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

Hui Yang, Jinyuan Wu, Xiaochang Huang, Yunyan Zhou, Yifeng Zhang, Min Liu, Qin Liu, Shanlin Ke, Maozhang He, Hao Fu, Shaoming Fang, Xinwei Xiong, Hui Jiang, Zhe Chen, Zhongzi Wu, Huanfa Gong, Xinkai Tong, Yizhong Huang, Junwu Ma, Jun Gao, Carole Charlier, Wouter Coppieters, Lev Shagam, Zhiyan Zhang, Huashui Ai, Bin Yang, Michel Georges (), Congying Chen () and Lusheng Huang ()
Additional contact information
Hui Yang: Jiangxi Agricultural University
Jinyuan Wu: Jiangxi Agricultural University
Xiaochang Huang: Jiangxi Agricultural University
Yunyan Zhou: Jiangxi Agricultural University
Yifeng Zhang: Jiangxi Agricultural University
Min Liu: Jiangxi Agricultural University
Qin Liu: Jiangxi Agricultural University
Shanlin Ke: Jiangxi Agricultural University
Maozhang He: Jiangxi Agricultural University
Hao Fu: Jiangxi Agricultural University
Shaoming Fang: Jiangxi Agricultural University
Xinwei Xiong: Jiangxi Agricultural University
Hui Jiang: Jiangxi Agricultural University
Zhe Chen: Jiangxi Agricultural University
Zhongzi Wu: Jiangxi Agricultural University
Huanfa Gong: Jiangxi Agricultural University
Xinkai Tong: Jiangxi Agricultural University
Yizhong Huang: Jiangxi Agricultural University
Junwu Ma: Jiangxi Agricultural University
Jun Gao: Jiangxi Agricultural University
Carole Charlier: Jiangxi Agricultural University
Wouter Coppieters: University of Liege
Lev Shagam: University of Liege
Zhiyan Zhang: Jiangxi Agricultural University
Huashui Ai: Jiangxi Agricultural University
Bin Yang: Jiangxi Agricultural University
Michel Georges: Jiangxi Agricultural University
Congying Chen: Jiangxi Agricultural University
Lusheng Huang: Jiangxi Agricultural University

Nature, 2022, vol. 606, issue 7913, 358-367

Abstract: Abstract The composition of the intestinal microbiome varies considerably between individuals and is correlated with health1. Understanding the extent to which, and how, host genetics contributes to this variation is essential yet has proved to be difficult, as few associations have been replicated, particularly in humans2. Here we 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 the 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 gene encoding N-acetyl-galactosaminyl-transferase that underpins the ABO blood group in humans. We show that this deletion is a ≥3.5-million-year-old trans-species polymorphism under balancing selection. We demonstrate that it decreases the concentrations of N-acetyl-galactosamine in the gut, and thereby reduces the abundance of Erysipelotrichaceae that can import and catabolize N-acetyl-galactosamine. Our results provide very strong evidence for an effect of the host genotype on the abundance of specific bacteria in the intestine combined with insights into the molecular mechanisms that underpin this association. Our data pave the way towards identifying the same effect in rural human populations.

Date: 2022
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DOI: 10.1038/s41586-022-04769-z

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