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.
MS is a chronic inflammatory disease of the CNS involving T cell and B cell responses. Recently, several studies have described modifications of specific bacterium abundances of gut microbiota in patients with remitting-relapsing MS compared with healthy individuals (see for review 1 ). This was often associated with an increase in Akkermansia muciniphila bacteria. In experimental autoimmune encephalomyelitis, transfer of gut microbiota from patients with MS to mice induced proinflammatory responses and exacerbation of the disease, whereas microbiota from healthy volunteers (HVs) were less inflammatory. 2,3 Because bacteria in the gut modulate immune responses, we assessed the antibody production against A muciniphila in patients with MS. In CSF, levels of anti-A muciniphila immunoglobulin G (IgG) were increased in patients with MS compared with controls, whereas no difference was found for levels of IgG against Escherichia coli, Fusobacterium necrophorum, Acinetobacter baumannii, Prevotella melaninogenica, and Bacteroides fragilis. MethodsPatients with relapsing-remitting MS (RRMS, n = 62) were enrolled in the neurology department of CHU de Nantes. Sex and age-matched patients (HVs, n = 41), patients with noninflammatory neurologic disease (e.g., suffering from sudden headaches or idiopathic intracranial hypertension) (noninflammatory neurologic disease [NIND], n = 23), and patients with inflammatory neurologic disease (peripheral neuropathy, brain lymphoma) (inflammatory neurological disease [IND], n = 10) were used for comparison. Informed written consent was obtained from all the patients before any study-related procedure was performed. Patients had not received any disease-modifying drugs before the sampling.IgG concentration was measured with an immunonephelometric assay performed using a Beckman Immage Analyzer (Beckman Coulter). To detect antibody against bacteria, ELISA tests were performed using serum and CSF samples. Briefly, bacteria lysates from A muciniphila, F necrophorum, A baumannii, P melaninogenica, and E coli were coated on plates (Nunc) at 1 μg/mL of proteins in phosphate buffer saline (PBS). Bovine serum albumin (Sigma Aldrich) at 1% in PBS was used for blocking. Patient samples were incubated for 2 hours at 37°C in PBS (dilutions 1/ 100 for serum, 1/10 for CSF) and 1% bovine serum albumin. Antihuman IgG antibodies coupled with horseradish peroxidase (Bethyl Laboratories) at 1/5,000, 1 hour at 37°C, were used. The reaction with the substrate (3,3',5,5'-Tetramethylbenzidine, BD Biosciences) was stopped with sulfuric acid (0.18M, Sigma Aldrich). Plates were read at 450 nm using a Spark 10M multimode
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