<i>Lacticaseibacillus casei</i> HY2782 improves the intestinal barrier and tract environment and ultimately prolongs the lifespan of <i>Caenorhabditis elegans</i>

<i>Caenorhabditis elegans</i> 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 <i>C. elegans</i> by evaluating the gastrointestinal tract conditions and intestinal permeability of <i>C. elegans</i> fed <i>Lacticaseibacillus casei</i> HY2782 alone or fermented fecal products. The anti-inflammatory effects of <i>L. casei</i> HY2782 were determined based on interleukin 8 (IL-8) levels and intestinal permeability in human intestinal epithelial cells. In the <i>C. elegans</i> model, intestinal permeability was assessed in the N2 wild-type as well as <i>skn-1</i>, <i>pmk-1</i>, <i>daf-16</i>, and <i>aak-2</i> mutant worms. During simulated colonic fecal fermentation, changes in short chain fatty acid and microbial composition were investigated. <i>L. casei</i> HY2782 reduced IL-8 production and intestinal permeability from 1646.8 to 1009.1 pg mL^-1 and 265.5 to 115.1%, respectively (<i>p</i> < 0.01). Additionally, <i>L. casei</i> HY2872 attenuated intestinal leakage in <i>C. elegans</i> and prolonged its lifespan <i>via</i> the DAF-16/FOXO and SKN-1/NRF2 pathways and <i>gst-4</i> gene expression. Moreover, <i>L. casei</i> HY2782 inhibited intestinal leakage in aged worms. During fermentation, <i>L. casei</i> HY2782 produced butyrate under both normal and high-protein conditions. Additionally, <i>L. casei</i> HY2782 contributed to butyrate production by genera, such as <i>Faecalibacterium</i> and <i>Lachnospira</i> (<i>p</i> < 0.01), while inhibiting <i>Fusobacterium</i> (<i>p</i> < 0.05). <i>L. casei</i> HY2782 also prolonged lifespan of intestinally damaged worms (<i>p</i> < 0.001). Furthermore, <i>C. elegans</i> fed <i>L. casei</i> HY2782-fermented fecal products lived significantly longer than those fed the vehicle control (<i>p</i> < 0.001). Overall, <i>L. casei</i> HY2782 restored the intestinal tract by mitigating inflammation and microbial metabolic dysbiosis, ultimately extending the lifespan of <i>C. elegans</i>.