Insights into the genetic influences of the microbiota on the life span of a host

Escherichia coli ( E. coli ) mutant strains have been reported to extend the life span of Caenorhabditis elegans ( C. elegans ). However, the specific mechanisms through which the genes and pathways affect aging are not yet clear. In this study, we fed Drosophila melanogaster (fruit fly) various E. coli single-gene knockout strains to screen mutant strains with an extended lifespan. The results showed that D. melanogaster fed with E. coli purE had the longest average lifespan, which was verified by C. elegans. We conducted a whole-genome sequencing and analysis of C. elegans fed with E. coli purE (a single-gene knockout mutant) to further explore the underlying molecular mechanism. We used the differential gene analysis (DGA), enrichment analysis, and gene set enrichment analysis (GSEA) to screen vital pathways and modules with significant changes in overall expression and two differential genes (cfz-2 and catp-4) associated with known longevity pathways. Our results suggest that E. coli mutant strains may affect the host lifespan by regulating the protein synthesis rate (cfz-2) and ATP level (catp-4). To conclude, our study could provide new insights into the genetic influences of the microbiota on the life span of a host and a basis for developing anti-aging probiotics and drugs.