Publications
280 results found
Yip AYG, King OG, Omelchenko O, et al., 2023, Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites
<jats:p>The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. We used ex vivo faecal cultures to measure the impact of antibiotics (that promote CRE intestinal colonisation) on the faecal microbiota from healthy human donors. We demonstrated that antibiotics decreased the abundance of gut commensals (including Bifidobacteriaceae and Bacteroidales) in human faecal microbiota, resulting in an enrichment of nutrients and a depletion of microbial metabolites. The nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae strains were measured. Nutrients (which were elevated with antibiotics) acted as carbon and nitrogen sources to support CRE growth, where CRE showed an ordered preference for specific nutrients. These nutrients were also increased in faeces from antibiotic-treated mice but decreased following intestinal colonisation with carbapenem-resistant E. coli. Microbial metabolites (which decreased with antibiotics) were inhibitory towards CRE growth in vitro. Carbapenem-resistant E. coli growth was decreased in faecal samples from mice treated with a mixture of inhibitory metabolites compared with PBS-treated mice. These findings demonstrate that killing gut commensals with antibiotics disrupts colonisation resistance by enriching nutrients that support CRE growth and depleting metabolites that inhibit CRE growth. These results support the development of new microbiome therapeutics to prevent CRE intestinal colonisation, which would also prevent the subsequent development of invasive CRE infections.</jats:p>
Mullish BH, Tohumcu E, Porcari S, et al., 2023, The role of faecal microbiota transplantation in chronic noncommunicable disorders, Journal of Autoimmunity, ISSN: 0896-8411
Forlano R, Stanic T, Jayawardana S, et al., 2023, Prospective evaluation of screening strategies for NAFLD in people with type-2 diabetes mellitus in the community, Publisher: Elsevier BV, Pages: S17-S18, ISSN: 1590-8658
Jambulingam N, Forlano R, Preston B, et al., 2023, Metabolic Profile Reflects Stages of Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease, International Journal of Molecular Sciences, Vol: 24, Pages: 3563-3563
<jats:p>Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, with fibrosis stage being the main predictor for clinical outcomes. Here, we present the metabolic profile of NAFLD patients with regards to fibrosis progression. We included all consecutive new referrals for NAFLD services between 2011 and 2019. Demographic, anthropometric and clinical features and noninvasive markers of fibrosis were recorded at baseline and at follow-up. Significant and advanced fibrosis were defined using liver stiffness measurement (LSM) as LSM ≥ 8.1 kPa and LSM ≥ 12.1 kPa, respectively. Cirrhosis was diagnosed either histologically or clinically. Fast progressors of fibrosis were defined as those with delta stiffness ≥ 1.03 kPa/year (25% upper quartile of delta stiffness distribution). Targeted and untargeted metabolic profiles were analysed on fasting serum samples using Proton nuclear magnetic resonance (1H NMR). A total of 189 patients were included in the study; 111 (58.7%) underwent liver biopsy. Overall, 11.1% patients were diagnosed with cirrhosis, while 23.8% were classified as fast progressors. A combination of metabolites and lipoproteins could identify the fast fibrosis progressors (AUROC 0.788, 95% CI: 0.703–0.874, p < 0.001) and performed better than noninvasive markers. Specific metabolic profiles predict fibrosis progression in patients with nonalcoholic fatty liver disease. Algorithms combining metabolites and lipids could be integrated in the risk-stratification of these patients.</jats:p>
Alexander JL, Mullish BH, Danckert NP, et al., 2023, The gut microbiota and metabolome are associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients, eBioMedicine, Vol: 88, Pages: 104430-104430, ISSN: 2352-3964
Smith PJ, 2023, GI highlights from the literature, Gut, Vol: 72, Pages: 404-405, ISSN: 0017-5749
Mullish BH, Michael DR, Webberley TS, et al., 2023, The gastrointestinal status of healthy adults: a post hoc assessment of the impact of three distinct probiotics, Beneficial Microbes, ISSN: 1876-2883
Radhakrishnan ST, Gallagher KI, Mullish BH, et al., 2023, Rectal swabs as a viable alternative to faecal sampling for the analysis of gut microbiota functionality and composition., Sci Rep, Vol: 13
Faecal or biopsy samples are frequently used to analyse the gut microbiota, but issues remain with the provision and collection of such samples. Rectal swabs are widely-utilised in clinical practice and previous data demonstrate their potential role in microbiota analyses; however, studies to date have been heterogenous, and there are a particular lack of data concerning the utility of swabs for the analysis of the microbiota's functionality and metabolome. We compared paired stool and rectal swab samples from healthy individuals to investigate whether rectal swabs are a reliable proxy for faecal sampling. There were no significant differences in key alpha and beta diversity measures between swab and faecal samples, and inter-subject variability was preserved. Additionally, no significant differences were demonstrated in abundance of major annotated phyla. Inferred gut functionality using Tax4Fun2 showed excellent correlation between the two sampling techniques (Pearson's coefficient r = 0.9217, P < 0.0001). Proton nuclear magnetic resonance (1H NMR) spectroscopy enabled the detection of 20 metabolites, with overall excellent correlation identified between rectal swab and faecal samples for levels all metabolites collectively, although more variable degrees of association between swab and stool for levels of individual metabolites. These data support the utility of rectal swabs in both compositional and functional analyses of the gut microbiota.
