Abstract
Intestinal microbiota play an essential role in the health of a host organism. Here, we define how commensal Escherichia coli (E. coli) alters its host after long term exposure to glucose using a Caenorhabditis elegans-E. coli system where only the bacteria have direct contact with glucose. Our data reveal that bacterial processing of glucose results in reduced lifespan and healthspan including reduced locomotion, oxidative stress resistance, and heat stress resistance in C. elegans. With chronic exposure to glucose, E. coli exhibits growth defects and increased advanced glycation end products. These negative effects are abrogated when the E. coli is not able to process the additional glucose and by the addition of the anti-glycation compound carnosine. Physiological changes of the host C. elegans are accompanied by dysregulation of detoxifying genes including glyoxalase, glutathione-S-transferase, and superoxide dismutase. Loss of the glutathione-S-transferase, gst-4 shortens C. elegans lifespan and blunts the animal's response to a glucose fed bacterial diet. Taken together, we reveal that added dietary sugar may alter intestinal microbial E. coli to decrease lifespan and healthspan of the host and define a critical role of detoxification genes in maintaining health during a chronic high-sugar diet.
Highlights
Intestinal microbiota play an essential role in the health of a host organism
We questioned the mechanism of the high glucose effect: was the effect attributable to direct contact with sugar by the worm, the bacteria, or both? These previous published protocols have variations with regard to how the glucose was applied to the agar, whether the bacteria were alive or dead, how the bacteria were killed, whether the bacteria had any direct contact with the g lucose[16,17,18,19,20,21], and the age of animal exposed to the g lucose[22,23]
Studies on the effects of glucose toxicity in C. elegans altered several variables including the age of animal exposed to the g lucose[22,23], whether the bacterial diet was alive or dead, and the duration of and exposure time of the E. coli and C. elegans to g lucose[16,17,18,19,20,21]
Summary
Intestinal microbiota play an essential role in the health of a host organism. Here, we define how commensal Escherichia coli (E. coli) alters its host after long term exposure to glucose using a Caenorhabditis elegans-E. coli system where only the bacteria have direct contact with glucose. We reveal that added dietary sugar may alter intestinal microbial E. coli to decrease lifespan and healthspan of the host and define a critical role of detoxification genes in maintaining health during a chronic high-sugar diet. Studies on the effects of a high-glucose diet in C. elegans involved adding glucose either to the agar media directly or to the top of the agar medium growth p late[16,17,18,19,20,21] This high glucose diet led to a decreased lifespan, reduced healthspan (locomotion), and changes in fat storage. To separate the effects of C. elegans consuming a glucose fed bacteria diet, here, we developed a new experimental procedure based on previous studies 26 In this new protocol, prior to seeding the bacteria on the plate, the bacteria are incubated with or without glucose for three days. This protocol is unique since it allows us to control contact between the glucose and C. elegans
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