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非酒精性脂肪性肝病发病机制的生物学机制多组学分析

Multi-omics analysis of the biological mechanism of the pathogenesis of non-alcoholic fatty liver disease.

作者信息

Lin Jie, Zhang Ruyi, Liu Huaie, Zhu Yunzhen, Dong Ningling, Qu Qiu, Bi Hongyan, Zhang Lihua, Luo Ou, Sun Lei, Ma Mengjuan, You Jing

机构信息

Department of General Practice, The First Affiliated Hospital of Kunming Medical University, Kunming, China.

Department of Infectious Diseases and Hepatology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.

出版信息

Front Microbiol. 2024 Jul 26;15:1379064. doi: 10.3389/fmicb.2024.1379064. eCollection 2024.

DOI:10.3389/fmicb.2024.1379064
PMID:39132138
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11310135/
Abstract

BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is a type of liver metabolic syndrome. Employing multi-omics analyses encompassing the microbiome, metabolome and transcriptome is crucial for comprehensively elucidating the biological processes underlying NAFLD.

METHODS

Hepatic tissue, blood and fecal samples were obtained from 9 NAFLD model mice and 8 normal control mice. Total fecal microbiota DNA was extracted, and 16S rRNA was amplified, to analyze alterations in the gut microbiota (GM) induced by NAFLD. Subsequently, diagnostic strains for NAFLD were screened, and their functional aspects were examined. Differential metabolites and differentially expressed genes were also screened, followed by enrichment analysis. Correlations between the differential microbiota and metabolites, as well as between the DEGs and differential metabolites were studied. A collinear network involving key genes-, microbiota-and metabolites was constructed.

RESULTS

and , both belonging to Firmicutes; , and from Bacteroidota; and , and from Actinobacteriota were identified as characteristic strains associated with NAFLD. Additionally, differentially expressed metabolites were predominantly enriched in tryptophan, linoleic acid and methylhistidine metabolism pathways. The functions of 2,510 differentially expressed genes were found to be associated with disease occurrence. Furthermore, a network comprising 8 key strains, 14 key genes and 83 key metabolites was constructed.

CONCLUSION

Through this study, we conducted a comprehensive analysis of NAFLD alterations, exploring the gut microbiota, genes and metabolites of the results offer insights into the speculated biological mechanisms underlying NAFLD.

摘要

背景

非酒精性脂肪性肝病(NAFLD)是一种肝脏代谢综合征。采用涵盖微生物组、代谢组和转录组的多组学分析对于全面阐明NAFLD潜在的生物学过程至关重要。

方法

从9只NAFLD模型小鼠和8只正常对照小鼠中获取肝组织、血液和粪便样本。提取粪便微生物群总DNA,扩增16S rRNA,以分析NAFLD诱导的肠道微生物群(GM)变化。随后,筛选NAFLD的诊断菌株,并检查其功能方面。还筛选了差异代谢物和差异表达基因,随后进行富集分析。研究了差异微生物群与代谢物之间以及差异表达基因(DEGs)与差异代谢物之间的相关性。构建了一个涉及关键基因、微生物群和代谢物的共线网络。

结果

属于厚壁菌门的 和 ;属于拟杆菌门的 、 和 ;以及属于放线菌门的 、 和 被鉴定为与NAFLD相关的特征菌株。此外,差异表达的代谢物主要富集在色氨酸、亚油酸和甲基组氨酸代谢途径中。发现2510个差异表达基因的功能与疾病发生有关。此外,构建了一个由8个关键菌株、14个关键基因和83个关键代谢物组成的网络。

结论

通过本研究,我们对NAFLD的变化进行了全面分析,探索了肠道微生物群、基因和代谢物,研究结果为NAFLD潜在的生物学机制提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/f2a056402cb6/fmicb-15-1379064-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/532278e4ff57/fmicb-15-1379064-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/172ae99c2a85/fmicb-15-1379064-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/33848ff8d66d/fmicb-15-1379064-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/9a0bc4b37b2a/fmicb-15-1379064-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/dfa1fc352b8c/fmicb-15-1379064-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/b8323c28fac5/fmicb-15-1379064-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/d48d054a80a9/fmicb-15-1379064-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/b01306ad5610/fmicb-15-1379064-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/f2a056402cb6/fmicb-15-1379064-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/532278e4ff57/fmicb-15-1379064-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/172ae99c2a85/fmicb-15-1379064-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/33848ff8d66d/fmicb-15-1379064-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/9a0bc4b37b2a/fmicb-15-1379064-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/dfa1fc352b8c/fmicb-15-1379064-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/b8323c28fac5/fmicb-15-1379064-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/d48d054a80a9/fmicb-15-1379064-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/b01306ad5610/fmicb-15-1379064-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7b/11310135/f2a056402cb6/fmicb-15-1379064-g009.jpg

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