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The low-FODMAP diet (LFD) has become almost synonymous with IBS care, yet the challenges associated with this rigorous therapeutic approach are often underacknowledged. Despite positive outcomes in RCTs, comparator groups frequently exhibit substantial response rates, raising questions about the definition of 'response'. Whilst the assessment of response in drug trials has evolved to utilize the more stringent FDA/EMA primary clinical endpoints, trials of the LFD have not yet followed. The aim of this article is to opine whether the current approach to the measurement of clinical response to the LFD in clinical trials should be reconsidered. A comprehensive literature review of LFD clinical trials from the past decade was conducted, focusing on recorded response metrics for primary clinical endpoints. While response definitions vary, the 50-point IBS-SSS delta emerged as the predominant metric. Notably, no trials to date have adopted the more stringent primary clinical endpoints used in drug trials. Other response measures included binary response metrics (such as 'adequate clinical response'), changes in visual analogue scales or stool form/output, reductions in abdominal pain, as well as changes the magnitude of the IBS-SSS delta. Whether these metrics correspond to a clinically meaningful improvement for the patient is less clear, and as such aligning patient-clinician expectations can be challenging. A paradigm shift in the conceptualization of 'response' coupled with an emphasis on harder clinical endpoints in the context of clinical trials may serve to better justify the trade-off between symptom-improvement and the inherent challenges associated with this burdensome therapeutic approach. [ABSTRACT FROM AUTHOR]

Abstract Background Real-life data on vedolizumab effectiveness in inflammatory bowel disease (IBD) are still emerging. Data on the comparative safety of the gut selective profile are of particular interest. Aims To assess clinical outcome and safety in IBD patients treated with vedolizumab. Methods We retrospectively collected data of patients treated with vedolizumab at eight UK hospitals (August 2014–January 2018). Clinical response and remission at 14 and 52 weeks evaluated through Physician Global Assessment (PGA) and adverse events were recorded. Possible predictors of clinical response were examined. Results Two hundred and three IBD patients (mean treatment 16 ± 8 months) were included. Of these, 135 patients (mean age 40.6 ± 16.0 years; F:M 1.9:1) had CD and 68 (mean age 44.5 ± 18.1 years; F:M 1:1.2) had UC. According to PGA, 106/135 (78.5%) CD and 62/68 (91.2%) UC patients (p = 0.02) had a clinical response/remission at 14 weeks, whereas 76/119 (63.9%) CD and 52/63 (82.5%) UC patients (p < 0.01) showed a sustained response or remission at 52 weeks, with a high adherence rate (97%). No predictors of clinical response were found. The cumulative incidence of infectious diseases was 11.9 per 100 person-years. Conclusion Vedolizumab is an effective therapy for inducing and maintaining remission of IBD, with better results for UC, and with a good safety profile. [ABSTRACT FROM AUTHOR]

Background & Aims Dietary interventions are effective in management of patients with irritable bowel syndrome (IBS), although responses vary. We investigated whether fecal levels of volatile organic compounds (VOCs) associate with response to dietary interventions in patients with IBS. Methods Adults who fulfilled the Rome III criteria for IBS were recruited to a 2x2 factorial randomized controlled trial. Patients were randomly assigned to a group counselled to follow a diet low in fructans, galacto-oligosaccharides, lactose, fructose, and polyols (low-FODMAP diet, n = 46) or a group that received placebo dietary advice (sham diet, n = 47) for 4 weeks. Patients from each group were also given either a multi-strain probiotic or placebo supplement. Response was defined as a reduction of 50 points or more on the validated IBS symptom scoring system. Fecal samples were collected from participants at baseline and end of the 4-week study period; VOCs were analyzed by a gas-chromatography sensor device. VOC profiles were determined using a pipeline involving wavelet transformation followed by feature selection based on random forest. A partial least squares classifier was constructed to classify VOC profiles by response and accuracies were determined using 10-fold cross-validation. Results Data from 93 patients who completed the study (63 female) were used in the final analysis. More patients responded to the low-FODMAP diet (37/46, 80%) than the sham diet (21/47, 45%) ( P < .001), but there was no difference in response between patients given the probiotic (31/49, 63%) vs the placebo (27/44, 61%) ( P = .850), with no interaction between the diet and supplement interventions. At baseline, VOC profiles contained 15 features that classified response to the low-FODMAP diet with a mean accuracy of 97% (95% CI, 96%–99%) and 10 features that classified response to probiotic with a mean accuracy of 89% (95% CI, 86%–92%). End of treatment models achieved similar predictive powers and accuracies. Conclusion Fecal VOC profiling is a low cost, non-invasive tool that might be used to predict responses of patients with IBS to low-FODMAP diet and probiotics and identify their mechanisms of action. ISRCTN registry no: 02275221. [ABSTRACT FROM AUTHOR]

