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Journal articleEriksen LL, Støy S, Hansen MM, et al., 9900,
Dynamics in circulating immune cell subsets after faecal microbiota transplantation for recurrent Clostridioides difficile infection
, Clinical and Translational Gastroenterology, ISSN: 2155-384XBackground: Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI). Adverse reactions to FMT occur early, and cellular immune responses after FMT may contribute to effects and reactions. We compared early changes in peripheral immune cell subsets and clinical outcomes in patients with rCDI who received either FMT and antibiotics or antibiotics alone in a randomized trial. Methods: Thirty-five patients with rCDI were randomized to vancomycin and FMT (n=20) or vancomycin alone (n=15). Blood samples were drawn before (wk0) and one week (wk1) after treatment. In three additional patients, blood samples were drawn before, and 24 hours and wk1 after FMT. Adaptive and innate immune cell subsets and gut-homing memory (CD45RO+integrinβ7+) and effector (CD45RO-integrinβ7+) T cells were analysed by flow cytometry. Results: FMT induced subtle changes in immune cell subsets with no clear pattern from wk0 to wk1. The Treg fraction tended to decrease after FMT, and a similar decrease at 24 hours indicated rapid Tregs dynamics. NKT cells increased during the first 24 hours and returned to baseline level at wk1. Regardless of FMT, patients with clinical resolution from rCDI had a decrease in non-classical monocytes and a shift in gut-homing memory to effector cells at wk1. Conclusion: In rCDI, FMT induced subtle and transient dynamics in peripheral immune cell subsets. Tregs and NKT cells seemed responsive and should be further studied. Cure of CDI may be associated with an increase in circulating gut-homing T cells. © 2026 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology
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Journal articleLiu CS, Merrick B, Taboun Z, et al., 2026,
Poster Session I - A36 OPTIMIZING AND STANDARDIZING DONOR SCREENING FOR FECAL MICROBIOTA TRANSPLANTATION: A DELPHI REVIEW
, J Can Assoc Gastroenterol, Vol: 9, ISSN: 2515-2084Fecal microbiota transplantation (FMT) transfers stool from healthy donors to recipients and is highly effective for preventing recurrent Clostridioides difficile infection. However, rare cases of FMT-associated infections have resulted in morbidity and even mortality. Despite the critical importance of screening, evidence-based approaches to developing donor-screening protocols remain limited.This review aimed to evaluate the evidence underpinning current FMT donor screening protocols by critically appraising existing literature on pathogen transmission dynamics.We conducted a comprehensive review up to November 2024. Key factors considered included the geographical distribution of pathogens, likelihood of fecal-oral transmission via FMT, and the clinical consequences of potential transmission events. A Delphi process involving 25 experts in stool banking, donor screening, and FMT preparation and administration was undertaken to establish consensus on the transmissibility of pathogens via FMT, defined as ≥ 80% agreement. Transmission was categorized as definite when supported by documented evidence (e.g., case reports or confirmed donor-to-recipient transmission), possible when fecal-oral transmission was plausible but unconfirmed, and not possible when such transmission was considered unlikely.We identified 58 potentially-relevant pathogens and summarized their prevalence, transmissibility, disease severity, and likelihood of FMT-related transmission (Table 1). This was followed by three rounds of the Delphi process generating 21 consensus statements (Table 2), all achieving a consensus of at least 80% except for SARS-CoV-2 (78%). Although fecal-oral transmission of SARS-CoV-2 is unproven, its detection in stool precluded full consensus. Similarly, hepatitis B, hepatitis C, and HIV showed no evidence of FMT-related transmission, though excluding infected donors remains prudent given potential immune and microbiome alterations. Finally, while CMV i
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Journal articleRadhakrishnan ST, Mullish BH, Olbei ML, et al., 2025,
Deciphering the microbiome–metabolome landscape of an inflammatory bowel disease inception cohort
, Gut Microbes, Vol: 17, ISSN: 1949-0976 -
Journal articleDecker V, Qureshi K, Roberts L, et al., 2025,
The emerging role of the gut microbiota in vaccination responses.
