Publications
128 results found
Pinato DJ, Gramenitskaya D, Altmann DM, et al., 2019, Antibiotic therapy and outcome from immune-checkpoint inhibitors, Journal for ImmunoTherapy of Cancer, Vol: 7
Cammarota G, Ianiro G, Kelly CR, et al., 2019, International consensus conference on stool banking for faecal microbiota transplantation in clinical practice, Gut, Vol: 68, Pages: 2111-2121, ISSN: 0017-5749
<jats:p>Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent <jats:italic>Clostridioides difficile</jats:italic> infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.</jats:p><jats:p>Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,</jats:p><jats:p>Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.</jats:p>
Allegretti JR, Mullish BH, 2019, Faecal microbiota transplantation for the treatment of urinary tract infections: an interesting but incomplete story - Authors' reply, The Lancet, ISSN: 0140-6736
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, ISSN: 1756-2848
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 randomised 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 and logistics of its administration, as well as mechanistic underpinnings, still remain. This article aims to highlight these gaps by reviewing evidence and makes key recommendations on the direction of future studies in this field. In addition, we provide an overview of the current evidence of potential mechanistics of FMT in IBD.
Mullish BH, Forlano R, Abeles RD, et al., 2019, Letter: role of mean platelet volume levels in the prediction of major acute cardiovascular events in patients with non-alcoholic fatty liver disease-authors' reply, Alimentary Pharmacology & Therapeutics, Vol: 50, Pages: 1140-1141, ISSN: 0269-2813
Fessas P, Possamai LA, Clark J, et al., 2019, Immunotoxicity from checkpoint inhibitor therapy: clinical features and underlying mechanisms., Immunology, ISSN: 0019-2805
Immune checkpoint inhibition with monoclonal antibodies is becoming increasingly commonplace in cancer medicine, having contributed to a widening of therapeutic options across oncological indications. Disruption of immune tolerance is the key mechanism of action of checkpoint inhibitors and, whilst immune-related adverse events are a typical class effect of these compounds, the relationship between toxicity and response is not fully understood. Awareness and vigilance are paramount in recognising potentially life-threatening toxicities and managing them in a timely manner. In this review article, we provide an overview of the clinical features, pathologic findings and management principles of common immune-related toxicities, attempting to provide mechanistic insight into an increasingly common complication of cancer therapy.
Forlano R, Mullish B, Giannakeas N, et al., 2019, IMPACT OF BMI AND ETHNICITY ON HISTOLOGY AS ASSESSED BY AUTOMATED QUANTITATION IN LIVER BIOPSIES OF PATIENTS WITH NAFLD, Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Publisher: WILEY, Pages: 1359A-1359A, ISSN: 0270-9139
Allegretti JR, Mullish B, Hurtado J, et al., 2019, Short Chain Fatty Acid Profiles Are Altered by Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease and Recurrent Clostridioides difficile Infection, American Journal of Gastroenterology, Vol: 114, Pages: S484-S485, ISSN: 0002-9270
Allegretti JR, Mullish B, Nativ L, et al., 2019, Evaluating Dynamics of Bile Acid Metabolism to Predict Recurrence of Clostridioides difficile Infection, American Journal of Gastroenterology, Vol: 114, Pages: S113-S114, ISSN: 0002-9270
Mullish BH, McDonald JAK, Pechlivanis A, et al., 2019, Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection, Gut, Vol: 68, Pages: 1791-1800, ISSN: 0017-5749
<jats:sec><jats:title>Objective</jats:title><jats:p>Faecal microbiota transplant (FMT) effectively treats recurrent <jats:italic>Clostridioides difficile</jats:italic> infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect <jats:italic>C. difficile</jats:italic> germination or vegetative growth. We hypothesised that loss of gut microbiota-derived bile salt hydrolases (BSHs) predisposes to CDI by perturbing gut bile metabolism, and that BSH restitution is a key mediator of FMT’s efficacy in treating the condition.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Using stool collected from patients and donors pre-FMT/post-FMT for rCDI, we performed 16S rRNA gene sequencing, ultra performance liquid chromatography mass spectrometry (UPLC-MS) bile acid profiling, BSH activity measurement, and qPCR of <jats:italic>bsh</jats:italic>/<jats:italic>bai</jats:italic>CD genes involved in bile metabolism. Human data were validated in <jats:italic>C. difficile</jats:italic> batch cultures and a C57BL/6 mouse model of rCDI.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>From metataxonomics, pre-FMT stool demonstrated a reduced proportion of BSH-producing bacterial species compared with donors/post-FMT. Pre-FMT stool was enriched in taurocholic acid (TCA, a potent <jats:italic>C. difficile</jats:italic> germinant); TCA levels negatively correlated with key bacterial genera containing BSH-producing organisms. Post-FMT samples demonstrated recovered BSH activity and <jats:italic>bsh</jats:italic>/<jats:italic>bai</jats:italic>CD gene copy number compared with pretreatment (p<0.05). In batch cultures, supernatant from engineered <jats:italic>bsh</jats:italic>-expressing <jats:italic>E
Allegretti JR, Mullish BH, Kelly C, et al., 2019, The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications., Lancet, Vol: 394, Pages: 420-431
Developments in high-throughput microbial genomic sequencing and other systems biology techniques have given novel insight into the potential contribution of the gut microbiota to health and disease. As a result, an increasing number of diseases have been characterised by distinctive changes in the composition and functionality of the gut microbiota; however, whether such changes are cause, consequence, or incidental to the disease in question remains largely uncertain. Restoration of the gut microbiota to a premorbid state is a key novel therapeutic approach of interest, and faecal microbiota transplantation-the transfer of prescreened stool from healthy donors into the gastrointestinal tract of patients-is gaining increasing importance in both the clinical and research settings. At present, faecal microbiota transplantation is only recommended in the treatment of recurrent Clostridioides difficile infection, although a large number of trials are ongoing worldwide exploring other potential therapeutic indications.
