Comparison of prebiotic candidates in ulcerative colitis using an in vitro fermentation model

Aims This study explored the effect of three different prebiotics, the human milk oligosaccharide (HMO) 2’-Fucosyllactose (2’-FL), an oligofructose-enriched inulin (fructo-oligosaccharide, or FOS), and a galacto-oligosaccaride (GOS) mixture, on the faecal microbiota from patients with ulcerative colitis (UC) using in vitro batch culture fermentation models. Changes in bacterial groups and short-chain fatty acid (SCFA) production were compared. Methods and Results In vitro, pH controlled batch culture fermentation was carried out over 48 hours on samples from three healthy controls and three patients with active UC. Four vessels were ran, one negative control and one for each of the prebiotic substrates. Bacterial enumeration was carried out using fluorescence in situ hybridisation with flow cytometry. SCFA quantification was performed using gas chromatography mass spectrometry. All substrates had a positive effect on the gut microbiota and led to significant increases in total SCFA and propionate concentrations at 48 hours. 2’-FL was the only substrate to significantly increase acetate and led to the greatest increase in total SCFA concentration at 48 hours. 2’-FL best suppressed Desulfovibrio spp., a pathogen associated with UC. Conclusions 2’FL, FOS and GOS all significantly improved the gut microbiota in this in vitro study and also led to increased SCFA

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery. Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines. Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015). Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD

Letters - NICE on refeeding syndrome - Attitudes to NICE guidance on refeeding syndrome

Any discussion on the risks of the refeeding syndrome should include the increased threat of infection that may often be silent in malnutrition.1 Malnourished patients may develop infection without showing the usual septic markers—such as an increased temperature, leucocyte count, or C reactive protein. We therefore advocate septic screening and a low threshold for broad spectrum antibiotic cover for any patients with unexplained hypothermia, hypoglycaemia, and evidence of malnutrition. Patients at high risk of the syndrome may also be at risk of acute renal failure, which may be missed as they have only slightly raised urea and creatinine measurements because of low muscle mass, leading to low production of these metabolites. When this occurs, renal dysfunction may hide low serum and total body electrolyte concentrations, and hence serum potassium, magnesium, and phosphate may be reassuringly normal or even high. They are at even greater risk of precipitate falls in these circulating electrolytes once simultaneous nutritional and fluid therapy has started

A review on the use of prebiotics in ulcerative colitis

The gut microbiome in the inflammatory bowel disease, ulcerative colitis (UC), is different to that of healthy controls. Patients with UC have relative reductions in abundance of Firmicutes and Bifidobacterium in the colon, and an increase in sulfate-reducing bacteria. Prebiotics are dietary substrates which are selectively metabolised by the human colonic microbiota to confer health benefits to the host. This review explores our current understanding of the potential benefits of prebiotics on various clinical, biochemical, and microbiological endpoints in UC, including new perspectives gained from recent studies in the field. This review looks to the future and highlights the need for appropriately designed trials to explore this potentially exciting new avenue for the treatment of UC

Unexpectedly high incidence of indigenous acute hepatitis E within South Hampshire: time for routine testing?

Hepatitis E indigenous to developed countries (hepatitis EIDC) is a form of hepatitis E in persons with no travel history to highly endemic areas. It has been recognized recently as an emerging clinical entity in a significant number of economically developed countries including UK. However, it is still perceived as a rare disease and routine laboratory testing for hepatitis E is not performed. A series of 13 cases of hepatitis EIDC, diagnosed in a 13-month period from June 2005 within a single center in South Hampshire, UK, is presented. These patients were identified after implementing a novel-screening algorithm that introduced routine hepatitis E serological investigations. Patients were middle aged or elderly and males were affected more commonly. Four patients (31%) required hospital admission. All reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed cases carried hepatitis E virus (HEV) genotype-3, which bore close sequence homology to HEV circulating in UK pigs. None of these patients recalled eating undercooked pork products or close contact with pigs during the 2 months preceding the onset of acute hepatitis. In comparison, during the same period, only two cases of hepatitis A and five cases of acute hepatitis B were diagnosed. These data illustrate the importance of introducing routine hepatitis E testing in all patients with unexplained acute liver disease and absence of relevant travel history. Routine testing can clarify hepatitis E epidemiology whilst improving the clinical management of patients with acute liver disease