High-fat diet impairs gut barrier through intestinal microbiota-derived reactive oxygen species

被引：0

作者：

Nianyi Zeng ^{[1
]}

Fan Wu ^{[1
]}

Junqi Lu ^{[2
]}

Xiang Li ^{[1
]}

Shaomei Lin ^{[1
]}

Lang Zhou ^{[1
]}

Zhongwei Wang ^{[1
]}

Guangyan Wu ^{[1
]}

Qingfa Huang ^{[1
]}

Daowen Zheng ^{[1
]}

Jie Gao ^{[1
]}

Shan Wu ^{[2
]}

Xiaojiao Chen ^{[1
]}

Muxuan Chen ^{[1
]}

Fanguo Meng ^{[3
]}

Haitao Shang ^{[4
]}

Yan He ^{[1
]}

Peng Chen ^{[5
]}

Hong Wei ^{[4
]}

Zhuang Li ^{[1
]}

Hongwei Zhou ^{[1
,2
]}

机构：

[1] Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University

[2] Department of Environmental Health, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University

[3] Redox Medical Center for Public Health, Soochow University

[4] Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University

[5] Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University

来源：

Science China(Life Sciences) | 2024年 / 67卷 / 05期

关键词：

D O I：

暂无

中图分类号：

R151.1 [营养生理学];

学科分类号：

100403 ;

摘要：

Gut barrier disruption is a key event in bridging gut microbiota dysbiosis and high-fat diet(HFD)-associated metabolic disorders. However,the underlying mechanism remains elusive. In the present study, by comparing HFD-and normal diet(ND)-treated mice, we found that the HFD instantly altered the composition of the gut microbiota and subsequently damaged the integrity of the gut barrier. Metagenomic sequencing revealed that the HFD upregulates gut microbial functions related to redox reactions, as confirmed by the increased reactive oxygen species(ROS) levels in fecal microbiota incubation in vitro and in the lumen, which were detected using in vivo fluorescence imaging. This microbial ROS-producing capability induced by HFD can be transferred through fecal microbiota transplantation(FMT) into germ-free(GF) mice, downregulating the gut barrier tight junctions. Similarly, mono-colonizing GF mice with an Enterococcus strain excelled in ROS production, damaged the gut barrier, induced mitochondrial malfunction and apoptosis of the intestinal epithelial cells, and exacerbated fatty liver, compared with other low-ROS-producing Enterococcus strains. Oral administration of recombinant high-stability-superoxide dismutase(SOD) significantly reduced intestinal ROS, protected the gut barrier, and improved fatty liver against the HFD. In conclusion, our study suggests that extracellular ROS derived from gut microbiota play a pivotal role in HFD-induced gut barrier disruption and is a potential therapeutic target for HFD-associated metabolic diseases.

引用

页码：879 / 891

页数：13