Effects of Long-term Weightless Stimulating by Tail Suspension on the Gut Microbiota as well as the Gut-liver Axis Homeostasis in Rat

BACKGROUND: Recent advances in understanding gut‒liver axis homeostasis has been made because of the promising beneficial effects of these systems on health maintenance and performance promotion. However, little is known about the effects of long-term microgravity exposure on the gut-liver axis or about effective countermeasures to prevent disruptions in gut-liver axis homeostasis. Hence, we conducted a well-controlled study to determine the effects of long-term microgravity exposure on liver activity, the gut microbiota and gut-liver axis homeostasis via a hindlimb suspension rat model. METHOD: The animal model suffering microgravity exposure was achieved using hindlimb unloading approaches. Afterwards, the histomorphology of liver and colon was acquired using hematoxylin-eosin (H&E) staining and the lipid accumulation was observed by oil red O staining. Plasm/serum indexes were detected by Enzyme-linked immunosorbent assay (ELISA) analysis. In addition, the gut microbiota was characterized through 16S rRNA gene Sequencing and the metabolome was conducted on UHPLC‒MS/MS system. RESULTS: Interestingly, long-term microgravity exposure increased lipid deposition, oxidative stress and inflammation in the liver; increased proportions of opportunistic enteric pathogens; and disrupted intestinal barrier integrity, paralleling with dysregulation of gut-liver axis homeostasis, which especially underlined portal influx of secondary bile acid (mainly ursodeoxycholic acid and lithocholic acid) and tryptophan metabolism. CONCLUSION: Taken together, our findings suggest that gut microbiota is an effective target for maintaining gut-liver axis homeostasis as well as protecting astronauts from inflammation when deal with microgravity exposure in further long-term manned space mission.