An ancient deletion in the ABO gene affects the composition of the porcine microbiome by altering intestinal N-acetyl-galactosamine concentrations

Yang, Hui; Wu, Jinyuan; Huang, Xiaowan; Zhou, Yunyan; Zhang, Yifeng; Liu, Min; Liu, Qin; Ke, Shanlin; He, Maozhang; Fu, Hao; Fang, Shouguo; Xiong, Xinwei; Jiang, Hui; Chen, Zhe; Wu, Zhongzi; Gong, Haiming; Tong, Xinkai; Huang, Yongjun; Ma, Junwu; Gao, Jun; Charlier, Carole; Coppieters, Wouter; Shagam, Lev; Zhang, Zhiyan; Ai, Huashui; Yang, Bin; Georges, Michel; Chen, Congying; Huang, Lusheng

doi:10.1101/2020.07.16.206219

Cited by 6 publications

(4 citation statements)

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“…Genetic associations at ABO have been reported previously in populations of different ethnicities 22,29 and in nonhuman species, including pigs 30 . A deletion at this locus that inactivates the ABO acetylgalactosaminyltransferase has been shown to change porcine microbiome composition by altering intestinal N-acetylgalactosamine concentrations and consequently reducing the abundance of Erysipelotrichaceae strains, which have the capacity to import and catabolize N-acetylgalactosamine 31 . We did not detect any evidence of interaction with diet at the ABO locus, although this could be due to limitations in available information, as the recording of dietary information and stool collection were done at different times.…”

Section: Discussionmentioning

confidence: 99%

Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

et al. 2022

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statistics from other independent studies 13,17,18 , we identify novel host-microbiota interactions. Furthermore, we explore the impact of potential confounding factors in modulating these genetic effects and identify potential diet-dependent host-microbiota interactions. We further assess the potential causal relationships between the gut microbiome and dietary habits, biomarkers and disease using Mendelian randomization (MR). Finally, we carry out a power analysis showing how microbiome studies, even at the current sample size, are underpowered to reveal the complex genetic architecture by which host genetics regulates the gut microbiome. ResultsGenome-wide associations with bacterial taxa and pathways. We investigated 5.5 million common (minor allele frequency (MAF) > 0.05) genetic variants on all autosomes and the X chromosome using linear mixed models 19 to test their association with 207 taxa and 205 bacterial pathways in 7,738 individuals from the DMP cohort (Methods and Supplementary Table 1) 19 . There was no evidence for test statistic inflation (median genomic lambda 1.002 (range, 0.75-1.03) for taxa and 1.004 (range, 0.87-1.04) for pathways). We identified 37 single nucleotide polymorphism (SNP)trait associations at 24 independent loci at a genome-wide P value threshold of 5 × 10 −8 (Fig. 1 and Supplementary Table 2). Genetic variants at two loci passed the more stringent study-wide threshold of 1.89 × 10 −10 that accounts for the number of independent tests performed (Methods).The strongest signal was seen for rs182549 located in an intron of MCM6, a perfect proxy of rs4988235 (r 2 = 1, 1000 Genomes Project European populations), one of the variants known to regulate the LCT gene and responsible for lactase persistence in adults (ClinVar accession RCV000008124). The T allele of rs182549, which confers lactase persistence through a dominant model of inheritance, was found to be associated with decreased abundances of the species Bifidobacterium adolescentis (P = 7.6 × 10 −14 ) and Bifidobacterium longum (P = 3.2 × 10 −08 ), as well as decreased abundances of higher-level taxa (Supplementary Table 2 (ref. 5 )). Associations at this locus were also seen for other taxa of the same genus but at lower levels of significance (Bifidobacterium catenulatum, P = 3.9 × 10 −5 ) and for species of the Collinsella genus (Extended Data Fig. 1). The genetic association at the LCT locus has been previously described, albeit only at the genus level, in Dutch, UK and US cohorts 6,8,14 , as well as in a recent large-scale meta-analysis 13 .The second locus that passed study-wide significance consisted of genetic variants near the ABO gene. ABO encodes the BGAT protein, a histo-blood group ABO system transferase. Associations found at this locus include species Bifidobacterium bifidum (rs8176645, p = 5.5 × 10 −15 ) and Collinsella aerofaciens (rs550057, P = 2.0 × 10 −8 , r 2 = 0.59 with rs8176645 in 1000 Genomes Project Europeans) and higher-order taxa (rs550057, genus Collinsella, P = 9.3 × 10 −11 ; family Coriobacteriac...

