One of the physiological changes experienced by astronauts in space is loss of bone density. Now, researchers report that changes to the gut microbiomes in space might be associated with this bone loss. The findings suggest that rodents that spent a month or more on the International Space Station had altered and more diverse microbiomes. In addition, the bacterial species that increased while their host was in space may have contributed to the increased production of molecules that are known to influence the bone remodeling process.

“This is just another vivid example showing the dynamic interactions between the microbiome and mammalian hosts. The gut microbiome is constantly monitoring and reacting, and that’s also the case when you’re exposed to microgravity,” said Wenyuan Shi, PhD, CEO at the Forsyth Institute. “We’ve yet to find out whether there’s a causal link between changes to the microbiome and the observed bone loss in microgravity and if it is simply a consequence or an active compensation to mitigate, but the data are encouraging and create new avenues for exploration.”

This work is published in Cell Reports in the article, “Specific host metabolite and gut microbiome alterations are associated with bone loss during spaceflight.

Recent studies have suggested that gut microbes might impact bone remodeling via various mechanisms including interactions with the immune and hormonal systems. In addition, some of the metabolites made by microbes interact indirectly with the cells responsible for bone remodeling.

To study how the microbiome changes during prolonged exposure to microgravity, and to investigate possible links between these changes and bone density, the researchers sent 20 rodents to the International Space Station. Ten of these rodents returned alive to Earth after 4.5 weeks, and the researchers tracked how their microbiomes recovered upon return. The remaining 10 space rodents remained in orbit for a total of nine weeks. Twenty “ground control” rodents were housed in identical conditions—although minus the microgravity—on Earth. The team characterized and compared the microbial communities for the different groups over time: before launch, after return to Earth, and at end of the study. They also evaluated changes in serum metabolites for the space rodents that were exposed to microgravity for the full nine weeks.

“This is the first time in NASA history that a rodent has been returned to Earth alive,” said Shi. “This meant we were able to gather information about the change in space, and then monitor their microbiome’s recovery when they returned. The good news is that even though the microbiome changes in space, these alterations don’t appear to persist upon returning to Earth.”

When the team characterized and compared the gut microbiomes of the space and ground control rodents, they found that the space rodents had more diverse gut microbiomes. Two types of bacteria—Lactobacillus and Dorea species—were much more abundant in rodents that were exposed microgravity, and their abundance was even higher in rodents that were in space for nine weeks versus 4.5 weeks. The metabolism of these two bacteria also could have contributed to the elevated metabolites that were detected and associated with microgravity exposure.

“When we mapped the genetic pathways for Lactobacillus and Dorea, they seemed to line up with the metabolites that were elevated during microgravity exposure,” said Joseph K. Bedree, PhD, who began the work while at UCLA and continued it at the Forsyth Institute. “When someone’s in microgravity and experiencing bone loss, it would make sense that their body would try to compensate and that the biological systems within would be doing that as well, but we need to do more mechanistic studies to truly validate these hypotheses.”

One non-microgravity factor that may have influenced the rodents’ changing microbiome in space is the fact that they were not able to engage in coprophagy, a normal rodent behavior whereby they eat their own feces, which reintroduces microbes back into the gut. However, the rodents that returned from space after 4.5 weeks were able to engage in coprophagy upon return, and this probably contributed to their microbiomes’ recovery.

While this study sheds light on how the microbiome changes during space travel, the authors say that more work needs to be done to understand the possible link between the microbiome and bone density. They plan to continue the research here on Earth.

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