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The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis. We conducted a multicentre, double-blind, randomised, placebo-controlled trial at three hospitals in Australia. We randomly allocated patients with active ulcerative colitis (Mayo score 4–10) in a 1:1 ratio, using a pre-established randomisation list, to either faecal microbiota transplantation or placebo colonoscopic infusion, followed by enemas 5 days per week for 8 weeks. Patients, treating clinicians, and other study staff were unaware of the assigned treatment. Faecal microbiota transplantation enemas were each derived from between three and seven unrelated donors. The primary outcome was steroid-free clinical remission with endoscopic remission or response (Mayo score ≤2, all subscores ≤1, and ≥1 point reduction in endoscopy subscore) at week 8. Analysis was by modified intention-to-treat and included all patients receiving one study dose. We performed 16S rRNA stool analysis to assess associated microbial changes. This trial is registered with ClinicalTrials.gov, number NCT01896635. The trial has ended; this report presents the final analysis. From November, 2013, to May, 2015, 85 patients were enrolled to our trial, of whom 42 were randomly assigned faecal microbiota transplantation and 43 were allocated placebo. One patient assigned faecal microbiota transplantation and three allocated placebo did not receive study treatment and were excluded from the analysis. The primary outcome was achieved in 11 (27%) of 41 patients allocated faecal microbiota transplantation versus three (8%) of 40 who were assigned placebo (risk ratio 3·6, 95% CI 1·1–11·9; p=0·021). Adverse events were reported by 32 (78%) of 41 patients allocated faecal microbiota transplantation and 33 (83%) of 40 who were assigned placebo; most were self-limiting gastrointestinal complaints, with no significant difference in number or type of adverse events between treatment groups. Serious adverse events occurred in two patients assigned faecal microbiota transplantation and in one allocated placebo. Microbial diversity increased with and persisted after faecal microbiota transplantation. Several bacterial taxa were associated with clinical outcome; in particular, the presence of Fusobacterium spp was associated with lack of remission. Intensive-dosing, multidonor, faecal microbiota transplantation induces clinical remission and endoscopic improvement in active ulcerative colitis and is associated with distinct microbial changes that relate to outcome. Faecal microbiota transplantation is, thus, a promising new therapeutic option for ulcerative colitis. Future work should focus on precisely defining the optimum treatment intensity and the role of donor–recipient matching based on microbial profiles. Broad Medical Research Program, Gastroenterological Society of Australia, Mount Sinai (New York) SUCCESS fund, University of New South Wales.

Abstract Background Emulsifiers are implicated in the pathogenesis of inflammatory bowel disease (IBD). Few studies have examined emulsifier intake in people with existing IBD. We aimed to describe the frequency of exposure to 6 selected emulsifiers in a contemporary cohort of people with IBD and compare intake with healthy controls (HCs). Methods Baseline food records from participants in an Australian prospective cohort study examining the microbiome of IBD patients and HCs were analyzed. Exposure to inflammatory emulsifiers polysorbate-80 (P80); carboxymethylcellulose (CMC); carrageenan; xanthan gum (XG); lecithin (soy and sunflower) and mono- and diglycerides of fatty acids (MDGs) were determined by examining ingredient lists. Frequency of emulsifier exposure between groups (IBD vs HC, Crohn’s disease [CD] vs ulcerative colitis [UC], IBD children vs adults, active disease vs remission) was examined after controlling for confounders. Results Records from 367 participants were analyzed (n = 176 IBD, of which there were 101 CD, 75 UC, and 191 HC patients). In total, 5022 unique food items were examined, with 18% containing 1 or more emulsifier of interest. Inflammatory bowel disease participants had significantly higher total daily emulsifier exposure compared with HCs (2.7 ± 1.8 vs 2.3 ± 1.6, P = .02). In IBD participants, emulsifiers with the highest daily exposure were MDGs (1.2 ± 0.93), lecithin (0.85 ± 0.93), and XG (0.38 ± 0.42). There were no recorded exposures to P80. Conclusions Inflammatory bowel disease participants were exposed to more emulsifiers than HCs. Intake of inflammatory emulsifiers were low or nonexistent, suggesting their presence in the food supply are not as common as frequently stated. Graphical Abstract Graphical Abstract

Current inflammatory bowel disease (IBD) treatments including non-biological, biological, and nutritional therapies aim to achieve remission and mucosal healing. Treatment efficacy, however, is highly variable, and there is growing evidence that the gut microbiota influences therapeutic efficacy. The aim of this study was to conduct a systematic review and meta-analysis to define changes in the gut microbiota following IBD treatment and to identify microbial predictors of treatment response. A systematic search using MEDLINE/Embase and PubMed was performed in July 2022. The review was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Studies were included if they reported longitudinal microbiota analysis (>2 weeks) using next-generation sequencing or high-throughput sequencing of faecal/mucosal samples from IBD patients commencing treatment. Meta-analysis on alpha-diversity changes following infliximab treatment was conducted. Thirty-nine studies met the inclusion criteria, and four studies were included in the meta-analysis. An increase in alpha diversity was observed following treatment with 5-aminosalicylates, corticosteroids, and biological therapies in most studies. Characteristic signatures involving the enrichment of short-chain-fatty-acid-producing bacteria including Faecalibacterium prausnitzii and a reduction of pathogenic bacteria including various Proteobacteria were demonstrated following treatment with specific signatures identified based on treatment outcome. The meta-analysis demonstrated a statistically significant increase in bacterial richness following infliximab treatment (standardised mean difference −1.16 (−1.50, −0.83), p < 0.00001). Conclusion: Distinct microbial signatures are seen following treatment and are associated with treatment response. The interrogation of large longitudinal studies is needed to establish the link between the gut microbiota and IBD therapeutic outcomes.

