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A potential causal factor is <jats:italic>N<\/jats:italic>\u2010glycolylneuraminic acid (Neu5Gc) which metabolically incorporates into diverse glycoconjugates in humans. This study aims to investigate the impact of exposure to Neu5Gc\u2010rich red meat on healthy cytidine\u20105\u2032\u2010monophospho\u2010<jats:italic>N<\/jats:italic>\u2010acetylneuraminic acid hydroxylase (<jats:italic>Cmah<\/jats:italic>) knock\u2010out mice and the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p><jats:italic>CMAH<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice are fed Neu5Gc\u2010rich diet for short\u2010term (4 months) and long\u2010term (10 months). Health status and levels of inflammatory cytokines are assessed. Caco\u20102 cells are used to investigate the intestinal absorption of Neu5Gc\u2010containing glycoprotein, and in vitro fermentation is used to investigate the Neu5Gc utilization by gut microbiota. Neu5Gc\u2010rich diets show neither measurable abnormality in physio\u2010biochemical and inflammatory indexes nor observable alterations of liver tissue in mice. Glycosylation of lactoferrin limits its intestinal epithelial absorption, and the absorption of Neu5Gc attach onto glycoprotein is thus limited. Neu5Gc is also simultaneously utilized by microorganisms under simulated gut conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results indicate that the long\u2010term intake of Neu5Gc\u2010rich red meat has no adverse effect on the health of <jats:italic>CMAH<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, which may be related to the limited absorption of Neu5Gc that is regulated by protein glycosylation, and the metabolism of Neu5Gc by gut microorganisms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202100615","type":"journal-article","created":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T17:18:38Z","timestamp":1639847918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Protein Glycosylation and Gut Microbiota Utilization Can Limit the In Vitro and In Vivo Metabolic Cellular Incorporation of 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