NemaCapsules: microfluidics-integrated biocells for investigating C. elegans host-microbiome interactions in spaceflight

Abstract Spaceflight studies in humans show that microgravity alters the gut microbiome, posing a risk to health. Understanding how microbiomes and host genetics influence physiology is critical for long-duration missions. The low-cost spaceflight model C. elegans provides a suitable means to study host-microbiome interactions. However, whole-organism measurements are limited by lacking suitable flight-ready hardware that enables long-term nematode culture compatible with on-orbit imaging. These limitations were addressed through development of NemaCapsules— microfluidics-integrated biocells, for spaceflight assessment of C. elegans locomotion under defined microbiome conditions, with minimal astronaut workload. This provided a fully sealed, gas-permeable system with media reservoir, enabling passive, long-term nematode culturing. NemaCapsules were evaluated across four host strains and three model microbiomes. Multi-day worm viability studies demonstrated high resilience across diverse host strains and microbiomes except for daf-16 mutants. Crawling and swimming studies of worms with model microbiomes of C. elegans natural microbiota exhibited distinct locomotory activity from those exposed to E. coli OP50. Wild-type N2 generally exhibited the highest activity, followed by wild isolate strains; daf-16 mutants demonstrated lowest activity. Compared to crawling, swimming better revealed differences arising from host-microbiome interactions. NemaCapsules provide a modular solution for on-orbit, multi-functional readouts in C. elegans with minimal crew intervention.