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SIRIUS in Space: The ISS metabolome

As we prepare for longer human missions beyond Earth, understanding the invisible ecosystems of space habitats has become critical for astronaut health. The International Space Station (ISS) is not just a home and laboratory—it is also a closed microbial and chemical environment unlike anything on Earth. This study mapped the ISS microbiome and metabolome in unprecedented detail, uncovering its vast chemical “dark matter” using SIRIUS.
The International Space Station (ISS) is a unique, closed system, entirely isolated from Earth. (Photo by NASA on Unsplash)

As humanity pushes the boundaries of long-duration space travel, a comprehensive understanding of the isolated, built environments that astronauts inhabit is crucial for maintaining their health. The International Space Station (ISS) is a unique, closed system, entirely isolated from Earth, presenting unique challenges for the health of its inhabitants.

Astronauts commonly experience persistent rashes, atypical allergies, and spaceflight-associated immune dysfunction1. A common issue is the reactivation of latent viruses during spaceflight2 and fungal or bacterial infections. This heightened vulnerability is compounded by the fact that spaceflight can increase antimicrobial resistance, biofilm formation, and the virulence of microorganisms3.

The Problem with Space Environments

The environment on the ISS, and other long-duration space habitats, presents several potential threats to astronaut health4,5. Studies have found chemical contaminants on the ISS that exceed levels seen in terrestrial indoor environments6. Modern life has introduced human-made compounds like medications, pesticides, and plasticizers that were not present in our evolutionary history7. Many of these synthetic chemicals are associated with adverse health effects such as cancer, endocrine disruption, and neurotoxicity8.

Another notable concern is the lack of beneficial microbes. This is significant because reduced exposure to diverse microbes, a consequence of modern indoor living and hygiene, is increasingly linked to chronic inflammatory diseases in developed nations9.

An ISS 3D-Map

A recent study by a large research team led by Pieter Dorrestein and Rob Knight from UC San Diego provided the most extensive dataset to date on the microbial and chemical landscape of a space habitat10. The research team conducted a three-dimensional microbial mapping survey by analysing 803 surface samples from the United States Orbital Segment of the ISS. Using multi-omic sequencing and metabolomics, they created a comprehensive 3D map to understand how the unique space environment, isolated from Earth, shapes its microbiology and chemistry.

The ISS Microbiome: Striking Loss of Diversity

When compared with thousands of samples from built and natural environments on Earth, the ISS exhibits a striking loss of microbial diversity. This positions the space station at the extreme end of an urbanization gradient, representing a highly controlled and industrialized environment with limited exposure to the free-living microbes common on Earth.

The study found that each ISS module possesses a distinct microbial composition, driven more by the activities performed within them than by shared environmental conditions like atmospheric pressure. For instance, the dining unit showed higher contributions from food-related microbes, while the Waste and Hygiene Compartment had signatures linked to human waste.

Source tracking analysis revealed that human skin is the primary source of microbes on ISS surfaces. The microbiota is dominated by human-associated microbes, such as Staphylococcus, and lacks the terrestrial, environmentally associated microbes typically found on Earth. The study identified numerous antimicrobial resistance genes and genomes of high-risk ESKAPE pathogens. The study also detected human viruses known to reactivate during spaceflight, including Epstein-Barr virus, demonstrating the potential for environmental surveillance to provide non-invasive insights into crew health.

ESKAPE11 is an acronym for a group of six bacteria that are the leading cause of hospital-acquired (nosocomial) infections and are notable for their ability to “escape” the effects of commonly used antibiotics. These pathogens are a major global health threat due to their high virulence and potential to develop multidrug resistance. The acronym stands for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.

The ISS Metabolome: Uncovering Chemical Dark Matter with SIRIUS

Untargeted metabolomics was used to inventory the detectable molecules on ISS surfaces. However, traditional annotation methods fell short, as only about 3% of the chemical features could be annotated by matching them against existing spectral libraries. This “dark matter” of unknown molecules required advanced computational tools.

SIRIUS was employed to analyse the vast number of unknown molecules. The software was used to predict molecular formulas, generate molecular fingerprints, and predict the compound classes. SIRIUS dramatically increased the chemical characterization at the chemical class level from 3% to nearly complete coverage (97%). Molecules were hierarchically clustered using Qemistree12, to generate a tree-based visualization for the structural relationships between features. 

The study revealed a deeper understanding of the ISS metabolome. The researchers found distinct “chemical hotspots” linked to module function. For example, corrosion inhibitors were found near exercise equipment, urinary metabolites near the Waste and Hygiene Compartment, and food-related compounds at the dining table. The ISS metabolome is dominated by human inputs, sharing many synthetic chemicals with urban homes on Earth, such as polyethylene glycol surfactants and quaternary ammonium disinfectants. The study also found that disinfection activities significantly influenced the chemical profiles on ISS surfaces. Interestingly, the signal intensity of cleaning products showed a positive correlation with microbial diversity. This could be due to two reasons. It’s possible that cleaning chemicals are applied more frequently and intensively to areas that already have a high concentration of microbes, like hygiene and exercise modules. Alternatively, disinfection might create a “clean slate” effect that promotes new bacterial colonization. This isn’t unique to space; a similar positive correlation between cleaning product usage and fungal diversity has been observed in terrestrial homes13.

