Genome-wide screening to find potential pro-longevity gut microbes using Caenorhabditis elegans / Escherichia coli system

In humans, the number of gut microbes reach to 10 times of human cells. Gut microbes play a variety of roles such as metabolism of non-digestible sugars, defense against pathogenic bacteria, supplying vitamin, and the development of the host immune system. Imbalance of gut microbes can cause many diseases such as not only gastrointestinal disorders but also obesity, cancer, metabolic syndrome, autoimmune diseases. Although most of these diseases are associated with aging, gut microbes and host correlation in aging is unknown. Here, we suggested that Escherichia coli and Caenorhabditis elegans as simple model system to study genetic interaction between gut microbes and host. Using Keio Collection, E. coli single gene knock out library, we performed genome-wide lifespan screening, measuring the survival rates of C. elegans fed E. coli single gene mutant. Consequently, we isolated 17 E. coli mutants which extend the lifespan of C. elegans and 25 E. coli mutants to reduce the lifespan of C. elegans by the extent of 20% thresholds. In this study, we show that E. coli lic2 mutant extend the lifespan of C. elegans by activating C. elegans daf-16 (mammalian FOXO ortholog). Currently, we are trying to reveal molecular mechanisms of this lifespan extension phenomenon. Through lifespan assay, we found that upstream of daf-16 which is activated by E. coli lic2 mutant is mTORC2 not IIS. Subsequently RNA seq was performed to find daf-16 downstream target genes, and we identified that target gene expression pattern activated by E. coli lic2 mutant is different from IIS. These data will provide molecular mechanisms regarding how gut microbes regulate host aging.