174 results found
Riaz Z, Wright M, Atkinson S, et al., 2019, Malignant and cirrhotic ascites demonstrate a similar microbiome profile, British Association for the Study of the Liver (BASL) Annual Meeting
Allegretti JA, Kassam Z, Carrellas M, et al., 2019, Fecal microbiota transplantation in patients with primary sclerosing cholangitis: A pilot clinical trial, American Journal of Gastroenterology, Vol: 114, Pages: 1071-1079, ISSN: 1572-0241
Background: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut microbiota has been described in association with PSC, and fecal microbiota transplantation (FMT) has been reported to restore the microbiome in other disease states. Accordingly, we aimed to evaluate the safety, change in liver enzymes, microbiota and metabolomic profiles in PSC patients after FMT.Methods: Open-label pilot study of PSC patients with concurrent inflammatory bowel disease (IBD) and ALP > 1.5X the upper limit of normal. Participants underwent a single FMT by colonoscopy. Liver enzyme profiles and stool microbiome and metabolomic analysis was conducted at baseline and week 1, 4, 8, 12 and 24 post-FMT. The primaryoutcome was safety and secondary outcomes include a decrease in ALP ≥50% from baseline by week 24 post-FMT, as well as stool microbiota (by 16S rRNA gene profiling) and metabonomic dynamics were assessed.Results. Ten patients underwent FMT. Nine patients had ulcerative colitis and 1 with Crohn’s colitis. The mean baseline ALP was 489 U/L. There were no related adverse events. Overall, 30% (3/10) experienced a ≥50% decrease ALP. The diversity increased in all patients post-FMT, as early as week 1 (p<0.01). Importantly, abundance of engrafter operational taxanomic units (OTUs) in patients post-FMT correlated with decreased ALP (p=0.02).Conclusion: To our knowledge, this first study to demonstrate that FMT in PSC is safe. Additionally, increases in bacterial diversity and engraftment may correlate with an improvement in ALP among PSC patients.
Nathwani R, Mullish BH, Kockerling D, et al., 2019, Recurrent bacteraemia following variceal haemorrhage, Gut, Vol: 69, Pages: 726-780, ISSN: 0017-5749
Ghani R, Gan C, Mullish BH, et al., 2019, P13-2 Prevalence of recurrent Extended Spectrum Beta-Lactamase (ESBL) urinary tract infections (UTIs) in patients within a Urology service and introducing the concept of Faecal Microbiota Transplantation (FMT) as a treatment modality, British Association of Urological Surgeons Annual Scientific Meeting, Publisher: SAGE Publications, Pages: 83-85, ISSN: 2051-4158
Mullish BH, Kumar N, Goldin RD, et al., 2019, 27 Liver Biopsy, Evidence-based Gastroenterology and Hepatology, 4th Edition, Editors: McDonald, Feagan, Jalan, Kahrilas, Publisher: Wiley, ISBN: 978-1-119-21138-9
Churchward MA, Michaud ER, Blanco JM, et al., 2019, Sa1924 – Effect of Short Chain Fatty Acids on Gut-Brain Axis Using a Microglial Cell Model, Gastroenterology, Vol: 156, Pages: S-455, ISSN: 0016-5085
Allegretti JR, Hurtado J, Carrellas M, et al., 2019, 7 – The Icon Study: Inflammatory Bowel Disease and Recurrent Clostridium Difficile Infection: Outcomes After Fecal Microbiota Transplantation, Gastroenterology, Vol: 156, ISSN: 0016-5085
McDonald JA, Perez JL, Mullish BH, et al., 2019, Mo1953 – Growth Inhibition of Clostridioides Difficile by Short and Medium Chain Fatty Acids, Gastroenterology, Vol: 156, Pages: S-898, ISSN: 0016-5085
Allegretti JR, Kassam Z, Chiang AL, et al., 2019, 621 – Fecal Microbiota Transplantation for the Treatment of Obesity: A Randomized, Placebo-Controlled Pilot Trial, Gastroenterology, Vol: 156, Pages: S-129, ISSN: 0016-5085
