evidence indicates that alterations in the composition and function of the gut microbiota are also associated with an increased risk of irAEs, particularly ICI-induced colitis. Indeed, these changes in the gut microbiota can contribute to the pathogenesis of irAEs. In this Review, we first summarize the current clinical challenges posed by irAEs. We then focus on reported correlations between alterations in the gut microbiota and irAEs, especially ICI-induced colitis, and postulate mechanisms by which these microbial changes influence the occurrence of irAEs. Finally, we highlight the potential value of gut microbial changes as biomarkers for predicting irAEs and discuss gut microbial interventions that might serve as new strategies for the management of irAEs, including faecal microbiota transplantation, probiotic, prebiotic and/or postbiotic supplements, and dietary modulations.},
}

@article {pmid40368261,
year = {2025},
author = {Murayama, R and Cai, Y and Nakamura, H and Hashimoto, K},
title = {Demyelination in Psychiatric and Neurological Disorders: Mechanisms, Clinical Impact, and Novel Therapeutic Strategies.},
journal = {Neuroscience and biobehavioral reviews},
volume = {},
number = {},
pages = {106209},
doi = {10.1016/j.neubiorev.2025.106209},
pmid = {40368261},
issn = {1873-7528},
abstract = {Demyelination, defined as the loss of myelin sheaths around neuronal axons, is increasingly recognized as a key factor in a broad range of psychiatric and neurological disorders, including schizophrenia, major depressive disorder, bipolar disorder, post-traumatic stress disorder, autism spectrum disorder, substance use disorders, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. This review investigates the core mechanisms driving demyelination, its clinical impact, and emerging therapeutic strategies aimed at maintaining or restoring myelin integrity. Disruption of myelin impairs crucial neural communication pathways, resulting in cognitive, motor, and behavioral deficits that substantially reduce quality of life and create significant economic and social challenges. Key contributors to demyelination include genetic predisposition, environmental triggers, immune dysregulation, neuroinflammation, and alterations in the gut-brain axis mediated by the vagus nerve. Promising therapies include sphingosine 1-phosphate receptor modulators and muscarinic acetylcholine receptor antagonists, both of which diminish immune-related myelin damage and may enhance neuroprotection. In addition, the novel antidepressant arketamine appears to boost myelination through transforming growth factor-β1 signaling pathways. Approaches targeting the gut-brain axis, such as noninvasive transcutaneous auricular vagus nerve stimulation and fecal microbiota transplantation, may also help reduce inflammation and support myelin repair. Future research should center on clarifying the precise molecular mechanisms of demyelination, developing targeted therapies, and leveraging advanced neuroimaging for earlier detection and personalized treatment. By combining immunomodulatory and neuroprotective strategies, there is potential to significantly improve outcomes for individuals affected by demyelinating psychiatric and neurological disorders.},
}

@article {pmid40364844,
year = {2025},
author = {Nazir, A and Hussain, FHN and Nadeem Hussain, TH and Al Dweik, R and Raza, A},
title = {Therapeutic targeting of the host-microbiota-immune axis: implications for precision health.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1570233},
pmid = {40364844},
issn = {1664-3224},
mesh = {Humans ; *Precision Medicine/methods ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; *Gastrointestinal Microbiome/immunology ; Animals ; *Host Microbial Interactions/immunology ; *Microbiota/immunology ; Immunomodulation ; },
abstract = {The human body functions as a complex ecosystem, hosting trillions of microbes that collectively form the microbiome, pivotal in immune system regulation. The host-microbe immunological axis maintains homeostasis and influences key physiological processes, including metabolism, epithelial integrity, and neural function. Recent advancements in microbiome-based therapeutics, including probiotics, prebiotics and fecal microbiota transplantation, offer promising strategies for immune modulation. Microbial therapies leveraging microbial metabolites and engineered bacterial consortia are emerging as novel therapeutic strategies. However, significant challenges remain, including individual microbiome variability, the complexity of host-microbe interactions, and the need for precise mechanistic insights. This review comprehensively examines the host microbiota immunological interactions, elucidating its mechanisms, therapeutic potential, and the future directions of microbiome-based immunomodulation in human health. It will also critically evaluate challenges, limitations, and future directions for microbiome-based precision medicine.},
}

