Effects of Long-term Microgravity Exposure on Liver Activity and the Gut Microbiota as well as on Gut-liver Axis Homeostasis in the Hindlimb Suspension Rat Model

Abstract

Abstract Background:Recent advances in understanding gut‒liver axis homeostasis have been made because of its promising beneficial effects on health maintenance and performance promotion. However, we still have little knowledge 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 and the gut microbiota and on gut-liver axis homeostasis via a hindlimb suspension rat model. Results: Interestingly, long-term microgravity exposure increased lipid deposition, oxidative stress and inflammation in the liver; increased proportions of enteric opportunistic pathogens; and disrupted intestinal barrier integrity, paralleling the dysregulation of gut-liver axis homeostasis, which especially underlined portal influx of secondary bile acid (mainly ursodeoxycholic acid and lithocholic acid). Notably, metabolites derived from the liver were strongly correlated with those from the colon, and the gut microbiota played a vital role in the cometabolism pathways of aminoacyl-tRNA biosynthesis, vitamin B6 metabolism, alanine, and aspartate and glutamate metabolism, which may emphasize the critical role of microbial homeostasis in maintaining hepatic synthesis and metabolism of amino acids upon microgravity. Conclusions: Taken together, our findings suggest that gut-liver axis disturbances resulting fromlong-term microgravity exposure should receive additional attention in further studies of manned space.