A healthy gut microbiome could protect space travelers from the rigors of space travel

Spending long periods of time in space can wreak havoc on space traveler health, including negative effects on metabolism, bone and muscle health, gastrointestinal health, immunity and mental health.

This could prevent us pursuing long-distance missions, such as a Mars landing.

However, a new review in open-access journal Frontiers in Physiology highlights that promoting a healthy gut microbiome could protect space travelers from the rigors of space travel.

Finding out which microbes provide the most benefit and the best way to use them could be key to reaching the red planet in one piece.

If humans are to ever walk on Mars, they will need to endure a long space flight, but space travel can have negative impacts on health, potentially limiting how far we can go. The microgravity environment can result in muscle breakdown and reduced bone mass.

It can cause nausea, meaning that sometimes space travelers struggle to eat enough (space food isn’t all that nice either). The change in diet aboard a spaceship can disrupt the gut microbiome, leading to further health issues.

These factors can contribute to malnourishment and gastrointestinal problems, such as infection and inflammation.

Space travelers can also experience metabolic disturbances, including decreased sensitivity to insulin. Other issues include immune system deficits, mental illness and cognitive decline.

A growing number of studies have focused on gut microbes, and their role in space-related health, prompting Prof. Silvia Turroni of the University of Bologna and Prof. Martina Heer of the University of Bonn to write this latest review.

Their review discusses a variety of studies suggesting that disruptions in the gut microbiome occur during space travel.

For instance, one study found that the microbiomes of space travelers on the same mission became more similar to each other during the journey. There was also an increase in bacteria associated with intestinal inflammation and a decrease in those with anti-inflammatory properties.

“Changes in the microbiome are likely to lead to the breakdown of the balanced and complex relationship between microbes and their human host, with potentially severe repercussions on the functionality of body systems,” said Turroni.

However, the review reveals that manipulating the gut microbiome may be a powerful way to maintain health on board a spacecraft.

“The literature suggests that nutritional countermeasures based on prebiotics and probiotics hold great promise to protect space travelers,” said Turroni.

So, what would these microbial treatments involve? They may be as simple as nutritionally balanced meals, with lots of fiber to kickstart microbial metabolism in the gut. Other options could be more targeted, including microbial supplements, such as bacteria that secrete immune-boosting substances, or those that synthesize vitamins required for bone growth.

In fact, there is a huge variety of pro-biotics and nutritional options to protect space travelers from specific issues they may encounter in space.

However, there is still plenty of work required to figure out which treatments are most effective and how best to use them for each space traveler.

“The well-being of the gut microbiome of space travelers should be among the primary goals of long-duration exploratory missions,” said Heer.

“To ensure the success of the mission, we must not overlook the myriad of microorganisms that reside in our gastrointestinal tract and make sure they are in balance.”

While future missions to Mars will undoubtedly look for evidence of microbial life on the red planet, this review suggests that it may be our homegrown microbes that get us there.

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Astronauts spending six months to a year at the International Space Station (ISS) undergo a wide variety of stresses that can impact crew health and productivity. These stresses range from environmental factors (e.g. microgravity and increased radiation) to social stresses (e.g. isolation, anxiety and sleep deprivation)1–4. Space flight presents the further danger of isolation from medical experts, making preventative measures to ensure astronaut health paramount.

For decades NASA has studied the effects of space travel on humans and has sought to identify factors that can be regulated to improve the chances of astronauts returning to Earth healthy3–7. As the duration of space missions increases, it becomes more and more important to maintain long term health in space to keep astronauts functioning at a high level3,8,9.

Previous inflight studies have shown that astronauts have reported a range of health issues ranging from GI distress, respiratory illness and skin irritation and infections10,11. Many of these symptoms have been associated with a weakening of the immune function as shown by reactivation of Epstein Bar Virus (EBV), and Varicella Zoster Virus (VZV) during space flight12,13.

Altered production of cytokines including increases in white blood cell counts have been measured during space flight and associated with altered adaptive immunity14. Further studies have shown astronauts experience immune dysregulation, changes in neutrophil functions, and neuroimmune response during space flight15–17.

A recent study documented a persistent skin rash in an astronaut at ISS that also correlated with immune dysregulation18. In addition to physiological changes and reductions in immune response experienced by astronauts, microgravity can also cause changes in homeostasis and microbial biochemistry19–21.

