Imperial College London

Dr Benjamin Mullish

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

NIHR Clinical Lecturer
 
 
 
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Contact

 

b.mullish

 
 
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Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

174 results found

Blanco JM, Liu Z, Selvarajah U, Mullish BH, Alexander JL, McDonald JA, Abraham S, Marchesi Jet al., 2020, Sa1923 IDENTIFICATION OF NEW ASSOCIATIONS BETWEEN PSORIATIC ARTHRITIS AND THE GUT MICROBIOTA, A PHENOMIC STUDY, Gastroenterology, Vol: 158, Pages: S-481, ISSN: 0016-5085

Journal article

Monaghan T, Russell L, Rosati E, Mullish BH, Roach B, Wong K, Wong GK, Polytarchou C, Franke A, Marchesi J, Kao DHet al., 2020, Mo1939 TEMPORAL MODULATION OF TCR REPERTOIRE FOLLOWING SEQUENTIAL FMT TREATMENT IN PATIENTS WITH SEVERE OR FULMINANT CLOSTRIDIOIDES DIFFICILE INFECTION, Gastroenterology, Vol: 158, ISSN: 0016-5085

Journal article

Allegretti JR, Kassam Z, Hurtado J, Carrellas M, Marchesi J, Mullish BH, Chiang AL, Cummings BP, Thompson CCet al., 2020, Tu1909 IMPACT OF FECAL MICROBIOTA TRANSPLANTATION ON PREVENTION OF METABOLIC SYNDROME AMONG PATIENTS WITH OBESITY, Gastroenterology, Vol: 158, ISSN: 0016-5085

Journal article

Martinez-Gili L, McDonald JA, Liu Z, Kao DH, Allegretti JR, Barker GF, Blanco JM, Holmes E, Thursz MR, Marchesi J, Mullish BHet al., 2020, 644 IDENTIFICATION OF NOVEL CHANGES IN MICROBIALLY-DERIVED METABOLITES AFTER FECAL MICROBIOTA TRANSPLANT FOR RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION, Publisher: Elsevier BV, ISSN: 0016-5085

Conference paper

Allegretti JR, Hurtado J, Carrellas M, Marcus J, Nemes S, Marchesi J, Mullish BH, McDonald JA, Phelps EL, Sagi S, Bohm M, Geradin Y, Silverstein M, Kelly CR, Kassam Z, Grinspan A, Fischer Met al., 2020, 121 ULCERATIVE COLITIS PATIENTS ACHEIVE MORE ROBUST ENGRAFTMENT COMPARED TO PATIENTS WITH CROHN'S DISEASE AFTER FECAL MICROBIOTA TRANSPLANTATION FOR THE TREATMENT OF RECURRENT C. DIFFICLE INFECTION, Gastroenterology, Vol: 158, Pages: S-22, ISSN: 0016-5085

Journal article

Smith PJ, 2020, GI highlights from the literature, Gut, Vol: 69, Pages: 963-964, ISSN: 0017-5749

Journal article

Ianiro G, Mullish BH, Kelly CR, Sokol H, Kassam Z, Ng SC, Fischer M, Allegretti JR, Masucci L, Zhang F, Keller J, Sanguinetti M, Costello SP, Tilg H, Gasbarrini A, Cammarota Get al., 2020, Screening of faecal microbiota transplant donors during the COVID-19 outbreak: suggestions for urgent updates from an international expert panel, The Lancet Gastroenterology & Hepatology, Vol: 5, Pages: 430-432, ISSN: 2468-1253

Journal article

Ghani R, Mullish BH, McDonald JA, Ghazy A, Williams HR, Brannigan E, Satta G, Gilchrist M, Duncan N, Corbett R, Pavlu J, Innes AJ, Thursz MR, Davies F, Marchesi Jet al., 2020, 1144 FECAL MICROBIOTA TRANSPLANT FOR MULTI-DRUG RESISTANT ORGANISMS: IMPROVED CLINICAL OUTCOMES BEYOND INTESTINAL DECOLONISATION, Gastroenterology, Vol: 158, ISSN: 0016-5085

