Publications
324 results found
Mullish BH, Martinez-Gili L, Chekmeneva E, et al., 2022, Assessing the clinical value of faecal bile acid profiling to predict recurrence in primary Clostridioides difficile infection., Aliment Pharmacol Ther, Vol: 56, Pages: 1556-1569
BACKGROUND: Factors influencing recurrence risk in primary Clostridioides difficile infection (CDI) are poorly understood, and tools predicting recurrence are lacking. Perturbations in bile acids (BAs) contribute to CDI pathogenesis and may be relevant to primary disease prognosis. AIMS: To define stool BA dynamics in patients with primary CDI and to explore signatures predicting recurrence METHODS: Weekly stool samples were collected from patients with primary CDI from the last day of anti-CDI therapy until recurrence or, otherwise, through 8 weeks post-completion. Ultra-high performance liquid chromatography-mass spectrometry was used to profile BAs. Stool bile salt hydrolase (BSH) activity was measured to determine primary BA bacterial deconjugation capacity. Multivariate and univariate models were used to define differential BA trajectories in patients with recurrence versus those without, and to assess faecal BAs as predictive markers for recurrence. RESULTS: Twenty (36%) of 56 patients (median age: 57, 64% male) had recurrence; 80% of recurrences occurred within the first 9 days post-antibiotic treatment. Principal component analysis of stool BA profiles demonstrated clustering by recurrence status and post-treatment timepoint. Longitudinal faecal BA trajectories showed recovery of secondary BAs and their derivatives only in patients without recurrence. BSH activity increased over time only among non-relapsing patients (β = 0.056; likelihood ratio test p = 0.018). A joint longitudinal-survival model identified five stool BAs with area under the receiver operating characteristic curve >0.73 for predicting recurrence within 9 days post-CDI treatment. CONCLUSIONS: Gut BA metabolism dynamics differ in primary CDI patients between those developing recurrence and those who do not. Individual BAs show promise as potential novel biomarkers to predict CDI recurrence.
Lythgoe MP, Mullish BH, Frampton AE, et al., 2022, Polymorphic microbes: a new emerging hallmark of cancer, Trends in Microbiology, Vol: 30, Pages: 1131-1134, ISSN: 0966-842X
Lythgoe M, Mullish B, Frampton A, et al., 2022, ORAL ADMINISTRATION OF MRX0518 IN TREATMENTNAIVE CANCER PATIENTS IS ASSOCIATED WITH COMPOSITIONAL TAXONOMIC AND METABOLOMIC CHANGES INDICATIVE OF ANTI-TUMORIGENIC EFFICACY, Publisher: BMJ PUBLISHING GROUP, Pages: A659-A659
Ianiro G, Mullish BH, Iqbal TH, et al., 2022, Minimising the risk of monkeypox virus transmission during faecal microbiota transplantation: recommendations from a European expert panel, The Lancet Gastroenterology & Hepatology, Vol: 7, Pages: 979-980, ISSN: 2468-1253
Routy B, Lenehan J, Daisley B, et al., 2022, 614 Microbiome modification with fecal microbiota transplant from healthy donors before anti-PD1 therapy reduces primary resistance to immunotherapy in advanced and metastatic melanoma patients, SITC 37th Annual Meeting (SITC 2022) Abstracts, Publisher: BMJ Publishing Group Ltd
Mullish BH, Paizs P, Alexander J, et al., 2022, Intestinal microbiota transplant for recurrent Clostridioides difficile infection restores microbial arylsulfatases and sulfatide degradation: a novel mechanism of efficacy?, UEG Week 2022, Pages: 823-823
Forlano R, Stanic T, Jayawardana S, et al., 2022, Clinical and cost-effectiveness analysis of community-based screening strategies for non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus
<jats:title>Abstract</jats:title> <jats:p>Background & Aims: We investigated the prevalence of non-alcoholic fatty liver disease(NAFLD) in patients with type 2 diabetes mellitus(T2DM) in primary care and developed a risk-stratification pathway. We also assessed the cost-utility of different screening strategies for NAFLD in the diabetic community.Methods Consecutive T2DM patients underwent screening for liver diseases, including liver stiffness measurement(LSM). Binary logistic was used to predict factors associated with significant fibrosis. We used independent predictors of significant and advanced fibrosis to generate a predictive score for this population (BIMAST),and validated it internally and externally. Five screening strategies were compared against standard of care (SOC): BIMAST score, ultrasound plus abnormal liver function tests, FIB-4, NAFLD fibrosis score, and fibroscan. A Markov model was built upon four health states based on fibrosis status. We generated the cost per quality-adjusted life year(QALY) gained and calculated the incremental