Publications

Journal article

Quraishi MN, Cheesbrough J, Rimmer P, Mullish BH, Sharma N, Efstathiou E, Acharjee A, Gkoutus G, Patel A, Marchesi JR, Camuzeaux S, Chappell K, Valdivia-Garcia MA, Ferguson J, Brookes MJ, Walmsley M, Rossiter AE, van Schaik W, McInnes RS, Cooney R, Trauner M, Beggs AD, Iqbal TH, Trivedi PJet al., 2025,

Open Label Vancomycin in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Improved Colonic Disease Activity and Associations With Changes in Host–Microbiome–Metabolomic Signatures

, Journal of Crohn's and Colitis, Vol: 19, ISSN: 1873-9946

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>We conducted a single-arm interventional study, to explore mucosal changes associated with clinical remission under oral vancomycin (OV) treatment, in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD); NCT05376228.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Fifteen patients with PSC and active colitis (median fecal calprotectin 459 µg/g; median total Mayo score 5) were treated with OV (125 mg QID) for 4 weeks and followed-up for a further 4 weeks of treatment withdrawal (8 weeks, end-of-study). Colonic biopsies were obtained at baseline and Week 4. Clinical assessments, and serum and stool samples (metagenomics, metatranscriptomics, and metabolomics) were collected at Weeks 0, 2, 4, and 8. The primary efficacy outcome measure was the induction of clinical remission.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Oral vancomycin resulted in clinical remission in 12/15 patients and significant reductions in fecal calprotectin. Oral vancomycin was associated with reduced abundances of Lachnospiraceae, genera Blautia and Bacteroides; and enrichment of Enterobacteriaceae, and genera Veillonella, Akkermansia, and Escherichia. Oral vancomycin treatment was associated with the downregulation of multiple metatranscriptomic pathways (including short-chain fatty acid [SCFA] metabolism and bile acid [BA] biotransformation), along with host genes and multiple pathways involved in inflammatory responses and antimicrobial defence; and an upregulation of genes associated with extracellular matrix repair. Oral vancomycin use r

Journal article

Porcari S, Mullish BH, Asnicar F, Ng SC, Zhao L, Hansen R, O'Toole PW, Raes J, Hold G, Putignani L, Hvas CL, Zeller G, Koren O, Tun H, Valles-Colomer M, Collado MC, Fischer M, Allegretti J, Iqbal T, Chassaing B, Keller J, Baunwall SM, Abreu M, Barbara G, Zhang F, Ponziani FR, Costello SP, Paramsothy S, Kao D, Kelly C, Kupcinskas J, Youngster I, Franceschi F, Khanna S, Vehreschild M, Link A, De Maio F, Pasolli E, Miguez AB, Brigidi P, Posteraro B, Scaldaferri F, Stojanovic MR, Megraud F, Malfertheiner P, Masucci L, Arumugam M, Kaakoush N, Segal E, Bajaj J, Leong R, Cryan J, Weersma RK, Knight R, Guarner F, Shanahan F, Cani PD, Elinav E, Sanguinetti M, de Vos WM, El-Omar E, Dorè J, Marchesi J, Tilg H, Sokol H, Segata N, Cammarota G, Gasbarrini A, Ianiro Get al., 2025,

International consensus statement on microbiome testing in clinical practice

, The Lancet Gastroenterology & Hepatology, Vol: 10, Pages: 154-167, ISSN: 2468-1253

Journal article

Al-Shakhshir S, Quraishi MN, Mullish B, Patel A, Vince A, Rowe A, Homer V, Jackson N, Gyimah D, Shabir S, Manzoor S, Cooney R, Alrubaiy L, Quince C, van Schaik W, Hares M, Beggs AD, Efstathiou E, Rimmer P, Weston C, Iqbal T, Trivedi PJet al., 2025,

FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial

, BMJ Open, Vol: 15, Pages: e095392-e095392, ISSN: 2044-6055

<jats:sec><jats:title>Introduction</jats:title><jats:p>Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot studies of faecal microbiota transplantation (FMT) in PSC and IBD are demonstrated to be safe and associated with increased gut bacterial diversity. However, the longevity of such changes and the impact on markers of disease activity and disease progression have not been studied. The aim of this clinical trial is to determine the effects of repeated FMT as a treatment for PSC-IBD.</jats:p></jats:sec><jats:sec><jats:title>Methods and analysis</jats:title><jats:p>FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO) is a phase IIa randomised placebo-controlled trial to assess the efficacy and safety of repeated colonic administration of FMT in patients with non-cirrhotic PSC-IBD. Fifty-eight patients will be recruited from six sites across England and randomised in a 1:1 ratio between active FMT or FMT placebo arms. FMT will be manufactured by the University of Birmingham Microbiome Treatment Centre, using stool collected from rigorously screened healthy donors. A total of 8 weekly treatments will be delivered; the first through colonoscopic administration (week 1) and the remaining seven via once-weekly enema (up to week 8). Participants will then be followed on a 12-weekly basis until week 48 from the first treatment visit. The primary efficacy outcome will be to determine the effect of FMT on serum alkaline phosphatase values over time (end of study at 48 weeks). Key secondary outcomes will be to evaluate the impact of FMT on other liver biochemical parameters, PSC risk scores, circulating and imaging markers of liver fibrosis, health-related

Journal article

Mullish BH, Thursz MR, 2024,

Alcohol-associated liver disease: Emerging therapeutic strategies.

