Distribution of Bacterial α1,3-Galactosyltransferase Genes in the Human Gut Microbiome

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 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 (GT) gene sequences from gut bacteria were selectively quantified for the first time in the gut microbiome shotgun sequences of 163 adult individuals from three published population-based metagenomics analyses. We showed that most of the gut microbiome of adult individuals contained a small set of bacteria bearing α1,3-GT genes. These bacteria belong mainly to the Enterobacteriaceae family, including Escherichia coli, but also to Pasteurellaceae genera, Haemophilus influenza and Lactobacillus species. α1,3-Gal antigens and α1,3-GT activity were detected in healthy stools of individuals exhibiting α1,3-GT bacterial gene sequences in their shotgun data.

Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Santé study

“…Importantly, the effect of diet on antibody responses was specific to Neu5Gc and could not be detected in response to other control dietary carbohydrates, Neu5Ac, and αGal. Neu5Ac is expressed on human cells but is considered to be a tolerized self-moiety [ 17 ], while αGal is only expressed by bacteria in the gut [ 46 , 54 ], and even if consumed could be cleaved into the non-immunogenic galactose. The novelty in the developed methodology is several fold: (a) the use of a defined cohort with multiple, detailed and well-dispersed online 24-h dietary records, in both men and women, from diverse age groups; (b) accurate assessment of consumed Neu5Gc quantities from common food items; and (c) several improved quantitative methods to measure and characterize anti-Neu5Gc antibodies that include a standard curve in both EIA and glycan microarrays, which provides internal quality control and facilitates accurate measurements independent of experimental day and conditions.…”

B Cell Responses in the Development of Mammalian Meat Allergy

“…This production of α-gal-specific antibodies is thought to be driven by the continuous exposure of B cells to α-gal expressed by microorganisms that colonize the gastrointestinal tract ( 45 , 50 , 51 ). α-gal has been found in a variety of bacteria of the human flora, including Escherichia coli, Klebsiella , and Salmonella strains isolated from human stool and blood, with some strains expressing α-gal on the carbohydrate portion of bacterial lipopolysaccharides ( 45 , 52 ). Furthermore, several human pathogens express α-gal.…”

SARS‐CoV‐2 replicating in nonprimate mammalian cells probably have critical advantages for COVID‐19 vaccines due to anti‐Gal antibodies: A minireview and proposals

“…Many bacteria (eg, Serratia marcescens) and protozoa (eg, Trypanosoma cruzi) synthesize and present Gal-Gs on the glycoproteins and glycolipids. 13,18,19 3 | ANTI-GAL ANTIBODIES (ANTI-GAL-ABS)…”

“…14 In contrast, humans, apes, and Old-World monkeys produce anti-Gal-Abs throughout life because of frequent antigenic stimulation by many gastrointestinal bacteria carrying Gal-Gs. 19 Anti-Gal-Abs are abundant in humans, constituting~1% of serum IgG, IgM, and IgA immunoglobulins. 18,20 Anti-Gal-Abs also exist as IgA and IgG in milk, colostrum, saliva, and bile.…”