Humans
*Precision Medicine/methods
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Prebiotics/administration & dosage
*Gastrointestinal Microbiome/immunology
Animals
*Host Microbial Interactions/immunology
*Microbiota/immunology
Immunomodulation

@article {pmid40364435,
year = {2025},
author = {Zhang, Y and Wei, Y and Han, X and Shi, L and Yu, H and Ji, X and Gao, Y and Gao, Q and Zhang, L and Duan, Y and Li, W and Yuan, Y and Shi, J and Cheng, L and Li, Y},
title = {Faecalibacterium prausnitzii prevents age-related heart failure by suppressing ferroptosis in cardiomyocytes through butyrate-mediated LCN2 regulation.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2505119},
doi = {10.1080/19490976.2025.2505119},
pmid = {40364435},
issn = {1949-0984},
mesh = {Animals ; *Myocytes, Cardiac/metabolism/drug effects/microbiology ; *Ferroptosis/drug effects ; *Heart Failure/prevention & control/microbiology/metabolism ; Rats ; Gastrointestinal Microbiome ; Humans ; *Butyrates/metabolism ; Fecal Microbiota Transplantation ; Male ; *Faecalibacterium prausnitzii/physiology/genetics ; *Lipocalin-2/metabolism/genetics ; Aged ; Aging ; Dysbiosis/microbiology ; Female ; Rats, Sprague-Dawley ; },
abstract = {Aging is a primary driver of the escalating prevalence of heart failure (HF). Age-associated gut microbiota dysbiosis has been implicated in various age-related diseases, yet its role in age-related HF remains largely unexplored. In this study, we sought to explore the potential link between age-related gut microbiota alterations and HF in the elderly. We analyzed a publicly available single-cell sequencing dataset, which revealed markedly increased ferroptosis activity in cardiac myocytes of elderly individuals compared to their younger counterparts. Notably, treatment with the ferroptosis inhibitor, ferrostatin-1, mitigated cardiac ferroptosis and prevented cardiac dysfunction in aging rats. Furthermore, fecal microbiota transplantation from elderly HF patients significantly increased cardiac ferroptosis activity and induced cardiac dysfunction in healthy recipient rats. Integrated 16S rRNA sequencing and PCR quantification revealed a marked depletion of Faecalibacterium prausnitzii (F. prausnitzii) in elderly individuals, with a more pronounced decline in elderly patients with HF. Oral administration of F. prausnitzii or its metabolite butyrate effectively attenuated age-related HF through inhibiting ferroptosis. Additionally, gene-editing techniques were employed to generate F. prausnitzii BCoAT mutant deficient in butyrate production. Intriguingly, the protective effect was lost in the butyrate-deficient F. prausnitzii strain. Mechanistically, butyrate reduced intracellular iron accumulation and suppressed ferroptosis by downregulating LCN2 expression in senescent cardiomyocytes. Our findings highlight the critical role of aged microbiota-induced ferroptosis in HF and propose F. prausnitzii or butyrate may serve as potential targets for the prevention and treatment of age-related HF.},
}

Animals
*Myocytes, Cardiac/metabolism/drug effects/microbiology
*Ferroptosis/drug effects
*Heart Failure/prevention & control/microbiology/metabolism
Rats
Gastrointestinal Microbiome
Humans
*Butyrates/metabolism
Fecal Microbiota Transplantation
Male
*Faecalibacterium prausnitzii/physiology/genetics
*Lipocalin-2/metabolism/genetics
Aged
Aging
Dysbiosis/microbiology
Female
Rats, Sprague-Dawley

