Michael S. Goodson

Disruption of the gut microbiome has been linked to ill health, including impaired cognitive performance and mental health issues. Various aspects of a prolonged submarine deployment environment are known to disrupt the microbiome when they occur in other circumstances, including limited diet, altered circadian rhythm, poor sleep, and stress. In this study, we (i) characterize the changes of diet, mood, and the composition of the gut microbiome during a prolonged submarine deployment and (ii) determine whether any of these factors interact and affect submariner health and performance. Thirty-four U.S. Navy submariners, serving on a ballistic missile submarine (SSBN), provided fecal and blood samples and completed questionnaires relating to their diet and mood. Samples and questionnaires were collected at six time periods covering before, during, and after an 8-week deployment. Fecal samples were analyzed by 16S rRNA gene sequencing. Blood samples were analyzed to identify biomarkers with established links to stress, neurocognitive function, immune function, and gut barrier function. The dietary and mood questionnaires were analyzed to identify any changes over the course of the deployment. Results indicated that baseline gut microbial diversity was highly variable between individuals, although certain microbes had deployment-related changes to their composition. Changes in microbiota composition within individuals over the course of the deployment were correlated with changes in diet and mood, suggesting a link between microbiome composition and feelings of fatigue. Identification of microbial communities that confer resiliency to deployment stressors will enable future development of targeted interventions. IMPORTANCE: Submariners operate in a unique deployment environment, but their experiences may shed light on how the human body responds to extended duration missions in other confined spaces, such as spaceflight. Our study is the first to show how the human gut microbiome changes during an extended submarine deployment while also tracking dietary intake and mood.

Background: Inter-individual variation in response to insufficient or altered timing of sleep presents a challenge for the development of personalized approaches to fatigue monitoring and mitigation. Insufficient sleep has adverse health impacts, can result in impaired neurobehavioral performance, and can substantially increase the risk of injury and even mortality in safety–critical operations such as transportation. The present study provides a detailed exploration of physiological, neurobehavioral, and gene expression changes during sleep restriction, acute total sleep deprivation, and altered timing of sleep among 59 healthy volunteer participants who completed a 10-day inpatient study. Results: Reducing the quantity or altering the timing of sleep significantly impacts self-reported estimates of sleep duration, polysomnography-recorded sleep stages, and neurobehavioral performance test results. Impaired neurobehavioral performance was associated with transcriptomic changes in gene expression. A comparison of current and prior research on total sleep deprivation indicated that reproducible candidate gene expression biomarkers exist for at least one metric of attention, specifically, Psychomotor Vigilance Test (PVT) lapses. Conclusions: Candidate biomarkers of fatigue-related impairment were identified that responded to single neurobehavioral performance endpoints, as well as those that responded to multiple types or metrics of performance. Reproducible identification of biomarker candidates for PVT lapses during total sleep deprivation increases confidence in the ability to develop a molecular approach to fatigue-related impairment detection, while novel discoveries expanded the list of candidate genes to other impairment metrics. Molecular biomarkers for neurobehavioral performance impairment represent a potentially valuable tool to more precisely monitor the neurobehavioral performance deficits resulting from sleep loss, and further research and validation could eventually augment fatigue risk management practices that historically emphasize scheduling and rest opportunities. The data generated from self-assessment, polysomnography, neurobehavioral performance, and molecular investigations provide a wealth of information made publicly available for further data mining and scientific advancements. Trial registration: ClinicalTrials.gov, TRN: NCT04211506, Registered 23 December 2019.

Shigella is a significant cause of diarrhea, predominantly affecting children in low- and middle-income countries, as well as international travelers. Not all individuals exposed to Shigella or other enteropathogens have symptomatic responses, and investigating the differences between symptomatic and asymptomatic individuals can further our understanding of enteropathogen proliferation and symptomatic responses. Here, we profiled the fecal microbiomes of 45 individuals infected with Shigella sonnei strain 53G through 16S rRNA sequencing in a controlled human infection model before and during infection, after antibiotic treatment, and after clinical recovery. This model allowed for a detailed exploration of microbiome temporal dynamics during infection, as well as a comparative analysis between those with shigellosis (defined as severe symptoms caused by Shigella infection, including severe diarrhea, fever, and/or abdominal pain) and those without shigellosis. Alpha diversity decreased to a greater degree in individuals with shigellosis. Perturbations in microbial composition during infection and antibiotic treatment were significantly larger in individuals diagnosed with shigellosis than in those who were not. Participants with shigellosis had persistent changes to their microbiomes after recovery, while those without shigellosis recovered to a composition resembling their pre-infection microbiomes. These persistent changes included taxa associated with gut inflammation, such as a decrease in Faecalibacterium and an increase in Ruminococcus gnavus . Furthermore, the initial microbiomes of participants who did not develop shigellosis had a greater abundance of taxa associated with short-chain fatty acid production than participants who did develop shigellosis, including Bifidobacterium , Roseburia , and Faecalibacterium . These data could help prevent Shigella infection or symptoms. IMPORTANCE: Diarrheal disease is a major contributor to the global disease burden and can lead to an increased individual risk of chronic sequelae post-infection, such as irritable bowel syndrome, reactive arthritis, and altered gut permeability. Understanding the differential responses of individuals to enteropathogen exposure can elucidate factors that could lead to treatments or preventative measures to reduce the disease burden. Here, we use a controlled human infection model study to directly identify the effects of Shigella sonnei 53G infection on the microbiome. We identified taxa that were more or less abundant in participants who would develop shigellosis during the study, as well as persistent changes after recovery in the microbiomes of participants who developed severe symptoms. Understanding these changes could elucidate ways to prevent Shigella infection or recover altered microbiomes after recovery. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT02816346 .

