Imperial College London

Dr Benjamin Mullish

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

IPPRF Reseach Fellow
 
 
 
//

Contact

 

b.mullish

 
 
//

Location

 

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

//

Summary

 

Publications

Publication Type
Year
to

322 results found

Mullish BH, 2024, Pharmacotherapy in managing alcohol-use disorder, Gastroenterology, ISSN: 0016-5085

Journal article

Caon E, Forlano R, Mullish BH, Manousou P, Rombouts Ket al., 2024, Liver sinusoidal cells in the diagnosis and treatment of liver diseases: Role of hepatic stellate cells, Sinusoidal Cells in Liver Diseases: Role in Their Pathophysiology, Diagnosis, and Treatment, Pages: 1-20

Book chapter

Mullish BH, Bak A, Merrick B, Quraishi MN, Goldenberg SD, Williams HRTet al., 2024, Overview of the second edition of the joint British Society of Gastroenterology and Healthcare Infection Society faecal microbiota transplant guidelines, 2024, Journal of Hospital Infection, ISSN: 0195-6701

Journal article

Mullish BH, Merrick B, Quraishi MN, Bak A, Green CA, Moore DJ, Porter RJ, Elumogo NT, Segal JP, Sharma N, Marsh BL, Kontkowski G, Manzoor SE, Hart AL, Settle C, Keller JJ, Hawkey P, Iqbal TH, Goldenberg SD, Williams HRTet al., 2024, The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines, Gut, ISSN: 0017-5749

Journal article

Mullish BH, Merrick B, Quraishi MN, Bak A, Green CA, Moore DJ, Porter RJ, Elumogo NT, Segal JP, Sharma N, Marsh BL, Kontkowski G, Manzoor SE, Hart AL, Settle C, Keller JJ, Hawkey P, Iqbal TH, Goldenberg SD, Williams HRTet al., 2024, The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines, Journal of Hospital Infection, ISSN: 0195-6701

Journal article

Kragsnaes MS, Jensen JRB, Nilsson AC, Malik MI, Munk HL, Pedersen JK, Horn HC, Kruhøffer M, Kristiansen K, Mullish BH, Marchesi JR, Kjeldsen J, Röttger R, Ellingsen Tet al., 2024, Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial., RMD Open, Vol: 10

OBJECTIVES: The gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on 92 inflammation-associated plasma proteins. METHODS: This study relates to the FLORA trial cohort, where 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate treatment, were included in a 26-week, double-blind, randomised, sham-controlled trial. Participants were allocated to receive either one gastroscopic-guided healthy donor FMT (n=15) or sham (n=16). Patient plasma samples were collected at baseline, week 4, 12 and 26 while samples from 31 age-matched and sex-matched healthy controls (HC) were collected at baseline. Samples were analysed using proximity extension assay technology (Olink Target-96 Inflammation panel). RESULTS: Levels of 26 proteins differed significantly between PsA and HC pre-FMT (adjusted p<0.05), of which 10 proteins were elevated in PsA: IL-6, CCL20, CCL19, CDCP1, FGF-21, HGF, interferon-γ (IFN-γ), IL-18R1, monocyte chemotactic protein 3, and IL-2. In the FMT group, levels of 12 proteins changed significantly across all timepoints (tumour necrosis factor (TNF), CDCP1, IFN-γ, TWEAK, signalling lymphocytic activation molecule (SLAMF1), CD8A, CD5, Flt3L, CCL25, FGF-23, CD6, caspase-8). Significant differences in protein levels between FMT and sham-treated patients were observed for TNF (p=0.002), IFN-γ (p=0.011), stem cell factor (p=0.024), matrix metalloproteinase-1 (p=0.038), and SLAMF1 (p=0.042). FMT had the largest positive effect on IFN-γ, Axin-1 and CCL25 and the largest negative effect on CCL19 and IL-6. CONCLUSIONS: Patients with active PsA have a distinct immunological plasma protein signature compared with HC pre-FMT. FMT affects several of these disease markers, including sustained elevation of IFN-γ. TRIAL R

