Vidal, Daniela, Edwards, Hunter, Samuel, Buck, Vanpalli, Siva, Anupom, Taslim, Zhang, Fan
[
International Worm Meeting,
2021]
Dysregulation of the human gut microbiome has been linked to the development of many human diseases, including inflammatory disorders such as irritable bowel syndrome and ulcerative colitis. Moreover, studies have shown that the microorganisms colonizing the GI tract interact extensively with host signaling pathways, including the highly conserved ageing-related Insulin/IGF signaling pathway. The mechanisms by which the gut microbiota influences host gene expression and physiology remains unclear. With a rapid lifespan of less than one month, C. elegans have been used to study the relationship between host phenotypes and gene expression for decades. C. elegans are typically grown on a non-native singular food source, E. coli OP50, selected for its accessibility and ease of growth in the laboratory environment. The versatility of the soil dwelling nematode offers a unique platform to study complex microbial communities in a well-defined gnotobiotic environment, however very little is known about the effects of non-E.coli bacteria on C. elegans health and survival. Here we conduct comprehensive screen of select individual bacteria isolated from natural C. elegans microbiome. Sterile C. elegans can be housed in pillared microfluidic chambers where bacterial membership can be precisely controlled and readily delivered to control quality and quantity of the bacteria. Using this platform, we show that individual members of the natural microbiome colonize the C. elegans gut and exert variable effects on host physiology including delayed development and growth, stress resistance and survival. Specifically, we find that two bacterial isolates, which dominate the guts of C. elegans, Ochrobactrum BH3 and Myroides BIGb0244, extend lifespan and healthspan in our semi-liquid microfluidic environment. Our results lay the foundation for future, high-throughput screens of larger communities and panels of microbes, such as the BIGbiome and CeMbio model microbiomes. This robust system will allow for simultaneous and comprehensive assessment of the effects of both individual isolates and multi-member communities on host gene expression and aging related phenotypes.