Publications
324 results found
Barnes E, Goodyear CS, Willicombe M, et 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.
Smith PJ, 2023, GI highlights from the literature, Gut, Vol: 72, Pages: 1220-1221, ISSN: 0017-5749
Mullish BH, 2023, The Impact of Proportional Dietary Carbohydrate and Fat Content on Type 2 Diabetes and NAFLD, Gastroenterology, Vol: 164, Pages: 1338-1338, ISSN: 0016-5085
Alexander J, Danckert N, Patel R, et al., 2023, COVID-19 vaccine-induced antibody response is associated with oral microbiota composition in patients with inflammatory bowel disease, cirrhosis, and liver transplantation, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A92-A92, ISSN: 0017-5749
Edwards LA, Woodhouse C, Lee S, et al., 2023, Faecal microbiota transplant restores gut barrier function and augments ammonia metabolism in patients with advanced cirrhosis: a randomised single-blind placebo-controlled trial, Publisher: ELSEVIER, Pages: S7-S7, ISSN: 0168-8278
Forlano R, Jambulingam N, Preston B, et al., 2023, Metabolic profile reflects stages of fibrosis in patients with nonalcoholic fatty liver disease, Publisher: ELSEVIER, Pages: S719-S720, ISSN: 0168-8278
Habboub N, Mullish BH, Moore C, et al., 2023, Investigating the correlation of a poly-metabolic risk score to clinical features in non-alcoholic fatty liver disease patients throughout a faecal microbiota transplant clinical trial, Publisher: ELSEVIER, Pages: S344-S345, ISSN: 0168-8278
Forlano R, Martinez-Gili L, Blanco JM, et al., 2023, Altered gut barrier integrity as a mediator of host-microbiome interactions in diabetic patients with advanced Non-alcoholic fatty liver disease, Publisher: ELSEVIER, Pages: S601-S602, ISSN: 0168-8278
Sigon G, Forlano R, Mullish BH, et al., 2023, Poor performance at five times sit-to-stand test, but not at handgrip test, is related to significant liver fibrosis and correlates with major cardiovascular events in non-alcoholic fatty liver disease patients, Publisher: ELSEVIER, Pages: S624-S624, ISSN: 0168-8278
Patel R, Mullish BH, Hicks L, et al., 2023, Colonoscopy surveillance in primary sclerosing cholangitis patients during the COVID-19 pandemic - a tertiary centre experience, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A219-A220, ISSN: 0017-5749
Skov Kragsnaes M, Miguens Blanco J, Mullish B, et 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
Churchward MA, Michaud ER, Mullish BH, et al., 2023, Short-chain fatty and carboxylic acid changes associated with fecal microbiota transplant communally influence microglial inflammation, Heliyon, Vol: 9, Pages: e16908-e16908, ISSN: 2405-8440
Izzi-Engbeaya C, Eng P, Dunin-Borkowska A, et al., 2023, Increased risk of cirrhosis in post-menopausal women with NAFLD, 25th European Congress of Endocrinology, Publisher: Bioscientifica
Mullish BH, Danckert NP, Patel R, et al., 2023, SALIVARY MICROBIOTA COMPOSITION IS ASSOCIATED WITH ANTIBODY RESPONSE FOLLOWING COVID-19 VACCINATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE, CIRRHOSIS AND LIVER TRANSPLANTATION, Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S1144-S1145, ISSN: 0016-5085
Smith PJ, 2023, GI highlights from the literature, Gut, Vol: 72, Pages: 1016-1017, ISSN: 0017-5749
Mullish BH, Danckert NP, Patel R, et al., 2023, Tu1866 SALIVARY MICROBIOTA COMPOSITION IS ASSOCIATED WITH ANTIBODY RESPONSE FOLLOWING COVID-19 VACCINATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE, CIRRHOSIS AND LIVER TRANSPLANTATION, Publisher: Elsevier BV, ISSN: 0016-5085
Huang J, Sigon G, Mullish BH, et al., 2023, Applying Lipidomics to Non-Alcoholic Fatty Liver Disease: A Clinical Perspective, Nutrients, Vol: 15, Pages: 1992-1992
<jats:p>The prevalence of Non-alcoholic fatty liver disease (NAFLD) and associated complications, such as hepatocellular carcinoma (HCC), is growing worldwide, due to the epidemics of metabolic risk factors, such as obesity and type II diabetes. Among other factors, an aberrant lipid metabolism represents a crucial step in the pathogenesis of NAFLD and the development of HCC in this population. In this review, we summarize the evidence supporting the application of translational lipidomics in NAFLD patients and NAFLD associated HCC in clinical practice.</jats:p>
Forlano R, Sigon G, Mullish BH, et al., 2023, Screening for NAFLD—Current Knowledge and Challenges, Metabolites, Vol: 13, Pages: 536-536
