Mice sent to ISS reveal possible link between gut bacteria and bone loss

Changes to the gut bacteria of space travellers might be associated with bone loss, research into mice that were sent to the International Space Station (ISS) has revealed.

Mice that spent a month or more on the ISS had altered and more diverse gut microbiome – bacteria, the study found.

The findings suggest bacterial species that bloomed in space may have contributed to the increased production of molecules known to influence changes in bones.

Senior author Wenyuan Shi, a microbiologist and chief executive officer at the Forsyth Institute in the US, said: “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.

“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.”

According to the researchers, if scientists can establish which microbes support the maintenance of bone density, it could help astronauts stay healthier in space and could also help people on Earth who suffer bone loss, like those with osteoporosis.

To explore how the microbiome changes during prolonged exposure to microgravity, and to investigate possible links between these changes and bone density, the researchers sent 20 mice to the ISS.

Ten of these rodents returned alive to Earth after 4.5 weeks and the researchers tracked how they recovered.

The remaining 10 space mice stayed in orbit for a total of nine weeks.

Twenty “ground control” mice were housed in identical conditions – minus the microgravity – on Earth.

Researchers compared the microbial communities for the different groups over time – before launch, after return to Earth, and at the end of the study.

They found the space mice had more diverse gut microbiomes, with two specific types of bacteria much more abundant in rodents exposed to microgravity.

Levels of the bacteria were even higher in rodents that were in space for nine weeks versus 4.5 weeks.

Dr Shi said: “This is the first time in Nasa history that a rodent has been returned to Earth alive.

“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.”

Bones are not static,and even when people are fully grown, material is constantly being added, removed, and shifted around in a process called bone remodelling.

Recent studies have suggested gut microbes might impact this process via various mechanisms including interactions with the immune and hormonal systems.

Microbes also produce various molecules because of their own metabolism, and some of these interact indirectly with the cells responsible for bone remodelling.

First author and microbiologist Joseph Bedree, who began the work while at UCLA and continued it at the Forsyth Institute, said experts would expect space travel to affect microbiome for a number of reasons.

He 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, stress – and when those systems become imbalanced, the microbial communities potentially could be disrupted, too.”

The researchers suggest that 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.

This is normal rodent behaviour whereby they eat their own faeces, which reintroduces microbes back into the gut.

However, the mice that returned from space after 4.5 weeks were able to engage in coprophagy upon return and this probably contributed to the recovery of their microbiome.

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

Dr Shi said: “If we can figure out which microbes support the maintenance of bone density, it could help astronauts stay healthier in space.”

The researchers say this information could also help people back on Earth who suffer bone loss from non-gravity-related reasons.

“This could potentially lead to new tools for managing diseases like osteopenia or osteoporosis, so it’s not just an isolated story in space,” Dr Shi said.

The findings are published in the Cell Reports journal.