Optogenetic control of gut bacterial metabolism

Gut bacteria produce a wide range of metabolites that impact host biology. However, in situ studies of microbe-host interactions are challenging due to the poor accessibility of the gut environment. Here, we develop a method wherein light is used to remotely control E. coli gene expression in the C. elegans gastrointestinal tract. We go on to engineer an E. coli strain from which secretion of the longevity-enhancing exopolysaccharide colanic acid (CA) is regulated by light. We then combine this strain with our optogenetic method to discover that CA produced by gut bacteria protects intestinal mitochondria from stress-induced hyper-fragmentation. Finally, we exploit the quantitative control of CA secretion afforded by light to reveal that CA extends worm lifespan in a dose-dependent manner. Optogenetic control of gut bacterial metabolism will enable new mechanistic studies of how the microbiome impacts health and disease.