Publications
324 results found
Blanco JM, Danckert NP, Liu Z, et al., 2022, New links between psoriatic arthritis and the gut microbiome suggest a stronger role of the gut-joint axis, Digestive Disease Week® (DDW) 2022, Publisher: Elsevier, Pages: S456-S457, ISSN: 0016-5085
Blanco JM, Kragsnaes MS, Liu Z, et al., 2022, IMPACT ON GUT MICROBIAL METABOLITES FROM A 6-MONTH DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED TRIAL OF FECAL MICROBIOTA TRANSPLANTATION FOR ACTIVE PERIPHERAL PSORIATIC ARTHRITIS, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S829-S829, ISSN: 0016-5085
Alexander JL, Mullish BH, Danckert NP, et al., 2022, POOR RESPONSE TO ANTI-SARS-COV-2 VACCINATION IN IMMUNOSUPPRESSED INFLAMMATORY BOWEL DISEASE PATIENTS IS ASSOCIATED WITH ALTERED GUT MICROBIOTA FUNCTION, GASTROENTEROLOGY, Vol: 162, Pages: S653-S653, ISSN: 0016-5085
Habboub N, Forlano R, Goldin R, et al., 2022, EXAMINING THE CORRELATION OF HISTOLOGICAL FEATURES OF NAFLD WITH A POLYMETABOLIC RISK SCORE FOR PREDICTING PATIENTS WITH NAFLD, GASTROENTEROLOGY, Vol: 162, Pages: S1271-S1271, ISSN: 0016-5085
Paizs P, Mullish BH, Alexander JL, et al., 2022, INTESTINAL MICROBIOTA TRANSPLANT FOR RECURRENT <i>CLOSTRIODIOIDES</i> <i>DIFFICILE</i> INFECTION IS ASSOCIATED WITH RESTORATION OF MICROBIAL ARYLSULFATASES AND SULFATIDE DEGRADATION, GASTROENTEROLOGY, Vol: 162, Pages: S649-S649, ISSN: 0016-5085
Ghani R, Blanco JM, Forlano R, et al., 2022, RELATIVE CHANGE OF <i>ENTEROCOCCUS FAECIUM</i>, SELECTED COMMENSAL BACTERIA AND CYTOKINES ARE SEEN IN PATIENTS COLONIZED WITH MULTIDRUG-RESISTANT ORGANISMS WHO UNDERGO INTESTINAL MICROBIOTA TRANSPLANTATION, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S218-S219, ISSN: 0016-5085
Tarazi M, Jamel S, Mullish BH, et al., 2022, Impact of gastrointestinal surgery upon the gut microbiome: A systematic review, Surgery, Vol: 171, Pages: 1331-1340, ISSN: 0039-6060
Forlano R, Mullish BH, Martinez-Gili L, et al., 2022, Factors associated with increased gut permeability and severity of liver disease in diabetic patients with NAFLD, Digestive Disease Week® (DDW) 2022, Publisher: Elsevier, Pages: S1136-S1136, ISSN: 0016-5085
Ghani R, Mullish BH, Davies FJ, et al., 2022, How to adapt an intestinal microbiota transplantation programme to reduce the risk of invasive multidrug-resistant infection, Clinical Microbiology and Infection, Vol: 28, Pages: 502-512, ISSN: 1198-743X
Smith PJ, 2022, GI highlights from the literature, Gut, Vol: 71, Pages: 838-839, ISSN: 0017-5749
Mullish BH, Radhakrishnan ST, Gallagher KI, et al., 2022, Rectal swabs as a viable alternative to faecal sampling for the analysis of gut microbiota functionality and composition
<jats:title>Abstract</jats:title> <jats:p>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 is 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 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, <jats:italic>P</jats:italic> < 0.0001). Proton nuclear magnetic resonance (<jats:sup>1</jats:sup>H NMR) spectroscopy enabled the detection of 20 metabolites with good correlation between rectal swab and faecal samples for butyrate, succinate and 5-aminovalerate relative abundances, though more variable degrees of association for other identified metabolites. These data support the utility of rectal swabs in both compositional and functional analyses of the gut microbiota.</jats:p>
Forlano R, Mullish BH, Roberts LA, et al., 2022, The Intestinal Barrier and Its Dysfunction in Patients with Metabolic Diseases and Non-Alcoholic Fatty Liver Disease, International Journal of Molecular Sciences, Vol: 23, Pages: 662-662
<jats:p>Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease worldwide, mirroring the epidemics of obesity and metabolic syndrome. As there are still no licensed medications for treating the disease, there is an ongoing effort to elucidate the pathophysiology and to discover new treatment pathways. An increasing body of evidence has demonstrated a crosstalk between the gut and the liver, which plays a crucial role in the development and progression of liver disease. Among other intestinal factors, gut permeability represents an interesting factor at the interface of the gut–liver axis. In this narrative review, we summarise the evidence from human studies showing the association between increased gut permeability and NAFLD, as well as with type-2 diabetes and obesity. We also discuss the manipulation of the gut permeability as a potential therapeutical target in patients with NAFLD.</jats:p>