cost-effectiveness ratio (ICER) in the base-case analysis conducted over a lifetime horizon.Results Among 300 patients enrolled (287 included), 64% (186) had NAFLD and 10% (28) other causes of liver disease. Patients with significant fibrosis, advanced fibrosis, and cirrhosis due to NAFLD accounted for 17% (50/287), 11% (31/287), and 3% (8/287), respectively. BIMAST score validation showed an excellent diagnostic performance in primary care improving false negatives from 38–10% compared to FIB-4. In the cost-utility analysis, ICER was £2,337.92/QALY for BIMAST and £2,480/QALY for fibroscan. When transition probabilities, utilities, screening effect, and cost inputs were modified, we found a > 99% probability of NAFLD screening tests being cost-effective compared to SOC in all evaluated scenarios.Conclusion Screening for NAFLD in diabetic patient
Wang D, Durainayagam B, Forlano R, et al., 2022, Lipid profiling of extracellular vesicles and plasma in people with non-alcoholic fatty liver disease, EASL NAFLD Summit 2022, Publisher: EASL
Huang J, Forlano R, Wang D, et al., 2022, Anti-pd-1 treatment affects lipidomic profile in an animal model of NAFLD-HCC, EASL NAFLD summit 2022
Wang D, Durainayagam B, Forlano R, et al., 2022, Phosphatidylcholines (36:1) and (36:3) are increased in postmenopausal women with NAFLD, EASL NAFLD summit 2022
Huang J, Forlano R, Wang D, et al., 2022, A specific lipidomic fingerprint is associated with the development of nalfd-associated hcc in an animal model, EASL NAFLD summit 2022
Smith PJ, 2022, GI highlights from the literature, Gut, Vol: 71, Pages: 1916-1917, ISSN: 0017-5749
MiguensBlanco J, Mullish BH, 2022, New insights into host‐microbiome crosstalk in psoriatic skin, Clinical and Translational Discovery, Vol: 2, ISSN: 2768-0622
Humphry N, 2022, Recent Findings in the Gut-Liver Axis and Associated Disease Therapy, EMJ Hepatology, Pages: 4-16
<jats:p>Several presentations at the recent International Liver Congress™ (ILC), held in London, UK, from 22nd–26th of June 2022, addressed the role of the gut microbiome in chronic liver disease. Debbie L. Shawcross from the Department of Inflammation Biology, School of Immunology and Microbial Sciences, Institute of Liver Studies, King’s College London, UK, outlined the role of the gut-liver axis in the pathogenesis of cirrhosis, and how existing and novel therapies manipulate gut microbes.Emina Halilbasic from the Medical University of Vienna, Austria, and Benjamin H. Mullish from the Division of Digestive Diseases, Imperial College London, UK. Focused on the use of gut-based therapies in cholestatic liver disease. They explained the current understanding of the interplay between bile acids, microbiota, and the mucosal immune system, and the ways in which this may be manipulated for therapeutic gain.The role of gut barrier impairment in alcohol-related liver disease (ArLD) was presented by Shilpa Chokshi from the Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK, and School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, UK. Charlotte Skinner from the Department of Metabolism, Digestion, and Reproduction, Division of Digestive Diseases, Imperial College London, UK, described the role of gut proteases in this process, while Jasmohan S. Bajaj from the Virginia Commonwealth University, Richmond, USA, and Central Virginia Veterans Healthcare System, Richmond, USA, illustrated new therapies that target the gut-liver axis in this condition.Yue Shen from Zhongshan Hospital, Fudan University, Shanghai, China, and the Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, China, described a combined microbiome-metabolome study to characterise the gut microbiome in hepatitis B virus infection-associated liver diseases (HBV-CLD), an
Mullish BH, 2022, Further Insights Into the Impact of Bariatric Surgery on the Progression of Nonalcoholic Fatty Liver Disease., Gastroenterology, Vol: 163, Pages: 528-529
Mullish BH, 2022, National clinical expert consensus statement: Coronavirus monoclonal antibodies as a prophylactic therapy against COVID-19 for immunocompromised groups
- Novel long-acting coronavirus prophylactic monoclonal antibodytherapies have been shown to be effective in preventing COVID19 in immunocompromised individuals who are at increased riskfrom SARS-CoV-2.- Prophylactic antibody therapies should be made available in atimely manner to give an antibody immunity boost to vulnerablepatients.- Real world evaluations should be co-implemented to provideconfidence of ongoing effectiveness.- Successful delivery of a coronavirus prophylactic antibodytherapy programme would deliver significant benefits tohealthcare systems, communities and immunocompromisedindividuals.
