College of Pharmacy, Gachon University, Incheon 21936, Korea.
College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Int J Mol Sci. 2021 Jun 17;22(12):6515. doi: 10.3390/ijms22126515.
Leaky gut is a condition of increased paracellular permeability of the intestine due to compromised tight junction barriers. In recent years, this affliction has drawn the attention of scientists from different fields, as a myriad of studies prosecuted it to be the silent culprit of various immune diseases. Due to various controversies surrounding its culpability in the clinic, approaches to leaky gut are restricted in maintaining a healthy lifestyle, avoiding irritating factors, and practicing alternative medicine, including the consumption of supplements. In the current study, we investigate the tight junction-modulating effects of processed gel (PAG), comprising 5-400-kD polysaccharides as the main components. Our results show that oral treatment of 143 mg/kg PAG daily for 10 days improves the age-related leaky gut condition in old mice, by reducing their individual urinal lactulose/mannitol (L/M) ratio. In concordance with in vivo experiments, PAG treatment at dose 400 μg/mL accelerated the polarization process of Caco-2 monolayers. The underlying mechanism was attributed to enhancement in the expression of intestinal tight junction-associated scaffold protein zonula occludens (ZO)-1 at the translation level. This was induced by activation of the MAPK/ERK signaling pathway, which inhibits the translation repressor 4E-BP1. In conclusion, we propose that consuming PAG as a complementary food has the potential to benefit high-risk patients.
肠漏是一种由于紧密连接屏障受损导致肠道旁细胞通透性增加的病症。近年来，这种疾病引起了来自不同领域的科学家的关注，因为大量的研究表明它是各种免疫疾病的潜在元凶。由于其在临床上的罪责存在各种争议，肠漏的治疗方法仅限于保持健康的生活方式、避免刺激因素和采用替代医学，包括补充剂的摄入。在本研究中，我们研究了由 5-400kD 多糖组成的加工凝胶（PAG）对紧密连接的调节作用。我们的结果表明，每天口服 143mg/kg PAG 连续 10 天，可以改善老年小鼠的年龄相关肠漏情况，降低其个体尿中乳果糖/甘露醇（L/M）比值。与体内实验一致，400μg/mL 的 PAG 处理加速了 Caco-2 单层的极化过程。其潜在机制归因于肠道紧密连接相关支架蛋白封闭蛋白（ZO）-1的表达在翻译水平上的增强。这是通过激活 MAPK/ERK 信号通路来实现的，该通路抑制翻译抑制剂 4E-BP1。总之，我们提出食用 PAG 作为补充食品可能对高危患者有益。
