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The networks of human gut microbe-metabolite associations are different between health and irritable bowel syndrome.

ABSTRACT: The goal of this study was to determine if fecal metabolite and microbiota profiles can serve as biomarkers of human intestinal diseases, and to uncover possible gut microbe-metabolite associations. We employed proton nuclear magnetic resonance to measure fecal metabolites of healthy children and those diagnosed with diarrhea-predominant irritable bowel syndrome (IBS-D). Metabolite levels were associated with fecal microbial abundances. Using several ordination techniques, healthy and irritable bowel syndrome (IBS) samples could be distinguished based on the metabolite profiles of fecal samples, and such partitioning was congruent with the microbiota-based sample separation. Measurements of individual metabolites indicated that the intestinal environment in IBS-D was characterized by increased proteolysis, incomplete anaerobic fermentation and possible change in methane production. By correlating metabolite levels with abundances of microbial genera, a number of statistically significant metabolite-genus associations were detected in stools of healthy children. No such associations were evident for IBS children. This finding complemented the previously observed reduction in the number of microbe-microbe associations in the distal gut of the same cohort of IBS-D children.

SUBMITTER: Shankar V

PROVIDER: S-EPMC4511929 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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The networks of human gut microbe-metabolite associations are different between health and irritable bowel syndrome.

Shankar Vijay V Homer Daniel D Rigsbee Laura L Khamis Harry J HJ Michail Sonia S Raymer Michael M Reo Nicholas V NV Paliy Oleg O

The ISME journal 20150130 8

The goal of this study was to determine if fecal metabolite and microbiota profiles can serve as biomarkers of human intestinal diseases, and to uncover possible gut microbe-metabolite associations. We employed proton nuclear magnetic resonance to measure fecal metabolites of healthy children and those diagnosed with diarrhea-predominant irritable bowel syndrome (IBS-D). Metabolite levels were associated with fecal microbial abundances. Using several ordination techniques, healthy and irritable ...[more]

PMID: 25635640

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Project description:BackgroundModifiable factors were found to be associated with the risk of irritable bowel syndrome (IBS) in observational studies, but whether these associations are causal is uncertain. We conducted a Mendelian randomization (MR) study to systematically explore the causal associations of modifiable factors with IBS.MethodsSummary-level statistical data for IBS was obtained from a genome-wide association study (GWAS) meta-analysis of UK Biobank (40,548 cases and 293,220 controls) and the international collaborative Bellygenes initiative (12,852 cases and 139,981 controls). Genetic instruments associated with the exposures at the genome-wide significance (p < 5 × 10-8) level were selected from previous GWASs. Mendelian randomization was performed using inverse-variance weighted (IVW) method, supplemented with several sensitivity analyses to evaluate potentially causal relationships between identified contributing factors and IBS. Furthermore, we applied another database from FinnGen (8,116 IBS cases and 276,683 controls) to testify the reliability of the significant associations.ResultsSeven convincing modifiable factors were significantly associated with IBS after correction for multiple testing. Genetically predicted smoking initiation (OR = 1.12, 95% CI = 1.06-1.18, p = 1.03 × 10-4), alcohol consumption (OR = 0.47, 95% CI = 0.34-0.64, p = 3.49 × 10-6), sedentary behavior (OR = 1.17, 95% CI = 1.07-1.28, p = 4.02 × 10-4), chronotype (OR = 0.92, 95% CI = 0.88-0.96, p = 4.42 × 10-4), insomnia (OR = 1.19, 95% CI = 1.15-1.24, p = 7.59 × 10-19), education (OR = 0.80, 95% CI = 0.74-0.88, p = 5.34 × 10-7), and visceral adiposity (OR = 1.15, 95% CI = 1.06-1.24, p = 7.96 × 10-4). We additionally identified several suggestive factors, including serum magnesium, serum phosphorus, physical activity, lifetime smoking, intelligence, lean body mass, and body mass index (BMI). After pooling the effect estimates from FinnGen, the associations remained significant except for chronotype.ConclusionThis MR analysis verified several modifiable risk factors for IBS, thus prevention strategies for IBS should be considered from multiple perspectives on these risk factors.

Dataset Information

The networks of human gut microbe-metabolite associations are different between health and irritable bowel syndrome.

Publications

The networks of human gut microbe-metabolite associations are different between health and irritable bowel syndrome.

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