Ghani R, Gan C, Mullish B, et al., 2019, MP71-15 Prevalence of recurrent extended-spectrum beta-lactamase (ESBL) urinary tract infections (UTIs) in patients within a urology service. Introducing the concept of Faecal Microbiota transplantation (FMT) as a treatment modality., AUA 2019, Publisher: Elsevier, ISSN: 0022-5347
Tyson LD, Atkinson S, Pechlivanis A, et al., 2019, Serum bile acid profiles distinguish severe alcoholic hepatitis from decompensated alcohol-related cirrhosis, International Liver Congress / 54th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER, Pages: E108-E108, ISSN: 0168-8278
Forlano R, Mullish BH, Giannakeas N, et al., 2019, SAT-294. Automated quantitation of steatosis, inflammation, ballooningand fibrosis using machine learning in routine histologicalimages of liver biopsies of patients with NAFLD, International Liver Congress (ILC), Publisher: Elsevier, Pages: e767-e768, ISSN: 0168-8278
Abeles RD, Mullish BH, Forlano R, et al., 2019, Derivation and validation of a cardiovascular risk score for prediction of major acute cardiovascular events in non-alcoholic fatty liver disease: The importance of an elevated mean platelet volume, International Liver Congress / 54th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER, Pages: E305-E305, ISSN: 0168-8278
Forlano R, Mullish BH, Yee M, et al., 2019, Liver function tests in NAFLD: Changes in upper normal limits, does it really matter?, International Liver Congress / 54th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER, Pages: E295-E295, ISSN: 0168-8278
Abeles RD, Mullish BH, Forlano R, et al., 2019, Derivation and validation of a cardiovascular risk score for prediction of major acute cardiovascular events in non-alcoholic fatty liver disease; the importance of an elevated mean platelet volume, Alimentary Pharmacology and Therapeutics, Vol: 49, Pages: 1077-1085, ISSN: 0269-2813
Background: Atherosclerotic cardiovascular disease is a key cause of morbidity in non-alcoholic fatty liver disease (NAFLD) but appropriate means to predict major acute cardiovascular events (MACE) are lacking. Aims: To design a bespoke cardiovascular risk score in NAFLD. Methods: A retrospective derivation (2008-2016, 356 patients) and a prospective validation (2016- 2017, 111 patients) NAFLD cohort study was performed. Clinical and biochemical data were recorded at enrolment and mean platelet volume (MPV), Qrisk2 and Framingham scores were recorded one year prior to MACE (Cardiovascular death, acute coronary syndrome, stroke, and transient ischaemic attack). Results: The derivation and validation cohorts were well matched with MACE prevalence 12.6% and 12% respectively. On univariate analysis, age, diabetes, advanced fibrosis, collagen proportionate area >5%, MPV and liver stiffness were associated with MACE. After multivariate analysis, age, diabetes and MPV remained independently predictive. The ‘NAFLD CV-risk score’ was generated using binary logistic regression: 85860.06*(Age) + 0.963*(MPV) + 0.26*(DM1) – 16.441 Diabetes mellitus: 1: present; 2: absent. (AUROC 0.84). A cut-off of -3.98 gave a Sensitivity 97%, Specificity 27%, PPV 16%, NPV 99%. An MPV alone of >10.05 gave a sensitivity 97%, specificity 59%, PPV 24% and NPV 97% (AUROC 0.83). Validation cohort AUROCs were comparable at 0.77 (NAFLD CV-risk) and 0.72 (MPV). In the full cohort, the NAFLD CV-risk score and MPV outperformed both Qrisk2 and Framingham scores. Conclusions: The NAFLD CV risk score and MPV accurately predict 1-year risk of MACE thereby allowing better identification of patients that require optimisation of their cardiovascular risk profile.