Journal article

Mullish BH, Michael DR, Dabcheva M, Webberley TS, Coates N, John DA, Wang D, Luo Y, Plummer SF, Marchesi JRet al., 2024, A double-blind, randomized, placebo-controlled study assessing the impact of probiotic supplementation on the symptoms of irritable bowel syndrome in females., Neurogastroenterol Motil

BACKGROUND: A previous exploratory study demonstrated the ability of the Lab4 probiotic to alleviate the symptoms of IBS, and post hoc data analysis indicated greatest improvements in the female subgroup. The aim of this study is to confirm the impact of this multistrain probiotic on IBS symptom severity in females. METHODS: An 8-week, single-center, randomized, double-blinded, placebo-controlled, superiority study in 70 females with Rome IV-diagnosed irritable bowel syndrome (IBS) receiving the Lab4 probiotic (25 billion colony-forming units) daily or a matched placebo. Changes from baseline in the IBS-symptom severity score (IBS-SSS), daily bowel habits, anxiety, depression, IBS-related control, and avoidance behavior, executive function, and the fecal microbiota composition were assessed. The study was prospectively registered: ISRCTN 14866272 (registration date 20/07/22). KEY RESULTS: At the end of the study, there were significant between-group reductions in IBS-SSS (-85.0, p < 0.0001), anxiety and depression scores (-1.9, p = 0.0002 and -2.4, p < 0.0001, respectively), and the IBS-related control and avoidance behavior score (-7.5, p = 0.0002), all favoring the probiotic group. A higher proportion of the participants in the probiotic group had normal stool form (p = 0.0106) and/or fewer defecations with loose stool form (p = 0.0311). There was little impact on the overall diversity of the fecal microbiota but there were significant differences in Roseburia, Holdemanella, Blautia, Agathobacter, Ruminococcus, Prevotella, Bacteroides, and Anaerostipes between the probiotic and placebo groups at the end of the study. CONCLUSIONS & INFERENCES: Daily supplementation with this probiotic may represent an option to be considered in the management of IBS.

Journal article

Balarajah S, Martinez-Gili L, Alexander J, Mullish B, Perry R, Li J, Marchesi J, Parkes M, Orchard T, Hicks L, Williams Het al., 2024, OP07 Consistent IBD treatment approaches across South Asian and White ethnicities despite phenotypic variations: a study of 33,157 patients using the IBD BioResource, Publisher: Oxford University Press (OUP), Pages: i13-i13, ISSN: 1873-9946

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>The current evidence suggests ethnic distinctions in IBD phenotype, and differences in the provision of treatment have been reported. This multi-centre cohort study utilised the UK IBD BioResource dataset to evaluate phenotypic differences between South Asian (SA) and White (WH) IBD, and to explore if these were associated with differences in treatment.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Phenotypic and outcome data were extracted from the IBD BioResource. Chi2 (categorical data) and Mann-Whitney U (continuous data) tests were used. Propensity score matching (PSM) accounted for age at diagnosis, sex, smoking status, disease location and behaviour and perianal disease (CD). Differences in medication use (multivariable logistic regression) and surgical outcomes (Kaplan-Meier and Cox regression analysis) were assessed in propensity-matched (PM) cohorts.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>33,157 (31,932 WH; 1225 SA) individuals were included (48.1% CD, 45.4% UC, 6.5% IBD-U). UC was the predominant disease subtype in SA (UC, SA 57.3% vs WH 44.9%, p&amp;lt;0.001). SA were younger at diagnosis [CD, SA 24 (IQR 17-36) vs WH 26 (IQR 19-39) years, p&amp;lt;0.001; UC, SA 29 (IQR 22-38) vs WH 35 (25-48) years, p&amp;lt;0.001]. SA CD had less ileal disease (SA 30.3% vs WH 38.4%, padj=0.008), and more perianal involvement (SA 38.5% vs WH 32.3%, p=0.009) than WH. SA CD had less stricturing disease (SA 16.9% vs WH 25.6%, padj&amp;lt;0.001). SA UC were more likely to have extensive disease (SA 41.7% vs WH 34.1%, padj&amp;lt;0.00