Forlano R, Sivakumar M, Mullish BH, et al., 2022, Gut Microbiota—A Future Therapeutic Target for People with Non-Alcoholic Fatty Liver Disease: A Systematic Review, International Journal of Molecular Sciences, Vol: 23, Pages: 8307-8307
<jats:p>Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease, affecting one-third of the population worldwide. Despite many medications being in the pipeline to treat the condition, there is still no pharmaceutical agent licensed to treat the disease. As intestinal bacteria play a crucial role in the pathogenesis and progression of liver damage in patients with NAFLD, it has been suggested that manipulating the microbiome may represent a therapeutical option. In this review, we summarise the latest evidence supporting the manipulation of the intestinal microbiome as a potential therapy for treating liver disease in patients with NAFLD.</jats:p>
Smith PJ, 2022, GI highlights from the literature, Gut, Vol: 71, Pages: 1440-1441, ISSN: 0017-5749
Forlano R, Mullish BH, Martinez-Gili L, et al., 2022, Factors associated with increased gut permeability and severity of liver disease in diabetic patients with NAFLD, The International Liver CongressTM 2022, Publisher: Elsevier, Pages: S674-S675, ISSN: 0168-8278
Habboub N, Manousou P, Forlano R, et al., 2022, Designing a polymetabolic risk score for non-alcoholic steatohepatitis patients by differentiating their metabolic profiles from healthy controls, JOURNAL OF HEPATOLOGY, Vol: 77, Pages: S179-S179, ISSN: 0168-8278
Forlano R, Stanic T, Jayawardana S, et al., 2022, Clinical and economic evaluation of community-based preventative screening strategies for non-alcoholic fatty liver disease in people with Type-2 diabetes melllitus, JOURNAL OF HEPATOLOGY, Vol: 77, Pages: S444-S444, ISSN: 0168-8278
Mullish BH, McDonald JAK, Marchesi JR, 2022, Intestinal microbiota transplantation: do not forget the metabolites, The Lancet Gastroenterology & Hepatology, Vol: 7, Pages: 594-594, ISSN: 2468-1253
Marjot T, Murray S, Pose E, et al., 2022, Humoral and cellular immune responses to SARS-CoV-2 vaccination across multiple vaccine platforms and liver disease types: an EASL registry multicentre prospective cohort study, JOURNAL OF HEPATOLOGY, Vol: 77, Pages: S54-S55, ISSN: 0168-8278
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Moore-Gillon C, Cole A, Bashyam M, et al., 2022, A study evaluating outcomes of a virtual specialist liver cirrhosis clinic, Journal of Hepatology, Vol: 77, Pages: S345-S346
Skinner C, Marchesi J, Mullish BH, et al., 2022, Tight junction damage and increased gut permeability in alcohol-related liver disease may be mediated by gut proteases, JOURNAL OF HEPATOLOGY, Vol: 77, Pages: S121-S122, ISSN: 0168-8278
Kearns P, Siebert S, willicombe M, et al., 2022, Examining the immunological effects of COVID-19 vaccination in patients with conditions potentially leading to diminished immune response capacity – the OCTAVE trial
SARS-COV-2 vaccines have been shown to be efficacious primarily in healthy volunteer populations and population level studies. Immune responses following SARS-CoV-2 vaccination are less well characterised in potentially immune vulnerable patient groups, including those with immune-mediated inflammatory and chronic diseases (inflammatory arthritis [IA] incorporating rheumatoid arthritis [RA] and psoriatic arthritis [PsA]; ANCA-Associated Vasculitis [AAV]; inflammatory bowel disease [IBD]); hepatic disease (HepD), end stage kidney disease requiring haemodialysis (HD) without or with immunosuppression (HDIS); solid cancers (SC) and haematological malignancies (HM), and those that have undergone haemopoietic stem cell transplant (HSCT). The OCTAVE trial is a multi-centre, multi-disease, prospective