Background & Aims: The histopathology of nonalcoholic fatty liver disease (NAFLD) is similar to that of alcoholic liver disease. Colonic bacteria are a source of many metabolic products, including ethanol and other volatile organic compounds (VOC) that may have toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein. Recent data suggest that the composition of the gut microbiota in obese human beings is different from that of healthy-weight individuals. The aim of this study was to compare the colonic microbiome and VOC metabolome of obese NAFLD patients (n = 30) with healthy controls (n = 30). Methods: Multitag pyrosequencing was used to characterize the fecal microbiota. Fecal VOC profiles were measured by gas chromatography–mass spectrometry. Results: There were statistically significant differences in liver biochemistry and metabolic parameters in NAFLD. Deep sequencing of the fecal microbiome revealed over-representation of Lactobacillus species and selected members of phylum Firmicutes (Lachnospiraceae; genera, Dorea, Robinsoniella, and Roseburia) in NAFLD patients, which was statistically significant. One member of phylum Firmicutes was under-represented significantly in the fecal microbiome of NAFLD patients (Ruminococcaceae; genus, Oscillibacter). Fecal VOC profiles of the 2 patient groups were different, with a significant increase in fecal ester compounds observed in NAFLD patients. Conclusions: A significant increase in fecal ester VOC is associated with compositional shifts in the microbiome of obese NAFLD patients. These novel bacterial metabolomic and metagenomic factors are implicated in the etiology and complications of obesity. [Copyright &y& Elsevier]

Background: Gut fungal composition and its metabolites have not been assessed simultaneously in Parkinson's disease (PD) despite their potential pathogenic contribution.Objective: To evaluate the faecal metabolome and mycobiome in PD by assessing volatile organic compounds (VOCs) and fungal rRNA.Methods: Faecal VOCs from 35 PD patients and two control groups (n = 35; n = 15) were assessed using gas chromatography and mass spectrometry. DNA was extracted from 44 samples: 18S rRNA gene amplicons were prepared and sequenced. Metabolomics, mycobiome and integrated analyses were performed.Results: Several VOCs were more abundant and short chain fatty acids were less abundant in PD. Hanseniaspora, Kazachstania, uncultured Tremellaceae and Penicillium genera were more abundant, and Saccharomyces less abundant in PD (FDR<0.0007). Torulaspora was associated with PD and two VOCs.Conclusion: PD patients had a distinct metabolome and mycobiome suggesting that fungal dysbiosis may contribute to PD pathogenesis. [ABSTRACT FROM AUTHOR]

Adverse drug reactions affecting the gastrointestinal (GI) tract are a serious burden on patients, healthcare providers and the pharmaceutical industry. GI toxicity encompasses a range of pathologies in different parts of the GI tract. However, to date no specific mechanistic diagnostic/prognostic biomarkers or translatable pre-clinical models of GI toxicity exist. This review will cover the current knowledge of GI ADRs, existing biomarkers and models with potential application for toxicity screening/monitoring. We focus on the current gaps in our knowledge, the potential opportunities and recommend that a systematic approach is needed to identify mechanism-based GI biomarkers with potential for clinical translation. [ABSTRACT FROM AUTHOR]

Abstract: This study set out to validate the Hs27 ReadyCell assay (RCCNA) as an alternative CCNA method compared against a commonly used commercial enzyme immunoassay (EIA) method and toxigenic culture (TC) reference standard. A total of 860 samples were identified from those submitted to the Health Protection Agency microbiology laboratories over a 30-week period. RCCNA performed much better than EIA when using TC as a gold standard, with sensitivities of 90.8% versus 78.6% and positive predictive value of 87.3% to 81.9%, respectively. The Hs27 Human Foreskin Fibroblast ReadyCells are an easy-to-use and a sensitive CCNA method for the detection of toxigenic Clostridium difficile directly from stool. A turnaround time of up to 48 h for a negative result and possible need for repeat testing make it an unsuitable method to be used in most clinical laboratory setting. [Copyright &y& Elsevier]