Bae Won-Young, Nguyen Uyen Tran Tu, Le Tram Anh Ngoc, Tran Son Hung, Lee Sohyun, Hong Sung-Chul, Cha Kwang Hyun, Choi Il-Dong, Kang Kyungsu
Center for Natural Product Systems Biology, Gangneung Institute of Natural Products, Korea Institute of Science and Technology (KIST), Gangneung, Gangwon-do, 25451, South Korea.
Natural Product Applied Science, KIST School, University of Science and Technology (UST), Gangneung, Gangwon-do, 25451, South Korea.
Food Funct. 2025 Jul 14;16(14):5871-5884. doi: 10.1039/d5fo01239b.
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 .
由于其短生命周期和人类直系同源基因的存在，它被广泛用作研究长寿的模型。本研究旨在通过评估单独喂食HY2782或发酵粪便产物的秀丽隐杆线虫的胃肠道状况和肠道通透性，最终延长其寿命。基于人肠上皮细胞中的白细胞介素8（IL-8）水平和肠道通透性确定了HY2782的抗炎作用。在秀丽隐杆线虫模型中，在N2野生型以及daf-16、skn-1、age-1和eat-2突变体蠕虫中评估了肠道通透性。在模拟结肠粪便发酵过程中，研究了短链脂肪酸和微生物组成的变化。HY2782使IL-8产生量从1646.8降至1009.1 pg/mL，肠道通透性从265.5%降至115.1%（P<0.01）。此外，HY2872减轻了秀丽隐杆线虫的肠道渗漏，并通过DAF-16/FOXO和SKN-1/NRF2途径以及hsp-16.2基因表达延长了其寿命。此外，HY2782抑制了老龄蠕虫的肠道渗漏。在发酵过程中，HY2782在正常和高蛋白条件下均产生丁酸盐。此外，HY2782促进了丁酸弧菌属和真杆菌属等属的丁酸盐产生（P<