Mullish BH, Martinez Gili L, Allegretti JR, 2023, Editorial: the acid test—can bile acids predict recurrence of Clostridioides difficile infection? Authors' reply, Alimentary Pharmacology and Therapeutics, Vol: 57, Pages: 169-170, ISSN: 0269-2813
Augustin A, Guennec AL, Umamahesan C, et al., 2023, Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome., Clin Transl Med, Vol: 13
BACKGROUND: Gut-brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease-modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide. METHODS: We characterised 77 participants with diagnosed-PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time. Complete-linkage hierarchical cluster analysis of metabolites discriminant for PD-status was performed. RESULTS: Longer colonic transit was linked to deficits in faecal short-chain-fatty acids outside PD, to a 'tryptophan-containing metabolite cluster' overall. Phenotypic cluster analysis aggregated colonic transit with brady/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan-cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole-ring compound (anti-fungals) and vitamin B3 (anti-inflammatory) and with higher serum CCL20 (chemotactic for lymphocytes/dendritic cells towards mucosal epithelium). The faster pulse in PD was irrespective of postural hypotension. The benzoic acid-cluster deficit was linked to (well-recognised) lower caffeine and alcohol intakes, tryptophan-cluster deficit to higher maltose intake. Free-sugar intake was increased in PD, maltose intake being 63% higher (p = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [p = .001, adjusted for proton-pump inhibitors (p = .001)], with 16% of PD-probands exceeding a cut-point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut-point. CONCLUSIONS: Emerging picture is of (i) clinical phenotype being described by deficits in microbial metabolites es
Mullish BH, 2023, The Impact of Proportional Dietary Carbohydrate and Fat Content on Type 2 Diabetes and NAFLD, Gastroenterology, ISSN: 0016-5085
Ghani R, Mullish BH, Roberts LA, et al., 2022, The potential utility of fecal (or intestinal) microbiota transplantation in controlling infectious diseases, Gut Microbes, Vol: 14, ISSN: 1949-0976
Bustamante J-M, Dawson T, Loeffler C, et al., 2022, Impact of Fecal Microbiota Transplantation on Gut Bacterial Bile Acid Metabolism in Humans, Nutrients, Vol: 14, Pages: 5200-5200
<jats:p>Fecal microbiota transplantation (FMT) is a promising therapeutic modality for the treatment and prevention of metabolic disease. We previously conducted a double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients in which we found that FMT enhanced gut bacterial bile acid metabolism and delayed the development of impaired glucose tolerance relative to the placebo control group. Therefore, we conducted a secondary analysis of fecal samples collected from these patients to assess the potential gut microbial species contributing to the effect of FMT to improve metabolic health and increase gut bacterial bile acid metabolism. Fecal samples collected at baseline and after 4 weeks of FMT or placebo treatment underwent shotgun metagenomic analysis. Ultra-high-performance liquid chromatography-mass spectrometry was used to profile fecal bile acids. FMT-enriched bacteria that have been implicated in gut bile acid metabolism included Desulfovibrio fairfieldensis and Clostridium hylemonae. To identify candidate bacteria involved in gut microbial bile acid metabolism, we assessed correlations between bacterial species abundance and bile acid profile, with a focus on bile acid products of gut bacterial metabolism. Bacteroides ovatus and Phocaeicola dorei were positively correlated with unconjugated bile acids. Bifidobacterium adolescentis, Collinsella aerofaciens, and Faecalibacterium prausnitzii were positively correlated with secondary bile acids. Together, these data identify several candidate bacteria that may contribute to the metabolic benefits of FMT and gut bacterial bile acid metabolism that requires further functional validation.</jats:p>
Powles STR, Gallagher KI, Chong LWL, et al., 2022, Effects of bowel preparation on intestinal bacterial associated urine and faecal metabolites and the associated faecal microbiome, BMC Gastroenterology, Vol: 22
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Urinary and faecal metabolic profiling have been extensively studied in gastrointestinal diseases as potential diagnostic markers, and to enhance our understanding of the intestinal microbiome in the pathogenesis these conditions. The impact of bowel cleansing on the microbiome has been investigated in several studies, but limited to just one study on the faecal metabolome.</jats:p> </jats:sec><jats:sec> <jats:title>Aim</jats:title> <jats:p>To compare the effects of bowel cleansing on the composition of the faecal microbiome, and the urine and faecal metabolome.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Urine and faecal samples were obtained from eleven patients undergoing colonoscopy at baseline, and then at day 3 and week 6 after colonoscopy. 16S rRNA gene sequencing was used to analyse changes in the microbiome, and metabonomic analysis was performed using proton nuclear magnetic resonance (<jats:sup>1</jats:sup>H NMR) spectroscopy.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Microbiomic analysis demonstrated a reduction in alpha diversity (Shannon index) between samples taken at baseline and three days following bowel cleansing (<jats:italic>p</jats:italic> = 0.002), and there was no significant difference between samples at baseline and six weeks post colonoscopy. Targeted and non-targeted analysis of urinary and faecal bacterial associated metabolites showed no significant impact following bowel cleansing.</jats:p> </jats:sec><jats:sec>
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
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 M, Mullish B, Frampton A, et al., 2022, 627 Oral administration of MRx0518 in treatment-naïve cancer patients is associated with compositional taxonomic and metabolomic changes indicative of anti-tumorigenic efficacy, SITC 37th Annual Meeting (SITC 2022) Abstracts, Publisher: BMJ Publishing Group Ltd
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
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
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
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
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
MiguensBlanco J, Mullish BH, 2022, New insights into host‐microbiome crosstalk in psoriatic skin, Clinical and Translational Discovery, Vol: 2, ISSN: 2768-0622
Smith PJ, 2022, GI highlights from the literature, Gut, Vol: 71, Pages: 1916-1917, ISSN: 0017-5749
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
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