When humans travel to space, we often forget that we bring along trillions of unwitting microbial stowaways. We have some idea of how our bodies change without Earth’s guiding force, but we don’t have a good sense of how those microbes fare. And because these critters have such a strong influence on our own health, studying how they thrive in space is crucial.

As we aim for more ambitious space goals, this question has become an area of active research. In 2020, a team of researchers led by Anand Kumar at Los Alamos National Laboratory In New Mexico blasted a bunch of gut microbes up into orbit aboard the International Space Station (ISS). They found that microgravity appeared to shift the gut microbiome in a way that fostered an unhealthy microbial environment rather than a healthy one.

This month, SpaceX launched a second round of experiments to the ISS that the Los Alamos team, along with partner Rhodium Scientific, hopes will help them better understand how exactly the microbial shift happens. The ultimate goal is to help us — and our microbiomes — stay happy in space as we travel the far reaches of our Solar System and beyond.

A history of our gut microbes’ journey in space

Since the 1970s, NASA has been monitoring how microbes known to affect human health thrive in space. During the Skylab program — the first US space station established in 1973 that stayed in orbit until 1979 — astronauts had their skin swabbed and their urine and poop collected before, during, and after every mission (the station itself also had its surfaces swabbed and air samples collected). Results from those investigations revealed a shift in the type of microbes, from anaerobes (bacteria that don’t require oxygen) to aerobes (bacteria that do). During the Apollo missions, NASA scientists observed an increase in bacteria like Staphylococcus aureus, usually a harmless bug found in the upper airways and skin but can cause staph infections under certain circumstances.

A few decades later, in 2015, during the landmark NASA Twins Study — in which astronaut Scott Kelly spent 340 consecutive days abroad on the ISS while his twin brother, then-astronaut, now-Senator Mark Kelly, remained on Earth — NASA personnel compared Scott’s bodily changes against Mark’s, ascertained through blood, saliva, urine, and stool samples. Because identical twins share the same genetic makeup, it makes it easier to associate any bodily changes observed as largely due to the environment rather than the person’s genetics.

Researchers published their findings from the Twin Study in 2019 in the journal Science. They reported that Scott Kelly’s gut microbiome experienced a pronounced shift in the composition of both good and bad bacteria during spaceflight. However, they also noted that this shift dialed back to normal once he returned to Earth.

Norberto González-Juarbe, a microbiologist at J. Craig Venter Institute who studies astronaut microbiomes but wasn’t involved in the Los Alamos research, tells Inverse that it’s well known that bacteria exist on the ISS and that the microgravity environment influences their behavior.

“It’s not unheard of that there’s bacteria that change when in space. Studies have shown that some bacteria that get isolated [in space] have differential virulence compared to the same bacteria on Earth.”

Another 2019 study looking at astronauts who spent anywhere from six months to a year in space found significant alterations in their skin microbiomes (potentially associated with the frequent complaint of skin rashes) as well as nose, tongue, and gastrointestinal microbes. While the study authors say it wasn’t clear whether these changes necessarily put the astronaut’s health at risk, it emphasizes a void in our understanding of how the environmental factors of space, or even the social stressors of sleep deprivation or isolation, influence our microbiomes.

Can our gut microbiome thrive in microgravity?

In their first experimental foray into unpacking how an environmental stressor like microgravity shapes the gut microbiome, Kumar and his colleagues at Los Alamos took poop samples from a single healthy donor and extracted a sample of the gut microbiome.

In March 2020, around two dozen samples were sent via the SpaceX-20 mission to the ISS where they were kept in a climate-controlled incubator. Two dozen control samples were also kept in an incubator set to identical parameters on Earth but with the only difference being gravity.

Because bacteria are constantly growing (at least given the right conditions), the researchers wanted to see how much and what kinds were flourishing at different time points. Samples were taken out of the incubator at around three-hour intervals. The researchers discovered that microgravity allowed some bacteria to thrive while others floundered.

Among the good ones beneficial to human health were some species within the Dialister and Clostridia bacteria families, Armand Dichosa, a biologist at Los Alamos who co-led the project, told Inverse in an email. But others were not too good. Some belonged to the potentially pathogenic arm of the Clostridia clan as well as Pseudomonas (which can cause severe infections in those with weak or otherwise compromised immune systems) and Enterobacter (some members can cause hospital-acquired infections from surgical wounds or catheters, and is becoming increasingly resistant to antibiotics).

“It was very interesting that there are quite a few microbes which grow only in the microgravity environment compared to the controls,” says Kumar. “We think that potentially they got some [kind of] stimulus [from] the environment.”

For their second experiment, Kumar, Dichosa, and their colleagues want to focus on observing how individual bacteria — versus an entire community, as they did in the first experiment — are altered by space travel.

To do that, the Los Alamos team has sent fecal microbes from the same donor in specialized tubes that contain one microbe cloistered within one microscopic gel sphere called a microdroplet. Tiny pores drilled into the microdroplets prevent the bacterium from escaping while permitting the exchange of chemical signals between other microbes in other droplets, says Kumar (this is somewhat akin to a closed versus open workspace).

The researchers also hope to essentially redo their first experiment or at least see if those alterations they saw still hold true. When Covid-19 hit, and lockdowns ensued, the fecal donor samples collected had to be stored in subzero storage for about eight to nine months before they could be processed and sent to the ISS. Whether those extreme temperatures affected the microbes in any way is something the researchers are unsure of.

Gravity isn’t the only thing that changes in space

While these findings are illuminating to the field of the microbiome in space research, says González-Juarbe, microgravity isn’t the only environmental stressor impacting the microbiome. Genetic mutations that allow some bacteria to proliferate over others may be shaped by radiation, which is abundant in space.

“The space station is covered by all these layers to protect our astronauts, but there’s still an influx of radiation into the station,” he says. “So something else that might be happening here is that these signals are triggering changes in bacteria [saying to some], ‘You’re more hardy, so you grow now’ [while] others will not.”

In space, microbiomes are also chilling out and interacting with their host’s body, not outside, suspended in test tubes. These shifts in microbial diversity, the Los Alamos effort has observed, may not fully capture what’s going on in vivo, a limitation Kumar acknowledges.

In their current second experiment, Kumar, Dichosa, and their colleagues want to focus on individual bacterium. A more distant goal is to somehow replicate host-microbiome interactions under the influence of space on a small, easy-to-study scale.

“We have the capability to make a human gut and seed it with these gut microbes in microdroplets. We want to ship that to the ISS like a tiny box representing a small section of the human gut,” says Kumar. With the microbiome-in-a-gut box, the researchers can then track microbial changes alongside interactions with human tissue, hopefully in all its granularity.

Until his team can get the funding for that, it’s all about microbial astronauts going to infinity and beyond to ensure the survival of humans in space.