Inter-individual Variability in Gut Microbiota Composition Is Associated With Changes in the Fecal Metabolome of Individuals Consuming a Military Ration Diet

Abstract

ObjectivesThe fecal metabolome provides a functional readout of interactions between host, diet and the gut microbiota that may help identify gut microbiota-derived compounds associated with health outcomes. This study aimed to determine associations between inter-individual variability in gut microbiota composition, diet-induced changes in the fecal metabolome and gastrointestinal symptoms in adults consuming a diet consisting solely of military rations. MethodsSecondary analysis of a randomized-controlled trial in which 54 healthy adults (32 ± 14 yr, BMI 26 ± 3 kg/m2) were randomly assigned to consume their usual diet (Control) or a provided diet of Meal, Ready-to-Eat military rations (MRE) for 3wk. Fecal microbiota composition was measured by 16S rRNA sequencing and the fecal metabolome by untargeted UPLC-MS/MS at baseline and post-intervention. Self-reported gastrointestinal symptoms were measured weekly using the Irritable Bowel Severity Scoring System (IBSSS). ResultsPrincipal coordinates analysis of baseline gut microbiota composition separated MRE participants into two clusters determined primarily by ratio of Bacteroides to Prevotella (HIGH (n = 17) or LOW (n = 10)). Random Forest classification of changes in the fecal metabolome within Control, HIGH, and LOW produced error rates of 7%, 18% and 100%, respectively, suggesting a more discriminant metabolome response in HIGH than LOW. Between-group differences in 153 metabolites were detected by ANOVA (FDR <0.20). Among those, 39 identified and 20 unidentified metabolites demonstrated an association with the gut microbiota (HIGH vs. LOW, P < 0.05). Compounds within xenobiotic, peptide/amino acid, and lipid metabolism pathways comprised 29 of the microbiota-associated metabolites. Changes in microbiota-associated metabolites were not correlated with changes in IBSSS scores. ConclusionsChanges in the fecal metabolome of individuals consuming a short-term military ration diet are associated with inter-individual variability in gut microbiota composition, but changes in microbiota-associated fecal metabolites do not appear to impact gastrointestinal symptoms. Funding SourcesMilitary Operational Medicine Research Program. DisclaimerAuthors’ views do not reflect official DoD or Army policy.