Sun Junjie, Moon Yuseok
Laboratory of Food Systems Analytics, Department of Data Science, School of Data Science, Pusan National University, Busan 46241, Republic of Korea.
Department of Foodtech and PNU-Korea Maritime Institute (KMI) Collaborative Research Center, Pusan National University, Busan 46241, Republic of Korea.
Antioxidants (Basel). 2025 Jul 24;14(8):905. doi: 10.3390/antiox14080905.
The intestinal barrier governs organismal health through nutrient absorption, microbial homeostasis, and immune surveillance. While calorie restriction (CR) enhances metabolic health, the molecular mechanisms underlying its beneficial effects on gut integrity remain unclear. Here, we demonstrate that the aryl hydrocarbon receptor (AHR), a conserved xenobiotic sensor and metabolic regulator, is essential for CR-mediated improvements in intestinal function. Using (), we subjected wild-type (N2) and AHR-deficient strains (CZ2485 and ZG24) to ad libitum feeding (AL), intermittent fasting (IF), or complete food deprivation (FD). In wild-type animals, intermittent fasting markedly reduced intestinal permeability and bacterial burden while enhancing mitochondrial function and reducing reactive oxygen species. Complete food deprivation conferred modest benefits. Remarkably, these protective effects were severely compromised in AHR mutants, which exhibited increased gut leakage, bacterial colonization, and mitochondrial oxidative stress under fasting conditions. These findings establish AHR as a critical mediator of fasting-induced intestinal resilience, revealing a previously unrecognized regulatory axis linking metabolic sensing to gut barrier homeostasis. Our work illuminates fundamental mechanisms through which calorie restriction promotes gastrointestinal health and identifies AHR-dependent pathways as promising therapeutic targets for metabolic and inflammatory distress affecting the gut-systemic interface.
肠道屏障通过营养吸收、微生物稳态和免疫监视来维持机体健康。虽然热量限制（CR）可增强代谢健康，但其对肠道完整性产生有益影响的分子机制仍不清楚。在此，我们证明芳烃受体（AHR），一种保守的外源性物质传感器和代谢调节因子，对于CR介导的肠道功能改善至关重要。我们使用（），对野生型（N2）和AHR缺陷型菌株（CZ2485和ZG24）进行随意进食（AL）、间歇性禁食（IF）或完全食物剥夺（FD）。在野生型动物中，间歇性禁食显著降低了肠道通透性和细菌负荷，同时增强了线粒体功能并减少了活性氧。完全食物剥夺带来的益处不大。值得注意的是，这些保护作用在AHR突变体中严重受损，这些突变体在禁食条件下表现出肠道渗漏增加、细菌定植和线粒体氧化应激。这些发现确立了AHR作为禁食诱导的肠道恢复力的关键介质，揭示了一个以前未被认识的将代谢感知与肠道屏障稳态联系起来的调节轴。我们的工作阐明了热量限制促进胃肠道健康的基本机制，并确定AHR依赖性途径是影响肠道-全身界面的代谢和炎症应激的有希望的治疗靶点。
