Relationship between the gut microbiome and energy/nutrient intake in a confined bioregenerative life support system

Recent studies have suggested that the gut microbiome is modified in space analogs and that human health can be affected during actual spaceflight. However, the relationship between the gut microbiome and dietary intake in simulator subjects and astronauts remains unclear. Bioregenerative life support systems (BLSSs) are confined and self-sufficient ecosystems that enable exploration of this issue. Here, we correlate changes in gut microbes to the nutrient types present in controlled diets within subjects cohabitating in a BLSS. A metagenome-wide association study (MWAS) was performed on 55 shotgun-sequenced fecal samples longitudinally obtained from healthy Chinese subjects (n=4 in total, n=2 per sex) subjected to a 60-day BLSS stay and a specialized diet. Each food item was categorized based on nutrient type according to the Chinese Food Ingredients List (https://wenku.baidu.com/view/3f2b628488eb172 ded630b1c59eef8c75fbf9514.html?from=search). The physical parameters of each subject fluctuated within normal medical ranges. Sex- and individual-specific differences and a trend of individual convergence of the gut microbiome in the BLSS were observed. Depletion of bacterial taxa such as Faecalibacterium prausnitzii, Bifidobacterium longum, and Escherichia coli and functional modules such as shortchain fatty acid (SCFA) production, as well as an increase in an unidentified Lachnospiraceae and glutamate/tryptophan synthesis, were observed in the BLSS. Correlation analysis showed that these compositional and functional changes were associated with energy/nutrient intake during the BLSS stay. Our findings suggest that the gut microbiota is a useful indicator for monitoring health and that individual nutritive diets should be considered according to sex and individual differences in simulations or in spaceflight. IMPORTANCE The gut microbiome shows individual specificity and is affected by sex, environment, and diet; gut microbiome imbalance is related to cancer, cardiovascular diseases, and autoimmune diseases. Astronauts are faced with a challenging environment and limited diet in outer space. Recent studies indicate that the gut microbiome is altered in space simulators and space, but what happens to intestinal microorganisms when astronauts cohabitate in a self-sufficient ecosystem in which they plant and cook food is unclear. Bioregenerative life support systems (BLSSs) are ideal devices to investigate the above issues because they are closed and self-sufficient. Four healthy Chinese subjects cohabitated in a confined BLSS for 60 days, during which their physical parameters and energy/nutrient intake were recorded. We performed a metagenome-wide association study (MWAS) on 55 shotgun-sequenced fecal samples longitudinally obtained from the subjects. Alterations occurred in the gut microbial composition and function, and their relationships with energy/nutrient intake were explored.