Systems genetics uncovers associations among host amylase locus, gut microbiome, and metabolic traits in mice.

IF 13.8 1区生物学 Q1 MICROBIOLOGY

Microbiome Pub Date : 2025-04-21 DOI:10.1186/s40168-025-02093-y

Qijun Zhang, Evan R Hutchison, Calvin Pan, Matthew F Warren, Mark P Keller, Alan D Attie, Aldons J Lusis, Federico E Rey

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引用次数: 0

Abstract

Background: Population studies have revealed associations between host genetic and gut microbiome in humans and mice. However, the molecular bases for how host genetic variation impacts the gut microbial community and bacterial metabolic niches remain largely unknown.

Results: We leveraged 90 inbred hyperlipidemic mouse strains from the hybrid mouse diversity panel (HMDP), previously studied for a variety of cardio-metabolic traits. Metagenomic analysis of cecal DNA followed by genome-wide association analysis identified genomic loci that were associated with microbial enterotypes in the gut. Among these, we detected a genetic locus surrounding multiple amylase genes that were associated with abundances of Firmicutes (Lachnospiraceae family) and Bacteroidetes (Muribaculaceae family) taxa encoding distinct starch and sugar degrading capabilities. The genetic variants at the amylase gene locus were associated with distinct gut microbial communities (enterotypes) with different predicted metabolic capacities for carbohydrate degradation. Mendelian randomization analysis revealed host phenotypes, including liver fibrosis and plasma HDL-cholesterol levels, that were associated with gut microbiome enterotypes.

Conclusions: This work reveals novel relationships among host genetic variation, gut microbial enterotypes, and host metabolic traits and supports the notion that variation of host amylase may represent a key determinant of gut microbiome in mice. Video Abstract.

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系统遗传学揭示了宿主淀粉酶位点、肠道微生物组和小鼠代谢性状之间的关联。

背景：种群研究已经揭示了人类和小鼠的宿主遗传和肠道微生物组之间的关联。然而，宿主遗传变异如何影响肠道微生物群落和细菌代谢生态位的分子基础仍然很大程度上未知。结果：我们利用了来自杂交小鼠多样性小组（HMDP）的90个近交系高脂血症小鼠品系，这些品系先前研究了各种心脏代谢特征。盲肠DNA的宏基因组分析随后进行全基因组关联分析，确定了与肠道微生物肠型相关的基因组位点。其中，我们发现了一个围绕多个淀粉酶基因的遗传位点，这些基因与厚壁菌门（Lachnospiraceae）和拟杆菌门（Muribaculaceae）分类群的丰度相关，这些分类群编码不同的淀粉和糖降解能力。淀粉酶基因位点的遗传变异与具有不同碳水化合物降解预测代谢能力的不同肠道微生物群落（肠型）相关。孟德尔随机化分析揭示了宿主表型，包括肝纤维化和血浆高密度脂蛋白胆固醇水平，与肠道微生物组肠型相关。结论：这项工作揭示了宿主遗传变异、肠道微生物肠型和宿主代谢特征之间的新关系，并支持宿主淀粉酶变异可能是小鼠肠道微生物群的关键决定因素的观点。视频摘要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microbiome MICROBIOLOGY-

CiteScore

21.90

自引率

2.60%

发文量

198

审稿时长

4 weeks

期刊介绍： Microbiome is a journal that focuses on studies of microbiomes in humans, animals, plants, and the environment. It covers both natural and manipulated microbiomes, such as those in agriculture. The journal is interested in research that uses meta-omics approaches or novel bioinformatics tools and emphasizes the community/host interaction and structure-function relationship within the microbiome. Studies that go beyond descriptive omics surveys and include experimental or theoretical approaches will be considered for publication. The journal also encourages research that establishes cause and effect relationships and supports proposed microbiome functions. However, studies of individual microbial isolates/species without exploring their impact on the host or the complex microbiome structures and functions will not be considered for publication. Microbiome is indexed in BIOSIS, Current Contents, DOAJ, Embase, MEDLINE, PubMed, PubMed Central, and Science Citations Index Expanded.