Journal article

Allegretti JR, Kassam Z, Mullish BH, Chiang A, Carrellas M, Hurtado J, Marchesi JR, McDonald JAK, Pechlivanis A, Barker GF, Miguens Blanco J, Garcia Perez I, Wong WF, Gerardin Y, Silverstein M, Kennedy K, Thompson Cet al., 2020, Effects of fecal microbiota transplantation with oral capsules in obese patients, Clinical Gastroenterology and Hepatology, Vol: 18, Pages: 855-863.e2, ISSN: 1542-3565

Background & AimsStudies in mice have shown that the intestinal microbiota can contribute to obesity via the anorexigenic gut hormone glucagon-like peptide 1 (GLP1) and bile acids, which affect lipid metabolism. We performed a randomized, placebo-controlled pilot study of the effects of fecal microbiota transplantation (FMT) in obese, metabolically uncompromised patients.MethodsWe performed a double-blind study of 22 obese patients (body mass index [BMI] ≥ 35kg/m2) without a diagnosis of diabetes, non-alcoholic steatohepatitis, or metabolic syndrome. Participants were randomly assigned (1:1) to groups that received FMT by capsules (induction dose of 30 capsules at week 4 and maintenance dose of 12 capsules at week 8) or placebo capsules. FMT capsules were derived from a single, lean donor (BMI, 17.5 kg/m2). Patients were followed through week 26; the primary outcome was safety. Stool and serum samples were collected from patients at baseline and at weeks 1, 4, 6, 8 and 12 after administration of the first dose of FMT or placebo and analyzed by 16S RNA gene sequencing. Stool and serum samples were analyzed for metabolomics by liquid chromatography-mass spectrometry. Additional outcomes were change in area under the curve for GLP1 at week 12.ResultsWe observed no significant differences in adverse events between patients who received FMT vs placebo. There was no increase in the area under the curve of GLP1 in either group. Patients who received FMT had sustained shifts in microbiomes associated with obesity toward those of the donor (P<.001). Patients who received FMT had a sustained decrease in stool levels of taurocholic acid (P<.05), compared with baseline; bile acid profiles began to more closely resemble those of the donor. We did not observe significant changes in mean BMI at week 12 in either group.ConclusionsIn a placebo-controlled pilot study, we found that FMT capsules (derived from a lean donor) were safe but did not reduce BMI in obese metabol

Journal article

Smith PJ, 2020, GI highlights from the literature, Gut, Vol: 69, Pages: 781-782, ISSN: 0017-5749

Journal article

Manousou P, Forlano R, Mullish BH, Nathwani R, Dhar A, Thursz Met al., 2020, Non-Alcoholic Fatty Liver Disease and Vascular Disease, Current Vascular Pharmacology, Vol: 18, ISSN: 1570-1611

<jats:sec><jats:title>:</jats:title><jats:p>Non-Alcoholic Fatty Liver Disease (NAFLD) represents an increasing cause of liver disease worldwide. However, notably, the primary cause of morbidity and mortality in patients with NAFLD is cardiovascular disease (CVD), with fibrosis stage being the strongest disease-specific predictor. It is globally-projected that NAFLD will become increasingly prevalent, especially among children and younger adults. As such, even within the next few years, NAFLD will contribute considerably to the overall CVD burden.In this review, we discuss the role of NAFLD as an emerging risk factor for CVD. In particular, this article aims to provide an overview of pathological drivers of vascular damage in patients with NAFLD. Moreover, the impact of NAFLD on the development, severity and the progression of subclinical and clinical CVD will be discussed. Finally, the review illustrates current and potential future perspectives for screening for CVD in this high-risk population.</jats:p></jats:sec>

Journal article

Mullish BH, Quraishi MN, Segal JP, Ianiro G, Iqbal THet al., 2020, The gut microbiome: what every gastroenterologist needs to know, Frontline Gastroenterology, ISSN: 2041-4137

<jats:p>The mucosal surfaces of the body are characterised by complex, specialised microbial communities, often referred to as the <jats:italic>microbiome</jats:italic>. However, only much more recently—with the development of technologies allowing exploration of the composition and functionality of these communities—has meaningful research in this area become feasible. Over the past few years, there has been rapid growth in interest in the gut microbiome in particular, and its potential contribution to gastrointestinal and liver disease. This interest has already extended beyond clinicians to pharmaceutical companies, medical regulators and other stakeholders, and is high profile among patients and the lay public in general. Such expansion of knowledge holds the intriguing potential for translation into novel diagnostics and therapeutics; however, being such a nascent field, there remain many uncertainties, unanswered questions and areas of debate.</jats:p>

