Shao Li, Zhang Binbin, Song Yu, Lyu Zhe, Zhang Weishi, Yang Wenjun, Fu Jinlong, Li Jie, Shi Junping
School of Clinical Medicine, Hangzhou Normal University, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 311121, Zhejiang, China.
Institute of Hepatology and Metabolic Diseases, Hangzhou Normal University, Hangzhou 310015, Zhejiang, China.
Can J Infect Dis Med Microbiol. 2024 Nov 27;2024:3652740. doi: 10.1155/cjid/3652740. eCollection 2024.
Intestinal barrier injury contributes to multiple diseases such as obesity and diabetes, whereas no treatment options are available. Due to close interactions between mucosal microbiome and intestinal barrier, we evaluated the potential of mucosal bacteria in providing targets for high-fat diet (HFD)-related intestinal barrier injury. Whole-genome metagenomics was used to evaluate mucosal microbiome, while intestinal barrier injury was estimated using serum LPS, FITC-dextran intensity, and ZO-1 protein. We found that HFD induced significant fat accumulation in epididymal tissue at weeks 4 and 12, while ALT, LDL, and TC increased at week 12. Intestinal barrier injury was confirmed by elevated serum LPS at both weeks, upregulated FITC-dextran intensity, and decreased ZO-1 protein at week 12. Fourteen species such as differed in HFD-fed mice. The co-occurrence network of mucosal microbiome shifted from scale-free graph in controls to nearly random graph in HFD-fed mice. Besides, 10 hub bacteria especially decreased drastically in both mucosal and fecal samples of HFD-fed mice, correlated with intestinal permeability, ALT, and KEGG pathways such as "Mitochondrial biogenesis" and "metabolism". Moreover, has been confirmed to improve intestinal barrier function in a recent study. Mucosal hub bacteria can provide potential targets for improving HFD-related intestinal barrier function.
肠道屏障损伤会导致多种疾病，如肥胖症和糖尿病，但目前尚无有效的治疗方法。由于黏膜微生物群与肠道屏障之间存在密切相互作用，我们评估了黏膜细菌在为高脂饮食（HFD）相关肠道屏障损伤提供靶点方面的潜力。采用全基因组宏基因组学评估黏膜微生物群，同时使用血清脂多糖（LPS）、异硫氰酸荧光素葡聚糖（FITC-葡聚糖）强度和闭合蛋白1（ZO-1）蛋白评估肠道屏障损伤。我们发现，高脂饮食在第4周和第12周诱导附睾组织显著脂肪堆积，而在第12周谷丙转氨酶（ALT）、低密度脂蛋白（LDL）和总胆固醇（TC）升高。在这两个时间点血清LPS升高、FITC-葡聚糖强度上调以及第12周ZO-1蛋白降低均证实了肠道屏障损伤。在高脂饮食喂养的小鼠中，有14个物种等存在差异。黏膜微生物群的共生网络从对照组的无标度图转变为高脂饮食喂养小鼠的近乎随机图。此外，10种核心细菌尤其是在高脂饮食喂养小鼠的黏膜和粪便样本中均大幅减少，与肠道通透性、ALT以及“线粒体生物发生”和“代谢”等京都基因与基因组百科全书（KEGG）通路相关。此外，最近的一项研究已证实可改善肠道屏障功能。黏膜核心细菌可为改善高脂饮食相关肠道屏障功能提供潜在靶点。
