Distribution of Bacterial α1,3-Galactosyltransferase Genes in the Human Gut Microbiome
Emmanuel Montassier, Gabriel A. Al‐Ghalith, Camille Mathé, Quentin Le Bastard, Venceslas Douillard, Abel Garnier, Rémi Guimon, Bastien Raimondeau, Yann Touchefeu, Émilie Duchalais, Nicolas Vince, Sophie Limou, Pierre‐Antoine Gourraud, David Laplaud, Arnaud Nicot, Jean‐Paul Soulillou, Laureline Berthelot
Abstract
Because of a loss-of-function mutation in the GGTA1 gene, humans are unable to synthetize α1,3-Galactose (Gal) decorated glycans and develop high levels of circulating anti-α1,3-Galactose antibodies (anti-Gal Abs). Anti-Gal Abs have been identified as a major obstacle of organ xenotransplantation responsible for hyperacute vascular rejection and delayed vascular insult, and play a role in several host-pathogen relationships including potential susceptibility to infection. Anti-Gal Abs are supposed to stem from immunization against the gut microbiota, an assumption derived from the observation that some pathogens display α1,3-Gal and that antibiotic treatment decreases the level of anti-Gal. However, there is little information to date concerning the microorganisms producing α1,3-Gal in the human gut microbiome. Here, available α1,3-Galactosyltransferase gene sequences from gut bacteria were selectively quantified for the first time in the gut microbiome shotgun sequences of 163 adult individuals from 2 published population-based metagenomics analyses. We showed that most of the gut microbiome of adult individuals contained a small set of bacteria able to synthetize the α1,3-Gal antigen. The Enterobacteriaceae family, including Escherichia coli, was found to be the major source of the α1,3-Gal antigen, which was also produced by Pasteurellaceae genera, Haemophilus influenza, and Lactobacillus species.