HY2782 improves the intestinal barrier and tract environment and ultimately prolongs the lifespan of .

is widely used as a model for investigating longevity owing to its short life cycle and the presence of human orthologs. This study aimed to ultimately prolong the lifespan of by evaluating the gastrointestinal tract conditions and intestinal permeability of fed HY2782 alone or fermented fecal products. The anti-inflammatory effects of HY2782 were determined based on interleukin 8 (IL-8) levels and intestinal permeability in human intestinal epithelial cells. In the model, intestinal permeability was assessed in the N2 wild-type as well as , , , and mutant worms. During simulated colonic fecal fermentation, changes in short chain fatty acid and microbial composition were investigated. HY2782 reduced IL-8 production and intestinal permeability from 1646.8 to 1009.1 pg mL and 265.5 to 115.1%, respectively ( < 0.01). Additionally, HY2872 attenuated intestinal leakage in and prolonged its lifespan the DAF-16/FOXO and SKN-1/NRF2 pathways and gene expression. Moreover, HY2782 inhibited intestinal leakage in aged worms. During fermentation, HY2782 produced butyrate under both normal and high-protein conditions. Additionally, HY2782 contributed to butyrate production by genera, such as and ( < 0.01), while inhibiting ( < 0.05). HY2782 also prolonged lifespan of intestinally damaged worms ( < 0.001). Furthermore, fed HY2782-fermented fecal products lived significantly longer than those fed the vehicle control ( < 0.001). Overall, HY2782 restored the intestinal tract by mitigating inflammation and microbial metabolic dysbiosis, ultimately extending the lifespan of .