, Gut Microbes, Vol: 17The gut microbiota has emerged as a key modulator of host immune responses, and growing evidence suggests it plays a role in shaping vaccine-induced immunity. While immunization remains vital for preventing infectious diseases, inter-individual variability in vaccine responses poses a persistent challenge. Traditional factors such as age, sex, genetics, and immune status do not fully account for this variability. Recent studies highlight the gut microbiome as a potential contributor. This review examines current evidence linking the gut microbiota to vaccine responses, with a focus on vaccines against SARS-CoV-2, hepatitis B virus, and influenza. Human studies show associations between microbial composition, particularly taxa like Bifidobacterium adolescentis, and immunogenicity. Microbial metabolites, such as short-chain fatty acids and bile acids, influence T-cell differentiation, antibody production, and cytokine responses. Factors that alter microbiota composition, including antibiotics, diet, and prebiotic or probiotic supplementation, can impact vaccine responses, highlighting a dynamic gut-immune relationship. Experimental models further support these observations, showing diminished responses in germ-free or antibiotic-treated animals and enhanced responses following microbial-based interventions. These findings also suggest the gut microbiota may be harnessed to improve vaccine efficacy. Future research should explore the potential for microbiota-targeted strategies to optimize vaccine efficacy, particularly in immunocompromised populations.
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Journal articleMullish BH, Javed A, Ghani R, et al., 2025,
Operational considerations for the running of an NHS faecal microbiota transplant (FMT) service
, Journal of Hospital Infection, Vol: 164, Pages: 105-110, ISSN: 0195-6701Faecal microbiota transplant (FMT; sometimes called ‘intestinal microbiota transplant’ (1)) is well-established in national (2-4) and international consensus documents and guidelines (5) as a clinically- and cost-effective treatment for recurrent Clostridioides difficile infection (rCDI). This infection presents several particular clinical challenges, impacting as it does upon infection prevention and control and antibiotic stewardship (AMS) strategies, healthcare-acquired infection rates, and clinical flow. Moreover, the lack of isolation facilities, inconsistencies in decontamination strategies and an ageing immunosuppressed population further adds to treatment challenge. In recent years, FMT has become embedded as an antimicrobial stewardship strategy particularly for patients with recurrent CDI as a means of limiting further exposure to antimicrobials. Additionally – following on from early signals related to the use of FMT in rCDI potentially mitigating the burden of antimicrobial resistance genes in the gut (6), and reducing the risk of future invasive infection (7) - FMT has been explored as a modality to reduce invasive infections in patients with intestinal colonisation with gram negative multidrug resistant organisms (GN-MDRO). These infections can be highly-resistant to last line systemic therapies, and FMT may offer a way to avoid selection pressures for these agents and aid overall AMS efforts. Specifically, FMT in this setting seems safe and effective when administered to immunocompromised patients with intestinal MDROs, potentially resulting in decolonisation, and reducing invasive infection and carbapenem use, with additional potential beneficial impacts upon morbidity and mortality (8-11).
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Journal articleMichael DR, John DA, Coates N, et al., 2025,
The impact of three distinct probiotic supplements on the gut microbiota and its metabolites in healthy adults.
, Benef Microbes, Pages: 1-14The effects of probiotics on the gut microbiota and microbial metabolites in healthy individuals are not well understood. Faecal and serum samples were collected at the start and end of a 3-month, double-blind, placebo-controlled, randomised study with three different probiotic formulations in free-living, healthy adults. The composition of the faecal microbiota and levels of faecal and/or serum short-chain fatty acids (SCFA) and bile acids (BA) were measured and the probiotic formulations were found to impart differing effects including shifts in the composition and structure of the faecal microbiota, enhanced levels of circulating short chain fatty acids such as butyrate and propionate, and elevated levels of sulphated bile acids in faeces. This was in contrast to the outcomes for the placebo population where very little change occurred over the study. These findings demonstrate that probiotic supplementation elicits formulation specific effects and that there are potential benefits for healthy individuals.
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Journal articleMullish BH, Ianiro G, 2025,
Preface to special edition: Microbiome, inflammation and cancer
, Best Practice & Research Clinical Gastroenterology, Vol: 77, Pages: 101952-101952, ISSN: 1521-6918 -
Journal articleCassir N, Ghani R, Biehl LM, et al., 2025,
Non-antimicrobial therapies for recurrent urinary tract infection in women: is there a place for faecal microbiota transfer?
