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Conference paperMullish BH, Innes AJ, Ghani R, et al., 2024, , American Society of Hematology (ASH) Annual Meeting & Exposition, Pages: 4892.1-4892.1, ISSN: 0006-4971
Background and significance: Reduced gut microbiome diversity pre-allogeneic hematopoietic cell transplantation (HCT) strongly correlates with poorer survival after the procedure. Most hematologic malignancy patients undergoing HCT have previously received intensive chemotherapy, resulting in prolonged neutropenic episodes and opportunistic infections (increasingly with multidrug-resistant organisms (MDRO)), requiring broad-spectrum antibiotics. The combination of chemotherapy and antimicrobial use has particularly been linked to reduced gut microbiome diversity.Intestinal microbiota transplant (IMT) is a novel treatment approach that can restore this perturbed diversity and has shown promise in a cohort of patients colonized with MDRO in their intestine by reducing post-HCT infection burden and improving overall survival. Given that most patients undergoing HCT will have a disrupted microbiome from prior therapies, we hypothesized that offering IMT prior to initiation of HCT conditioning could improve microbiome diversity during the early stages of HCT, with potential to reduce the frequency of infective complications, and improve outcomes of HCT. Studies using IMT post-HCT have shown variable results, but one distinctive aspect of this study is pre-HCT administration of IMT, aiming to ‘prehabilitate’ the gut prior to the microbiota insults inherent to HCT.Study Design and Methods: The trial is registered (ClinicalTrials.gov ID: NCT 6355583) and recruitment started in 2024.Fifty adult patients planned to receive allogeneic HCT for hematologic malignancies will be recruited into this phase IIa trial, and randomized 1:1 to receive capsulized IMT (10 capsules of EBX-102-02, a next generation, full-spectrum microbiome product derived from pooled screened donor stool; EnteroBiotix Ltd) or matched placebo at 14 days prior to initiation of HCT conditioning, and followed for up to 12 months. The trial will be performed at seven UK centers.Patients will be eligi
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Journal articleAllegretti JR, Khanna S, Mullish BH, et al., 2024, , Gastroenterology, Vol: 167, Pages: 885-902, ISSN: 0016-5085
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Journal articleTurner BRH, Jenkinson PI, Huttman M, et al., 2024, , Alcoholism: Clinical and Experimental Research, Vol: 48, Pages: 1451-1465, ISSN: 0145-6008
Alcohol is the most widely abused substance in the world, the leading source of mortality in 15–49-year-olds, and a major risk factor for heart disease, liver disease, diabetes, and cancer. Despite this, alcohol is regularly misused in wider society. Consumers of excess alcohol often note a constellation of negative symptoms, known as the alcohol hangover. However, the alcohol hangover is not considered to have long-term clinical significance by clinicians or consumers. We undertook a critical review of the literature to demonstrate the pathophysiological mechanisms of the alcohol hangover. Hereafter, the alcohol hangover is re-defined as a manifestation of sickness behavior secondary to alcohol-induced inflammation, using the Bradford-Hill criteria to demonstrate causation above correlation. Alcohol causes inflammation through oxidative stress and endotoxemia. Alcohol metabolism is oxidative and increased intake causes relative tissue hypoxia and increased free radical generation. Tissue damage ensues through lipid peroxidation and the formation of DNA/protein adducts. Byproducts of alcohol metabolism such as acetaldehyde and congeners, sleep deprivation, and the activation of nonspecific inducible CYP2E1 in alcohol-exposed tissues exacerbate free radical generation. Tissue damage and cell death lead to inflammation, but in the intestine loss of epithelial cells leads to intestinal permeability, allowing the translocation of pathogenic bacteria to the systemic circulation (endotoxemia). This leads to a well-characterized cascade of systemic inflammation, additionally activating toll-like receptor 4 to induce sickness behavior. Considering the evidence, it is suggested that hangover frequency and severity may be predictors of the development of later alcohol-related diseases, meriting formal confirmation in prospective studies. In light of the mechanisms of alcohol-mediated inflammation, research into gut permeability and the gut microbiome may be an exciting
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Journal articlePerry R, Mullish BH, Alexander JL, et al., 2024, , Scientific Reports, Vol: 14, ISSN: 2045-2322
Investigating the gut microbiome and metabolome frequently requires faecal samples, which can be difficult to obtain. Previous studies have shown that rectal swabs are comparable to faecal samples for analysing gut microbiota composition and key metabolites. In this study, 3D printed rectal swabs were compared with conventional flocked swabs and faecal samples, due to the potential advantages 3D printing as a technique offers for swab production and development. 16S rRNA gene sequencing, qPCR and metabolite profiling (using 1H-NMR spectroscopy) were performed on swab and faecal samples from healthy participants. Faecal calprotectin and total protein analysis were performed on samples from inflammatory bowel disease (IBD) patients. There were no significant differences between both swab types and faecal samples when assessing key measures of alpha and beta diversity, and differences in the abundance of major phyla. There was a strong correlation between both swab types and faecal samples for all combined metabolites detected by NMR. In IBD patients, there was no significant difference in faecal calprotectin and total protein levels between both swab types and faecal samples. These data lead us to conclude that 3D printed swabs are equivalent to flocked swabs for the analysis of the gut microbiome, metabolome and inflammation.
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Journal articleMullish BH, Merrick B, Quraishi MN, et al., 2024, , Gut, Vol: 73, Pages: 1052-1075, ISSN: 0017-5749
The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.
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Journal articleEdwards L, Auch B, Portlock T, et al., 2024, , Journal of Hepatology, Vol: 80, Pages: S46-S47, ISSN: 0168-8278
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Journal articleMullish BH, Merrick B, Quraishi MN, et al., 2024, , Journal of Hospital Infection, Vol: 148, Pages: 189-219, ISSN: 0195-6701
The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past five years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with NICE-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points, and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations, and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.
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Conference paperRadhakrishnan ST, Alexander JL, Mullish BH, et al., 2024, , Publisher: BMJ PUBLISHING GROUP, Pages: A126-A127, ISSN: 0017-5749
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Journal articleMullish BH, Bak A, Merrick B, et al., 2024, , Journal of Hospital Infection, Vol: 148, Pages: 178-188, ISSN: 0195-6701
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Journal articleMullish BH, Michael DR, Dabcheva M, et al., 2024, , Neurogastroenterology & Motility, Vol: n/a, ISSN: 1350-1925
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