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肠道微生物组稳态分析在核黄素治疗酒精性肝病中的作用。

Intestinal microbiota homeostasis analysis in riboflavin-treated alcoholic liver disease.

机构信息

Department of Pharmacology (National Key Laboratory of Frigid Zone Cardiovascular Diseases, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, PR China.

Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, PR China.

出版信息

Commun Biol. 2024 Aug 21;7(1):1030. doi: 10.1038/s42003-024-06722-4.

Abstract

Alcoholic liver disease (ALD) is a disease with high incidence, limited therapies, and poor prognosis. The present study aims to investigate the effect of riboflavin on ALD and explore its potential therapeutic mechanisms. C57BL/6 mice were divided into the control, alcohol, and alcohol+ riboflavin groups. 16S rRNA-seq and RNA-seq analysis were utilized to analyze the polymorphism of intestinal microbiota and the transcriptome heterogeneity respectively. KEGG and GO enrichment analysis were performed. CIBERSORTx was applied to evaluate the immune cell infiltration level. Publicly available transcriptome data of ALD was enrolled and combined with the RNA-seq data to identify the immune subtypes of ALD. Pathological and histology analysis demonstrated that riboflavin reversed the progression of ALD. 16S rRNA-seq results showed that riboflavin could regulate alcohol-induced intestinal microbiota alteration. Intestinal microbiota polymorphism analysis indicated that VLIDP may contribute to the progression of ALD. Based on the VLIDP pathway, two subtypes were identified. Immune microenvironment analysis indicated that the upregulated inflammatory factors may be important regulators of ALD. In conclusion, intestinal microbiota homeostasis was associated with the protective effect of riboflavin against ALD, which was likely mediated by modulating inflammatory cell infiltration. Riboflavin emerges as a promising therapeutic candidate for the management of ALD.

摘要

酒精性肝病(ALD)是一种发病率高、治疗方法有限、预后差的疾病。本研究旨在探讨核黄素对 ALD 的影响,并探讨其潜在的治疗机制。将 C57BL/6 小鼠分为对照组、酒精组和酒精+核黄素组。分别利用 16S rRNA-seq 和 RNA-seq 分析来分析肠道微生物组的多态性和转录组的异质性。进行了 KEGG 和 GO 富集分析。应用 CIBERSORTx 来评估免疫细胞浸润水平。纳入了公开的 ALD 转录组数据,并将其与 RNA-seq 数据相结合,以鉴定 ALD 的免疫亚型。病理学和组织学分析表明,核黄素逆转了 ALD 的进展。16S rRNA-seq 结果表明,核黄素可以调节酒精引起的肠道微生物群改变。肠道微生物组多态性分析表明,VLIDP 可能有助于 ALD 的进展。基于 VLIDP 通路,鉴定出了两种亚型。免疫微环境分析表明,上调的炎症因子可能是 ALD 的重要调节剂。总之,肠道微生物组的平衡与核黄素对 ALD 的保护作用有关,这可能是通过调节炎症细胞浸润来介导的。核黄素作为治疗 ALD 的一种有前途的候选药物出现了。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbaf/11339332/dc64f9f3fe7c/42003_2024_6722_Fig1_HTML.jpg

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