通过口服微生物组衍生的肌苷减轻小鼠葡聚糖硫酸钠诱导的结肠炎及其机制。

Mitigation of Dextran-Sodium-Sulfate-Induced Colitis in Mice through Oral Administration of Microbiome-Derived Inosine and Its Underlying Mechanisms.

机构信息

State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China.

School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

出版信息

Int J Mol Sci. 2023 Sep 8;24(18):13852. doi: 10.3390/ijms241813852.

BACKGROUND

Colonic and serum inosine are significantly reduced in patients with inflammatory bowel disease (IBD).

METHODS

This study aimed to explore whether microbiome-derived inosine alleviates colitis and its underlying mechanisms.

RESULTS

An inosine intervention effectively improved the clinical signs in colitis mice, suppressed inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β) by regulating the nuclear factor-kappa B (NF-κB) pathway, and elevated the activities of anti-oxidative enzymes (including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) by regulating the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway. Additionally, the inosine intervention significantly elevated the expression of tight junction proteins (ZO-1, occudin, and claudin-1) in mice with colitis. High-throughput sequencing revealed that the inosine intervention also prevented gut microbiota disorder by increasing the abundance of beneficial bacteria (, , , 1, and ) and reducing the abundance of harmful bacteria (, , and ) in mice with colitis.

CONCLUSIONS

Inosine played a significant role in mitigating colitis-related intestinal barrier injury and could potentially be used for therapy in clinical practice.

背景

炎症性肠病（IBD）患者的结肠和血清肌苷明显减少。

方法

本研究旨在探讨微生物组衍生的肌苷是否能缓解结肠炎及其潜在机制。

结果

肌苷干预可有效改善结肠炎小鼠的临床症状，通过调节核因子-κB（NF-κB）通路抑制炎症细胞因子（肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β）的表达，并通过调节核因子红细胞 2 相关因子 2（Nrf2）通路提高抗氧化酶（包括超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px））的活性。此外，肌苷干预可显著提高结肠炎小鼠的紧密连接蛋白（ZO-1、occludin 和 claudin-1）的表达。高通量测序显示，肌苷干预还可通过增加有益菌（、、、1 和）的丰度和减少结肠炎小鼠中有害菌（、和）的丰度来预防肠道微生物群紊乱。