Conference paper

Radhakrishnan ST, Alexander JL, Mullish BH, Danckert NP, Valdivia-Garcia MA, Serrano-Contreras JI, Balarajah S, Perry R, Gallagher KI, Hicks LC, Powell N, Li JV, Marchesi JR, Williams HRTet al., 2024, P1209 Baseline gut microbiota composition and function reflect response to 5-ASA treatment in Ulcerative Colitis, Publisher: Oxford University Press (OUP), Pages: i2152-i2152, ISSN: 1873-9946

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Mesalazine (5-ASA) is a key initial treatment of ulcerative colitis (UC); recent studies have highlighted the role of the gut microbiota in 5-ASA metabolism. There is no established means of predicting treatment outcome. We sought to investigate changes in the gut microbiota and metabolome with 5-ASA treatment, and whether such changes may reflect clinical outcomes.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Longitudinal faeces, serum and urine samples were collected from patients with newly diagnosed UC before and after 5-ASA treatment. We documented longitudinal microbiota and metabolome changes with 5-ASA treatment and compared baseline gut microbiota and metabolome in responders (simple clinical colitis activity index (SCCAI) of &amp;lt;4 and faecal calprotectin (FC) of &amp;lt;100 µg/g) and non-responders to 5-ASA. Stool bacterial profiling was performed via 16S rRNA gene sequencing of the V1/V2 hypervariable regions. Host and microbial metabolites in stool, serum and urine were detected and semi-quantitated using liquid chromatography mass spectroscopy (LC-MS) and nuclear magnetic resonance spectroscopy (1H-NMR). Kruskal-Wallis tests and paired analyses using a Wilcoxon rank test were used and p values were adjusted using Benjamini-Hochberg false discovery rate (FDR) correction.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>37 patients newly diagnosed with UC were recruited. Samples were collected at baseline and a median of 83 days (IQR 22.5 days) later; there were 27 responders and 10 non-responders. Comparing pre- and post- 5

Conference paper

Forlano R, Stanic T, Jayawardana S, Mullish BH, Yee M, Mossialos E, Goldin R, Petta S, Tsochatzis E, Thursz M, Manousou Pet al., 2024, A prospective study on the prevalence of MASLD in people with type-2 diabetes in the community. Cost effectiveness of screening strategies, Liver International, Vol: 44, Pages: 61-71, ISSN: 1478-3223

Background and AimsAs screening for the liver disease and risk-stratification pathways are not established in patients with type-2 diabetes mellitus (T2DM), we evaluated the diagnostic performance and the cost-utility of different screening strategies for MASLD in the community.MethodsConsecutive patients with T2DM from primary care underwent screening for liver diseases, ultrasound, ELF score and transient elastography (TE). Five strategies were compared to the standard of care: ultrasound plus abnormal liver function tests (LFTs), Fibrosis score-4 (FIB-4), NAFLD fibrosis score, Enhanced liver fibrosis test (ELF) and TE. Standard of care was defined as abnormal LFTs prompting referral to hospital. A Markov model was built based on the fibrosis stage, defined by TE. We generated the cost per quality-adjusted life year (QALY) gained and calculated the incremental cost-effectiveness ratio (ICER) over a lifetime horizon.ResultsOf 300 patients, 287 were included: 64% (186) had MASLD and 10% (28) had other causes of liver disease. Patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287) and 3% (8/287), respectively. Among those with significant fibrosis classified by LSM≥8.1 kPa, false negatives were 54% from ELF and 38% from FIB-4. On multivariate analysis, waist circumference, BMI, AST levels and education rank were independent predictors of significant and advanced fibrosis. All the screening strategies were associated with QALY gains, with TE (148.73 years) having the most substantial gains, followed by FIB-4 (134.07 years), ELF (131.68 years) and NAFLD fibrosis score (121.25 years). In the cost-utility analysis, ICER was £2480/QALY for TE, £2541.24/QALY for ELF and £2059.98/QALY for FIB-4.ConclusionScreening for MASLD in the diabetic population in primary care is cost-effective and should become part of a holistic assessment. However, traditional screenin