, Hepatology, Vol: 80, Pages: 1372-1389

The large and growing burden of alcohol-associated liver disease-and the considerable burden of morbidity and mortality associated with it-has been a drive toward ongoing research into novel strategies for its treatment, with a particular focus upon alcohol-associated hepatitis (AH). Management of alcohol-use disorder forms the central pillar of alcohol-associated liver disease care, with evidence-based psychological and pharmacological approaches being well established, and certain models demonstrating improved clinical outcomes when hepatology and addiction services are co-located. Corticosteroids have previously been used somewhat indiscriminately in patients with severe AH, but effective tools now exist to assess early response (and limit futile ongoing exposure). Techniques to predict risk of corticosteroid-related infection are also available, although current clinical strategies to mitigate this risk are limited. A variety of novel therapeutic approaches to AH are at different phases of trials and evidence gathering, with some of the most promising signals related to cytokine manipulation, epigenetic modulation, and targeting of the gut microbiota (ie, by means of fecal microbiota transplant). While remaining an ongoing source of debate, early liver transplant in severe AH has grown in interest and acceptability over the past decade as evidence supporting its efficacy builds, in the process challenging paradigms about mandatory pretransplant sobriety periods. However, uncertainty remains regarding the optimal selection criteria, and whether liver transplant has a role for only a highly limited proportion of patients with AH or more widespread application. This review aims to provide an overview of this fast-moving field.

Journal article

Mullish BH, Innes AJ, Roberts LA, Anim-Burton S, Webber L, Johnson NA, Ghani R, Farshi P, Khan AB, Kinsella F, Kottaridis P, Krishnamurthy P, Nicholson E, Palanicawandar R, Wheeler GM, Davies FJ, Marchesi JR, Pavlu Jet al., 2024,

Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multi-centre, double-blinded, placebo-controlled, phase IIa trial

, BMJ Open, Vol: 14, ISSN: 2044-6055

Introduction Lower diversity of the gut microbiome prior to allogeneic haematopoietic cell transplantation (HCT) correlates with reduced survival after the intervention. Most patients undergoing HCT for a haematological malignancy have previously received intensive chemotherapy, resulting in prolonged neutropenic episodes requiring broad-spectrum antibiotics; use of these has been linked to reduced microbiome diversity. Intestinal microbiota transplant (IMT) is a novel treatment approach that restores this diversity. We hypothesised that IMT performed prior to initiation of HCT conditioning restores microbiome diversity during the early stages of HCT, leading to decreased frequency of complications and improved outcomes of HCT.Methods and analysis 50 adult patients receiving allogeneic HCT will be recruited into this phase IIa trial and randomised 1:1 to receive capsulised IMT or matched placebo shortly prior to initiation of HCT conditioning and followed for up to 12 months. The primary outcome will be to assess the increase in alpha diversity between pre-IMT and that measured at ~42 days after IMT administration (day +28 of HCT), comparing the difference between patients receiving IMT compared with placebo. Secondary outcomes will include tolerability, the dynamics of gut microbiome diversity metrics and taxonomy over all time points assessed, as well as clinical outcomes (including burden of invasive infections, days of fever, admission to intensive care, development of graft-vs-host disease and mortality).Ethics and dissemination This study was approved by a UK Research Ethics Committee (REC reference: 23/NE/0105). Dissemination of results will be in concert with patient and public involvement group input and is expected to be primarily via abstract presentation at conferences and manuscripts in peer-reviewed journals.

Conference paper

Mullish BH, Innes AJ, Ghani R, Anim-Burton S, Webber L, Wheeler G, Johnson NA, Roberts L, Davies FJ, Marchesi JR, Pavlu Jet al., 2024,

Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST): A Multi-Center Randomized Double-Blinded Placebo-Controlled Phase IIa Trial

, Publisher: American Society of Hematology, Pages: 4892.1-4892.1, ISSN: 0006-4971

<jats:sec> <jats:title/> <jats:p>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.</jats:p> <jats:p>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.</jats:p> <jats:p>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 L

Journal article

Allegretti JR, Khanna S, Mullish BH, Feuerstadt Pet al., 2024,

The Progression of Microbiome Therapeutics for the Management of Gastrointestinal Diseases and Beyond

, Gastroenterology, Vol: 167, Pages: 885-902, ISSN: 0016-5085

Journal article

Mullish BH, Ianiro G, 2024,

Preface to special edition: Microbiome, inflammation and cancer

, Best Practice & Research Clinical Gastroenterology, Pages: 101952-101952, ISSN: 1521-6918

Journal article

Turner BRH, Jenkinson PI, Huttman M, Mullish BHet al., 2024,

Inflammation, oxidative stress and the gut microbiome perturbation: a narrative review of mechanisms and treatment of the alcohol hangover

, 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

Journal article

Perry R, Mullish BH, Alexander JL, Shah R, Danckert N, Miguens Blanco J, Roberts L, Liu Z, Chrysostomou D, Radhakrishnan S, Balarajah S, Barry R, Hicks L, Williams HRT, Marchesi JRet al., 2024,

3D printed rectal swabs for assessing the gut microbiome, metabolome and inflammation

, 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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