A gene co-association network regulating gut microbial communities in a Duroc pig population
Reverter, Antonio (Agriculture and Food. CSIRO)
Ballester Devis, Maria (Institut de Recerca i Tecnologia Agroalimentàries)
Alexandre, Pamela A. (Agriculture and Food. CSIRO)
Mármol-Sánchez, Emilio (Centre de Recerca en Agrigenòmica)
Dalmau Bueno, Antoni (Institut de Recerca i Tecnologia Agroalimentàries)
Quintanilla, Raquel (Institut de Recerca i Tecnologia Agroalimentàries)
Ramayo-Caldas, Yuliaxis (Institut de Recerca i Tecnologia Agroalimentàries)

Data:	2021
Resum:	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.
Ajuts:	European Commission 665919 Ministerio de Economía y Competitividad RYC-2013-12573 Ministerio de Educación y Ciencia FPU15-01733 Ministerio de Economía y Competitividad AGL2016-75432-R Ministerio de Economía y Competitividad AGL2017-88849-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1719
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Microbiota ; Pig ; Gene network ; Regulators ; Protist ; Bacteria
Publicat a:	Microbiome, Vol. 9 (February 2021) , art. 52, ISSN 2049-2618

DOI: 10.1186/s40168-020-00994-8
PMID: 33612109

16 p, 1.8 MB

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