Terrestrial studies of the human microbiome suggest that many of the maladies experienced by astronauts can be caused or exacerbated by microbiome dysfunction.

Early astronaut microbiome studies documented the diversity of microbes associated with astronauts and the transfer of the pathogen Staphylococcus aureus from one astronaut to another22,23. While these early studies collected a wide range of samples, they were limited to investigating the small fraction of organisms that could be grown in pure culture.

This study documented the diversity of microbes associated with astronauts before, during and after long duration space missions at the ISS using culture independent 16S rRNA gene analysis. The evidence presented herein shows that space travel can have both transient and longer lasting impacts on the microbiome of astronauts, and that these changes are associated with alteration of immune function.

Impact of space travel on the alpha diversity of the astronaut’s microbiome

To measure changes to the diversity of crew microbiomes during space-travel we performed comparative analysis of the Shannon alpha diversity index and richness for each of the five human body locations surveyed (Fig. 3).

This analysis showed no alteration in alpha diversity or richness of the tongue microbiota associated with space travel. However, in the GI, Shannon alpha diversity and richness significantly increased in space and returned to their baseline preflight levels after crew members return to Earth (Fig. 3).

The only exception was AstB, whose GI microbiota had the highest preflight and postflight alpha diversity and species richness levels among all astronauts and did not significantly change over the course of the mission (Supplementary Fig. S4). In addition, we observed a significant reduction in alpha diversity of the nares microbiome during space flight that returned to preflight levels after returning to Earth.

Contrary to alpha diversity, overall species richness of nasal microbiota did not change significantly during the mission, indicating that the inflight changes in alpha diversity were due to a reorganization of the relative abundance of microbial taxa (Fig. 3).

Initial analysis of the two skin sites surveyed, forearm and forehead, revealed no consistent trend in the way the ISS environment affects the skin microbiota of individual crew members (Figs 3 and S4).

While Shannon alpha diversity and richness became significantly higher in the forearm skin during spaceflight, no change was evident in forehead skin samples. However, further inspection at the subject level showed that in five out of the nine astronauts’ forehead and forearm samples, skin alpha diversity and richness became significantly higher in space (Supplementary Figs S4 and S5) and remained elevated at least 60 days after their return to Earth.

In the remaining four astronauts, these two indexes showed a downward trend in space that changed to preflight levels after astronauts returned from space, except for forehead alpha diversity (Supplementary Figs S4 and S5). Notably, within the same subject, forehead and forearm skin microbiome samples showed similar upward or downward shifts (Supplementary Fig. S4).

Changes in beta diversity of the astronauts’ microbiota

To measure overall changes in astronaut microbiome composition associated with space travel we performed comparative weighted and unweighted beta diversity analyses of taxonomic profiles between pre, in and postflight samples (Fig. 4).

This comparison revealed inflight qualitative (unweighted) and quantitative (weighted) changes in the microbial composition of the GI and skin microbiomes that persisted in postflight samples (Fig. 4).

Spaceflight-associated changes in the nares microbiota were only significant when considering qualitative differences in the microbial composition between pre and inflight samples. These changes remained significant for at least 60 days after the return to Earth.

The tongue microbiota presented inflight changes associated with shifts in the relative abundance of bacterial species, but these quantitative differences disappeared once the crew returned to Earth (Fig. 4).

To determine the influence that the amount of time spent at ISS has in any observed changes in astronaut microbiomes, we compared inflight and postflight time points to all preflight time points (as a baseline) using the mean Bray-Curtis (BC) dissimilarity distance (Supplementary Fig. S6).

This analysis showed that compositional changes of the nose, skin and GI microbiomes were rapid and became evident by FD7. These changes persisted for at least six months until the end of the mission at the ISS.

Furthermore, beta diversity changes did not significantly increase with the time astronauts spent in space, although preflight-inflight BC distances of the two skin sites and the nose microbiota showed a very modest upward trend associated with time spent inflight (Supplementary Fig. S6).

In addition, compositional shifts in the skin and nose microbiomes persisted for at least 60 days after the astronauts returned to Earth. However, the composition of the GI microbiota became similar to preflight samples within two months of the astronauts’ return from the ISS.

Interestingly, PCoA plots of weighted dissimilarity distances showed that the GI microbiome became more similar across astronauts in space compared to preflight samples (Supplementary Fig. S7). The only exception was AstB, whose GI microbiome also had the highest preflight alpha diversity and richness values (Supplementary Fig. S4).