@article {pmid40361641,
year = {2025},
author = {Mafe, AN and Büsselberg, D},
title = {Could a Mediterranean Diet Modulate Alzheimer's Disease Progression? The Role of Gut Microbiota and Metabolite Signatures in Neurodegeneration.},
journal = {Foods (Basel, Switzerland)},
volume = {14},
number = {9},
pages = {},
doi = {10.3390/foods14091559},
pmid = {40361641},
issn = {2304-8158},
support = {NPRP 14S0311-210033//Qatar National Research Fund/ ; },
abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), the most common form of dementia, represent a growing global health crisis, yet current treatment strategies remain primarily palliative. Recent studies have shown that neurodegeneration through complex interactions within the gut-brain axis largely depends on the gut microbiota and its metabolites. This review explores the intricate molecular mechanisms linking gut microbiota dysbiosis to cognitive decline, emphasizing the impact of microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, and tryptophan metabolites, on neuroinflammation, blood-brain barrier (BBB) integrity, and amyloid-β and tau pathology. The paper highlights major microbiome signatures associated with Alzheimer's disease, detailing their metabolic pathways and inflammatory crosstalk. Dietary interventions have shown promise in modulating gut microbiota composition, potentially mitigating neurodegenerative processes. This review critically examines the influence of dietary patterns, such as the Mediterranean and Western diets, on microbiota-mediated neuroprotection. Bioactive compounds like prebiotics, omega-3 fatty acids, and polyphenols exhibit neuroprotective effects by modulating gut microbiota and reducing neuroinflammation. Furthermore, it discusses emerging microbiome-based therapeutic strategies, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation (FMT), as potential interventions for slowing Alzheimer's progression. Despite these advances, several knowledge gaps remain, including interindividual variability in microbiome responses to dietary interventions and the need for large-scale, longitudinal studies. The study proposes an integrative, precision medicine approach, incorporating microbiome science into Alzheimer's treatment paradigms. Ultimately, cognizance of the gut-brain axis at a mechanistic level could unlock novel therapeutic avenues, offering a non-invasive, diet-based strategy for managing neurodegeneration and improving cognitive health.},
}

@article {pmid40361238,
year = {2025},
author = {Maschek, S and Østergaard, TH and Krych, L and Zachariassen, LF and Sørensen, DB and Junker Mentzel, CM and Hansen, AK and Sjögren, JM and Barfod, KK},
title = {Investigating fecal microbiota transplants from individuals with anorexia nervosa in antibiotic-treated mice using a cross-over study design.},
journal = {Journal of eating disorders},
volume = {13},
number = {1},
pages = {82},
pmid = {40361238},
issn = {2050-2974},
abstract = {Anorexia nervosa (AN) is a complex and serious mental disorder, which may affect individuals of all ages and sex, but primarily affecting young women. The disease is characterized by a disturbed body image, restrictive eating behavior, and a lack of acknowledgment of low body weight. The underlying causes of AN remain largely unknown, and current treatment options are limited to psychotherapy and nutritional support. This paper investigates the impact of Fecal Microbiota Transplants (FMT) from patients with AN on food intake, body weight, behavior, and gut microbiota into antibiotic-treated mice. Two rounds of FMT were performed using AN and control (CO) donors. During the second round of FMT, a subset of mice received gut microbiota (GM) from a different donor type. This split-group cross-over design was chosen to demonstrate any recovery effect of FMT from a non-eating disorder state donor. The first FMT, from donors with AN, resulted in lower food intake in mice without affecting body weight. Analysis of GM showed significant differences between AN and CO mice after FMT1, before cross-over. Specific bacterial genera and families Ruminococcaceae, Lachnospiraceae, and Faecalibacterium showed different abundances in AN and CO receiving mice. Behavioral tests showed decreased locomotor activity in AN mice after FMT1. After FMT2, serum analysis revealed higher levels of appetite-influencing hormones (PYY and leptin) in mice receiving AN-GM. Overall, the results suggest that AN-GM may contribute to altered food intake and appetite regulation, which can be ameliorated with FMT from a non-eating disorder state donor potentially offering FMT as a supportive treatment for AN.},
}