Journal article

Murray SM, Pose E, Wittner M, Londoño M-C, Schaub G, Cook J, Dimitriadis S, Meacham G, Irwin S, Lim Z, Duengelhoef P, Sterneck M, Lohse AW, Perez V, Trivedi P, Bhandal K, Mullish BH, Manousou P, Provine NM, Avitabile E, Carroll M, Tipton T, Healy S, Burra P, Klenerman P, Dunachie S, Kronsteiner B, Maciola AK, Pasqual G, Hernandez-Gea V, Garcia-Pagan JC, Lampertico P, Iavarone M, Gines P, Lütgehetmann M, Schulze Zur Wiesch J, Russo FP, Barnes E, Marjot T, OCTAVE Collaborative Group, PITCH study, and the EASL supported COVID-Hep vaccine networket al., 2024, Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and liver transplant recipients., J Hepatol, Vol: 80, Pages: 109-123

BACKGROUND & AIMS: Comparative assessments of immunogenicity following different COVID-19 vaccines in patients with distinct liver diseases are lacking. SARS-CoV-2-specific T-cell and antibody responses were evaluated longitudinally after one to three vaccine doses, with long-term follow-up for COVID-19-related clinical outcomes. METHODS: A total of 849 participants (355 with cirrhosis, 74 with autoimmune hepatitis [AIH], 36 with vascular liver disease [VLD], 257 liver transplant recipients [LTRs] and 127 healthy controls [HCs]) were recruited from four countries. Standardised immune assays were performed pre and post three vaccine doses (V1-3). RESULTS: In the total cohort, there were incremental increases in antibody titres after each vaccine dose (p <0.0001). Factors associated with reduced antibody responses were age and LT, whereas heterologous vaccination, prior COVID-19 and mRNA platforms were associated with greater responses. Although antibody titres decreased between post-V2 and pre-V3 (p = 0.012), patients with AIH, VLD, and cirrhosis had equivalent antibody responses to HCs post-V3. LTRs had lower and more heterogenous antibody titres than other groups, including post-V3 where 9% had no detectable antibodies; this was heavily influenced by intensity of immunosuppression. Vaccination increased T-cell IFNγ responses in all groups except LTRs. Patients with liver disease had lower functional antibody responses against nine Omicron subvariants and reduced T-cell responses to Omicron BA.1-specific peptides compared to wild-type. 122 cases of breakthrough COVID-19 were reported of which 5/122 (4%) were severe. Of the severe cases, 4/5 (80%) occurred in LTRs and 2/5 (40%) had no serological response post-V2. CONCLUSION: After three COVID-19 vaccines, patients with liver disease generally develop robust antibody and T-cell responses to vaccination and have mild COVID-19. However, LTRs have sustained no/low antibody titres and appear most vulner

Journal article

Forlano R, Martinez-Gili L, Takis P, Miguens-Blanco J, Liu T, Triantafyllou E, Skinner C, Loomba R, Thursz M, Marchesi JR, Mullish BH, Manousou Pet al., 2024, Disruption of gut barrier integrity and host-microbiome interactions underlie MASLD severity in patients with type-2 diabetes mellitus., Gut Microbes, Vol: 16

Aberration of the "gut-liver axis" contributes to the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we use multi-omics to analyze the gut microbiota composition and metabolic profile of patients with type-2 diabetes mellitus (T2DM). T2DM patients were screened for liver disease by blood tests, ultrasound, and liver stiffness measurements. Stool microbiota was analyzed by 16S rRNA gene sequencing; metabolomic profiling by Nuclear Magnetic Resonance spectroscopy and Ultra-High Performance-Mass Spectrometry. Microbiome and metabolic signatures were analyzed in the whole cohort and in matched subsets to identify signatures specific for steatosis (MASLD±) or fibrosis (Fibrosis±). Gut permeability was assessed in-vitro using monolayers of MDCK cells and trans-epithelial electric resistance (TEER). Cytokine profile was assessed in serum and stools.Overall, 285 patients were enrolled: 255 serum, 252 urine and 97 stool samples were analyzed. Anaeroplasma and Escherichia/Shigella ASVs were higher, while Butyricicoccus ASVs were lower in those with normal liver. In MASLD±, Butyricicoccus ASV was significantly higher in those with steatosis. In the Fibrosis±, Butyricicoccus ASV was significantly lower in those with fibrosis. Glycochenodeoxycholic acid-3-sulfate (G-UDCA-3S) appeared to be higher in MASLD with fibrosis. Fecal water from patients with MASLD and fibrosis caused the greatest drop in the TEER vs those with normal liver; this was reversed with protease inhibitors. Finally, fecal IL-13 was lower in MASLD with fibrosis. We identified microbiome signatures which were specific for steatosis and fibrosis and independent of other metabolic risk factors. Moreover, we conclude that protease-related gut permeability plays a role in those MASLD patients with fibrosis, and that disease progression is linked to a gut-liver axis which is at least partially independent of T2DM.