<jats:p>Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver function tests worldwide, with an estimated prevalence ranging between 19–46% in the general population. Of note, NAFLD is also expected to become a leading cause of end-stage liver disease in the next decades. Given the high prevalence and severity of NAFLD, especially in high-risk populations (i.e., patients with type-2 diabetes mellitus and/or obesity), there is a major interest in early detection of the disease in primary care. Nevertheless, substantial uncertainties still surround the development of a screening policy for NAFLD, such as limitations in currently used non-invasive markers of fibrosis, cost-effectiveness and the absence of a licensed treatment. In this review, we summarise current knowledge and try to identify the limitations surrounding the screening policy for NAFLD in primary care.</jats:p>
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., Benef Microbes, Pages: 1-14
There is a growing awareness that supplementation with probiotic bacteria can impart beneficial effects during gastrointestinal disease, but less is known about the impact of probiotics on healthy subjects. Here, we report the outcomes of a post hoc analysis of recorded daily gastrointestinal events and bowel habits completed by healthy adults participating in a placebo-controlled, single-centre, randomised, double-blind, quadruple-arm probiotic tolerability study. Extensive screening ensured the healthy status of subjects entering the study and during a 2-week pre-intervention run-in period, a burden of gastrointestinal events (stomach pains, indigestion, acid reflux, stomach tightening, nausea and vomiting, stomach rumbling, bloating, belching and flatulence) was identified suggesting GI discomfort within the population. In the subsequent 12-week intervention period with 3 distinct probiotic formulations and a matched-placebo, reductions in the incidence rates of bloating, borborygmus, stomach pains, slow faecal transit and incomplete defecations were observed in the probiotic groups compared to the placebo. These results highlighted differing responses among the probiotic formulations tested and indicated potential anti-constipation effects. Product specific modulations in circulating interleukin-6 levels and in the composition of the gut microbiota were also detected. Together, these data suggest a role for probiotic supplementation to exert beneficial effects on the gastrointestinal functioning of healthy subjects and highlight the need for further longer-term studies in healthy populations to gain a greater understanding of the impact of probiotics.
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 SCIENCE INC, 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>
Smith PJ, 2023, GI highlights from the literature, Gut, Vol: 72, Pages: 404-405, ISSN: 0017-5749
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
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
Airola C, Severino A, Porcari S, et al., 2023, Future Modulation of Gut Microbiota: From Eubiotics to FMT, Engineered Bacteria, and Phage Therapy
The human gut is inhabited by a multitude of bacteria, yeasts, and viruses. A dynamic balance among these microorganisms is associated with the well-being of the human being, and a large body of evidence supports a role of dysbiosis in the pathogenesis of several diseases. Given the importance of the gut microbiota in the preservation of human health, probiotics, prebiotics, synbiotics, and postbiotics have been classically used as strategies to modulate the gut microbiota and achieve beneficial effects for the host. Nonetheless, several molecules not typically included in these categories have demonstrated a role in restoring the equilibrium among the components of the gut microbiota. Among these, rifaximin, as well as other antimicrobial drugs, such as triclosan, or natural compounds (including evodiamine and polyphenols) have common pleiotropic characteristics. On one hand, they suppress the growth of dangerous bacteria while promoting beneficial bacteria in the gut microbiota. On the other hand, they contribute to the regulation of the immune response in the case of dysbiosis by directly influencing the immune system and epithelial cells or by inducing the gut bacteria to produce immune-modulatory compounds, such as short-chain fatty acids. Fecal microbiota transplantation (FMT) has also been investigated as a procedure to restore the equilibrium of the gut microbiota and has shown benefits in many diseases, including inflammatory bowel disease, chronic liver disorders, and extraintestinal autoimmune conditions. One of the most significant limits of the current techniques used to modulate the gut microbiota is the lack of tools that can precisely modulate specific members of complex microbial communities. Novel approaches, including the use of engineered probiotic bacteria or bacteriophage-based therapy, have recently appeared as promising strategies to provide targeted and tailored therapeutic modulation of the gut microbiota, but their role in clinical practic
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>
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