Wang Yongcai, Xiao Juan, Wei Sumei, Su Ying, Yang Xia, Su Shiqi, Lan Liancheng, Chen Xiuqi, Huang Ting, Shan Qingwen
Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Dazhou Central Hospital, Dazhou, China.
Front Microbiol. 2024 May 23;15:1407091. doi: 10.3389/fmicb.2024.1407091. eCollection 2024.
The aim of the study is to investigate the function and mechanism of Zinc Gluconate (ZG) on intestinal mucosal barrier damage in antibiotics and Lipopolysaccharide (LPS)-induced mice.
We established a composite mouse model by inducing intestinal mucosal barrier damage using antibiotics and LPS. The animals were divided into five groups: Control (normal and model) and experimental (low, medium, and high-dose ZG treatments). We evaluated the intestinal mucosal barrier using various methods, including monitoring body weight and fecal changes, assessing pathological damage and ultrastructure of the mouse ileum, analyzing expression levels of tight junction (TJ)-related proteins and genes, confirming the TLR4/NF-κB signaling pathway, and examining the structure of the intestinal flora.
In mice, the dual induction of antibiotics and LPS led to weight loss, fecal abnormalities, disruption of ileocecal mucosal structure, increased intestinal barrier permeability, and disorganization of the microbiota structure. ZG restored body weight, alleviated diarrheal symptoms and pathological damage, and maintained the structural integrity of intestinal epithelial cells (IECs). Additionally, ZG reduced intestinal mucosal permeability by upregulating TJ-associated proteins (ZO-1, Occludin, Claudin-1, and JAM-A) and downregulating MLCK, thereby repairing intestinal mucosal barrier damage induced by dual induction of antibiotics and LPS. Moreover, ZG suppressed the TLR4/NF-κB signaling pathway, demonstrating anti-inflammatory properties and preserving barrier integrity. Furthermore, ZG restored gut microbiota diversity and richness, evidenced by increased Shannon and Observed features indices, and decreased Simpson's index. ZG also modulated the relative abundance of beneficial human gut bacteria (, , , , , and ) and harmful bacteria ( and ), repairing the damage induced by dual administration of antibiotics and LPS.
ZG attenuates the dual induction of antibiotics and LPS-induced intestinal barrier damage and also protects the intestinal barrier function in mice.
本研究旨在探讨葡萄糖酸锌（ZG）对抗生素和脂多糖（LPS）诱导的小鼠肠黏膜屏障损伤的作用及机制。
我们通过使用抗生素和LPS诱导肠黏膜屏障损伤建立了复合小鼠模型。动物被分为五组：对照组（正常和模型组）和实验组（低、中、高剂量ZG处理组）。我们使用多种方法评估肠黏膜屏障，包括监测体重和粪便变化、评估小鼠回肠的病理损伤和超微结构、分析紧密连接（TJ）相关蛋白和基因的表达水平、确认TLR4/NF-κB信号通路以及检查肠道菌群结构。
在小鼠中，抗生素和LPS的双重诱导导致体重减轻、粪便异常、回盲部黏膜结构破坏、肠屏障通透性增加以及微生物群结构紊乱。ZG恢复了体重，减轻了腹泻症状和病理损伤，并维持了肠上皮细胞（IECs）的结构完整性。此外，ZG通过上调TJ相关蛋白（ZO-1、闭合蛋白、Claudin-1和JAM-A）并下调肌球蛋白轻链激酶（MLCK）来降低肠黏膜通透性，从而修复抗生素和LPS双重诱导引起的肠黏膜屏障损伤。此外，ZG抑制了TLR4/NF-κB信号通路，显示出抗炎特性并保持屏障完整性。此外，ZG恢复了肠道微生物群的多样性和丰富度，表现为香农指数和观测特征指数增加，辛普森指数降低。ZG还调节了有益人类肠道细菌（、、、、、和）和有害细菌（和）的相对丰度，修复了抗生素和LPS联合给药引起的损伤。
ZG减轻了抗生素和LPS双重诱导引起的肠屏障损伤，并保护了小鼠的肠屏障功能。
