DECOUPLING OF REPRODUCTION AND LIFESPAN TRADE-OFF IN CAENORHABDITIS ELEGANS THROUGH MICROBIAL PROGRAMMING

The microbiome is increasingly recognized as a major regulator of host physiology. Using the Caenorhabditis elegans model, we investigated how natural commensal bacteria modulate host reproduction and lifespan through internal egg hatching, a phenotype in which retained embryos hatch within the maternal body. Screening strains from the CeMbio collection identified four focal strains Ochrobactrum BH3, Lelliottia JUb66, Pantoea BIGb0393, and Enterobacter CEent1 that significantly increased internal egg hatching during the late reproductive period. This contrasts with pathogenic bacteria, which induce early-onset internal egg hatching. Across the focal strains, worms exhibited reduced total brood size but an expanded reproductive window relative to worms grown on the standard Escherichia coli OP50. To determine whether these microbial effects act through host insulin/IGF-1 signaling (IIS), internal egg hatching was quantified in IIS mutants. In BH3 this phenotype likely acts via DAF-16/FOXO. In JUb66. BIGb0393, and CEent1, the phenotype likely acts independently of DAF-16. Lifespan analyses further demonstrated bacterial specificity, BH3 uniquely extended host lifespan, whereas the remaining three strains reduced lifespan relative to OP50. Together, these results show that natural commensal bacteria can reshape host reproductive timing, internal hatching dynamics, and longevity. This work underscores the microbiome as a potent driver of life-history variation in C. elegans.