Abstract
Background: Recent advances in understanding gut‒liver axis homeostasis have 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.
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). Notably, metabolites (mostly prostaglandins, kynurenine and derivatives) derived from the liver reflected the aggravating oxidative stress and inflammation and were strongly associated with those from the colon. In addition, the gut microbiota played a vital role in 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 liver activities as well as intestinal barrier integrity upon microgravity.
Conclusions: Taken together, our findings suggest that enteric microorganism 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.