cohort that will comprehensively assess SARS-CoV-2 vaccine responses within and between the abovementioned disease cohorts using common analytical platforms in patients recruited across the United Kingdom (UK). The majority of subjects received either COVID-19 mRNA Vaccine BNT162b2 (Pfizer/BioNTech) or ChAdOx1 Vaccine (AstraZeneca formerly AZD1222) as part of the UK National COVID19 vaccination programme. As of 13 th August 2021; 2,583 patients have been recruited. We report herein the humoral and T cell immune response results from the first 600 participants recruited where serology data are available at baseline, pre-second vaccine dose (boost) and/or 4 weeks post second dose. We also include in the analysis, data obtained from 231 healthy individuals from the PITCH (Protective Immunity from T cells in Healthcare workers) study. Overall, in comparison to PITCH where 100% of tested individuals (n=93) generated anti-Spike antibodies after vaccine doses, 89% of patients within OCTAVE seroconverted 4 weeks after second vaccine dose. By corollary, approximately 11% of patients across all disease cohorts fail to generate antibodies that react to SARS-CoV-2 spike 4 weeks after t
Alexander J, Mullish B, Danckert N, et al., 2022, COVID-19 VACCINATION RESPONSE IN IMMUNOSUPPRESSED PATIENTS WITH IBD IS ASSOCIATED WITH ALTERED GUT MICROBIOTA FUNCTION, Publisher: BMJ PUBLISHING GROUP, Pages: A36-A36, ISSN: 0017-5749
Zhang D, Mullish BH, Wang J, et al., 2022, Identifying transient and stable bacteria- metabolite interactions from longitudinal multi-omics data
<jats:title>Abstract</jats:title> <jats:p>Background Understanding the complex relationships between bacteria and metabolites in ecological systems are extremely important in studies of different microbiomes. Longitudinal multi-omics study is adopted to investigate interactions between bacteria and metabolites, by directly associating their longitudinal profiles. Since a bacteria/metabolite may involve in many different biological processes, the longitudinal profile is an average of different interactions. Therefore, direct association could only uncover the strongest interactions.Results Here we present a computational approach that can rebuild short- and long-term bacteria-metabolite interactions from longitudinal multi-omics datasets. For this task, we re-analyse data (both microbial sequencing and metabolomic analysis) from an <jats:italic>in vitro</jats:italic> model of <jats:italic>Clostridioides difficile</jats:italic> infection and faecal microbiota transplant, a disease state and mode of therapy in which perturbed microbiome-metabolome interactions (and their reversal) are well-established to be pertinent. By analysing such a dataset, we generated both a short-term and a long-term interaction network, which predicted many new interactions. Four new interactions were randomly selected to be validated. In batch culture experiments, we validated two of them: (1) <jats:italic>Ruminococcus gnavus</jats:italic> and <jats:italic>Ruminococcus luti</jats:italic> could generate 3-ketocholanic acid (2) <jats:italic>Blautia obeum</jats:italic> could consume succinate.Conclusions The deconvolution of the raw longitudinal signal into short- and long-term trends can help users to gain a deeper understanding of their data. This tool will be useful for high-throughput screening of microbe/metabolite/host interactions from a longitudinal multi-omics setting.</jats:p>
Forlano R, Stanic T, Jayawardana S, et al., 2022, CLINICAL AND ECONOMICAL EVALUATION OF COMMUNITY-BASED PREVENTATIVE SCREENING STRATEGIES FOR NON-ALCOHOLIC FATTY LIVER DISEASE, GASTROENTEROLOGY, Vol: 162, Pages: S1134-S1134, ISSN: 0016-5085
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