Red meat diet affects level and repertoire of serum antibodies against the non-human carbohydrate Neu5Gc

N-Glycolylneuraminic acid (Neu5Gc) is an immunogenic non-human sialic acid carbohydrate found in mammalian-derived food, and all humans have diverse anti-Neu5Gc antibodies suggested to exacerbate chronic-inflammation-mediated diseases. We hypothesized that red meat and dairy diet could affect the expression of serum anti-Neu5Gc antibodies. Based on 24h-dietary records, daily Neu5Gc intake was calculated for 19,621 subjects aged ≥ 18 years of the NutriNet-Santé Study, a 10-year web-based French prospective cohort designed to investigate association between nutrition and health. Then, serum anti-Neu5Gc antibodies were evaluated by ELISA and glycan microarrays in representative 120 individuals, each with at least eighteen 24h-dietary records (10 men/women per quartile; aged 45–60: Q1 – Q4; aged >60 per: Q1 and Q4). Men consumed more Neu5Gc than women, mostly from red meat (p=0.0015), and exhibited higher overall serum anti-Neu5Gc IgG levels by ELISA (3.94 ng/µl versus 2.22 ng/µl, respectively; p=0.039). Detailed glycan microarray analysis against 56 different sialic acid-containing glycans revealed high Neu5Gc-specificity with increased anti-Neu5Gc IgG and altered repertoires, associated with higher consumption of Neu5Gc from red meat and cow dairy. Affinity-purification of serum anti-Neu5Gc antibodies revealed increased levels and biased array repertoire patterns, without increase in antibodies affinity, in individuals consuming higher Neu5Gc levels. Altogether, we found a clear link between the levels and repertoire of serum anti-Neu5Gc IgG and Neu5Gc-intake from red meat and dairy. Studies in mice suggest that anti-Neu5Gc antibodies binding to Neu5Gc on epithelial and endothelial cells exacerbate cancer and cardiovascular diseases, hence investigating their association with such human diseases is warranted.