Optogenetic control of gut bacterial metabolism to promote longevity

Abstract Gut microbial metabolism is associated with host longevity. However, because it requires direct manipulation of microbial metabolism in situ, establishing a causal link between these two processes remains challenging. We demonstrate an optogenetic method to control gene expression and metabolite production from bacteria residing in the host gut. We genetically engineer an Escherichia coli strain that synthesizes and secretes colanic acid (CA) under the quantitative control of light. Using this optogenetically-controlled strain to induce CA production directly in the Caenorhabditis elegans gut, we reveal the local effect of CA in protecting intestinal mitochondria from stress-induced hyper-fragmentation. We also exploit different intensities of light to determine that the lifespan-extending effect of CA is positively correlated with its levels produced from bacteria. Our results show that optogenetic control offers a rapid, reversible and quantitative way to fine-tune gut bacterial metabolism and uncover its local and systemic effects on host health and aging.