1. Risk of infection is a problem anywhere on Earth, but can be an emergency during spaceflight. Spaceflight has profound effects on microbial characteristics, including altering virulence of dangerous pathogenic organisms. Furthermore, studies in recent years have established that the human immune system is dysregulated during spaceflight, which alters astronauts’ risk of acquiring infectious diseases during flight. The current proposed research would create a new assessment tool that not only measures the risks of pathogens detected in flight, but also considers alterations in host and environmental factors. We hypothesize that using machine learning, we can create a predictive risk assessment tool that considers spaceflight-induced changes to host and pathogen in the context of a flight environment, based on previous changes in microbial populations, current pathogen ecology, and host immunologic profiles unique to flight. This tool will not only aid in future microbial surveillance and response, but also on the implementation of countermeasures and planning of protocols for disease prevention, diagnosis, and treatment during long-term missions. We propose to address our hypothesis with the following three aims:
Aim 1: Characterize the historical pathogen population aboard the ISS to create a spaceflight microbiome signature.
Aim 2: Translation of molecular approaches to microbial monitoring to clinically relevant risk profiles.
Aim 3: Define the infection-specific risks developed in astronauts to create a spaceflight host signature.
2. The data acquired from these studies will finally bridge the gap between surveillance data and risks of infection based on clinical relevancy of factors from both host and pathogen. The risk assessment tool developed from this research will have wide applications, as it can be incorporated into a software program to monitor infection risks in spacecraft and terrestrial facilities, including hospitals, schools, and airports.
To date, research efforts have focused on Aim 1. The historical pathogen population of the ISS environment, defined by samples from air and surfaces in/on the ISS and tested for bacterial and fungal growth, has been described. Importantly, this definition has been of a descriptive and clinically relevant nature, focusing on the presence of and changes in populations of potential pathogens that can cause harm to crewmembers during flight missions. The pathogen population results served as the baseline for a clinical-relevancy scoring system, which will be used throughout this project. This scoring system was designed to define known pathogens, potential/opportunistic pathogens, and harmless environmental microbes in the setting of the ISS. Importantly, potential/known pathogens were divided into categories based on the disease they are known to cause on Earth, including respiratory, urinary tract, foodborne/gastrointestinal, skin/wound, sepsis, and resistant (to host defense and/or antimicrobials) infections/diseases. The presence of these pathogens was described in a spatial and temporal way, to allow for visualization of the most clinically relevant pathogen populations over the course of the lifespan of the ISS and throughout the environment in which the astronauts live and work.
The spaceflight microbiome signature has been constructed with the goal of using the signature in machine learning analysis. Briefly, metadata from microbial monitoring, including location of samples, culture/colony description/quantification, and species/genus of identified organisms were added to the clinical relevance scoring system to construct the metadata. Machine learning analysis has been applied to this metadata and comparisons across the data revealed the potential to use this analysis as a predictive tool for microbial load (pathogen presence and amounts over time), which demonstrates its value to risk assessment.
3. These findings are the results of the efforts for Aim 1 and represent the first prototype for the ISS environmental microbial signature tool. In addition, the description and clinical relevance of the historical pathogen population of the ISS environment helps define the risks to astronauts who live and work in this environment. These findings provide a benchmark for microbial population findings from future monitoring efforts, which can be used to inform planning and execution of countermeasures to address infection risk.
4. In the coming year, the focus of the efforts toward this project will be on Aims 2 and 3. First, implementation of molecular microbe monitoring into the ISS environmental microbiome signature, and/or translation of this monitoring into clinically relevant findings, will be completed. Second, the spaceflight host signature prototype will be constructed in a similar fashion to the microbial signature prototypes, but with host/astronaut immune/physiological changes induced by spaceflight. Together, the findings from these future efforts will be the products of this research and will be important contributions to the future of host/pathogen monitoring and response approaches during spaceflight.