Mullish BH, Forlano R, Abeles RD, et al., 2019, Editorial: importance of an elevated mean platelet volume for prediction of major adverse cardiovascular events in non-alcoholic fatty liver disease - authors' reply., Aliment Pharmacol Ther, Vol: 49, Pages: 1093-1094
Ovadia C, Perdones-Montero A, Mullish B, et al., 2019, Ursodeoxycholic acid treatment of cholestatic pregnancy can alter the gut microbiota to enhance bile acid modification and production of metabolically-active secondary bile acids - an explanation for 'responders' and 'non-responders'?, Publisher: WILEY, Pages: 17-17, ISSN: 1470-0328
Mcilroy JR, Segal JP, Mullish BH, et al., 2019, Current and future targets for faecal microbiota transplantation, Human Microbiome Journal, Vol: 11, Pages: 100045-100045, ISSN: 2452-2317
Kockerling D, Nathwani R, Forlano R, et al., 2019, Current and future pharmacological therapies for managing cirrhosis and its complications., World J Gastroenterol, Vol: 25, Pages: 888-908
Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective beta-blockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective, haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore, statins are suggested to have protective effects upon fibrosis progression, decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence
Ghani R, Gan C, Mullish B, et al., 2019, Prevalence of recurrent extended-spectrum beta-lactamase (ESBL) urinary tract infections (UTIs) in patients within a urology service. Introducing the concept of Faecal Microbiota transplantation (FMT) as a treatment modality., Journal of Clinical Urology
Mullish BH, Ghani R, McDonald J, et al., 2019, Faecal microbiota transplant for eradication of multidrug-resistant Enterobacteriaceae: a lesson in applying best practice? Re: 'A five-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: A Randomized Clinical Trial', Clinical Microbiology and Infection, Vol: 25, Pages: 912-913, ISSN: 1198-743X
Segal JP, Mullish B, Quraishi MN, et al., 2019, The application of omics techniques to understand the role of the gut microbiota in inflammatory bowel disease, Therapeutic Advances in Gastroenterology, Vol: 12, Pages: 1-13, ISSN: 1756-2848
The aetiopathogenesis of inflammatory bowel diseases (IBD) involves the complex interaction between a patient’s genetic predisposition, environment, gut microbiota and immune system. Currently, however, it is not known if the distinctive perturbations of the gut microbiota that appear to accompany both Crohn’s disease and ulcerative colitis are the cause of, or the result of, the intestinal inflammation that characterizes IBD.With the utilization of novel systems biology technologies, we can now begin to understand not only details about compositional changes in the gut microbiota in IBD, but increasingly also the alterations in microbiota function that accompany these. Technologies such as metagenomics, metataxomics, metatranscriptomics, metaproteomics and metabonomics are therefore allowing us a deeper understanding of the role of the microbiota in IBD. Furthermore, the integration of these systems biology technologies through advancing computational and statistical techniques are beginning to understand the microbiome interactions that both contribute to health and diseased states in IBD.This review aims to explore how such systems biology technologies are advancing our understanding of the gut microbiota, and their potential role in delineating the aetiology, development and clinical care of IBD.
Yalchin M, Segal JP, Mullish BH, et al., 2019, Gaps in knowledge and future directions for the use of faecal microbiota transplant in the treatment of inflammatory bowel disease, Therapeutic Advances in Gastroenterology, Vol: 12, Pages: 175628481989103-175628481989103, ISSN: 1756-2848
<jats:p> Faecal microbiota transplant (FMT) has now been established into clinical guidelines for the treatment of recurrent and refractory Clostridioides difficile infection (CDI). Its therapeutic application in inflammatory bowel disease (IBD) is currently at an early stage. To date, there have been four randomized controlled trials for FMT in IBD and a multitude of observational studies. However, significant gaps in our knowledge regarding optimum methods for FMT preparation, technical aspects and logistics of its administration, as well as mechanistic underpinnings, still remain. In this article, we aim to highlight these gaps by reviewing evidence and making key recommendations on the direction of future studies in this field. In addition, we provide an overview of the current evidence of potential mechanisms of FMT in treating IBD. </jats:p>
Monaghan T, Mullish BH, Patterson J, et al., 2019, Effective fecal microbiota transplantation for recurrent Clostridioides difficile infection in humans is associated with increased signalling in the bile acid-farnesoid X receptor-fibroblast growth factor pathway., Gut Microbes, Vol: 10, Pages: 142-148
The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with restored gut microbiota-bile acid interactions representing one possible explanation. Furthermore, the potential implications for host physiology of these FMT-related changes in gut bile acid metabolism are also not well explored. In this study, we investigated the impact of FMT for rCDI upon signalling through the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we identify that in addition to restoration of gut microbiota and bile acid profiles, FMT for rCDI is accompanied by a significant, sustained increase in circulating levels of FGF19 and reduction in FGF21. These FGF changes were associated with weight gain post-FMT, to a level not exceeding the pre-rCDI baseline. Collectively, these data support the hypothesis that the restoration of gut microbial communities by FMT for rCDI is associated with an upregulated FXR-FGF pathway, and highlight the potential systemic effect of FMT.
