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 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.
Highlights
Microbiome studies have identified correlations between bacteria and host aging (Kundu et al, 2017; O’Toole and Jeffery, 2015)
Our experiments reveal that green light-induced colanic acid (CA) from bacteria residing in the host gut is sufficient to modulate mitochondrial dynamics and lifespan
By using light to induce their expression in the gut and measuring acute host responses such as changes in mitochondrial dynamics, the role of these genes in gut microbe-host interactions could be further explored
Summary
Microbiome studies have identified correlations between bacteria and host aging (Kundu et al, 2017; O’Toole and Jeffery, 2015). Recent studies have revealed that bacterial metabolism can produce specific products to directly influence the aging process in the host C. elegans or modulate the effects of environmental cues on C. elegans lifespan (Cabreiro et al, 2013; Pryor et al, 2019; Virk et al, 2016). These findings highlight the significance of bacterial metabolism in regulating host physiology during the aging process and have inspired interest in directly manipulating bacterial metabolism in situ in the host gastrointestinal (GI) tract
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