Bacterial processing of glucose modulates C. elegans lifespan and healthspan

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 C. elegans-E. coli system. Our data reveal that bacterial processing of glucose, rather than direct ingestion by the animal, results in reduced lifespan and healthspan, including reduced locomotion, oxidative stress resistance, and heat stress resistance in C. elegans. Chronic exposure of E. coli to glucose produces growth defects and increased advanced glycation end products within the E. coli. 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 gst-4 shortens C. elegans lifespan and blunts the animal's response to a glucose-fed bacteria 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 the critical role of detoxification genes in maintaining health during a chronic high-sugar diet.

Increased fermentable carbohydrate intake alters colonic mucus barrier function through glycation processes and increased mast cell counts

“…We saw a prevention of these negative effects by co‐treatment with pyridoxamine, which is a known anti‐glycation agent, 27–30 which points to the involvement of glycation processes in the generation of these effects by the dietary interventions. Recently, elegant work by Kingsley and colleagues show that microbial processing of glucose plays a crucial role in the increased dicarbonyl stress and negative health effects of high sugar intake in a C. elegans model 31 . In our mouse model too, the increase in glycation most likely stems from elevated levels of microbial fermentation products, as proposed in the toxic bacterial metabolite hypothesis by Campbell et al 4 We have recently published results more broadly in support of this hypothesis; in a mouse model of IBS‐symptoms induced by fermentable carbohydrates, the increase in colonic epithelial AGER expression, the increase in mucosal mast cells, as well as the resulting abdominal hypersensitivity induced by elevated intake of the fermentable carbohydrates lactose and FOS could be prevented by anti‐glycation agent pyridoxamine 10 .…”

“…Recently, elegant work by Kingsley and colleagues show that microbial processing of glucose plays a crucial role in the increased dicarbonyl stress and negative health effects of high sugar intake in a C. elegans model. 31 In our mouse model too, the increase in glycation most likely stems from elevated levels of microbial fermentation products, as proposed in the toxic bacterial metabolite hypothesis by Campbell et al 4 We have recently published results more broadly in support of this hypothesis; in a mouse model of IBS-symptoms induced by fermentable carbohydrates, the increase in colonic epithelial AGER expression, the increase in mucosal mast cells, as well as the resulting abdominal hypersensitivity induced by elevated intake of the fermentable carbohydrates lactose and FOS could be prevented by anti-glycation agent pyridoxamine. 10 Reactive glycation agents interact with proteins to produce glycated residues, leading to the formation of AGEs, 6 which can directly stimulate mast cells, 8 and mast cells in turn are capable of causing mucus discharge by goblet cells.…”