Identifying genetic host factors affecting the intestinal microbiome

As part of a Chinese Thousand Talents Program Award, we collaborated with the laboratory of Professor Lusheng Huang (Nanchang, China) to study the effect of the host genome on the composition of its intestinal microbiota.  To that end, we took advantage of an exceptional mosaic pig population with exacerbated genetic diversity yet reduced environmental variation established in a >10 years effort by Professor Huang.  It allowed us to demonstrate the heritable nature of the abundance of at least some bacterial taxa, and - most importantly – to identify a locus with major effect on the abundance of specific Erysipelotrichaceae genera.  We showed that the causative variant is a null allele in the porcine gene corresponding to the ABO blood group in human.  We showed that this allele acts by reducing the abundance of GalNAc in the intestinal mucus.   This affects the growth of bacteria that use GalNAC as carbon source using a non-inducible GalNAc operon.

Preliminary results point towards the fact that the balanced AO blood group polymorphism in the pig host sustains a balanced polymorphism of the GalNAc operon in the p.75.a5 Erysipelotrichaceae.

Key publication

ABO genotype alters the gut microbiota by regulating GalNAc levels in pigs. Yang H, Wu J, Huang X, Zhou Y, Zhang Y, Liu M, Liu Q, Ke S, he M, Fu H, Fang S, Xiong X, Jiang H, Chen Z, Wu Z, Gong H, Tong X, Huang Y, Ma J, Gao J, Charlier C, Coppieters W, Shagam L, Zhang Z, Ai H, Yang B, Georges M#, Chen C#, Huang L#. Nature 606: 358-367 (2022). # Co-lead, co-corresponding authors.