The Role of 4-Phenylbutyric Acid in Gut Microbial Dysbiosis in a Mouse Model of Simulated Microgravity.

The altered gut microbes of astronauts during space travel may contribute to health issues after their return to Earth. Previously, an association between the elevated endoplasmic reticulum (ER) stress and gut microbial dysbiosis has been described. Herein, we induced gut microbial changes in mice under a simulated microgravity environment in an established model of hindlimb unloaded (HU) mice. The intestinal metabolomic profiles under microgravity conditions using the HU model were examined, along with the potential role of 4-phenylbutyric acid (4-PBA), a potent ER stress inhibitor. For a microgravity environment, the mice were suspended in special cages individually for three weeks. Mice were sacrificed, and gut dissections were performed, followed by amplicon sequencing analysis of bacterial species via DNA extraction and 16S rRNA analysis. The results indicate that the gut bacterial communities of mice differed under gravity and microgravity conditions. Principal component analyses revealed differences in the bacterial community structure in all groups. Around 434 operational taxonomic units (OTUs) were specific to mice seen in controls, while 620 OTUs were specific to HU mice. Additionally, 321 bacterial OTUs were specific to HU mice treated with 4-PBA. When the relative abundance of taxa was analyzed, Bacteroidetes dominated the gut of control and HU mice treated with 4-PBA.. In contrast, the untreated HU mice were dominated by Firmicutes. At the genus level, a reduction in beneficial species of