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
Nathwani R, Mullish BH, Kockerling D, et al., 2019, A review of liver fibrosis and emerging therapies, European Medical Journal: Hepatology
With an increasing burden of liver cirrhosis, the most advanced stage of hepatic fibrosis, there is an emphasis to better understand the pathological processes and mechanisms to target specific treatments to reverse or cease fibrosis progression. Antiviral therapy for hepatitis B and C has effectively treated underlying causes of chronic liver disease and has induced fibrosis reversal in some however, this has not been targeted for the majority of aetiologies for cirrhosis including alcohol or non-alcoholic steatohepatitis. Fibrosis, characterized by the accumulation of extracellular matrix proteins, occurs due to chronic injury from toxic, infectious or metabolic causes. The primary event of fibrogenesis is increased matrix production and scar formation mediated by the hepatic stellate cell, the principal cell type involved. Experimental models using rodent and human cell lines of liver injury have assisted in better understanding fibrogenesis especially in recognising the role of procoagulant factors. This has led to interventional studies using anticoagulants in animal models with reversal of fibrosis as the primary endpoint. Though these trials have been encouraging, no antifibrotic therapies are currently licenced for human use. This literature review discusses current knowledge in the pathophysiology of hepatic fibrosis, including characteristics of the extracellular matrix, signalling pathways and hepatic stellate cells. We also review current types of experimental models used to induce fibrosis and up-to46 date anticoagulant therapies and agents targeting the hepatic stellate cell that have been trialled in animal and human studies with anti-fibrotic properties.
Allegretti JR, Kassam Z, Mullish BH, et al., 2019, Effects of fecal microbiota transplantation with oral capsules in obese patients, Clinical Gastroenterology and Hepatology, ISSN: 1542-3565
Background & AimsStudies in mice have shown that the intestinal microbiota can contribute to obesity via the anorexigenic gut hormone glucagon-like peptide 1 (GLP1) and bile acids, which affect lipid metabolism. We performed a randomized, placebo-controlled pilot study of the effects of fecal microbiota transplantation (FMT) in obese, metabolically uncompromised patients.MethodsWe performed a double-blind study of 22 obese patients (body mass index [BMI] ≥ 35kg/m2) without a diagnosis of diabetes, non-alcoholic steatohepatitis, or metabolic syndrome. Participants were randomly assigned (1:1) to groups that received FMT by capsules (induction dose of 30 capsules at week 4 and maintenance dose of 12 capsules at week 8) or placebo capsules. FMT capsules were derived from a single, lean donor (BMI, 17.5 kg/m2). Patients were followed through week 26; the primary outcome was safety. Stool and serum samples were collected from patients at baseline and at weeks 1, 4, 6, 8 and 12 after administration of the first dose of FMT or placebo and analyzed by 16S RNA gene sequencing. Stool and serum samples were analyzed for metabolomics by liquid chromatography-mass spectrometry. Additional outcomes were change in area under the curve for GLP1 at week 12.ResultsWe observed no significant differences in adverse events between patients who received FMT vs placebo. There was no increase in the area under the curve of GLP1 in either group. Patients who received FMT had sustained shifts in microbiomes associated with obesity toward those of the donor (P<.001). Patients who received FMT had a sustained decrease in stool levels of taurocholic acid (P<.05), compared with baseline; bile acid profiles began to more closely resemble those of the donor. We did not observe significant changes in mean BMI at week 12 in either group.ConclusionsIn a placebo-controlled pilot study, we found that FMT capsules (derived from a lean donor) were safe but did not reduce BMI in obese metabol
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.
Forlano R, Mullish BH, Nathwani R, et al., 2019, Non-alcoholic fatty liver disease and vascular disease, Current Vascular Pharmacology, ISSN: 1570-1611
Non-Alcoholic Fatty Liver Disease (NAFLD) represents an increasing cause of liver disease worldwide. However, notably, the primary cause of morbidity and mortality in patients with NAFLD is cardiovascular disease (CVD), with fibrosis stage being the strongest disease-specific predictor. It is globally-projected that NAFLD will become increasingly prevalent, especially among children and younger adults. As such, even within the next few years, NAFLD will contribute considerably to the overall CVD burden. In this review, we discuss the role of NAFLD as an emerging risk factor for CVD. In particular, this article aims to provide an overview of pathological drivers of vascular damage in patients with NAFLD. Moreover, the impact of NAFLD on the development, severity and the progression of subclinical and clinical CVD will be discussed. Finally, the review illustrates current and potential future perspectives for screening for CVD in this high-risk population.
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
Nathwani R, Mullish BH, Kockerling D, et al., 2019, Recurrent bacteraemia following variceal haemorrhage, Gut, ISSN: 0017-5749
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
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
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
McSweeney B, Allegretti JR, Fischer M, et al., 2019, In search of stool donors: a multicentre study of prior knowledge, perceptions, motivators and deterrents among potential donors for fecal microbiota transplantation, Gut Microbes, ISSN: 1949-0984
Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.
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
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
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
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
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