126 results found
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.
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
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 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.
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
Allegretti JR, Mullish B, Kassam Z, et al., 2018, Bile Acid Profiles are Not Altered by Fecal Microbiota Transplantation for the Treatment of Primary Sclerosing Cholangitis: Category Award (Liver): Presidential Poster Award, Publisher: Ovid Technologies (Wolters Kluwer Health), Pages: S574-S576, ISSN: 0002-9270
Mullish BH, Pechlivanis A, Barker GF, et al., 2018, Functional microbiomics: Evaluation of gut microbiota-bile acid metabolism interactions in health and disease., Methods (San Diego, Calif.), Vol: 149, Pages: 49-58, ISSN: 1046-2023
There is an ever-increasing recognition that bile acids are not purely simple surfactant molecules that aid in lipid digestion, but are a family of molecules contributing to a diverse range of key systemic functions in the host. It is now also understood that the specific composition of the bile acid milieu within the host is related to the expression and activity of bacterially-derived enzymes within the gastrointestinal tract, as such creating a direct link between the physiology of the host and the gut microbiota. Coupled to the knowledge that perturbation of the structure and/or function of the gut microbiota may contribute to the pathogenesis of a range of diseases, there is a high level of interest in the potential for manipulation of the gut microbiota-host bile acid axis as a novel approach to therapeutics. Much of the growing understanding of the biology of this area reflects the recent development and refinement of a range of novel techniques; this study applies a number of those techniques to the analysis of human samples, aiming to illustrate their strengths, drawbacks and biological significance at all stages. Specifically, we used microbial profiling (using 16S rRNA gene sequencing), bile acid profiling (using liquid chromatography-mass spectrometry), bsh and baiCD qPCR, and a BSH enzyme activity assay to demonstrate differences in the gut microbiota and bile metabolism in stool samples from healthy and antibiotic-exposed individuals.
Segal J, Penez L, Mohsen S, et al., 2018, Long term outcomes of initial Infliximab therapy for inflammatory pouch pathology: a multi-centre retrospective study, Scandinavian Journal of Gastroenterology, Vol: 53, Pages: 1051--1058, ISSN: 0036-5521
Background: Restorative proctocolectomy with ileal pouch-anal anastomosis is considered the procedure of choice in patients with ulcerative colitis refractory to medical therapy. Subsequent inflammation of the pouch is a common complication and in some cases pouchitis fails to respond to antibiotics, the mainstay of treatment. In such cases, corticosteroids, immunomodulatory or biologic treatments are options. However, our understanding of the efficacy of anti-tumour necrosis factor medications in both chronic pouchitis and Crohn’s-like inflammation are based on studies that include relatively small numbers of patients. Methods: This was an observational, retrospective, multi-centre study to assess the long-term effectiveness and safety of infliximab for inflammatory disorders related to the ileoanal pouch. The primary outcome was the development of infliximab failure defined by early failure to infliximab or secondary loss of response to infliximab. Results: Thirty-four patients met the inclusion criteria; 18/34 (53%) who were initiated on infliximab for inflammatory disorders of the pouch had infliximab failure, 3/34 (8%) had early failure, and 15/34 (44%) had secondary loss of response with a median follow-up of 280 days (range 3-47 months). In total, 24/34 (71%) avoided an ileostomy by switching to other medical therapies at a median follow-up of follow-up of 366 days (1-130 months). Conclusions:Initial infliximab therapy for pouch inflammatory conditions is associated with Infliximab failure in just over half of all patients. Despite a high failure rate, an ileostomy can be avoided in almost three quarters of patients at four years by using other medical therapies.
Mullish BH, Osborne LS, Marchesi JR, et al., 2018, The implementation of omics technologies in cancer microbiome research, Ecancermedicalscience, Vol: 12, Pages: 1-11, ISSN: 1754-6605
Whilst the interplay between host genetics and the environment plays a pivotal role in the aetiopathogenesis of cancer, there are other key contributors of importance as well. One such factor of central and growing interest is the contribution of the microbiota to cancer. Even though the field is only a few years old, investigation of the ’cancer microbiome’ has already lead to major advances in knowledge of the basic biology of cancer risk and progression, opened novel avenues for biomarkers and diagnostics, and given better understanding of mechanisms underlying response to therapy. Recent developments in microbial DNA sequencing techniques (and the bioinformatics required for analysis of these datasets) has allowed much more in-depth profiling of the structure of microbial communities than was previously possible. However, for more complete assessment of the functional implications of microbial changes, there is a growing recognition of the importance of the integration of microbial profiling with other ‘omics modalities, with metabonomics (metabolite profiling) and proteomics (protein profiling) both gaining particular recent attention. In this review, we give an overview of some of the key scientific techniques being used to unravel the role of the cancer microbiome. We have aimed to highlight practical aspects related to sample collection and preparation, choice of modality of analysis, and examples of where different ‘omics technologies have been complementary to each other to highlighting the significance of the cancer microbiome.
