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

Abstract

The composition of the intestinal microbiome varies considerably between individuals and is correlated with health 1 . 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 humans 2 . 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.

Gut Microbiota Composition and Diversity in Different Commercial Swine Breeds in Early and Finishing Growth Stages

“…Gut microbial composition varies between individuals and affects health [33]. Over the past decade, many studies have investigated the influence of breed [8,34], age [35] and sex [36] on the variation of pig gut microbiota, and recent studies have greatly expanded current knowledge of the impact of host genes on the pig gut microbiota [16]. Throughout pig growth development, maximum growth rate is estimated by the growth inflection point, which suggests that metabolism and digestive functions are active.…”

“…Interestingly, the family Erysipelotrichaceae could be used as a marker to distinguish Duroc pigs from the other two breeds at both the early and finishing growth stages. A recent study showed that a 2.3 kb deletion in the N-acetyl-galactosamine transferase gene caused an altered abundance of Erysipelotrichaceae in pig gut microbiota, hence providing strong evidence for the influence of host genes on the abundance of specific bacteria in the gut [16]. Thus, it can be assumed that specific genetic backgrounds might affect microbial colonization as a result of altered levels of metabolites in the body.…”

“…Latest research has shown that variation in the expression of the ABO gene was related to decreased abundance of Erysipelotrichaceae by reducing GalNAc levels in the gut. In addition, it has been demonstrated that genetic factors can alter gut microbiota composition [16]. Yorkshire, Landrace and Duroc, three famous commercial pig breeds, are widely used in the pig industry.…”

Fucosyltransferase 2: A Genetic Risk Factor for Intestinal Diseases

“…Recently, an animal study using FUT2 ΔIEC mice ( FUT2 gene knockout mice) found more serious intestinal inflammation and destructive barrier functions that occurred in FUT2 ΔIEC mice compared with WT mice when DSS was treated; simultaneously, while at the same time, less diversity of intestinal microbiota was observed in FUT2 ΔIEC mice (Tang et al, 2021 ). It is found that N -acetylgalactosamine, one of the compounds synthesized by HGBA, may change gut microbiota in pigs (Yang et al, 2022 ). Contributing to the up-to-date progress in next-generation sequencing technology, IBD patients have been found to have alterations in the composition and function of the gut microbiota, termed dysbiosis, which is thought to play a central role in the pathogenesis of IBD (McGovern et al, 2010 ).…”

Human gut metagenomes encode diverse GH156 sialidases

“…Host glycans, composing the bulk of the mucous, offer a plentiful nutrient source for the microbes capable of depolymerizing them into constituent sugars (26)(27)(28)(29), as well as those that scavenge the mucosal sugars released into the environment. Overall, host-glycan consumption is essential to the maintenance and persistence of a stable microbiota capable of providing colonization resistance to enteric pathogens, and its been reported that mucosal glycan structures, at least insofar as blood group antigen type and secretor status are concerned, can help select microbial community composition (30)(31)(32)(33)(34)(35). However, the repertoire of glycans produced by the host (and accessible to the gut microbiota) is altered in response to inflammatory signals (36,37), which act as complementary immunoregulatory signals (7,8).…”