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Section: Discussionmentioning

confidence: 99%

Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

et al. 2022

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“…In the Dutch population, the same and other variants in LD are associated with Bifidobacterium abundance, the lactose-degradation pathway and Collinsella abundance. The association of the ABO locus with the gut microbiome was also reported in pigs, in which a common deletion that inactivates the ABO gene is associated with the abundance of the family Erysipelotrichaceae 24 .…”

Section: The Abo Locus and Its Interaction With Fut2mentioning

confidence: 71%

Challenges and future directions for studying effects of host genetics on the gut microbiome

Kurilshikov

Graaf

et al. 2022

Nat Genet

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“…Neo-transgenic expression in transgenic pigs showed a significant increase in the relative abundance of some bacteria ( Firmicutes, Bacteroidetes , and Proteobacteria ) with a reduction of potentially harmful bacteria such as Escherichia–Shigella–Hafnia ( 87 ). A recent study by Yang et al ( 88 ) showed inactivation of the ABO acetyl-galactosaminyl-transferase gene through a deletion of 2.3 Kb, potentially affecting the microbiota composition and its relative abundance (particularly Christensenellaceae and Erysipelotrichaceae families).…”

Section: Genetic Manipulation Of Rumen Microbiotamentioning

confidence: 99%

Phytogenic Additives Can Modulate Rumen Microbiome to Mediate Fermentation Kinetics and Methanogenesis Through Exploiting Diet–Microbe Interaction

et al. 2020

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Ruminants inhabit the consortia of gut microbes that play a critical functional role in their maintenance and nourishment by enabling them to use cellulosic and non-cellulosic feed material. These gut microbes perform major physiological activities, including digestion and metabolism of dietary components, to derive energy to meet major protein (65–85%) and energy (ca 80%) requirements of the host. Owing to their contribution to digestive physiology, rumen microbes are considered one of the crucial factors affecting feed conversion efficiency in ruminants. Any change in the rumen microbiome has an imperative effect on animal physiology. Ruminal microbes are fundamentally anaerobic and produce various compounds during rumen fermentation, which are directly used by the host or other microbes. Methane (CH 4 ) is produced by methanogens through utilizing metabolic hydrogen during rumen fermentation. Maximizing the flow of metabolic hydrogen in the rumen away from CH 4 and toward volatile fatty acids (VFA) would increase the efficiency of ruminant production and decrease its environmental impact. Understanding of microbial diversity and rumen dynamics is not only crucial for the optimization of host efficiency but also required to mediate emission of greenhouse gases (GHGs) from ruminants. There are various strategies to modulate the rumen microbiome, mainly including dietary interventions and the use of different feed additives. Phytogenic feed additives, mainly plant secondary compounds, have been shown to modulate rumen microflora and change rumen fermentation dynamics leading to enhanced animal performance. Many in vitro and in vivo studies aimed to evaluate the use of plant secondary metabolites in ruminants have been conducted using different plants or their extract or essential oils. This review specifically aims to provide insights into dietary interactions of rumen microbes and their subsequent consequences on rumen fermentation. Moreover, a comprehensive overview of the modulation of rumen microbiome by using phytogenic compounds (essential oils, saponins, and tannins) for manipulating rumen dynamics to mediate CH 4 emanation from livestock is presented. We have also discussed the pros and cons of each strategy along with future prospective of dietary modulation of rumen microbiome to improve the performance of ruminants while decreasing GHG emissions.

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An ancient deletion in the ABO gene affects the composition of the porcine microbiome by altering intestinal N-acetyl-galactosamine concentrations

Cited by 6 publications

References 117 publications

Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

Challenges and future directions for studying effects of host genetics on the gut microbiome

Phytogenic Additives Can Modulate Rumen Microbiome to Mediate Fermentation Kinetics and Methanogenesis Through Exploiting Diet–Microbe Interaction

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