Future Space Habitats

This study provides an essential baseline for designing future space habitats. The ISS is an extreme example of an industrialized, human-input-dominated built environment, characterized by a striking loss of microbial diversity compared to built and natural environments on Earth. By leveraging SIRIUS to overcome the limitations of sparse spectral libraries, the research team was able to characterize the uncharted territory of the ISS metabolome. The findings could inform zoning strategies to isolate high bio-burden areas, such as hygiene and exercise modules, in future space habitats.

References
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  2. Mehta SK, Laudenslager ML, Stowe RP, Crucian BE, Sams CF, Pierson DL. Multiple latent viruses reactivate in astronauts during Space Shuttle missions. Brain Behav Immun. 2014 Oct;41:210-7. doi: 10.1016/j.bbi.2014.05.014. ↩︎
  3. Bijlani S, Stephens E, Singh NK, Venkateswaran K, Wang CCC. Advances in space microbiology. iScience. 2021 Apr 3;24(5):102395. doi: 10.1016/j.isci.2021.102395. ↩︎
  4. Novikova N, De Boever P, Poddubko S, Deshevaya E, Polikarpov N, Rakova N, Coninx I, Mergeay M. Survey of environmental biocontamination on board the International Space Station. Res Microbiol. 2006 Jan-Feb;157(1):5-12. doi: 10.1016/j.resmic.2005.07.010. ↩︎
  5. Mora M, Wink L, Kögler I, Mahnert A, Rettberg P, Schwendner P, Demets R, Cockell C, Alekhova T, Klingl A, Krause R, Zolotariof A, Alexandrova A, Moissl-Eichinger C. Space Station conditions are selective but do not alter microbial characteristics relevant to human health. Nat Commun. 2019 Sep 5;10(1):3990. doi: 10.1038/s41467-019-11682-z. ↩︎
  6. Harrad S, Abdallah MA, Drage D, Meyer M. Persistent Organic Contaminants in Dust from the International Space Station. Environ Sci Technol Lett. 2023 Aug 8;10(9):768-772. doi: 10.1021/acs.estlett.3c00448. ↩︎
  7. Vermeulen R, Schymanski EL, Barabási AL, Miller GW. The exposome and health: Where chemistry meets biology. Science. 2020 Jan 24;367(6476):392-396. doi: 10.1126/science.aay3164. ↩︎
  8. Johnson AC, Jin X, Nakada N, Sumpter JP. Learning from the past and considering the future of chemicals in the environment. Science. 2020 Jan 24;367(6476):384-387. doi: 10.1126/science.aay6637 ↩︎
  9. Sonnenburg JL, Sonnenburg ED. Vulnerability of the industrialized microbiota. Science. 2019 Oct 25;366(6464):eaaw9255. doi: 10.1126/science.aaw9255. ↩︎
  10. Salido RA, Zhao HN, McDonald D, Mannochio-Russo H, Zuffa S, Oles RE, Aron AT, El Abiead Y, Farmer S, González A, Martino C, Mohanty I, Parker CW, Patel L, Portal Gomes PW, Schmid R, Schwartz T, Zhu J, Barratt MR, Rubins KH, Chu H, Karouia F, Venkateswaran K, Dorrestein PC, Knight R. The International Space Station has a unique and extreme microbial and chemical environment driven by use patterns. Cell. 2025 Apr 3;188(7):2022-2041.e23. doi: 10.1016/j.cell.2025.01.039. ↩︎
  11. Mulani MS, Kamble EE, Kumkar SN, Tawre MS, Pardesi KR. Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review. Front Microbiol. 2019 Apr 1;10:539. doi: 10.3389/fmicb.2019.00539. ↩︎
  12. Tripathi A, Vázquez-Baeza Y, Gauglitz JM, Wang M, Dührkop K, Nothias-Esposito M, Acharya DD, Ernst M, van der Hooft JJJ, Zhu Q, McDonald D, Brejnrod AD, Gonzalez A, Handelsman J, Fleischauer M, Ludwig M, Böcker S, Nothias LF, Knight R, Dorrestein PC. Chemically informed analyses of metabolomics mass spectrometry data with Qemistree. Nat Chem Biol. 2021 Feb;17(2):146-151. doi: 10.1038/s41589-020-00677-3. ↩︎
  13. McCall LI, Callewaert C, Zhu Q, Song SJ, Bouslimani A, Minich JJ, Ernst M, Ruiz-Calderon JF, Cavallin H, Pereira HS, Novoselac A, Hernandez J, Rios R, Branch OH, Blaser MJ, Paulino LC, Dorrestein PC, Knight R, Dominguez-Bello MG. Home chemical and microbial transitions across urbanization. Nat Microbiol. 2020 Jan;5(1):108-115. doi: 10.1038/s41564-019-0593-4. ↩︎

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