Abstract: In this study, the effect of 18 weeks of dietary supplementation of porcine submaxillary gland mucin (PSM) as an abundant source of N-hydroxyacetylneuraminic acid (Neu5Gc) on the expression of proteins involved in the nuclear factor kappa-B (NF-κB) signaling pathway in the liver, serum interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha (TNF-α), serum amyloid A protein (SAA) and the gut microbiota in cytidine-5’-monophosphate-N-acetylneuraminic acid knockout (Cmah-/-) mice was investigated. Meanwhile, the effect of gender on Neu5Gc-induced inflammation in Cmah-/- mice was analyzed. The results showed that Neu5Gc activated the NF-κB signaling pathway and significantly increased the serum concentration of IL-6, IL-1β, TNF-α and SAA in both male and female mice when compared with normal controls. In the PSM-treated male mice, the ratio of Bacteroidetes to Firmicutes (B/F) significantly increased, the relative abundance of Muribaculaceae and Prevotellaceae significantly decreased, and the relative abundance of Clostridia UCG-014 and Prevotellaceae_NK3B31_group, which are positively associated with intestinal inflammation, significantly increased. In the PSM-treated female mice, the richness of gut microbiota significantly decreased, and so did the relative abundance of Lachnospiraceae and Oscillospiraceae. In conclusion, Neu5Gc in PSM could promote inflammatory responses in Cmah-/- mice through significantly down-regulating the abundance of relevant bacterial communities, facilitating the growth of bacterial communities positively associated with intestinal inflammation, leading to structural disorders of gut microbiota, activating the NF-κB signaling pathway and increasing the secretion of serum inflammatory cytokines, and inflammatory response induced in mice by Neu5Gc was affected by gender. Our study provides a reference for a healthy diet.

Key words: N-glycolylneuraminic acid; inflammatory cytokines; gut microbiota; sex differences; chronic inflammation