@article {pmid40359452,
year = {2025},
author = {Yang, G and Li, M and Zheng, X and Chen, X and Peng, Y and Li, J and Yang, S and Chen, H and Wang, Y and Zhang, H and Gong, C and Hu, F and Wan, J and Zhu, Z and Zhang, L and Li, R},
title = {Trehalose Acts as a Mediator: Imbalance in Brain Proteostasis Induced by Polystyrene Nanoplastics via Gut Microbiota Dysbiosis during Early Life.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.5c01639},
pmid = {40359452},
issn = {1936-086X},
abstract = {As an emerging contaminant, nanoplastics have evolved into a global ecological issue. Studies have shown that nanoplastics induce neurotoxicity across species, however, the causal mechanism remains unknown. This study aimed to explore the mechanism underlying the neurotoxicity caused by polystyrene nanoplastics (PS-NPs) via microbiota-gut-brain axis in immature mice, which serve as a model of infants and young children who are at higher exposure risk to NPs. The results indicated that while only a minority of PS-NPs reached the brain after exposure, they still had significant neurotoxic effects, as reflected by abnormalities in behavior, biochemical marker levels and histopathology. Proteomics and quantification analyses revealed that a proteostasis imbalance mediated by lysosomal and proteasome dysfunction in the brain is the key reason for the induced neurotoxicity. Further, we confirmed the indirect role of gut microbiota in the neurotoxicity induced by PS-NPs through 16S rDNA analyses and fecal microbiota transplantation. Crucial bacterial species such as Eubacterium coprostanoligenes potentially act as indicators for gut dysbiosis after PS-NPs exposure. Notably, we first estimated the indirect effect of gut microbiota on neurotoxicity attributed to PS-NPs in immature mice as 39.20% by high-dimensional mediation analysis. Trehalose was identified as a mediator connecting the gut microbiota and the brain, and the crucial role of trehalose supplementation was highlighted in remodeling the brain proteostasis to alleviate the neurotoxicity in immature mice. These findings are expected to contribute to a deeper understanding of the risk assessment and health protection of the nervous system from exposure to PS-NPs early in life.},
}

@article {pmid40359297,
year = {2025},
author = {Pakuwal, E and Tan, JL and Page, AJ and Stringer, AM and Woodman, RJ and Chinnaratha, MA},
title = {A systematic review and meta-analysis on the efficacy of fecal microbiome transplantation in patients with severe alcohol-associated hepatitis.},
journal = {European journal of gastroenterology & hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1097/MEG.0000000000003003},
pmid = {40359297},
issn = {1473-5687},
abstract = {BACKGROUND: Severe alcohol-associated hepatitis (sAH) has a high short-term mortality, with limited treatment options. Fecal microbiota transplantation (FMT) has shown benefits in small, uncontrolled studies.

AIM: Perform a systematic review and meta-analysis to provide updated evidence on the efficacy and safety of FMT in sAH patients.

METHOD: Electronic databases were searched till 4 December 2023 for studies comparing FMT with standard of care (SOC) in sAH patients. Sensitivity analysis (leave-one-out method) and subgroup analyses were performed. Pooled risk ratio (RR) was used to compare the survival outcomes.

RESULTS: Eight studies with 444 patients (FMT: 218; SOC: 226) met the eligibility criteria and were included in this meta-analysis. The 28- and 90-day survival range was higher in the FMT group (75-100% and 53-87%) compared to the SOC group (48-80% and 25-56%). The random-effects model showed a statistically significant increase in survival in the FMT arm at 28 days [RR (95% confidence interval) 2.30 (1.24-4.28), P = 0.01] and 90 days [2.53 (1.34-4.77), P < 0.001]. However, there was no statistically significant change in survival at the 6-month [1.89 (0.89-4.05), P = 0.10] and the 12-month time [1.86 (0.68-5.08), P = 0.23]. Sensitivity analysis showed no major changes in the overall effect sizes, and subgroup analysis showed that the survival benefit was restricted only to the retrospective studies. No serious treatment-related adverse events were reported.