Nathwani R, Kockerling D, Mullish BH, et al., 2022, Non-selective beta-blocker use in cirrhosis: the additional benefit in preventing secondary infections, Frontline Gastroenterology, Vol: 13, Pages: 86-88, ISSN: 2041-4137
Biliński J, Winter K, Jasiński M, et al., 2022, Rapid resolution of COVID-19 after faecal microbiota transplantation., Gut, Vol: 71, Pages: 230-232
Radhakrishnan ST, Alexander JL, Mullish BH, et al., 2022, Systematic review: the association between the gut microbiota and medical therapies in inflammatory bowel disease, Alimentary Pharmacology & Therapeutics, Vol: 55, Pages: 26-48, ISSN: 0269-2813
<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with <jats:italic>Faecalibacterium prausnitizii</jats:italic> associated with protection, and certain genera (including <jats:italic>Shigella</jats:italic> and <jats:italic>Escherichia</jats:italic>) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype.</jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p>To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α‐diversity was observed in responders versus non‐responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline <jats:italic>Faecalibacterium</jats:italic> predicted response to infliximab and ustekinumab. A post‐treatment increase in <jats:italic>Faecalibacterium prausnitzii</jats:italic> was noted in responders to aminosalicylates, anti‐TNF medications and ustekinumab; conversely, this speci
Smith PJ, 2022, GI highlights from the literature, Gut, Vol: 71, Pages: 210-211, ISSN: 0017-5749
Lythgoe MP, Ghani R, Mullish BH, et al., 2022, The potential of fecal microbiota transplantation in oncology, Trends in Microbiology, Vol: 30, Pages: 10-12, ISSN: 0966-842X
Forlano R, Mullish BH, Dhar A, et al., 2021, Liver function tests and metabolic-associated fatty liver disease: Changes in upper normal limits, does it really matter?, World Journal of Hepatology, Vol: 13, Pages: 2104-2112, ISSN: 1948-5182
Biliński J, Jasiński M, Tomaszewska A, et al., 2021, Fecal microbiota transplantation with ruxolitinib as a treatment modality for steroid‐refractory/dependent acute, gastrointestinal graft‐versus‐host disease: A case series, American Journal of Hematology, Vol: 96, ISSN: 0361-8609
Monaghan TM, Duggal NA, Rosati E, et al., 2021, A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection, Cells, Vol: 10, Pages: 3234-3234
<jats:p>Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.</jats:p>
Moore-Gillon C, Suleiman S, Mullish BH, et al., 2021, Faecal microbiota transplant in the treatment of Clostridioides difficile infection: an update, European Medical Journal Gastroenterology, Vol: 10, Pages: 60-68, ISSN: 2054-6203
Clostridioides difficile infection (CDI) presents a major global healthcare challenge. Recurrent/refractory disease is particularly hard to manage, and novel therapeutic strategies have recently been adopted. In particular, within the past decade, faecal microbiota transplant (FMT) has rapidly progressed from a “potential” treatment option of fringe interest to one of the mainstays of therapy for recurrent/refractory C. difficile infection (rCDI). The first randomised study of its use for this indication was published as recently as 2013, but the emergence of subsequent randomised studies has led to its rapid adoption into guidelines and treatment algorithms. Very rare but serious reports of infection transmission from donor to recipient have resulted in ongoing refinements to donor screening, including the adoption of routine screening for intestinal carriage of multi-drug resistant bacteria and SARS-CoV-2 status. Developments in the evidence base have given new insights into optimal recipient selection and preparation. Upper and lower gastrointestinal administration of FMT slurry are both safe and effective in treating rCDI, although the newer option of capsulised FMT has recently grown in popularity; ‘next generation’ FMT products of defined microbial communities derived from donor stool are in late phase clinical trials, and may become licensed for use in the near future. While different regulatory structures for FMT use have been adopted in different countries, the development of international networks of FMT-interested specialists has helped to harmonise best practice.