Journal article

Bibbò S, Porcari S, Del Vecchio LE, Severino A, Mullish BH, Ianiro G, Gasbarrini A, Cammarota Get al., 2023, Gut microbiota and immunotherapy of renal cell carcinoma, Human Vaccines &amp; Immunotherapeutics, Vol: 19, ISSN: 2164-5515

Journal article

Mullish BH, Tohumcu E, Porcari S, Fiorani M, Di Tommaso N, Gasbarrini A, Cammarota G, Ponziani FR, Ianiro Get al., 2023, The role of faecal microbiota transplantation in chronic noncommunicable disorders, Journal of Autoimmunity, Vol: 141, Pages: 103034-103034, ISSN: 0896-8411

Journal article

Smith PJ, 2023, GI highlights from the literature, Gut, ISSN: 0017-5749

Journal article

Hvas CL, Keller J, Baunwall SMD, Edwards LA, Ianiro G, Kupcinskas J, Link A, Mullish BH, Satokari R, Sokol H, Terveer E, Vehreshild MJGet al., 2023, European academic faecal microbiota transplantation (EURFMT) network: improving the safety and quality of microbiome therapies in Europe, Microbiota in Health and Disease, Vol: 5, ISSN: 2704-8845

Faecal microbiota transplantation (FMT) has evolved from an anecdotally reported last resort for the critically ill to a well-established first-line treatment for patients with recurrent Clostridioides difficile infection (CDI), supported by grade 1a evidence. Given our improved understanding of the intestinal microbiota and how it impacts human health, FMT is now being explored for a range of emerging indications beyond CDI. In light of the rapid emergence of FMT as a novel treatment strategy in medicine, a need for international harmonisation has arisen. Addressing this need, the recently published 5th edition of the Guide to the quality and safety of tissues and cells for human application, issued by the European Directorate for the Quality of Medicines & HealthCare of the Council of Europe (EDQM), harbours complete descriptions of the collection, procurement and application of donor faeces as a substance of human origin (SoHO). The proposed revision of the Blood Tissue and Cell Regulation of the European Union (EU) incorporates stool for FMT as a SoHO. This revised regulation will provide a regulatory framework for the future development of donor-derived microbiome therapies. To implement and underpin the safety and quality requirements for FMT in this newly designed legal context, and to facilitate clinical use, collaboration and research, we established the European Academic FMT Network (EurFMT network). The European FMT Registry plays a pivotal role within this network, facilitating its clinical activities and monitoring safety. In this document, we summarise the basis for using donor faeces-derived microbiome therapies as well as the aim and main scope for the EurFMT network.

Journal article

Routy B, Lenehan JG, Miller WH, Jamal R, Messaoudene M, Daisley BA, Hes C, Al KF, Martinez-Gili L, Punčochář M, Ernst S, Logan D, Belanger K, Esfahani K, Richard C, Ninkov M, Piccinno G, Armanini F, Pinto F, Krishnamoorthy M, Figueredo R, Thebault P, Takis P, Magrill J, Ramsay L, Derosa L, Marchesi JR, Parvathy SN, Elkrief A, Watson IR, Lapointe R, Segata N, Haeryfar SMM, Mullish BH, Silverman MS, Burton JP, Maleki Vareki Set al., 2023, Author Correction: Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial., Nat Med

