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Everywhere people go, they bring microbes with them—including to space. Space travel alters the form and function of microbial communities living in, on and around astronauts, with potential health consequences for both microbe and host. To date, most space microbiology research has taken place via ground-based simulations and aboard the (ISS)—a spacecraft floating in low Earth orbit (LEO), about 475 km (295 mi) above the planet’s surface. However, scientists are shifting their focus to long-duration missions to deep space, including to Mars. How might these journeys affect microbes, and their interactions with humans? Researchers are still figuring that out. What is clear is that microbes may be key for making deep space missions happen at all. From using bacteria to manufacture pharmaceuticals and food, to harnessing microbes for the synthesis of durable materials, the next frontier in space exploration may depend on the teeniest astronauts.

Space Travel Alters Microbial Physiology

“If you want to live and work in the space environment, you have to have a very comprehensive understanding of all the space hazards [and] how they are affecting microbes and the surfaces [and organisms] with which they interact,” said , a professor of microbiology and cell science at the University of Florida, during º£½ÇÉçÇøappMicrobe 2022.

Experiments in real and simulated space environments are all influenced by space conditions, including microgravity and radiation. For example, Foster (who studies symbiotic relationships between microbes and their hosts) and her colleagues found that, a bioluminescent bacterium that symbiotically colonizes the light organ of bobtail squid. These changes may be linked to microgravity-associated alterations in squid light organ development, in which V. fischeri plays a key role.

Antimicrobial Resistance and Virulence in Space 

In the context of human health, space also influences processes related to bacterial pathogenesis and antimicrobial resistance (AMR). For example, compared to bacteria on Earth, Salmonella typhimurium grown aboard the Space Shuttle mission STS-115 in a murine infection model. This was due to an upregulation of Hfq, a regulator that helps the bacteria respond to environmental stress. Another report showed that Escherichia coli grown on the ISS of the antibiotic gentamicin compared to samples on Earth. This is intriguing, given evidence that astronauts aboard the ISS compared to pre-flight samples. Relatedly, the ISS surface microbiome (which largely consists of microbes found on human skin) , many of which make up the ISS’ “medical toolkit,” like beta-lactams and fluoroquinolones.

Does this mean bacteria are more virulent and drug-resistant in space than they are on Earth? The relationship between microbial adaptations and host health in space is somewhat murky. One study showed that the , suggesting the threat of AMR is comparable. The researchers emphasized that microbial adaptations associated with biofilm formation and surface interactions may pose a greater problem for the structural integrity of the ISS itself, and less so for human health.

The Intersection Between Astronaut Microbiomes and Health

Still, AMR is only 1 part of the story. People are packed with microbes that help regulate everything from digestion to immune responses. During spaceflight, , among other issues. Are space-induced changes to their microbiomes to blame?

Microbiome analyses of 9 astronauts spending 6-12 months aboard the ISS of skin bacteria implicated in skin hypersensitivity or rashes. There were also more gut bacteria associated with intestinal inflammation (e.g., Parasutterella) and fewer with anti-inflammatory characteristics (e.g., Fusicatenibacter and Pseudobutyvibrio). The researchers stated these changes “may contribute to the moderate increase in the inflammatory immune response observed in the crew during space fight.” However, the health implications of this study, and others, are largely speculative. In addition, space-associated microbiome shifts vary between astronauts, studies and body locations (e.g., skin, gut or saliva). What is consistent is that astronaut microbiomes generally return to baseline back on Earth, highlighting the unique pressures of space. A better understanding of the intersection between astronaut microbiomes and health can help scientists plan future space missions with microbiology in mind.

The Next Frontier in Space Microbiology: Mars and Beyond

To that end, a new era of space travel is on the horizon, one in which missions will be longer and destinations millions of miles away. In fact, the National Aeronautics and Space Administration (NASA) is developing technologies that . What will this mean for astronauts and the microbes they interact with?

“There’re a lot of hazards we don’t know about,” Foster said. “In LEO, we are protected by our magnetosphere, we are protected by space radiation. If we go outside of that, all of the sudden we have galactic cosmic rays we have to deal with, we have a lot of solar particles we have to deal with and we also have variable gravity,” (i.e., astronauts would experience microgravity during travel to Mars, but one-third of Earth’s gravity upon landing on the planet).
 
According to , a professor of physiology and biophysics at Weill Cornell Medicine, even a short flight beyond ISS altitude impacts various aspects of human physiology and microbiome composition. He pointed to a preliminary study using samples from the crew of SpaceX’s 3-day , which reached 590 km (366 mi) at peak orbit (over 100 km, or 62 mi, higher than the ISS). Along with other physiological changes, including alterations in serum proteins related to immune responses, his team observed shifts in crew microbiome diversity and composition. They specifically noted an expansion of Alphaproteobacteria at various body sites, though have yet tease apart what the changes could mean. A separate ground-based simulation of a round-trip mission to Mars showed that, ” with strong interindividual variability. However, some key microbes exhibited consistent changes (e.g., fluctuations in bacteria that produce butyrate, a compound important for intestinal health).

These results hint that deep space missions will impact human-associated microbial communities, yet it is unclear if or how these impacts will differ from those observed during LEO missions (the details of which are also foggy). Finding out is important, though. Foster said that “working and living…beyond LEO [may] require novel microbial treatments and interventions that we don’t have to do on Earth.” She added that standard probiotic formulations used to replenish beneficial microbiome members would degrade quickly during a mission beyond LEO. As such, there is a need for technologies that shape the microbiome of astronauts to “restore species that potentially went extinct half-way to Mars.” This will mean continuing to study how microbes respond to deep space conditions while also characterizing community-level dynamics.

Harnessing Microbes to Advance Missions to Deep Space 

For , a professor in bioengineering at the University of California, Berkeley, the future depends not just on learning how microbes adapt to deep space, but also upon using them to get there. Rather than bringing supplies along on journeys to far-flung planets like Mars, Arkin and his colleagues  to produce food, pharmaceuticals, building materials and clean water and air using resources obtained from the Red Planet (e.g., carbon, nitrogen and light, among others). This could reduce the cost, and improve the sustainability of, deep space missions.

Already, researchers have made progress toward turning these possibilities into reality. For instance, scientists recently used bacteria to . The process relies on Sporomusa ovata, an autotrophic bacterium, which converts CO₂ to acetate. The acetate is then used by the aerobic organism, Cuprivadus basilenus to produce PHB. The researchers are now working on developing platforms that allow for production of a broad array of plastics. In addition, Arkin’s team engineered a strain of Arthrospira, a photosynthetic microalgae, to express acetaminophen.

The above capabilities are important on their own, but Arkin and his fellow researchers are thinking bigger. “We’ve been building this series of technologies, each of which gives you a capability of making a new food, type of material or sequestering more material from the atmosphere...[to form an] ” he said. The plant is essentially an “autonomous, reliable, programmable [and] easily changeable” system replete with modules for in situ resource utilization, production and recycling of food, drugs and biomaterials. 

Creating this system is no small feat. It requires meticulously calculating which materials and products must be produced to support long-duration missions, and identifying microbes that can help make them. The project is largely in the conceptual phase. Still, Arkin and his colleagues are working toward sending the so-called “biomanufactory” into the great beyond, transforming microbes from space hitchhikers to mission-critical crew members.
 

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