Journal article

Ghani R, Mullish B, Mcdonald J, Williams H, Gilchrist M, Brannigan E, Satta G, Taube D, Duncan N, Pavlu J, Ghazy A, Thursz M, Davies F, Marchesi Jet al., 2020, Cohort study of Faecal Microbiota Transplantation for patient’s colonised with MDROs - successful prevention of invasive disease despite low decolonisation rates, Access Microbiology, Vol: 2

Journal article

Ghani R, Mullish B, Thursz M, Marchesi J, Ghazy A, Davies Fet al., 2020, Case-control study of recurrent Extended-Spectrum Beta Lactamase Enterobacteriaceae Urinary Tract Infections (ESBL UTIs): the management challenges, Access Microbiology, Vol: 2

Journal article

Fessas P, Possamai LA, Clark J, Daniels E, Gudd C, Mullish BH, Alexander JL, Pinato DJet al., 2020, Immunotoxicity from checkpoint inhibitor therapy: clinical features and underlying mechanisms., Immunology, Vol: 159, Pages: 167-177

Immune checkpoint inhibition with monoclonal antibodies is becoming increasingly commonplace in cancer medicine, having contributed to a widening of therapeutic options across oncological indications. Disruption of immune tolerance is the key mechanism of action of checkpoint inhibitors and although immune-related adverse events are a typical class effect of these compounds, the relationship between toxicity and response is not fully understood. Awareness and vigilance are paramount in recognizing potentially life-threatening toxicities and managing them in a timely manner. In this review article, we provide an overview of the clinical features, pathological findings and management principles of common immune-related toxicities, attempting to provide mechanistic insight into an increasingly common complication of cancer therapy.

Journal article

Segal J, Mullish B, Clark S, Marchesi J, Hart Aet al., 2020, P844 Higher proportions of genera and species in the Firmicutes phylum are associated with a healthy pouch compared with patients with chronic pouchitis, Journal of Crohn's and Colitis, Vol: 14, Pages: S652-S652, ISSN: 1873-9946

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Studies highlighting changes in bacterial composition in the ileoanal pouch are limited by heterogeneity in analysis techniques and sampling strategies Therefore, caution must be used when interpreting microbiota data. Similar to findings in IBD, a decrease in bacterial diversity and ‘dysbiosis’ are associated with acute and chronic inflammation in the pouch. Changes in Clostridium spp. and E. coli are associated with inflamed pouches and treatment response. This study aimed to compare the bacterial microbiota composition in patients with chronic pouchitis who responded to antibiotics vs. those who did not.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Patients with confirmed chronic pouchitis defined by a pouch disease activity score ≥ 7 were treated with antibiotics. If patients were already on antibiotics, they were offered the opportunity to stop. Follow up was at 4 weeks to check clinical status. Patients who came off antibiotics who flared were given the opportunity to restart the antibiotics to prevent deterioration. Patients were analysed as either on antibiotics if they received antibiotics 2 weeks prior to the clinic or off antibiotics if they had stopped all antibiotics 2 weeks prior to follow-up. Stool was collected from patients on follow-up and DNA was extracted from this stool. Sequencing was performed on an Illumina platform. Statistical analysis was performed using STAMP 2.1.3 software with Welch’s two-sided t-test for comparing two groups with false discovery rate correction.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <j

Journal article

Segal JP, Mullish BH, Quraishi MN, Iqbal T, Marchesi JR, Sokol Het al., 2020, Mechanisms underpinning the efficacy of faecal microbiota transplantation in treating gastrointestinal disease, Therapeutic Advances in Gastroenterology, Vol: 13, Pages: 175628482094690-175628482094690, ISSN: 1756-2848

<jats:p> Faecal microbiota transplantation (FMT) is currently a recommended therapy for recurrent/refractory Clostridioides difficile infection (CDI). The success of FMT for CDI has led to interest in its therapeutic potential in many other disorders. The mechanisms that underpin the efficacy of FMT are not fully understood. Importantly, FMT remains a crucial treatment in managing CDI and understanding the mechanisms that underpin its success will be critical to improve its clinical efficacy, safety and usability. Furthermore, a deeper understanding of this may allow us to expose FMT’s full potential as a therapeutic tool for other disease states. This review will explore the current understanding of the mechanisms underlying the efficacy of FMT across a variety of diseases. </jats:p>

