Abstract

INTRODUCTION There is large variation in response to diet in irritable bowel syndrome (IBS) and determinants for differential response are poorly understood. OBJECTIVES Our aim was to investigate differential clinical and molecular responses to provocation with fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) and gluten in individuals with IBS. METHODS Data were used from a crossover study with week-long interventions with either FODMAPs, gluten or placebo. The study also included a rapid provocation test. Molecular data consisted of fecal microbiota, short chain fatty acids, and untargeted plasma metabolomics. IBS symptoms were evaluated with the IBS severity scoring system. IBS symptoms were modelled against molecular and baseline questionnaire data, using Random Forest (RF; regression and clustering), Parallel Factor Analysis (PARAFAC), and univariate methods. RESULTS Regression and classification RF models were in general of low predictive power (Q2 ≤ 0.22, classification rate < 0.73). Out of 864 clustering models, only 2 had significant associations to clusters (0.69 < CR < 0.73, p < 0.05), but with no associations to baseline clinical measures. Similarly, PARAFAC revealed no clear association between metabolome data and IBS symptoms. CONCLUSION Differential IBS responses to FODMAPs or gluten exposures could not be explained from clinical and molecular data despite extensive exploration with different data analytical approaches. The trial is registered at www. CLINICALTRIALS gov as NCT03653689 31/08/2018.

Abstract

Probiotics are exploited for adjuvant treatment in IBS, but reliable guidance for selecting the appropriate probiotic to adopt for different forms of IBS is lacking. We aimed to identify markers for recognizing non-constipated (NC) IBS patients that may show significant clinical improvements upon treatment with the probiotic strain Lacticaseibacillus paracasei DG (LDG). To this purpose, we performed a post-hoc analysis of samples collected during a multicenter, double-blind, parallel-group, placebo-controlled trial in which NC-IBS patients were randomized to receive at least 24 billion CFU LDG or placebo capsules b.i.d. for 12 weeks. The primary clinical endpoint was the composite response based on improved abdominal pain and fecal type. The fecal microbiome and serum markers of intestinal (PV1 and zonulin), liver, and kidney functions were investigated. We found that responders (R) in the probiotic arm (25%) differed from non-responders (NR) based on the abundance of 18 bacterial taxa, including the families Coriobacteriaceae, Dorea spp. and Collinsella aerofaciens, which were overrepresented in R patients. These taxa also distinguished R (but not NR) patients from healthy controls. Probiotic intervention significantly reduced the abundance of these bacteria in R, but not in NR. Analogous results emerged for C. aerofaciens from the analysis of data from a previous trial on IBS with the same probiotic. Finally, C. aerofaciens was positively correlated with the plasmalemmal vesicle associated protein-1 (PV-1) and the markers of liver function. In conclusion, LDG is effective on NC-IBS patients with NC-IBS with a greater abundance of potential pathobionts. Among these, C. aerofaciens has emerged as a potential predictor of probiotic efficacy.

Abstract

BACKGROUND AND AIM Functional bowel disorders (FBDs), including irritable bowel syndrome (IBS) and others, are conditions without a physically identifiable etiology that, as a result, are difficult to treat. Alternatives to traditional medical interventions are needed because IBS patients require more of physician time and higher healthcare spending. The goal of this study was to determine the efficacy of alternative lifestyle interventions for patients with FBDs seen in an integrative medicine (IM) clinic at an academic medical center. METHODS We performed a retrospective chart review to determine whether patients with FBDs had improvement in symptoms following predominantly nutrition-based IM interventions that included recommendations for dietary supplements and elimination diets. We measured symptoms before and after intervention (average time between measurements 8.75 months) using a medical symptoms questionnaire (MSQ) commonly used to quantify symptom change in IM clinics. RESULTS Digestive tract symptoms, as measured by the MSQ, improved significantly in patients (n = 57) with FBDs following IM intervention. The MSQ Digestive Tract subtotal for FBD patients decreased from 10.2 (SD, 5.4) to 7.2 (SD, 5.2) (P < 0.001) after IM intervention. CONCLUSIONS Patients in an IM clinic had improved digestive tract symptoms scores following IM intervention. Because nutrition-based interventions were the primary intervention recommended by IM providers, primary care physicians and gastroenterologists may wish to consider referring FBD patients to registered dietitian-nutritionists (RDNs) skilled in implementing elimination diets.