Journal article

Kragsnaes MS, Miguens Blanco J, Mullish BH, Contreras Serrano JI, Kjeldsen J, Horn HC, Pedersen JK, Munk HL, Nilsson AC, Salam A, Lewis MR, Chekmeneva E, Kristiansen K, Marchesi JR, Ellingsen Tet al., 2023, Small intestinal permeability and metabolomic profiles in feces and plasma associate with clinical response in patients with active psoriatic arthritis participating in a fecal microbiota transplantation trial: exploratory findings from the FLORA trial, ACR Open Rheumatology, Vol: 5, Pages: 583-593, ISSN: 2578-5745

ObjectiveWe investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate-treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT).MethodsThis exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate-treatment, were included in a 26-week, double-blind, 1:1 randomized, sham-controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose-to-mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using 1H Nuclear Magnetic Resonance.ResultsTrial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017-0.33]) vs. 0.012 [0-0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N-acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient = 0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient = 27, P = 0.02).ConclusionIntestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.

Journal article

Izzi-Engbeaya C, Eng PC, Dunin-Borkowska A, Forlano R, Mullish BH, Sigon G, Lin V, Tan T, Yee M, Manousou P, Dhillo WSet al., 2023, THU642 Progression To Cirrhosis And All-cause Mortality Are Increased In Postmenopausal Women With NAFLD, Publisher: The Endocrine Society

<jats:title>Abstract</jats:title> <jats:p>Disclosure: C. Izzi-Engbeaya: None. P. Eng: None. A. Dunin-Borkowska: None. R. Forlano: None. B.H. Mullish: None. G. Sigon: None. V. Lin: None. T. Tan: None. M. Yee: None. P. Manousou: None. W.S. Dhillo: None.</jats:p> <jats:p>Background: Up to 30% of adults worldwide are estimated to have Non-alcoholic Liver Disease (NAFLD), ranging from hepatic steatosis alone to steatohepatitis and cirrhosis. Due to underlying metabolic and hepatic pathology, patients with NAFLD require specialist input from Endocrinologists and Hepatologists. Worryingly, postmenopausal women with NAFLD are more likely to progress to advanced fibrosis and experience more frequent liver decompensation events than men, but the causes of these disparate outcomes are incompletely understood. Methodology: We performed a retrospective cohort study utilising a database of consecutive patients managed in the multidisciplinary Metabolic Endocrinology and Hepatology Clinic at Imperial College Healthcare NHS Trust (London, UK) who had their first clinic review between January 2009 and December 2020. NAFLD was diagnosed clinically or histologically. Clinical, biochemical and histological data were collected up to December 2022. Postmenopausal women were defined as women aged ≥55 years at their initial clinic visit. Cirrhosis was diagnosed based on a combination of clinical and radiological features or based on histology, when available. Multivariate logistic regression was performed to identify variables independently associated with cirrhosis. Statistical significance was set at p&amp;lt;0.05. Results: 739 patients were included in this study (n=286 female, n=244 White, median (IQR) age: 52 (42-60) years), with a median follow-up of 6 (3-8) years. All-cause mortality was highest amongst postmenopausal women (proportion who died during follow-up: men &amp;lt;55y 2% vs men ≥55y 9% vs women &am

Conference paper

Mullish BH, 2023, Alcohol Minimum Unit Pricing Reduces Alcohol-Specific Hospitalizations and Deaths, Gastroenterology, Vol: 165, Pages: 1089-1090, ISSN: 0016-5085

Journal article

Kirupakaran T, Couffon M, Martino B, Sigon G, Mullish B, Yee M, Thursz M, Forlano R, Manousou Pet al., 2023, P26 Exploring the association between quality of life, diet, physical activity, and binge eating disorder in NAFLD patients in a tertiary centre of care, Abstracts of the British Association for the Study of the Liver Annual Meeting, 19–22 September 2023, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology

Conference paper

Forlano R, Malik MH, Sigon G, Lin MV, Huang J, Kirupakaran MT, Couffon MM, Shapoor MM, Mullish B, Thursz PM, Manousou Pet al., 2023, O6 The beneficial hepatic-effect of glucagon-like peptide 1 receptor agonists in diabetic patients with non-alcoholic fatty liver disease, Abstracts of the British Association for the Study of the Liver Annual Meeting, 19–22 September 2023, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology

