Glucomannan Hydrolysate Promotes Gut Proliferative Homeostasis and Extends Life Span in Drosophila melanogaster

Dietary supplementation of glucomannan has been shown to have multiple health benefits, but its effect on life span has not been investigated. Here, we show that glucomannan hydrolysate (GMH) treatment extends mean life span of the model organism Drosophila melanogaster. To unravel the underlying mechanisms, we first examined the effect of GMH on the gut microbiota. We found that GMH treatment is associated with an elevated bacterial load in aged flies but overall has limited effects on the relative microbiota composition. We also demonstrated that GMH inhibits age-associated hyperproliferation of intestinal stem cells and thus delays the deterioration of gut integrity. Further analysis of the midgut transcriptome revealed that both EGFR/MAPK and JAK/STAT signaling pathways are suppressed in GMH groups. Multiple key regulators or effectors of EGFR/MAPK pathway, Ets21c, Mkp3, and Rho, are downregulated by GMH treatment. In the JAK/STAT pathway, major ligands (eg, Upd2 and Upd3) and negative feedback inhibitors (eg, Socs36e) are all significantly downregulated. Additionally, the expression of genes encoding antimicrobial peptides is elevated by GMH treatment. Taken together, our study shows that dietary supplementation of GMH can prolong life span, possibly through regulating gut proliferative homeostasis.