Gut microbiota changes are related to intestinal permeability in adults under physiologic stress

Previous research has shown that chemical and physical stress are major influencers of the physiology and ecology of the all microbes that have coevolved with a host. However, the physiologic effects of gut microbiome responses to physiologic stress have been poorly studied in humans.

A recent study, led by Dr. Stefan Pasiakos from the Military Nutrition Division at the United States Army Research Institute of Environmental Medicine in Natick (Massachusetts, USA), has found that changes in gut microbiota composition and metabolic activity are related to intestinal permeability in adults undergoing military training, an environment of physiologic stress.

The researchers studied the effects of a multiple-stressor military training environment as a model of physiologic stress-including prolonged physical and psychological stress, sleep deprivation, and environmental extremes-on gut microbiota composition and metabolic activity and intestinal permeability (IP) in 73 Norwegian Army Soldiers (2 females) > 18 years of age. Soldiers were provided with 3 Norwegian rations/day with or without protein- or carbohydrate-based supplements (control group received 3 rations/day, n=18; carbohydrate group received 3 rations/day and 4 carbohydrate-based snack bars/day, n=27; protein group received 3 rations/day and 4 protein-based snack bars/day, n=28) during a 4-day cross-country ski march of a 51 km during which volunteers skied in 50:10 min per hour work-to-rest ratios while carrying a ~45 kg backpack (STRESS).

Dietary intake of each group can be found in the tables from the original paper. IP (assessed by quantifying the urinary excretion of orally ingested sucralose and mannitol), inflammatory biomarkers (assessed by plasma/serum lipopolysaccharide, serum high-sensitivity C-reactive protein and creatine kinase), stool microbiota composition, and stool and plasma metabolites were measured before and during the 4-day training exercise.

IP increased 62% during the 4-day training period, independent of diet group, and was correlated with increased plasma LPS and IL-6 inflammatory biomarkers. According to the authors, both altered intestinal barrier integrity and stress-induced muscle damage could potentially contribute to inflammation by inducing tight junction dysfunction.

Stool samples were collected over the 2 d prior to STRESS, and the night of or day after completing STRESS in a self-selected subset of volunteers. Of all 73 participants, 38 volunteers provided stool samples, 26 of whom provided both pre- and post-STRESS samples. In all diet groups gut microbiota diversity increased and was mainly characterized by an increase in abundances of less dominant taxa at the expense of more dominant taxa such as Bacteroides; this included an increased relative abundance of potentially deleterious and infectious bacteria from several taxa.

When focusing on gut microbiota metabolic activity, 23% of bacterial metabolites were significantly altered in stool after the 4-day training period. Several associations between stool microbiota composition, stool and plasma metabolites, intestinal permeability, and inflammation were reported. Among stool metabolites associated with changes in IP during military training were several amino acids and lipids and xenobiotics. Decreased concentrations of the metabolites arginine and cysteine were associated with increased IP.

In conclusion, these results demonstrate that a physical stressor such as in a military training environment may induce short-term increases in IP together with alterations in markers of inflammation, and with gut microbiota composition and metabolic function. Provided that such changes are persistent and of disease-relevant quantity and quality, these data open the future possibility of targeting the gut microbiota for preventing IP during periods of physiologic stress in adults.

Reference:

Karl JP, Margolis LM, Madslien EH, et al. Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiologic stress. Am J Physiol Gastrointest Liver Physiol. 2017; doi: 10.1152/ajpgi.00066.2017.