Food Microbiology and Function Research Laboratories, Division of Research and Development, Meiji Co., Ltd., Hachiouji, Tokyo 192-0919, Japan.
Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Nutrients. 2023 Jun 7;15(12):2655. doi: 10.3390/nu15122655.
Autophagy is an important system conserved in eukaryotes that maintains homeostasis by degrading abnormal proteins. Autophagy incompetence in intestinal epithelial cells causes the abnormal function of intestinal stem cells and other cells and damages intestinal barrier function. The disruption of the intestinal barrier causes chronic inflammation throughout the body, followed by impaired glucose and lipid metabolism. OLL2712 (OLL2712) is a lactic acid bacterium that induces interleukin-10 production from immune cells, alleviates chronic inflammation, and improves glucose and lipid metabolism. In this study, we hypothesized that OLL2712 exerts anti-inflammatory effects by inducing autophagy and ameliorating intestinal barrier dysfunction, and we investigated its autophagy-inducing activities and functions. Caco-2 cells stimulated with OLL2712 for 24 h showed an increased number of autolysosomes per cell, compared with unstimulated cells. Therefore, the permeability of fluorescein isothiocyanate dextran 4000 (FD-4) was suppressed by inducing autophagy. In contrast, mucin secretion in HT-29-MTX-E12 cells was also increased by OLL2712 but not via autophagy induction. Finally, the signaling pathway involved in autophagy induction by OLL2712 was found to be mediated by myeloid differentiation factor 88 (MYD88). In conclusion, our findings suggest that OLL2712 induces autophagy in intestinal epithelial cells via MYD88, and that mucosal barrier function is strengthened by inducing autophagy.
自噬是真核生物中一种重要的系统，通过降解异常蛋白质来维持体内平衡。肠上皮细胞中的自噬功能不全会导致肠干细胞和其他细胞的异常功能，并损害肠道屏障功能。肠道屏障的破坏会导致全身慢性炎症，随后出现葡萄糖和脂质代谢受损。OLL2712（OLL2712）是一种乳酸菌，它能诱导免疫细胞产生白细胞介素-10，减轻慢性炎症，改善葡萄糖和脂质代谢。在这项研究中，我们假设 OLL2712 通过诱导自噬和改善肠道屏障功能来发挥抗炎作用，并研究了它的自噬诱导活性和功能。与未刺激的细胞相比，用 OLL2712 刺激 24 小时的 Caco-2 细胞每个细胞中的自噬溶酶体数量增加。因此，通过诱导自噬抑制了荧光素异硫氰酸酯葡聚糖 4000（FD-4）的通透性。相比之下，OLL2712 也增加了 HT-29-MTX-E12 细胞中的粘蛋白分泌，但不是通过诱导自噬。最后，发现 OLL2712 诱导自噬的信号通路是通过髓样分化因子 88（MYD88）介导的。总之，我们的研究结果表明，OLL2712 通过 MYD88 诱导肠上皮细胞中的自噬，通过诱导自噬增强粘膜屏障功能。
