Mouse “Astronauts” Reveal Possible Links Between Gut Bacteria and Bone Loss in Microgravity

A new study in mice has found that changes to the gut microbiome during spaceflight – which is experienced by both humans and mice – may be associated with bone loss. The study is published in Cell Reports.

Bone loss in microgravity

Astronauts lose approximately 1–1.5% of their bone density for every month that they are in space, no longer subject to the loads and forces exerted by gravity here on Earth.

Our bones are constantly being remodeled, even during adulthood. Bone material is continuously added, removed and transported. Recent research has suggested that the process of bone remodeling may be influenced by the bacteria present in our guts, which form part of the gut microbiome. These gut microbes may interact with our immune and hormonal systems, producing molecules that can indirectly affect the cells responsible for bone remodeling.

Interestingly, space flight is also associated with changes in the microbiome of both humans and rodents. This may be for several different reasons, as Dr. Joseph K. Bedree, lead author of the current study, explained: “First and foremost, there are the physical forces at play, such as microgravity and cosmic radiation exposure, which affect not only the bacterial cells but also the human cells.”

“Likewise, there are numerous resulting effects on host biological systems from microgravity exposure – immune system irregularities, musculoskeletal changes, altered circadian rhythm [and] stress – and when those systems become imbalanced, the microbial communities potentially could be disrupted, too,” Bedree added.

Bedree and colleagues aimed to investigate how microgravity changes the microbiome and uncover possible links to decreased bone density – by sending a cohort of mice on a mission to the International Space Station (ISS).

A NASA first

The researchers selected 20 mice to experience microgravity on the ISS, of which half were returned to Earth after 4.5 weeks and the other half after 9 weeks – the first study in NASA’s history in which rodents had been returned alive back to Earth. Upon their return, the researchers analyzed how their microbiomes changed and recovered, comparing them against a group of 20 “ground control” mice which had been identically housed back on Earth.

The bacterial communities in the gut microbiome were analyzed from three defined time periods – before launch, after returning to Earth and at the end of the study. Additionally, changes in the levels of blood metabolites were monitored in the 10 mice that were in space for the full 9 weeks.

“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,” said Dr. Wenyuan Shi, senior author and microbiologist and chief executive officer at the Forsyth Institute.

Findings revealed that mice returning from spaceflight had more diverse gut microbiomes and had higher levels of Lactobacillus and Dorea bacterial species. Additionally, levels of these species were even higher in mice that experienced 9 weeks of spaceflight compared to 4.5 weeks.

The researchers suggest that these bacterial species may have influenced increased levels of metabolites associated with microgravity exposure detected in the mice. “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 Bedree. “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.”

Implications for bone density conditions

The authors note that the gut microbiome of the mice may have been affected as they were unable to engage in coprophagy during the study – a normal rodent behavior in which they consume their own feces, and which may be able to return microbes to the gut. This may have been beneficial for gut microbiome recovery in mice that spent 4.5 weeks in space, as they were able to engage in coprophagy on their return.

Furthermore, though these results provide insights into how the gut microbiome may change during spaceflight, further studies are required to investigate its possible link to bone density in more detail. Understanding how microbes may influence bone density could help improve astronaut health, and could potentially benefit the management of diseases such as osteoporosis back on Earth.

“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 Shi. “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.”

Reference: Bedree JK, Kerns K, Chen T, et al. Specific host metabolite and gut microbiome alterations are associated with bone loss during spaceflight. Cell Rep. 2023. doi: 10.1016/j.celrep.2023.112299

This article is a rework of a press release issued by Cell Press. Material has been edited for length and content.