High Energy Expenditure and Negative Energy Balance Modulate Composition and Metabolism of the Gut Microbiota
Authors: Karl J. Philip , Margolis Lee M. , Murphy Nancy E. , Martini Svein , Gundersen Yngvar , Castellani John W. , Carrigan Christopher T. , Teien Hilde K. , Madsilen Elisabeth H. , Chakraborty Nabarun , Kumar Raina , Hoke Allison , Gautam Aarti , Hammamieh Rasha , Montain Scott J. , Pasiakos Stefan M. 
Published: June 2021

Dietary intake and acute physiologic stress may modulate health in part by influencing interactions between the gut microbiome and host, but these relationships remain poorly characterized. This study explored relationships between gut microbiota composition and activity, and diet, gastrointestinal permeability and inflammation in Soldiers participating in a 4‐d, 51 km cross‐country ski march (SKI) characterized by high energy expenditure (6155 ± 515 kcal/d) and negative energy balance (2.7 ± 1.2 kg weight loss). During SKI, 73 Soldiers (20 ± 1 yr, BMI 23 ± 2 kg/m2) were provided 3 combat rations/d, or 3 rations/d supplemented with 1000 kcal/d from protein‐ or carbohydrate‐based snacks generating variability in energy, protein and carbohydrate intakes. Stool, blood and urine samples were collected from 26 Soldiers before and after SKI. Stool was analyzed for bacterial composition by 16S rDNA sequencing, and global metabolite profiling by UPLC‐MS/MS. Gastrointestinal permeability was assessed by dual sugar absorption test, and plasma lipopolysaccharide (LPS) and serum IL‐6 were measured as markers of microbial translocation and inflammation, respectively. Ordination, cluster and classification analyses of gut microbiota composition data indicated a pronounced alteration of gut microbiota composition during SKI independent of diet group. This effect was characterized by a more heterogeneous distribution of taxa abundances within samples following SKI (Shannon index, P = 0.04), and changes in the relative abundance of >50% of identified genera (Q < 0.10). Changes included increases in the relative abundance of several potentially deleterious and infectious genera, and decreases in the relative abundance of several genera thought to deter pathogen invasion, reduce inflammation and promote immunity. Prediction models linked changes in gut microbiota composition to 69 of 299 metabolites that were significantly altered in stool, with decreases in amino acid and nucleotide metabolites comprising the majority. Univariate analyses generally did not detect associations between changes in taxa relative abundance or concentrations of bacterially‐associated metabolites and energy or macronutrient intake, changes in gastrointestinal permeability, or changes in LPS and IL‐6 concentrations. These findings demonstrate pronounced changes in gut microbiota composition and metabolism in response to a multi‐stressor environment that appear to be independent of energy and macronutrient intakes within the ranges studied. The implications for health remain to be determined. The views expressed in this abstract are those of the authors and do not reflect official policy of the Dept. of Army, Dept. of Defense, or US Government.Support or Funding InformationFunded by US Army Medical Research and Material Command, the US Defense Health Program, and the Norwegian Defense Research Establishment agreement NO. W81XWH‐12‐0279.