Journal article

Allegretti JR, Mullish BH, 2020, Faecal microbiota transplantations and urinary tract infections – Authors' reply, The Lancet, Vol: 395, Pages: 271-271, ISSN: 0140-6736

Journal article

McSweeney B, Allegretti JR, Fischer M, Xu H, Goodman KJ, Monaghan T, McLeod C, Mullish BH, Petrof EO, Phelps EL, Chis R, Edmison A, Juby A, Ennis-Davis R, Roach B, Wong K, Kao Det al., 2020, In search of stool donors: a multicenter study of prior knowledge, perceptions, motivators, and deterrents among potential donors for fecal microbiota transplantation., Gut Microbes, Vol: 11, Pages: 51-62

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.

Journal article

Pinato DJ, Gramenitskaya D, Altmann DM, Boyton RJ, Mullish BH, Marchesi JR, Bower Met al., 2019, Antibiotic therapy and outcome from immune-checkpoint inhibitors, Journal for ImmunoTherapy of Cancer, Vol: 7

Journal article

Cammarota G, Ianiro G, Kelly CR, Mullish BH, Allegretti JR, Kassam Z, Putignani L, Fischer M, Keller JJ, Costello SP, Sokol H, Kump P, Satokari R, Kahn SA, Kao D, Arkkila P, Kuijper EJ, Vehreschild MJGT, Pintus C, Lopetuso L, Masucci L, Scaldaferri F, Terveer EM, Nieuwdorp M, López-Sanromán A, Kupcinskas J, Hart A, Tilg H, Gasbarrini Aet al., 2019, International consensus conference on stool banking for faecal microbiota transplantation in clinical practice, Gut, Vol: 68, Pages: 2111-2121, ISSN: 0017-5749

<jats:p>Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent <jats:italic>Clostridioides difficile</jats:italic> infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.</jats:p><jats:p>Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,</jats:p><jats:p>Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.</jats:p>

Journal article

Nathwani R, Mullish BH, Kockerling D, Forlano R, Manousou P, Dhar Aet al., 2019, A review of liver fibrosis and emerging therapies, European Medical Journal Gastroenterology, Vol: 4, Pages: 105-116, ISSN: 2054-6203

With an increasing burden of liver cirrhosis, the most advanced stage of hepatic fibrosis, there is an emphasis to better understand the pathological processes and mechanisms to target specific treatments to reverse or cease fibrosis progression. Antiviral therapy for hepatitis B and C has effectively treated underlying causes of chronic liver disease and has induced fibrosis reversal in some however, this has not been targeted for the majority of aetiologies for cirrhosis including alcohol or non-alcoholic steatohepatitis. Fibrosis, characterized by the accumulation of extracellular matrix proteins, occurs due to chronic injury from toxic, infectious or metabolic causes. The primary event of fibrogenesis is increased matrix production and scar formation mediated by the hepatic stellate cell, the principal cell type involved. Experimental models using rodent and human cell lines of liver injury have assisted in better understanding fibrogenesis especially in recognising the role of procoagulant factors. This has led to interventional studies using anticoagulants in animal models with reversal of fibrosis as the primary endpoint. Though these trials have been encouraging, no antifibrotic therapies are currently licenced for human use. This literature review discusses current knowledge in the pathophysiology of hepatic fibrosis, including characteristics of the extracellular matrix, signalling pathways and hepatic stellate cells. We also review current types of experimental models used to induce fibrosis and up-to46 date anticoagulant therapies and agents targeting the hepatic stellate cell that have been trialled in animal and human studies with anti-fibrotic properties.

Journal article

Mullish BH, Forlano R, Abeles RD, Thursz MR, Manousou Pet al., 2019, Letter: role of mean platelet volume levels in the prediction of major acute cardiovascular events in patients with non-alcoholic fatty liver disease-authors' reply, Alimentary Pharmacology & Therapeutics, Vol: 50, Pages: 1140-1141, ISSN: 0269-2813

Journal article

Forlano R, Mullish B, Giannakeas N, Tsipouras M, Tzallas A, Yee M, Lloyd J, Goldin RD, Thursz MR, Manousou Pet al., 2019, IMPACT OF BMI AND ETHNICITY ON HISTOLOGY AS ASSESSED BY AUTOMATED QUANTITATION IN LIVER BIOPSIES OF PATIENTS WITH NAFLD, Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Publisher: WILEY, Pages: 1359A-1359A, ISSN: 0270-9139

