Browsing by Author "Mullish, Benjamin H."

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    Effective fecal microbiota transplantation for recurrent Clostridioides difficile infection in humans is associated with increased signalling in the bile acid-farnesoid X receptor-fibroblast growth factor pathway
    (Taylor & Francis, 2018-09-05) Monaghan, Tanya; Mullish, Benjamin H.; Patterson, Jordan; Wong, Gane KS; Marchesi, Julian R.; Xu, Huiping; Jilani, Tahseen; Kao, Dina
    The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with restored gut microbiota-bile acid interactions representing one possible explanation. Furthermore, the potential implications for host physiology of these FMT-related changes in gut bile acid metabolism are also not well explored. In this study, we investigated the impact of FMT for rCDI upon signalling through the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we identify that in addition to restoration of gut microbiota and bile acid profiles, FMT for rCDI is accompanied by a significant, sustained increase in circulating levels of FGF19 and reduction in FGF21. These FGF changes were associated with weight gain post-FMT, to a level not exceeding the pre-rCDI baseline. Collectively, these data support the hypothesis that the restoration of gut microbial communities by FMT for rCDI is associated with an upregulated FXR-FGF pathway, and highlight the potential systemic effect of FMT.
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    Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent C. difficile Infection
    (Oxford University Press, 2021-08-19) Allegretti, Jessica R.; Kelly, Colleen R.; Grinspan, Ari; Mullish, Benjamin H.; Hurtado, Jonathan; Carrellas, Madeline; Marcus, Jenna; Marchesi, Julian R.; McDonald, Julie A.K.; Gerardin, Ylaine; Silverstein, Michael; Pechlivanis, Alexandros; Barker, Grace F.; Blanco, Jesus Miguens; Alexander, James L.; Gallagher, Kate I.; Pettee, Will; Phelps, Emmalee; Nemes, Sara; Sagi, Sashidhar V.; Bohm, Matthew; Kassam, Zain; Fischer, Monika; Medicine, School of Medicine
    Background: Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited. Methods: Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement-all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling. Results: Fifty patients enrolled in the study, among which 15 had Crohn's disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn's disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn's disease patients (P = 0.04). Conclusion: This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.
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    Outcomes of Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Diseases and Recurrent Clostridioides difficile Infection
    (Elsevier, 2020) Allegretti, Jessica R.; Kelly, Colleen R.; Grinspan, Ari; Mullish, Benjamin H.; Kassam, Zain; Fischer, Monika; Medicine, School of Medicine
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    Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic
    (BMJ Publishing Group, 2020-07-03) Ianiro, Gianluca; Mullish, Benjamin H.; Kelly, Colleen R.; Kassam, Zain; Kuijper, Ed J.; Ng, Siew C.; Iqbal, Tariq H.; Allegretti, Jessica R.; Bibbò, Stefano; Sokol, Harry; Zhang, Faming; Fischer, Monika; Costello, Samuel Paul; Keller, Josbert J.; Masucci, Luca; Prehn, Joffrey van; Quaranta, Gianluca; Quraishi, Mohammed Nabil; Segal, Jonathan; Kao, Dina; Satokari, Reetta; Sanguinetti, Maurizio; Tilg, Herbert; Gasbarrini, Antonio; Cammarota, Giovanni; Medicine, School of Medicine
    The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.
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    SARS-CoV-2 vaccines and donor recruitment for FMT
    (Elsevier, 2021) Ianiro, Gianluca; Mullish, Benjamin H.; Hvas, Christian Lodberg; Segal, Jonathan P.; Kuijper, Ed J.; Costello, Samuel P.; Kelly, Colleen R.; Allegretti, Jessica R.; Fischer, Monika; Iqbal, Tariq H.; Satokari, Reetta; Kao, Dina; van Prehn, Joffrey; Ng, Siew C.; Bibbò, Stefano; Dahl Baunwall, Simon Mark; Quraishi, Mohammed N.; Sokol, Harry; Zhang, Faming; Keller, Josbert; Masucci, Luca; Quaranta, Gianluca; Kassam, Zain; Sanguinetti, Maurizio; Tilg, Herbert; Gasbarrini, Antonio; Cammarota, Giovanni; Medicine, School of Medicine
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    Short-chain fatty and carboxylic acid changes associated with fecal microbiota transplant communally influence microglial inflammation
    (Elsevier, 2023-06-05) Churchward, Matthew A.; Michaud, Emily R.; Mullish, Benjamin H.; Blanco, Jesús Miguens; Garcia Perez, Isabel; Marchesi, Julian R.; Xu, Huiping; Kao, Dina; Todd, Kathryn G.; Biostatistics and Health Data Science, School of Medicine
    The intestinal microbiota has been proposed to influence human mental health and cognition through the gut-brain axis. Individuals experiencing recurrent Clostridioides difficile infection (rCDI) frequently report depressive symptoms, which are improved after fecal microbiota transplantation (FMT); however, mechanisms underlying this association are poorly understood. Short-chain fatty acids and carboxylic acids (SCCA) produced by the intestinal microbiota cross the blood brain barrier and have been proposed to contribute to gut-brain communication. We hypothesized that changes in serum SCCA measured before and after successful FMT for rCDI influences the inflammatory response of microglia, the resident immune cells of the central nervous system. Serum SCCA were quantified using gas chromatography-mass spectroscopy from 38 patients who participated in a randomized trial comparing oral capsule-vs colonoscopy-delivered FMT for rCDI, and quality of life was assessed by SF-36 at baseline, 4, and 12 weeks after FMT treatment. Successful FMT was associated with improvements in mental and physical health, as well as significant changes in a number of circulating SCCA, including increased butyrate, 2-methylbutyrate, valerate, and isovalerate, and decreased 2-hydroxybutyrate. Primary cultured microglia were treated with SCCA and the response to a pro-inflammatory stimulus was measured. Treatment with a combination of SCCA based on the post-FMT serum profile, but not single SCCA species, resulted in significantly reduced inflammatory response including reduced cytokine release, reduced nitric oxide release, and accumulation of intracellular lipid droplets. This suggests that both levels and diversity of SCCA may be an important contributor to gut-brain communication.