, Clinical Microbiology and Infection, ISSN: 1198-743XBackground:Recurrent urinary tract infection (rUTI) is a common condition, affecting approximately one-third of women after an initial UTI. It significantly impacts health care costs and patients' quality of life. The relationship between the pathophysiology of UTI and the gut and vaginal microbiota is recognized as a contributing factor to rUTI in women. As antibiotic resistance among uropathogens continues to increase, there is a clear need to develop novel therapeutic interventions. Faecal microbiota transfer (FMT) is a potent nonantimicrobial strategy for modulating the gut microbiota; however, its clinical relevance in the context of rUTI is unclear.Objectives:This narrative review aimed to summarize the current evidence on the use of FMT for the treatment of rUTI, focusing on women, excluding those with mechanical dysfunctions such as urinary incontinence, neurogenic bladder, and bladder cancer, compared with other nonantimicrobial interventions. We also discussed the pathophysiology and epidemiology of rUTI to identify patients for whom microbiota-targeting therapies may be the most effective.Content:Periurethral colonization and migration to the bladder of uropathogens that inhabit the gut and vagina have been linked to the aetiology of UTI in women, particularly in patients with multidrug-resistant organisms. FMT appears to be a promising approach for preventing the clinical development of rUTI, although prospective data remain limited. In contrast, other reported nonantimicrobial strategies targeting the gut and urogenital microbiota have shown variable significant clinical efficacy. Prospective randomized controlled clinical trials are then needed to further confirm a potential therapeutic benefit, optimize the FMT procedure, and better assess its cost-effectiveness.
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Journal articleKing OG, Yip AYG, Horrocks V, et al., 2025,
Vancomycin-resistant enterococci utilise antibiotic-enriched nutrients for intestinal colonisation
, Nature Communications, Vol: 16, ISSN: 2041-1723Antibiotic treatment significantly disrupts the gut microbiome and promotes vancomycin- resistant enterococci (VRE) intestinal colonisation. These disruptions cause the intestine to act as a reservoir for VRE that seed difficult-to-treat infections. Here we show that antibiotics that promote VRE intestinal colonisation increase the concentration of a wide range of nutrients and decrease the concentration of a wide range of microbial metabolites. We show significant but incomplete suppression of VRE growth by individual short chain fatty acids that were decreased in antibiotic-treated faecal microbiomes. However, mixtures of short chain fatty acids provide complete or near complete suppression of VRE growth. We show that VRE use most nutrients increased in antibiotic-treated faecal microbiomes as carbon or nitrogen sources to support their growth, where Enterococcus faecium and Enterococcus faecalis have some common and some distinct preferences for the use of these specific nutrients. Finally, we show that E. faecium and E. faecalis occupy overlapping but distinct nutrient-defined intestinal niches that promote high growth when cultured with each other and when cultured with carbapenem-resistant Enterobacteriaceae. Our results demonstrate that VRE occupy distinct intestinal niches in the antibiotic-treated intestine, defined by their abilities to utilise specific enriched nutrients and their abilities to grow with reduced concentrations of inhibitory microbial metabolites.
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Journal articleUmamahesan C, Pilcicka A, Yick J, et al., 2025,
Interplay of constipation, intestinal barrier dysfunction and fungal exposome in aetiopathogenesis of Parkinson’s disease: hypothesis with supportive data
, Biochemical Journal, Vol: 482, Pages: 807-821, ISSN: 0264-6021<jats:p>Constipation is a forerunner to Parkinson’s disease (PD) diagnosis, worsening thereafter. We explore the relationship of intestinal barrier dysfunction to constipation and whether intestinal fungal load is an aggravating factor. Fungal load was quantified by real-time PCR, using ITS1F-ITS2 primer set, on microbial DNA extract from stool in 68 participants with PD, 102 without. Fungal load was 60% higher per decade after age 60 years, with no PD status interaction with age. After age adjustment, it was associated inversely with dietary renal acid load. It was unrelated to the presence of constipation or barrier dysfunction. Neither consumption of antimicrobials nor of other targeted exogenous substances was associated. Enzyme-linked immunosorbent assays measured barrier dysfunction markers, faecal alpha-1 antitrypsin (AAT), zonulin and serum intestinal fatty acid-binding protein (I-FABP). Barrier dysfunction was associated with constipation and slower radiographic colonic transit. Functional constipation was 28% more frequent with a doubling of AAT concentration. More colonic-transit test markers were retained in the transverse colon, the higher the AAT and zonulin concentrations, anatomically spotlighting abnormality for the entire colon. In contrast, the concentration of the small intestinal barrier marker I-FABP was associated with looser stool consistency, which is consistent with secondary microbial overgrowth. By showing a relationship of intestinal barrier dysfunction to constipation, this study supports the hypothesis that dysfunction may be consequential. Dysfunction may be a necessary, but not sufficient, precursor to PD, in allowing inflammaging. Since ageing is the clearest risk for PD, a gut pathogen escalating in abundance from the sixth decade, integral to fungal load, and whose reproduction and virulence is favoured by alkalinity, tallies.</jats:p>
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