Ghani R, Gan C, Mullish B, et al., 2018, Prevalence of recurrent extended-spectrum beta-lactamase (ESBL) urinary tract infections (UTIs) in patients within a urology service. Introducing the concept of Faecal Microbiota transplantation (FMT) as a treatment modality., Annual EAU Congress, Publisher: Elsevier, Pages: e375-e376, ISSN: 1569-9056
Mullish BH, Forlano R, Manousou P, et al., 2018, Non-alcoholic fatty liver disease and cardiovascular risk: an update., Expert Rev Gastroenterol Hepatol, Vol: 12, Pages: 1175-1177
Mullish BH, Quraishi MN, Segal JP, et al., 2018, The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines., Gut, Vol: 67, Pages: 1920-1941
Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.
McDonald JAK, Mullish BH, Pechlivanis A, et al., 2018, Inhibiting Growth of Clostridioides difficile by Restoring Valerate, Produced by the Intestinal Microbiota., Gastroenterology, Vol: 155, Pages: 1495-1507.e15
BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is effective for treating recurrent Clostridioides difficile infection (CDI), but there are concerns about its long-term safety. Understanding the mechanisms of the effects of FMT could help us design safer, targeted therapies. We aimed to identify microbial metabolites that are important for C difficile growth. METHODS: We used a CDI chemostat model as a tool to study the effects of FMT in vitro. The following analyses were performed: C difficile plate counts, 16S rRNA gene sequencing, proton nuclear magnetic resonance spectroscopy, and ultra-performance liquid chromatography and mass spectrometry bile acid profiling. FMT mixtures were prepared using fresh fecal samples provided by donors enrolled in an FMT program in the United Kingdom. Results from chemostat experiments were validated using human stool samples, C difficile batch cultures, and C57BL/6 mice with CDI. Human stool samples were collected from 16 patients with recurrent CDI and healthy donors (n = 5) participating in an FMT trial in Canada. RESULTS: In the CDI chemostat model, clindamycin decreased valerate and deoxycholic acid concentrations and increased C difficile total viable counts and valerate precursors, taurocholic acid, and succinate concentrations. After we stopped adding clindamycin, levels of bile acids and succinate recovered, whereas levels of valerate and valerate precursors did not. In the CDI chemostat model, FMT increased valerate concentrations and decreased C difficile total viable counts (94% decrease), spore counts (86% decrease), and valerate precursor concentrations; concentrations of bile acids were unchanged. In stool samples from patients with CDI, valerate was depleted before FMT but restored after FMT. Clostridioides difficile batch cultures confirmed that valerate decreased vegetative growth, and that taurocholic acid was required for germination but had no effect on vegetative growth. Clost
Mullish BH, Quraishi MN, Segal J, et al., 2018, Introduction to the joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) faecal microbiota transplant guidelines, Journal of Hospital Infection, Vol: 100, Pages: 130-132, ISSN: 0195-6701
Ghani R, Mookerjee S, Mullish BH, et al., 2018, Impact on Length of Stay and Antibiotic Use in Allogenic and Autologous Stem Cell Transplant Patients Colonized with Carbapenemase-producing Enterobacteriaceae, IDWeek, Publisher: Oxford University Press, ISSN: 2328-8957
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