CONCLUSION: FMT is a safe and efficacious treatment option that improves short-term survival in sAH patients, without major adverse events. A multicentre randomized controlled trial with an adequate sample size is required to confirm these findings.},
}

@article {pmid40357397,
year = {2025},
author = {Xing, G and Cui, Y and Guo, Z and Han, B and Zhao, G},
title = {Progress on the mechanism of intestinal microbiota against colorectal cancer.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1565103},
pmid = {40357397},
issn = {2235-2988},
mesh = {*Colorectal Neoplasms/therapy/microbiology/prevention & control/immunology ; Humans ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Immunotherapy ; Signal Transduction ; },
abstract = {The intestinal microbiota plays a crucial role in the occurrence and development of colorectal cancer, and its anti - colorectal cancer mechanism has become a research hotspot. This article comprehensively expounds on the molecular mechanisms of the intestinal microbiota in anti - colorectal cancer, including aspects such as immune regulation, activation of carcinogenic signaling pathways (it should be noted that it is more reasonable to be "inhibition of carcinogenic signaling pathways"), metabolite - mediated effects, and maintenance of intestinal barrier function. At the same time, it explores the roles and potential mechanisms of intervention methods such as probiotic supplementation therapy, immunotherapy, and fecal microbiota transplantation. In addition, it analyzes the impact of the intestinal flora on the therapeutic efficacy of colorectal cancer. The existing research results are summarized, and the future research directions are prospected, with the aim of providing new theoretical bases and treatment ideas for the prevention and treatment of colorectal cancer.},
}

*Colorectal Neoplasms/therapy/microbiology/prevention & control/immunology
Humans
*Gastrointestinal Microbiome/physiology
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Animals
Immunotherapy
Signal Transduction

@article {pmid40108157,
year = {2025},
author = {Huang, R and Shen, ZY and Huang, D and Zhao, SH and Dan, LX and Wu, P and Tang, QZ and Ma, ZG},
title = {Microbiota-indole-3-propionic acid-heart axis mediates the protection of leflunomide against αPD1-induced cardiotoxicity in mice.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {2651},
pmid = {40108157},
issn = {2041-1723},
support = {82070410; 82270248//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Animals ; *Leflunomide/pharmacology/therapeutic use ; Mice ; *Cardiotoxicity/prevention & control/etiology/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Indoles/pharmacology/metabolism ; Myocytes, Cardiac/drug effects/metabolism ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Mice, Inbred C57BL ; *Heart/drug effects ; *Propionates/metabolism/pharmacology ; Male ; Receptors, Aryl Hydrocarbon/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Fecal Microbiota Transplantation ; Immune Checkpoint Inhibitors/adverse effects ; },
abstract = {Anti-programmed death 1 (αPD1) immune checkpoint blockade is used in combination for cancer treatment but associated with cardiovascular toxicity. Leflunomide (Lef) can suppress the growth of several tumor and mitigate cardiac remodeling in mice. However, the role of Lef in αPD1-induced cardiotoxicity remains unclear. Here, we report that Lef treatment inhibits αPD1-related cardiotoxicity without compromising the efficacy of αPD1-mediated immunotherapy. Lef changes community structure of gut microbiota in αPD1-treated melanoma-bearing mice. Moreover, mice receiving microbiota transplants from Lef+αPD1-treated melanoma-bearing mice have better cardiac function compared to mice receiving transplants from αPD1-treated mice. Mechanistically, we analyze metabolomics and identify indole-3-propionic acid (IPA), which protects cardiac dysfunction in αPD1-treated mice. IPA can directly bind to the aryl hydrocarbon receptor and promote phosphoinositide 3-kinase expression, thus curtailing the cardiomyocyte response to immune injury. Our findings reveal that Lef mitigates αPD1-induced cardiac toxicity in melanoma-bearing mice through modulation of the microbiota-IPA-heart axis.},
}

Animals
*Leflunomide/pharmacology/therapeutic use
Mice
*Cardiotoxicity/prevention & control/etiology/metabolism
*Gastrointestinal Microbiome/drug effects
*Indoles/pharmacology/metabolism
Myocytes, Cardiac/drug effects/metabolism
*Programmed Cell Death 1 Receptor/antagonists & inhibitors
Mice, Inbred C57BL
*Heart/drug effects
*Propionates/metabolism/pharmacology
Male
Receptors, Aryl Hydrocarbon/metabolism
Phosphatidylinositol 3-Kinases/metabolism
Fecal Microbiota Transplantation
Immune Checkpoint Inhibitors/adverse effects