This inflight similarity tended to dissipate once astronauts returned to Earth but remained significantly closer than preflight samples within two months of the return to Earth.

Alteration of the microbial composition of the crew microbiome associated with the space environment

To investigate the influence of the ISS as a contained and human built environment on the crew microbiomes, differential abundance analysis of bacterial taxa was performed between samples collected before, during and after the mission to the ISS (Fig. 5, Supplementary Fig. S8 and Table S5).

In addition, for each of the five crew microbiomes, we defined a core microbiome, composed of all bacterial taxa that were represented in at least 75% of all preflight samples (Supplementary Table S6).

This analysis identified 17 gastrointestinal genera whose abundance significantly changed in space (adjusted p-value by the false discovery rate (FDR) < 0.05). Thirteen out of the 17 genera belonged to the Phylum Firmicutes, mostly to the order Clostridiales, with nine genera being part of the GI core microbiota (Fig. 5B and Supplementary Table S5).

Among these taxonomic groups, there was a more than five-fold inflight reduction in Akkermansia and Ruminococcus, and a ~3-fold drop in Pseudobutyrivibrio and Fusicatenibacter. Most of these compositional changes reverted to preflight levels after astronauts returned to Earth, with the exemption of two genera of the phylum Firmicutes.

Examination of skin samples also revealed changes in the relative abundance of several bacterial phylotypes during the space mission, corresponding to 49 and 43 genera in the forearm and forehead respectively, ten of which belonged to the respective core microbiomes (Fig. 5, Supplementary Fig. S8 and Table S5).

Noteworthy, skin microbial communities whose abundance decreased in space were mostly Gram-negative Proteobacteria with a predominance of Gamma and Betaproteobacteria. These groups included bacteria from the genus Moraxella, Pseudomonas and Acinetobacter.

In contrast, most of the skin bacteria that became more abundant inflight belonged to the phylum Firmicutes, Bacteroidetes and Actinobacteria, including bacteria of the genus Streptococcus, Staphylococcus and Corynebacterium.

Postflight samples showed a similar trend as inflight samples, with lower Proteobacteria and higher Firmicutes, Bacteroidetes and Actinobacteria compared to Preflight skin (Fig. 5 and Supplementary Fig. S8).

In addition, we observed a similar but milder response of the nares microbiota to the space environment with a significant drop in two genera of Gram-negative bacteria that were also reduced in skin (Fig. 5, Supplementary Fig. S8 and Table S5). Likewise, nose inflight samples showed increases in five bacterial genera, four of which became more abundant on the skin of astronauts inflight.

Five out of the seven genera that changed during spaceflight were also part of the nares core microbiome. Many of the observed changes in the nares microbiota dissipated after the astronauts returned to Earth, with higher abundance of Bifidobacterium and Akkermansia, and lower levels of Pseudoalteromonas in postflight samples. In the tongue, only two Gram-positive genera, that also belonged to the core microbiome, were found significantly reduced during spaceflight, Rothia and an unclassified genus of the family Corynebacteriaceae, which also remained reduced in postflight samples (Fig. 5 and Supplementary Table S5).

The analyses of alpha and beta diversity above showed that the GI microbiota of AstB was compositionally different and responded differently to the ISS environment compared to the GI microbiome of the other four astronauts that also collected inflight stool samples.

The composition of the GI microbiome of AstB was compared to that of Astronauts C, D, F, and G across either preflight or inflight samples (Supplementary Table S7). Those comparisons exposed three genera that were differentially abundant in both pre and inflight samples between AstB and the other four crew members.

Before flight, 23 genera differed between the two groups of samples. One third of them belonged to the families Lachnospiraceae and Ruminococcaceae and were particularly enriched in the GI microbiome of AstB, while genera from the families Prevotellaceae and Veillonellaceae were more predominant in the GI of the other four astronauts.

Among inflight samples there were 11 distinct genera between the GI microbiota of AstB and the other four crew members, with the GI microbiome of AstB having higher relative abundance of Akkermansia and lower levels of Bifidobacterium and Pseudobutyrivibrio. Contrary to AstB, the GI microbiota of astronauts C, D, F and G became more similar in space.

To identify the bacterial species that made the largest contribution to the compositional similarity across astronauts in space, we compared the coefficient of variation (CV) of their relative abundance among preflight versus inflight GI microbial samples.