The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing among consortium members, which includes collaborators in academia and industry. The 2023 annual symposium was a hybrid meeting held in Washington DC on 26–27 September 2023 concurrent with the virtual attendance, with oral and poster presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) Environmental Microbiome Characterization; 2) Microbiome Analysis; 3) Human Microbiome Characterization; 4) Microbiome Engineering; and 5) In Vitro and In Vivo Microbiome Models. Collectively, the symposium provided an update on the scope of current DoD and DoD-affiliated microbiome research efforts and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 7th annual TSMC symposium.

Background: The COVID-19 pandemic highlighted the need for pathogen surveillance systems to augment both early warning and outbreak monitoring/control efforts. Community wastewater samples provide a rapid and accurate source of environmental surveillance data to complement direct patient sampling. Due to its global presence and critical missions, the US military is a leader in global pandemic preparedness efforts. Clinical testing for COVID-19 on US Air Force (USAF) bases (AFBs) was effective but costly with respect to direct monetary costs and indirect costs due to lost time. To remain operating at peak capacity, such bases sought a more passive surveillance option and piloted wastewater surveillance (WWS) at 17 AFBs to demonstrate feasibility, safety, utility, and cost-effectiveness from May 2021 to January 2022. Objective: We model the costs of a wastewater program for pathogens of public health concern within the specific context of US military installations using assumptions based on the results of the USAF and Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense pilot program. The objective was to determine the cost of deploying WWS to all AFBs relative to clinical swab testing surveillance regimes. Methods: A WWS cost projection model was built based on subject matter expert input and actual costs incurred during the WWS pilot program at USAF AFBs. Several SARS-CoV-2 circulation scenarios were considered, and the costs of both WWS and clinical swab testing were projected. Analysis was conducted to determine the break-even point and how a reduction in swab testing could unlock funds to enable WWS to occur in parallel. Results: Our model confirmed that WWS is complementary and highly cost-effective when compared to existing alternative forms of biosurveillance. We found that the cost of WWS was between US $10.5-$18.5 million less expensive annually in direct costs as compared to clinical swab testing surveillance. When the indirect cost of lost work was incorporated, including lost work associated with required clinical swab testing, we estimated that over two-thirds of clinical swab testing could be maintained with no additional costs upon implementation of WWS. Conclusions: Our results support the adoption of WWS across US military installations as part of a more comprehensive and early warning system that will enable adaptive monitoring during disease outbreaks in a more cost-effective manner than swab testing alone.

The physiological consequences of stress often manifest in the gastrointestinal tract. Traumatic or chronic stress is associated with widespread maladaptive changes throughout the gut, although comparatively little is known about the effects of acute stress. Furthermore, these stress‐induced changes in the gut may increase susceptibility to gastrointestinal disorders and infection, and impact critical features of the neural and behavioural consequences of the stress response by impairing gut–brain axis communication. Understanding the mechanisms behind changes in enteric nervous system circuitry, visceral sensitivity, gut barrier function, permeability, and the gut microbiota following stress is an important research objective with pathophysiological implications in both neurogastroenterology and psychiatry. Moreover, the gut microbiota has emerged as a key aspect of physiology sensitive to the effects of stress. In this review, we focus on different aspects of the gastrointestinal tract including gut barrier function as well as the immune, humoral and neuronal elements involved in gut–brain communication. Furthermore, we discuss the evidence for a role of stress in gastrointestinal disorders. Existing gaps in the current literature are highlighted, and possible avenues for future research with an integrated physiological perspective have been suggested. A more complete understanding of the spatial and temporal dynamics of the integrated host and microbial response to different kinds of stressors in the gastrointestinal tract will enable full exploitation of the diagnostic and therapeutic potential in the fast‐evolving field of host–microbiome interactions. image

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. The annual TSMC symposium is designed to enable information sharing between DoD scientists and leaders in the field of microbiome science, thereby keeping DoD consortium members informed of the latest advances within the microbiome community and facilitating the development of new collaborative research opportunities. The 2020 annual symposium was held virtually on 24–25 September 2020. Presentations and discussions centered on microbiome-related topics within four broad thematic areas: (1) Enabling Technologies; (2) Microbiome for Health and Performance; (3) Environmental Microbiome; and (4) Microbiome Analysis and Discovery. This report summarizes the presentations and outcomes of the 4th annual TSMC symposium.

Traveler’s diarrhea (TD) is a recurrent and significant issue for many travelers including the military. While many known enteric pathogens exist that are causative agents of diarrhea, our gut microbiome may also play a role in TD susceptibility. To this end, we conducted a pilot study of the microbiome of warfighters prior to- and after deployment overseas to identify marker taxa relevant to TD. This initial study utilized full-length 16S rRNA gene sequencing to provide additional taxonomic resolution toward identifying predictive taxa.16S rRNA analyses of pre- and post-deployment fecal samples identified multiple marker taxa as significantly differentially abundant in subjects that reported diarrhea, includingWeissella,Butyrivibrio,Corynebacterium, uncultivated Erysipelotrichaceae,Jeotgallibaca, unclassified Ktedonobacteriaceae,Leptolinea, and uncultivated Ruminiococcaceae. The ability to identify TD risk prior to travel will inform prevention and mitigation strategies to influence diarrhea susceptibility while traveling.