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., J Hosp Infect, Vol: 100 Suppl 1, Pages: S1-S31
Mullish BH, McDonald JAK, Thursz MR, et al., 2018, Antibiotic-Associated Disruption of Microbiota Composition and Function in Cirrhosis Is Restored by Fecal Transplant., Hepatology, Vol: 68
Forlano R, Giannakeas N, Mullish BH, et al., 2018, Automated Quantitation of Steatosis, Fibrosis and Ballooning Using Machine Learning in Routine Histological Images of Liver Biopsies of Patients with NAFLD, The Liver Meeting, American Association for the Study of Liver Diseases (AASLD), Publisher: Wiley, Pages: 971A-972A, ISSN: 0270-9139
Segal J, Penez L, Elkady SM, et al., 2018, PWE-052 Long term outcomes of initial IFX therapy for inflammatory pouch pathology: a multi-centre retrospective study, British Society of Gastroenterology, Annual General Meeting, Publisher: BMJ Publishing Group, Pages: A93-A93, ISSN: 0017-5749
Segal J, Penez L, Elkady S, et al., 2018, IDDF2018-ABS-0056 Long term outcomes of initial infliximab therapy for inflammatory pouch pathology: a multi-centre retrospective study, International Digestive Disease Forum 2018, Publisher: BMJ Publishing Group, Pages: A41-A41, ISSN: 0017-5749
Mullish BH, Williams HR, 2018, Clostridium difficile infection and antibiotic-associated diarrhoea., Clin Med (Lond), Vol: 18, Pages: 237-241
Antibiotic-associated diarrhoea is among the most common adverse events related to antibiotic use. Most cases are mild, but Clostridium difficile infection causes a spectrum of disease, ranging from occasional diarrhoea to colitis, toxic megacolon, and potentially death. Recent developments in our understanding of the biology of the gut microbiota have provided new insights into the pathogenesis of these conditions, and have revealed a role for manipulation of the gut microbiota as a novel therapeutic approach. This review will give an overview of the assessment of these conditions, before focusing on the rapidly developing area of their treatment.
Mullish BH, 2018, Letter: improvements in mental health after faecal microbiota transplantation-an underexplored treatment-related benefit?, Aliment Pharmacol Ther, Vol: 47, Pages: 1562-1563
McDonald JAK, Mullish BH, Pechlivanis A, et al., 2018, 0503 - A novel route for controlling Clostridioides difficile growth via bile acid and short chain fatty acid modulation, ISME17
Allegretti JR, Mullish BH, Bogart E, et al., 2018, 25 - Microbiome and metabolic markers of Clostridium Difficile recurrance, Digestive Diseases Week, Publisher: Elsevier, Pages: S8-S9, ISSN: 0016-5085
McDonald JAK, Mullish BH, Pechlivanis A, et al., 2018, 24 - A novel route to controlling Clostridioides Difficile growth via short chain fatty acid and bile acid modulation, Digestive Diseases Week, Publisher: Elsevier, Pages: S8-S8, ISSN: 0016-5085
McSweeney B, Allegretti JR, Fischer M, et al., 2018, Tu1894 - Potential Motivators and Deterents for Stool Donors: A Multicenter Study, Digestive Diseases Week, Publisher: Elsevier, Pages: S1051-S1051, ISSN: 0016-5085
Forlano R, Mullish BH, Katertsidis N, et al., 2018, A mobile application for the management and follow-up of patients with Non-Alcoholic Fatty Liver Disease, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S819-S819, ISSN: 0168-8278
Forlano R, Mullish BH, Katertsidis N, et al., 2018, A mobile application for the management and follow-up of patients with Non-Alcoholic Fatty Liver Disease, Journal of Hepatology, Vol: 68, Pages: S819-S819, ISSN: 0168-8278
Mullish BH, Mathew S, Dhar A, 2018, Gastrointestinal: Duodenal variceal bleeding secondary to thrombophilia-related portal vein thrombosis., J Gastroenterol Hepatol, Vol: 33
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