Randomized controlled pilot study assessing fructose tolerance during fructose reintroduction in non-constipated irritable bowel syndrome patients successfully treated with a low FODMAP diet.

BACKGROUND: Limited data exist to guide FODMAP (fermentable oligo-, di-, monosaccharides, and polyols) reintroduction to assess tolerance following a low FODMAP diet (LFD). Fructose reintroduction is often stepwise up to 7.5 g fructose (e.g., three tsp of honey). We aimed to determine the fructose tolerance threshold in non-constipated, LFD-responsive patients with irritable bowel syndrome (IBS) and assess whether stool microbiome predicted LFD response or fructose tolerance. METHODS: Thirty-nine non-constipated IBS patients (51% women, mean age 33.7 years) completed a 4-week LFD. LFD responders were defined as those who reported adequate relief of IBS symptoms following the LFD. Responders were randomized to one of the three solution groups (100% fructose, 56% fructose/44% glucose, or 100% glucose) and received four doses (2.5, 5, 10, 15 g) for 3 days each. Patients reached their tolerance dose if their mean daily IBS symptom severity (visual analog scale [VAS], 0-100 mm) was >20 mm higher than post-LFD VAS. Stool samples before and after LFD were analyzed using shotgun metagenomics. RESULTS: Seventy-nine percent of patients were LFD responders. Most responders tolerated the 15 g sugar dose. There was no significant difference in mean dose tolerated between solution groups (p = 0.56). Compared to baseline, microbiome composition (beta diversity) significantly shifted and six bacterial genes in fructose and mannose metabolism pathways decreased after LFD, irrespective of LFD response or the solution group. CONCLUSIONS: Non-constipated, LFD-responsive IBS patients should be reintroduced to fructose in higher doses than 15 g to assess tolerance. LFD is associated with significant changes in microbial composition and bacterial genes involved in FODMAP metabolism.

Risk Factors for Abdominal Pain-Related Disorders of Gut-Brain Interaction in Adults and Children: A Systematic Review.

BACKGROUND & AIMS: Many studies have assessed risk factors of irritable bowel syndrome (IBS) and other abdominal pain-related disorders of gut-brain interaction (AP-DGBI); however, the role of these factors is unclear due to heterogeneous study designs. The aim of this systematic review was to extensively evaluate the literature and determine clinical risk and protective factors for the presence and persistence of AP-DGBI in children and adults. METHODS: A PubMed search identified studies investigating potential risk and protective factors for AP-DGBI in adults and children. Inclusion criteria included fully published studies with a control group; exclusion criteria included poor-quality studies (using a validated scale). For each factor, the proportion of studies that found the factor to be a risk factor, protective factor, or neither was summarized. The number of studies, diagnostic criteria, number of subjects, and average study quality rating provided further context. Whenever possible, a meta-analysis generated pooled odds ratios or mean difference. RESULTS: The systematic review included 348 studies. Female sex, gastroenteritis, abuse, stress, psychological disorders, somatic symptoms, and poor sleep were consistent risk factors for developing AP-DGBI in adults and children. In adults, additional risk factors included obesity, smoking, and increased use of medical resources. Protective AP-DGBI factors in adults included social support and optimism; no studies for protective factors were found for children. CONCLUSIONS: There are multiple risk factors for AP-DGBI in adults and children. These include female sex, gastroenteritis, abuse, stress, poor sleep, obesity, psychological disorders, and somatic symptoms. Additional studies are needed in children, on protective factors, and on factors associated with persistence of AP-DGBI.

Systematic review and meta-analysis of the 2010 ASGE non-invasive predictors of choledocholithiasis and comparison to the 2019 ASGE predictors.

In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) guideline on the endoscopic management of choledocholithiasis modified the individual predictors of choledocholithiasis proposed in the widely referenced 2010 guideline to improve predictive performance. Nevertheless, the primary literature, especially for the 2019 iteration, is limited. We performed a systematic review with meta-analysis to examine the diagnostic performance of the 2010, and where possible the 2019, predictors. PROSPERO protocol CRD42020194226. A comprehensive literature search from 2001 to 2020 was performed to identify studies on the diagnostic performance of any of the 2010 and 2019 ASGE choledocholithiasis predictors. Identified studies underwent keyword screening, abstract review, and full-text review. The primary outcomes included multivariate odds ratios (ORs) and 95% confidence intervals for each criterion. Secondary outcomes were reported sensitivities, specificities, and positive and negative predictive value. A total of 20 studies met inclusion criteria. Based on reported ORs, of the 2010 guideline "very strong" predictors, ultrasound with stone had the strongest performance. Of the "strong" predictors, CBD > 6 mm demonstrated the strongest performance. "Moderate" predictors had inconsistent and/or weak performance; moreover, all studies reported gallstone pancreatitis as non-predictive of choledocholithiasis. Only one study examined the new predictor (bilirubin > 4 mg/dL and CBD > 6 mm) proposed in the 2019 guideline. Based on this review, aside from CBD stone on ultrasound, there is discordance between the proposed strength of 2010 choledocholithiasis predictors and their published diagnostic performance. The 2019 guideline appears to do away with the weakest 2010 predictors.