This analysis revealed that only a few bacterial genera, including Pseudbutyrivibrio, Dorea, Ruminococcus 2, Bifidobacterium, Blautia, Fusicatenibacter and Akkermansia accounted for more than 90% of the total CV reduction observed in the GI microbiome of AstC, D, F and G during their trip to the ISS (Supplementary Fig. S9).

Identification of microbial changes associated with Astronauts’ immune dysregulation in space

To gain insights into the potential impact of changes to the microbiome during space flight on immune functioning, changes to cytokine abundance in plasma were compared to changes in the composition of the GI microbiome (Fig. 6, Tables 1 and S3).

With control of the false-discovery rate (FDR) to 5%, we found 10 significant changes (p < 0.0068) in cytokine concentrations at various time points relative to pre-flight. By FD10, analysis of plasma cytokine profiles did not reveal any significant change in cytokine concentrations relative to preflight levels except for anti-inflammatory protein IL-1ra that was slightly higher (Fig. 6).

However, by FD180 we observed a moderate but significant increase in the concentration of several pro-inflammatory cytokines, MCP-1, IL-8, IL-1b and MIP-1β, and a near significant rise in TNFa (p = 0.0075, FDR q-value = 0.055). In addition, we detected elevated inflight levels of cytokines IL-2 and IL-1ra. Cytokine concentrations reverted to preflight levels within two months of returning to Earth.

Table 1

Association between changes in cytokine concentrations and the relative abundance of GI microbiota during a mission at the ISS and the posterior return to Earth.

Cytokine	Cytokine vs GI microbiota correlation (D)	SE	Correlation p-value	Inflight cytokine change	OTU	Genus	Inflight OTU change
CXCL8/IL-8	−0.581	0.144	5.43E-05	↑	Otu000010	Fusicatenibacter	↓
IL-1B	−0.622	0.126	8.57E-07	↑	Otu000010	Fusicatenibacter	↓
−0.36	0.087	3.69E-05		Otu000011	Dorea	↓
TNFa	−0.467	0.099	2.32E-06	↑	Otu000010	Fusicatenibacter	↓
IL-17	0.464	0.114	4.35E-05	ns	Otu000054	Faecalibacterium	↑↑↑
IL-1ra	−0.5	0.12	3.09E-05	↑	Otu000011	Dorea	↓
−0.5	0.102	8.89E-07		Otu000028	Ruminococcus_2	↓↓↓
IFNg	0.618	0.12	2.85E-07	ns	Otu000038	Akkermansia	↓↓
−0.611	0.06	4.33E-24	ns	Otu000165	Lachnospiraceae (uncl.)	↑
IL-2				↑
IL-4	−0.622	0.155	5.87E-05	ns	Otu000010	Fusicatenibacter	↓
IL-10	−0.379	0.103	2.46E-04	ns	Otu001908	Roseburia	↓↓
G-CSF	−0.364	0.08	5.67E-06	ns	Otu000016	Blautia	↑↑
FGF basic	0.357	0.098	2.85E-04	ns	Otu000054	Faecalibacterium	↑↑↑
Tpo	0.352	0.099	3.71E-04	ns	Otu000071	Lachnospiraceae (uncl.)	↓↓
VEGF	−0.556	0.087	1.72E-10	ns	Otu000010	Fusicatenibacter	↓
−0.42	0.106	7.08E-05		Otu000011	Dorea	↓
CCL2/MCP-1				↑
CCL4/MIP-1B	−0.38	0.1	1.49E-04	↑	Otu000011	Dorea	↓
CCL5/RANTES	0.521	0.138	1.55E-04	ns	Otu000060	Lachnoclostridium	↑

Further correlation analysis identified strong evidence of an association between changes in astronauts’ GI microbiome and changes in cytokine profiles (Table 1). Most notably, the abundance of OTU000010 of the genus Fusicatenibacter was negatively correlated with the concentration of pro-inflammatory cytokines IL-8, IL-1b, IL4, and TNFa.

In addition, changes in OTU000011 of the genus Dorea were also negatively correlated with changes in the level of several cytokines including IL-1b, IL-1ra VEGF, and MIP-1b, all of which were increased in space

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616552/

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More information: Silvia Turroni et al, Gut Microbiome and Space Travelers’ Health: State of the Art and Possible Pro/Prebiotic Strategies for Long-Term Space Missions, Frontiers in Physiology (2020). DOI: 10.3389/fphys.2020.553929