Methane and fatty acid metabolism pathways are predictive of Low-FODMAP diet efficacy for patients with irritable bowel syndrome

Objective: Identification of microbiota-based biomarkers as predictors of low-FODMAP diet response and design of a diet recommendation strategy for IBS patients. Design: We created a compendium of gut microbiome and disease severity data before and after a lowFODMAP diet treatment from published studies followed by unified data processing, statistical analysis and predictive modeling. We employed data-driven methods that solely rely on the compendium data, as well as hypothesis-driven methods that focus on methane and short chain fatty acid (SCFA) metabolism pathways that were implicated in the disease etiology. Results: The patient's response to a low-FODMAP diet was predictable using their pre-diet fecal samples with F1 accuracy scores of 0.750 and 0.875 achieved through data-driven and hypothesis-driven predictors, respectively. The fecal microbiome of patients with high response had higher abundance of methane and SCFA metabolism pathways compared to patients with no response (p-values < 6 x 10(-3)). The genera Ruminococcus 1, Ruminococcaceae UCG-002 and Anaerostipes can be used as predictive biomarkers of diet response. Furthermore, the low-FODMAP diet followers were identifiable given their microbiome data (F1-score of 0.656). Conclusion: Our integrated data analysis results argue that there are two types of patients, those with high colonic methane and SCFA production, who will respond well on a low-FODMAP diet, and all others, who would benefit a dietary supplementation containing butyrate and propionate, as well as probiotics with SCFA-producing bacteria, such as lactobacillus. This work demonstrates how data integration can lead to novel discoveries and paves the way towards personalized diet recommendations for IBS. (C) 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.