Smith PJ, 2021, GI highlights from the literature, Gut, Vol: 70, Pages: 2205-2206, ISSN: 0017-5749
Forlano R, Harlow C, Mullish BH, et al., 2021, Binge‐eating disorder is associated with an unfavorable body mass composition in patients with non‐alcoholic fatty liver disease, International Journal of Eating Disorders, Vol: 54, Pages: 2025-2030, ISSN: 0276-3478
<jats:title>Abstract</jats:title><jats:p>The interaction between eating disorders and non‐alcoholic fatty liver disease (NAFLD) remains unexplored, especially with regards to binge‐eating disorder (BED). Our team conducted a service evaluation project in order to assess risk factors for the presence of BED among patients with NAFLD and the impact of BED on body mass composition. The overall prevalence of patients screening positive to BED Screener‐7 (BEDS‐7) was 28.4%, while a previous diagnosis of depression and marital status (as single or separated) were independently associated with positive BED. Furthermore, patients with positive BEDS‐7 had higher BMI, with greater visceral component and overall lower muscle mass. There was no difference in terms of liver disease severity as assessed by noninvasive markers of fibrosis. However, as body mass composition and sarcopenia have been shown to be associated to disease progression in patients with NAFLD, further studies are required to ascertain the long‐term impact of BED in these patients. Moreover, further work is warranted to identify to implement multidisciplinary approach within clinical psychology for the management of patients with BED, who may be particularly challenging in terms of achieving lifestyle modifications. As a hepatology community, we should address NAFLD with a more holistic approach.</jats:p>
Monaghan TM, Seekatz AM, Mullish BH, et al., 2021, Clostridioides difficile: innovations in target discovery and potential for therapeutic success., Expert Opin Ther Targets, Vol: 25, Pages: 949-963
INTRODUCTION: Clostridioides difficile infection (CDI) remains a worldwide clinical problem. Increased incidence of primary infection, occurrence of hypertoxigenic ribotypes, and more frequent occurrence of drug resistant, recurrent, and non-hospital CDI, emphasizes the urgent unmet need of discovering new therapeutic targets. AREAS COVERED: We searched PubMed and Web of Science databases for articles identifying novel therapeutic targets or treatments for C. difficile from 2001 to 2021. We present an updated review on current preclinical efforts on designing inhibitory compounds against these drug targets and indicate how these could become the focus of future therapeutic approaches. We also evaluate the increasing exploitability of gut microbial-derived metabolites and host-derived therapeutics targeting VEGF-A, immune targets and pathways, ion transporters, and microRNAs as anti-C. difficile therapeutics, which have yet to reach clinical trials. Our review also highlights the therapeutic potential of re-purposing currently available agents . We conclude by considering translational hurdles and possible strategies to mitigate these problems. EXPERT OPINION: Considerable progress has been made in the development of new anti-CDI drug candidates. Nevertheless, a greater comprehension of CDI pathogenesis and host-microbe interactions is beginning to uncover potential novel therapeutic targets, which can be exploited to plug gaps in the CDI drug discovery pipeline.
