Light Controlled Production of Metabolites to Better Understand the Role of Gut Microbes in Health

The activities of the gut microbiome are clearly influential on long-term health and aging, and evidence suggests that this is perhaps a similarly sized effect to that of exercise. The gut microbiome changes with age, and while researchers have identified a number of microbial metabolites and species in which this shift can negatively affect health, such as by promoting chronic inflammation, the mapping of the microbiome and its relationship with aging is still in its early stages. Better tools will be needed in order to pick apart the relationships through item by item analysis of specific species and metabolites, and here researchers demonstrate one such tool.

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 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 demonstrate that the lifespan-extending effect of this strain is positively correlated with the intensity of green light, indicating a dose-dependent CA benefit on the host. Thus, optogenetics can be used to achieve quantitative and temporal control of gut bacterial metabolism in order to reveal its local and systemic effects on host health and aging.

Link: https://doi.org/10.7554/eLife.56849

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