ABO genotype alters the gut microbiota by regulating GalNAc levels in pigs.

[en] The composition of the intestinal microbiome varies considerably between individuals and is correlated with health1. Understanding to what extend and how host genetics contributes to this variation is paramount yet has proven difficult as few associations have been replicated, particularly in humans2. We herein study the effect of host genotype on the composition of the intestinal microbiota in a large mosaic pig population. We show that, under conditions of exacerbated genetic diversity and environmental uniformity, microbiota composition and abundance of specific taxa are heritable. We map a quantitative trait locus affecting the abundance of Erysipelotrichaceae species and show that it is caused by a 2.3-Kb deletion in the N-acetyl-galactosaminyl-transferase gene underpinning the ABO blood group in humans. We show that this deletion is a ≥3.5 million years old trans-species polymorphism under balancing selection. We demonstrate that it decreases the concentrations of N-acetyl-galactosamine in the gut thereby reducing the abundance of Erysipelotrichaceae that can import and catabolize N-acetyl-galactosamine. Our results provide very strong evidence for an effect of host genotype on the abundance of specific bacteria in the intestine combined with insights in the molecular mechanisms that underpin this association. They pave the way towards identifying the same effect in human rural populations.

Disciplines :

Genetics & genetic processes

Author, co-author :

Yang, Hui ^✱; National Key Laboratory for Swine genetic improvement and production technology, Ministry of Science and Technology of China, Jiangxi Agricultural University, NanChang, Jiangxi Province, PR China

Wu, Jinyuan ^✱; National Key Laboratory for Swine genetic improvement and production technology, Ministry of Science and Technology of China, Jiangxi Agricultural University, NanChang, Jiangxi Province, PR China

Huang, Xiaochang; National Key Laboratory for Swine genetic improvement and production technology, Ministry of Science and Technology of China, Jiangxi Agricultural University, NanChang, Jiangxi Province, PR China

Zhou, Yunyan; National Key Laboratory for Swine genetic improvement and production technology, Ministry of Science and Technology of China, Jiangxi Agricultural University, NanChang, Jiangxi Province, PR China

Zhang, Yifeng; National Key Laboratory for Swine genetic improvement and production technology, Ministry of Science and Technology of China, Jiangxi Agricultural University, NanChang, Jiangxi Province, PR China

Liu, Min; National Key Laboratory for Swine genetic improvement and production technology, Ministry of Science and Technology of China, Jiangxi Agricultural University, NanChang, Jiangxi Province, PR China

Liu, Qin; National Key Laboratory for Swine genetic improvement and production technology, Ministry of Science and Technology of China, Jiangxi Agricultural University, NanChang, Jiangxi Province, PR China

Ke, Shanlin; National Key Laboratory for Swine genetic improvement and production technology, Ministry of Science and Technology of China, Jiangxi Agricultural University, NanChang, Jiangxi Province, PR China

He, Maozhang; National Key Laboratory for Swine genetic improvement and production technology, Ministry of Science and Technology of China, Jiangxi Agricultural University, NanChang, Jiangxi Province, PR China

Fu, Hao; National Key Laboratory for Swine genetic improvement and production technology, Ministry of Science and Technology of China, Jiangxi Agricultural University, NanChang, Jiangxi Province, PR China

More authors (19 more)

^✱ These authors have contributed equally to this work.

Language :

English

Title :

ABO genotype alters the gut microbiota by regulating GalNAc levels in pigs.

Publication date :

27 April 2022

Journal title :

Nature

ISSN :

0028-0836

eISSN :

1476-4687

Publisher :

Springer Science and Business Media LLC, England

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.nature.com/articles/s41586-022-04769-z.pdf

Data Set :

10.1038/s41586-022-04769-z

Available on ORBi :

since 25 May 2022

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