Izzi-Engbeaya C, Forlano R, Mullish BH, et al., 2021, Outcomes of postmenopausal women with non-alcoholic fatty liver disease (NAFLD), Publisher: Bioscientifica
Baunwall SMD, Terveer EM, Dahlerup JF, et al., 2021, The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey, The Lancet Regional Health - Europe, Vol: 9, Pages: 100181-100181, ISSN: 2666-7762
Nathwani R, Mullish BH, Kockerling D, et al., 2021, Review of rifaximin: a summary of the current evidence and its benefits beyond its licensed use, European Medical Journal, Vol: 6, Pages: 94-99, ISSN: 2397-6764
Antibiotic resistance in patients with cirrhosis continues to draw significant attention. With a propensity to frequent hospitalisations, cirrhotics are subject to frequent antibiotic prescription. This increases their risk of developing resistance to one or more antimicrobial agents, making management of their condition particularly challenging. Despite advancements being made in the management of liver disease, mortality rates continue to rise; almost fivefold in those under 65 years, whilst remaining the leading cause of death in those between the ages of 35-49 years. Urgent alternative therapeutic options to prevent disease progression and cirrhosis-associated complications are urgently required. Rifaximin is one such example, with its use in patients with cirrhosis demonstrating additional benefits beyond its current licensed use. Its current licensed use in the UK is for the prevention of hepatic encephalopathy and traveller’s diarrhoea; however, its use in the context of enteric-driven pathologies has been explored. Through rifaximin’s key central action as a broad-spectrum antimicrobial, it has the ability to modulate the gut-liver axis via removal of gut microbial products associated with the progression of cirrhosis and its sequalae. The benefits of rifaximin use continues to gather some momentum, given its non-absorbable nature and well tolerated side-effect profile, and these require consideration. With broad spectrum antimicrobial properties, its use may assist in overcoming the conundrum posed of antibiotic resistance amongst cirrhotics. This literature review discusses the chemical and antimicrobial properties of rifaximin, its licenced indication for use, and its reported benefits beyond this. We also consider concerns regarding rifaximin resistance.
Smith PJ, 2021, GI highlights from the literature, Gut, Vol: 70, Pages: 1795-1796, ISSN: 0017-5749
Innes AJ, Mullish BH, Ghani R, et al., 2021, Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation, Frontiers in Cellular and Infection Microbiology, Vol: 11
<jats:p>The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT). This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDRO group), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival was significantly higher in the FMT-MDRO group (70% <jats:italic>versus</jats:italic> 36% <jats:italic>p</jats:italic> = 0.044). Post-HCT, fewer FMT-MDRO patients required intensive care (0% <jats:italic>versus</jats:italic> 46%, <jats:italic>P</jats:italic> = 0.045) or experienced fever (0.29 <jats:italic>versus</jats:italic> 0.11 days, <jats:italic>P</jats:italic> = 0.027). Intestinal MDRO decolonization occurred in 25% of FMT-MDRO patients <jats:italic>versus</jats:italic> 11% non-FMT MDRO patients. Despite the significant differences and statistically comparable patient/transplant characteristics, as the sample size was small, a matched-pair analysis between both groups to non-MDRO colonized control cohorts (2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% <jats:italic>versus</jats:italic> 61.9% respectively, <jats:italic>p</jats:italic>=0.012), and higher non relapse mortality (NRM; 60.2% <jats:italic>versus</jats:italic> 16.7% respectively, <jats:italic>p</jats:italic>=0.009) than their paired non-MDRO-colonized cohort. Conversely, there was no difference in survival (70% <jats:italic>versus</jats:italic> 43.4%, <jats:ita
Allegretti JR, Kelly CR, Grinspan A, et al., 2021, Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent <i>C. difficile</i> Infection, Inflammatory Bowel Diseases, Vol: 27, Pages: 1371-1378, ISSN: 1078-0998
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement—all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Fifty patients enrolled in the study, among which 15 had Crohn’s disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn’s disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn’s disease patients (P = 0.04).</jats:p>
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