Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress.
The magnitude, temporal dynamics, and physiological effects of intestinal microbiome responses to physiological stress are poorly characterized. This study used a systems biology approach and a multiple-stressor military training environment to determine the effects of physiological stress on intestinal microbiota composition and metabolic activity, as well as intestinal permeability (IP). Soldiers (n= 73) were provided three rations per day with or without protein- or carbohydrate-based supplements during a 4-day cross-country ski-march (STRESS). IP was measured before and during STRESS. Blood and stool samples were collected before and after STRESS to measure inflammation, stool microbiota, and stool and plasma global metabolite profiles. IP increased 62 ± 57% (mean ± SD,P< 0.001) during STRESS independent of diet group and was associated with increased inflammation. Intestinal microbiota responses were characterized by increased α-diversity and changes in the relative abundance of >50% of identified genera, including increased abundance of less dominant taxa at the expense of more dominant taxa such asBacteroidesChanges in intestinal microbiota composition were linked to 23% of metabolites that were significantly altered in stool after STRESS. Together, pre-STRESS Actinobacteria relative abundance and changes in serum IL-6 and stool cysteine concentrations accounted for 84% of the variability in the change in IP. Findings demonstrate that a multiple-stressor military training environment induced increases in IP that were associated with alterations in markers of inflammation and with intestinal microbiota composition and metabolism. Associations between IP, the pre-STRESS microbiota, and microbiota metabolites suggest that targeting the intestinal microbiota could provide novel strategies for preserving IP during physiological stress.NEW & NOTEWORTHYMilitary training, a unique model for studying temporal dynamics of intestinal barrier and intestinal microbiota responses to stress, resulted in increased intestinal permeability concomitant with changes in intestinal microbiota composition and metabolism. Prestress intestinal microbiota composition and changes in fecal concentrations of metabolites linked to the microbiota were associated with increased intestinal permeability. Findings suggest that targeting the intestinal microbiota could provide novel strategies for mitigating increases in intestinal permeability during stress.
Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, Massachusetts; james.p.karl.civ@mail.mil.
J Philip
JP
Karl
Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, Massachusetts.
Lee M
LM
Margolis
Norwegian Defense Research Establishment, Kjeller, Norway.
Elisabeth H
EH
Madslien
Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, Massachusetts.
Nancy E
NE
Murphy
Thermal and Mountain Medicine Division, United States Army Research Institute of Environmental Medicine, Natick, Massachusetts.
John W
JW
Castellani
Norwegian Defense Research Establishment, Kjeller, Norway.
Yngvar
Y
Gundersen
United States Army Center for Environmental Health Research, Fort Detrick, Maryland.|Geneva Foundation, Fort Detrick, Maryland; and.
Allison V
AV
Hoke
United States Army Center for Environmental Health Research, Fort Detrick, Maryland.|Geneva Foundation, Fort Detrick, Maryland; and.
Michael W
MW
Levangie
Frederick National Laboratory for Cancer Research, Frederick, Maryland.
Raina
R
Kumar
United States Army Center for Environmental Health Research, Fort Detrick, Maryland.|Geneva Foundation, Fort Detrick, Maryland; and.
Nabarun
N
Chakraborty
United States Army Center for Environmental Health Research, Fort Detrick, Maryland.
Aarti
A
Gautam
United States Army Center for Environmental Health Research, Fort Detrick, Maryland.
Rasha
R
Hammamieh
Norwegian Defense Research Establishment, Kjeller, Norway.
Svein
S
Martini
Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, Massachusetts.
Scott J
SJ
Montain
Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, Massachusetts.
Stefan M
SM
Pasiakos
D000293:Adolescent; D000367:Age Factors; D001419:Bacteria / Q000378:metabolism*; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000378:metabolism; D004044:Dietary Proteins / Q000008:administration & dosage / Q000378:metabolism; D004734:Energy Metabolism; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D054884:Host-Pathogen Interactions; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology*; D008297:Male; D055432:Metabolomics / Q000379:methods; D008887:Military Medicine; D009664:Norway; D009752:Nutritional Status; D010539:Permeability; D010807:Physical Endurance; D013312:Stress, Physiological; D049490:Systems Biology; D013997:Time Factors; D055815:Young Adult
D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D018836:Inflammation Mediators
energy metabolism; exercise; gut barrier; metabolomics; microbiology