Conference paper

Couffon M, Kirupakaran T, Sigon G, Martino B, Huang J, Mullish B, Yee M, Thursz M, Forlano R, Manousou Pet al., 2023, P18 A 5 sit-to-stand test may identify NAFLD patients at higher risk for worse clinical outcomes, Abstracts of the British Association for the Study of the Liver Annual Meeting, 19–22 September 2023, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology

Conference paper

Smith PJ, 2023, GI highlights from the literature, Gut, Vol: 72, Pages: 1795-1796, ISSN: 0017-5749

Journal article

Yip AYG, King OG, Omelchenko O, Kurkimat S, Horrocks V, Mostyn P, Danckert N, Ghani R, Satta G, Jauneikaite E, Davies FJ, Clarke TB, Mullish BH, Marchesi JR, McDonald JAKet al., 2023, Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites, Nature Communications, Vol: 14

<jats:title>Abstract</jats:title><jats:p>The intestine is the primary colonisation site for carbapenem-resistant <jats:italic>Enterobacteriaceae</jats:italic> (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show that antibiotic-induced reduction of gut microbial populations leads to an enrichment of nutrients and depletion of inhibitory metabolites, which enhances CRE growth. Antibiotics decrease the abundance of gut commensals (including <jats:italic>Bifidobacteriaceae</jats:italic> and <jats:italic>Bacteroidales</jats:italic>) in ex vivo cultures of human faecal microbiota; this is accompanied by depletion of microbial metabolites and enrichment of nutrients. We measure the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several CRE strains. We find that CRE can use the nutrients (enriched after antibiotic treatment) as carbon and nitrogen sources for growth. These nutrients also increase in faeces from antibiotic-treated mice and decrease following intestinal colonisation with carbapenem-resistant <jats:italic>Escherichia coli</jats:italic>. Furthermore, certain microbial metabolites (depleted upon antibiotic treatment) inhibit CRE growth. Our results show that killing gut commensals with antibiotics facilitates CRE colonisation by enriching nutrients and depleting inhibitory microbial metabolites.</jats:p>

Journal article

Routy B, Lenehan JG, Miller WH, Jamal R, Messaoudene M, Daisley BA, Hes C, Al KF, Martinez-Gili L, Punčochář M, Ernst S, Logan D, Belanger K, Esfahani K, Richard C, Ninkov M, Piccinno G, Armanini F, Pinto F, Krishnamoorthy M, Figueredo R, Thebault P, Takis P, Magrill J, Ramsay L, Derosa L, Marchesi JR, Parvathy SN, Elkrief A, Watson IR, Lapointe R, Segata N, Haeryfar SMM, Mullish BH, Silverman MS, Burton JP, Maleki Vareki Set al., 2023, Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial, Nature Medicine, Vol: 29, Pages: 2121-2132, ISSN: 1078-8956

Journal article

Payne T, Appleby M, Buckley E, van Gelder LMA, Mullish BH, Sassani M, Dunning MJ, Hernandez D, Scholz SW, McNeill A, Libri V, Moll S, Marchesi JR, Taylor R, Su L, Mazzà C, Jenkins TM, Foltynie T, Bandmann Oet al., 2023, A Double-Blind, Randomized, Placebo-Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson's Disease., Mov Disord, Vol: 38, Pages: 1493-1502

BACKGROUND: Rescue of mitochondrial function is a promising neuroprotective strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has shown considerable promise as a mitochondrial rescue agent across a range of preclinical in vitro and in vivo models of PD. OBJECTIVES: To investigate the safety and tolerability of high-dose UDCA in PD and determine midbrain target engagement. METHODS: The UP (UDCA in PD) study was a phase II, randomized, double-blind, placebo-controlled trial of UDCA (30 mg/kg daily, 2:1 randomization UDCA vs. placebo) in 30 participants with PD for 48 weeks. The primary outcome was safety and tolerability. Secondary outcomes included 31-phosphorus magnetic resonance spectroscopy (31 P-MRS) to explore target engagement of UDCA in PD midbrain and assessment of motor progression, applying both the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) and objective, motion sensor-based quantification of gait impairment. RESULTS: UDCA was safe and well tolerated, and only mild transient gastrointestinal adverse events were more frequent in the UDCA treatment group. Midbrain 31 P-MRS demonstrated an increase in both Gibbs free energy and inorganic phosphate levels in the UDCA treatment group compared to placebo, reflecting improved ATP hydrolysis. Sensor-based gait analysis indicated a possible improvement of cadence (steps per minute) and other gait parameters in the UDCA group compared to placebo. In contrast, subjective assessment applying the MDS-UPDRS-III failed to detect a difference between treatment groups. CONCLUSIONS: High-dose UDCA is safe and well tolerated in early PD. Larger trials are needed to further evaluate the disease-modifying effect of UDCA in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Journal article