Background and aims Management of inflammatory bowel disease is constantly evolving, increasing the importance for gastroenterologists to keep up to date with guidelines. Traditional implementation strategies have had only small positive impacts on clinical practice. eHealth strategies such as the European Crohn’s and Colitis Organisation e-guide may be beneficial for clinician decision making in keeping with guidelines. The aim of this study was to evaluate the feasibility and acceptability of the e-guide. Methods A mixed methods approach was used to evaluate feasibility and acceptability. Cognitive (think-aloud) interviews were conducted with Australian gastroenterologists while using the e-guide. Two clinical scenarios were developed to allow evaluation of various aspects of the e-guide. Content analysis was applied to the qualitative interview data and descriptive analysis to the quantitative and observational data. Results Seventeen participants completed the study. Data saturation were reached. The ECCO e-guide was largely feasible and acceptable, as demonstrated by most clinical questions answered correctly, 87% reaching the answer within 3 min, and most feeling it was useful, would be beneficial to their practice and would use it again. Issues raised included difficulties with website navigation, layout of the e-guide and difficulties with access (network firewalls, paid subscription required). Conclusions The ECCO e-guide is largely acceptable and feasible for gastroenterologists to use. Aspects of the e-guide could be modified to improve user experience. This study highlights the importance of engaging end-users in the development and evaluation of clinician educational tools.

OBJECTIVE. The goal of the evidence review was to evaluate the effectiveness of interventions for caregivers of people with Alzheimer’s disease and related major neurocognitive disorders that facilitate the ability to maintain participation in the caregiver role. METHOD. Scientific literature published in English between January 2006 and April 2014 was reviewed. Databases included MEDLINE, PsycINFO, CINAHL, OTseeker, and the Cochrane Database of Systematic Reviews. RESULTS. Of 2,476 records screened, 43 studies met inclusion criteria. Strong evidence shows that multicomponent psychoeducational interventions improve caregiver quality of life (QOL), confidence, and self-efficacy and reduce burden; cognitive reframing reduces caregiver anxiety, depression, and stress; communication skills training improves caregiver skill and QOL in persons with dementia; mindfulness-based training improves caregiver mental health and reduces stress and burden; and professionally led support groups enhance caregiver QOL. CONCLUSION. Strong evidence exists for a spectrum of caregiver interventions. Translation of effective interventions into practice and evaluation of sustainability is necessary.

Abstract Mirroring the global obesity epidemic, obesity rates in inflammatory bowel disease (IBD) patients is rising. Several epidemiological studies propose that 15%-40% of adult patients with IBD are obese, and an additional 25%-40% fall into the overweight category. This article examines the pathophysiologic relationship between obesity and IBD concerning the role of visceral adipose tissue, microbiota shifts, dietary patterns, and hunger hormone changes. Additionally, increasing evidence is demonstrating the negative impact that obesity is having on disease course and quality of life in patients with IBD. Obesity has been demonstrated to be associated with an attenuated response to immunomodulators and biological agents, as well as higher rates of peri-operative surgical complications. A better understanding of the relationship between obesity and IBD can be applied to clinical decision-making in personalizing treatment plans, promoting weight loss in patients with obesity, and identifying areas of future research. Lay Summary Recent trends reveal increasing rates of obesity in IBD patients, affecting disease management. This article explores links between obesity and IBD, including visceral fat, microbiota shifts, diet, and hormones. Understanding this relationship is crucial for personalising treatment and improving outcomes.

Emergency response relies on the assumption that essential health care services will continue to operate and be available to provide quality patient care during and after a patient surge. The observed successes and failures of health care systems during recent mass-casualty events and the concern that these assumptions are not evidence based prompted this review. The aims of this systematic review were to explore the factors associated with the intention of health care personnel (HCP) to respond to uncommon events, such as a natural disaster or pandemic, determine the state of the science, and bolster evidence-based measures that have been shown to facilitate staff response. Authors of the 70 studies (five mixed-methods, 49 quantitative, 16 qualitative) that met inclusion criteria reported a variety of variables that influenced the intent of HCP to respond. Current evidence suggests that four primary factors emerged as either facilitating or hindering the willingness of HCP to respond to an event: (1) the nature of the event; (2) competing obligations; (3) the work environment and climate; and (4) the relationship between knowledge and perceptions of efficacy. Findings of this study could influence and strengthen policy making by emergency response planners, staffing coordinators, health educators, and health system administrators.