Stress, a ubiquitous part of daily human life, has varied biological effects which are increasingly recognized as including modulation of commensal microorganisms residing in the gastrointestinal tract, the gut microbiota. In turn, the gut microbiota influences the host stress response and associated sequelae, thereby implicating the gut microbiota as an important mediator of host health. This narrative review aims to summarize evidence concerning the impact of psychological, environmental, and physical stressors on gut microbiota composition and function. The stressors reviewed include psychological stress, circadian disruption, sleep deprivation, environmental extremes (high altitude, heat, and cold), environmental pathogens, toxicants, pollutants, and noise, physical activity, and diet (nutrient composition and food restriction). Stressors were selected for their direct relevance to military personnel, a population that is commonly exposed to these stressors, often at extremes, and in combination. However, the selected stressors are also common, alone or in combination, in some civilian populations. Evidence from preclinical studies collectively indicates that the reviewed stressors alter the composition, function and metabolic activity of the gut microbiota, but that effects vary across stressors, and can include effects that may be beneficial or detrimental to host health. Translation of these findings to humans is largely lacking at present. This gap precludes concluding with certainty that transient or cumulative exposures to psychological, environmental, and physical stressors have any consistent, meaningful impact on the human gut microbiota. However, provocative preclinical evidence highlights a need for translational research aiming to elucidate the impact of stressors on the human gut microbiota, and how the gut microbiota can be manipulated, for example by using nutrition, to mitigate adverse stress responses.

Gut microbiome community dynamics are maintained by complex microbe-microbe and microbe-host interactions, which can be disturbed by stress. In vivo studies on the dynamics and manipulation of those interactions are costly and slow, but can be accelerated using in vitro fermentation. Herein, in vitro fermentation was used to determine how an acute stressor, a sudden change in diet, impacts interbacterial species competition for resistant starch-supplemented medium (RSM). Fermentation vessels were seeded with fecal samples collected from 10 individuals consuming a habitual diet or U.S. military rations for 21 days. Lactobacillus spp. growth in response to RSM was attenuated following ration consumption, whereas growth of Ruminococcus bromii was enhanced. These differences were not evident in the pre-fermentation samples. Findings demonstrate how incorporating in vitro fermentation into clinical studies can increase understanding of stress-induced changes in nutrient-microbiome dynamics, and suggest that sudden changes in diet may impact inter-species competition for substrates.

A naturally occurring antimicrobial peptide, SMAP-29, was synthesized with an n-terminal or c-terminal cysteine, termed c_SMAP and SMAP_c, respectively, for site-directed immobilization to superparamagnetic beads. Immobilized SMAP orientation-dependent activity was probed against multiple bacteria of clinical interest including Acinetobacter baumannii, Pseudomonas aeruginosa, Bacillus anthracis sterne and Staphylococcus aureus. A kinetic microplate assay was employed to reveal both concentration and time-dependent activity for elucidation of minimum bactericidal concentration (MBC) and sub-lethal effects. Immobilized SMAP activity was equivalent or reduced compared with soluble SMAP_c and c_SMAP regardless of immobilization orientation, with only one exception. A comparison of immobilized SMAP_c and c_SMAP activity revealed a bacteria-specific potency dependent on immobilization orientation, which was contrary to that seen in solution, wherein SMAP_c was more potent against all bacteria than c_SMAP. Sub-MBC kinetic studies displayed the influence of peptide exposure to the cells with multiple bacteria exhibiting increased susceptibility and efficacy at lower concentrations upon extended exposure (i.e. MBC enhancement). For instances in which complete killing was not achieved, two predominant effects were evident: retardation of growth rate and an increased lag phase. Both effects, seen independently and concomitantly, indicate some degree of induced cellular damage that can serve as a predictor toward eventual cell death. SMAP_c immobilized on glass through standard silanization chemistry was also investigated to ascertain the influence of substrate on activity against select bacteria.

The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among U.S. Department of Defense (DoD) organizations and to facilitate resource, material and information sharing among consortium members. The 2019 annual symposium was held 22-24 October 2019 at Wright-Patterson Air Force Base in Dayton, OH. Presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) human microbiomes; 2) transitioning products into Warfighter solutions; 3) environmental microbiomes; 4) engineering microbiomes; and 5) microbiome simulation and characterization. Collectively, the symposium provided an update on the scope of current DoD microbiome research efforts, highlighted innovative research being done in academia and industry that can be leveraged by the DoD, and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 3rd annual TSMC symposium.