Barnes E, Goodyear CS, Willicombe M, Gaskell C, Siebert S, I de Silva T, Murray SM, Rea D, Snowden JA, Carroll M, Pirrie S, Bowden SJ, Dunachie SJ, Richter A, Lim Z, Satsangi J, Cook G, Pope A, Hughes A, Harrison M, Lim SH, Miller P, Klenerman P, Richter AG, Mentzer A, Deeks A, Jamsen A, Brown A, Conlon C, Dold C, Duncan CJA, Skelly D, Kronsteiner B, Abraham P, Phillips E, Jeffery K, Turtle L, Frending L, Stafford L, Ali M, Rongkard P, Payne R, Adele S, Travis S, Gardiner S, Dobson SL, Malone T, Bibi S, Carroll M, Faustini S, Foulkes S, Frater J, Hall V, Hopkins S, Islam J, Lambe T, Longet S, Moore SC, Otter A, Rowland-Jones SL, Thaventhir JED, Wootton DG, Basu N, Gilmour A, Irwin S, Meacham G, Marjot T, Dimitriadis S, Kelleher P, Prendecki M, Clarke C, Mortimer P, McIntyre S, Selby R, Meardon N, Nguyen D, Tipton T, Longet S, Laidlaw S, Orchard K, Ireland G, Brown K, Amirthalingam G, Thomas D, Kearns P, Kirkham A, McInnes IB, Beesley R, Churchill V, Loughton H, Insch E, MacDonald E, Middleton G, Billingham L, Lowe F, Magwaro S, Al-Taei S, Arnott M, Bennett L, Brock J, Keillor V, Melville A, Melville L, Miller S, Najm A, Paterson C, Rodgers L, Rutherford M, Rundell S, Smith E, Stewart L, Sunzini F, Tong A, Woolcock K, Basheer F, Crawley C, Malladi R, King A, Lockey S, Uttenthal B, Koh MBC, Hansford S, Sandhar G, Kesavan M, Moore C, Manousou P, Hahn G, Mullish B, Atta M, Gleeson S, Lightstone L, Martin P, McAdoo S, Thomson T, Avenoso D, Sanderson R, Taylor C, Bhandal K, Hull D, Trivedi P, Filer A, Hurst E, Publicover A, Scouse K, Chalk J, Hanke D, Hanke J, Healy S, Provine N, Thomas S, Walker V, Win Z, Trown D, Faria P, Chackathayil J, Hutchison C, Richardson D, PITCH consortium, CONSENSUS, OCTAVE Collaborative Groupet al., 2023, SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease, Nature Medicine, ISSN: 1546-170X

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml−1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies.

Journal article

Skov Kragsnaes M, Miguens Blanco J, Mullish B, Contreras-Serrano JI, Horn HC, Munk H, Pedersen JK, Nilsson AC, Kristiansen K, Kjeldsen J, Marchesi J, Ellingsen Tet al., 2023, POS0423 PLASMA METABOLOMIC PROFILES OF PATIENTS WITH ACTIVE PERIPHERAL PSORIATIC ARTHRITIS CAN DIFFERENTIATE TREATMENT RESPONDERS FROM FAILURES: EXPLORATORY FINDINGS FROM THE FLORA TRIAL, EULAR 2023 European Congress of Rheumatology, 31 May - 3 June. Milan, Italy, Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism

Conference paper

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00350833&limit=30&person=true