调节猪肠道菌群的宿主基因调控网络
  • 纳入39种肠道微生物表型与390个猪的7万个SNP进行全基因组关联研究,推断出一个基因调控网络,含3561个基因和738913个边;
  • 最突出的5个调控因子是PRDM15、STAT1、ssc-mir-371、SOX9和RUNX2,主要与免疫细胞发育、信号通路及疫苗反应有关;
  • 预测的靶基因中有200个已知与猪、鼠和人的菌群相关的基因,如SLIT3、SLC39A8、NOS1、IL1R2、DAB1、TOX3、SPP1、THSD7B、ELF2、PIANP、A2ML1、IFNAR1;
  • 鉴定出与产丁酸菌和猪体重均相关的多个SNP。
主编推荐语
mildbreeze
Microbiome上发表的这项研究,建立了一个由3561个与猪肠道菌群表型(包括细菌和原生生物)相关的基因调控网络,对该网络的分析确定了与宿主对肠道菌群调控有关的关键调控因子、靶基因和机制,鉴定出的遗传标志物和候选基因或可用于改善宿主性能和微生物特征。
关键字
延伸阅读本研究的原文信息和链接出处,以及相关解读和评论文章。欢迎读者朋友们推荐!
图片
Microbiome [IF:14.65]

A gene co-association network regulating gut microbial communities in a Duroc pig population

调节杜洛克猪肠道微生物群落的基因共关联网络

10.1186/s40168-020-00994-8

2021-02-21, Article

Abstract & Authors:展开

Abstract:收起
Background: Analyses of gut microbiome composition in livestock species have shown its potential to contribute to the regulation of complex phenotypes. However, little is known about the host genetic control over the gut microbial communities. In pigs, previous studies are based on classical “single-gene-single-trait” approaches and have evaluated the role of host genome controlling gut prokaryote and eukaryote communities separately.
Results: In order to determine the ability of the host genome to control the diversity and composition of microbial communities in healthy pigs, we undertook genome-wide association studies (GWAS) for 39 microbial phenotypes that included 2 diversity indexes, and the relative abundance of 31 bacterial and six commensal protist genera in 390 pigs genotyped for 70 K SNPs. The GWAS results were processed through a 3-step analytical pipeline comprised of (1) association weight matrix; (2) regulatory impact factor; and (3) partial correlation and information theory. The inferred gene regulatory network comprised 3561 genes (within a 5 kb distance from a relevant SNP–P < 0.05) and 738,913 connections (SNP-to-SNP co-associations). Our findings highlight the complexity and polygenic nature of the pig gut microbial ecosystem. Prominent within the network were 5 regulators, PRDM15, STAT1, ssc-mir-371, SOX9 and RUNX2 which gathered 942, 607, 588, 284 and 273 connections, respectively. PRDM15 modulates the transcription of upstream regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency and regulates the production of Th1- and Th2-type immune response. The signal transducer STAT1 has long been associated with immune processes and was recently identified as a potential regulator of vaccine response to porcine reproductive and respiratory syndrome. The list of regulators was enriched for immune-related pathways, and the list of predicted targets includes candidate genes previously reported as associated with microbiota profile in pigs, mice and human, such as SLIT3, SLC39A8, NOS1, IL1R2, DAB1, TOX3, SPP1, THSD7B, ELF2, PIANP, A2ML1, and IFNAR1. Moreover, we show the existence of host-genetic variants jointly associated with the relative abundance of butyrate producer bacteria and host performance.
Conclusions: Taken together, our results identified regulators, candidate genes, and mechanisms linked with microbiome modulation by the host. They further highlight the value of the proposed analytical pipeline to exploit pleiotropy and the crosstalk between bacteria and protists as significant contributors to host-microbiome interactions and identify genetic markers and candidate genes that can be incorporated in breeding program to improve host-performance and microbial traits.

First Authors:
Antonio Reverter

Correspondence Authors:
Yuliaxis Ramayo-Caldas

All Authors:
Antonio Reverter,Maria Ballester,Pamela A Alexandre,Emilio Mármol-Sánchez,Antoni Dalmau,Raquel Quintanilla,Yuliaxis Ramayo-Caldas

评论