Conference paper

Allegretti JR, Mullish B, Nativ L, Marcus J, Marchesi J, McDonald JAK, Pechlivanis A, Kennedy K, Gerber G, Bry Let al., 2019, 185 Evaluating Dynamics of Bile Acid Metabolism to Predict Recurrence of Clostridioides difficile Infection, American Journal of Gastroenterology, Vol: 114, Pages: S113-S113, ISSN: 0002-9270

Journal article

Allegretti JR, Mullish B, Hurtado J, Carrellas M, Marcus J, Phelps E, Pettee W, Marchesi J, McDonald JAK, Barker G, Blanco JM, Garcia Perez I, Kelly CR, Grinspan A, Fischer Met al., 2019, 837 Short Chain Fatty Acid Profiles Are Altered by Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease and Recurrent Clostridioides difficile Infection, American Journal of Gastroenterology, Vol: 114, Pages: S484-S485, ISSN: 0002-9270

Journal article

Mullish BH, McDonald JAK, Pechlivanis A, Allegretti JR, Kao D, Barker GF, Kapila D, Petrof EO, Joyce SA, Gahan CGM, Glegola-Madejska I, Williams HRT, Holmes E, Clarke TB, Thursz MR, Marchesi JRet al., 2019, Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection, Gut, Vol: 68, Pages: 1791-1800, ISSN: 0017-5749

<jats:sec><jats:title>Objective</jats:title><jats:p>Faecal microbiota transplant (FMT) effectively treats recurrent <jats:italic>Clostridioides difficile</jats:italic> infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect <jats:italic>C. difficile</jats:italic> germination or vegetative growth. We hypothesised that loss of gut microbiota-derived bile salt hydrolases (BSHs) predisposes to CDI by perturbing gut bile metabolism, and that BSH restitution is a key mediator of FMT’s efficacy in treating the condition.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Using stool collected from patients and donors pre-FMT/post-FMT for rCDI, we performed 16S rRNA gene sequencing, ultra performance liquid chromatography mass spectrometry (UPLC-MS) bile acid profiling, BSH activity measurement, and qPCR of <jats:italic>bsh</jats:italic>/<jats:italic>bai</jats:italic>CD genes involved in bile metabolism. Human data were validated in <jats:italic>C. difficile</jats:italic> batch cultures and a C57BL/6 mouse model of rCDI.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>From metataxonomics, pre-FMT stool demonstrated a reduced proportion of BSH-producing bacterial species compared with donors/post-FMT. Pre-FMT stool was enriched in taurocholic acid (TCA, a potent <jats:italic>C. difficile</jats:italic> germinant); TCA levels negatively correlated with key bacterial genera containing BSH-producing organisms. Post-FMT samples demonstrated recovered BSH activity and <jats:italic>bsh</jats:italic>/<jats:italic>bai</jats:italic>CD gene copy number compared with pretreatment (p&lt;0.05). In batch cultures, supernatant from engineered <jats:italic>bsh</jats:italic>-expressing <jats:italic>E

Journal article

Mullish BH, 2019, The role of bile-metabolising enzymes in the pathogenesis of Clostridioides difficile infection, and the impact of faecal microbiota transplantation

Thesis dissertation

Allegretti JR, Mullish BH, Kelly C, Fischer Met al., 2019, The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications., Lancet, Vol: 394, Pages: 420-431

Developments in high-throughput microbial genomic sequencing and other systems biology techniques have given novel insight into the potential contribution of the gut microbiota to health and disease. As a result, an increasing number of diseases have been characterised by distinctive changes in the composition and functionality of the gut microbiota; however, whether such changes are cause, consequence, or incidental to the disease in question remains largely uncertain. Restoration of the gut microbiota to a premorbid state is a key novel therapeutic approach of interest, and faecal microbiota transplantation-the transfer of prescreened stool from healthy donors into the gastrointestinal tract of patients-is gaining increasing importance in both the clinical and research settings. At present, faecal microbiota transplantation is only recommended in the treatment of recurrent Clostridioides difficile infection, although a large number of trials are ongoing worldwide exploring other potential therapeutic indications.

Journal article

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