Oxidized cholesterol(OXC)is a harmful dietary substance.Although the consumption of OXC has been associated with colonic inflammation,related underlying mechanisms are still limited.We evaluated the influence of dietary OXC on gut health and ecology by applying the murine model.Results showed that the thickness of the mucus layer was significantly reduced in healthy mice treated with OXC.Short-term intake of OXC did not influence the expression of pro-inflammatory factors in healthy mice but it induced the decrease of Muc2 expression in the proximal colon,accompanied by an increase in the abundance of 2mucusdegrading bacteria,namely Akkermansia muciniphila and Bacteroides acidifaciens.Consistently,oral exposure of OXC promoted mucus barrier erosion in dextran sulfate sodium(DSS)-induced colitis mice and facilitated bacteria infiltration in the colon.The adverse effect of OXC on mucus layer disappeared in antibiotics-treated healthy mice,suggesting that the damaging effect of OXC on the gut mucus layer was not direct and instead was mediated by causing microbiota dysbiosis.Finally,the impact of OXC on the mucus layer and colitis was partly alleviated by green tea catechins.These studies demonstrated that the OXC-induced mucus barrier damage was mainly induced by the dysregulation of gut microbiota at least in this mouse model.
Chi YanShouhe HuangZixing ChenHuafang DingZhenyu Chen
As a member of mucins family,MUC2 is an important component of mucus,which is characterized by tandem and irregular repeat sequences rich in threonine and serine.It is strongly expressed by goblet cells that are involved in innate immunity.Japanese flounder is an economically important marine flatfish.In this study,two homologous genes of MUC2 were identified,named MUC2-1 and MUC2-2.Depending on phylogenetic and structural analysis,MUC2-1 and MUC2-2 were clustered in two clades,respectively.Paralichthys olivaceus MUC2-1 showed a closer relationship with MUC2 in the higher vertebrates.Various healthy tissues were analyzed to determine the expression patterns,and both MUC2 genes showed high expression levels in the gills and intestines.Following Edwardsiella tarda challenge,P.olivaceus MUC2-1 and MUC2-2 both showed significant up-regulated expression in intestine and kidney.Moreover,MUC2-1 was significantly up-regulated in gill cell lines following PGN and polyI:C stimulation,and MUC2-2 was significantly up-regulated in gill cell lines following LPS stimulation.In addition,ISH results revealed that MUC2-1 and MUC2-2 showed the same tissue localization in intestine tissues,but displayed different localization in gill.The siRNA-mediated knockdown of MUC2-1 and MUC2-2 genes in the gill cell lines of Japanese flounder affected the expressions of galnt family genes and smad pathway members that are related to mucosal immunity.The results provided a valuable insight into understanding the functions of MUC2 on mucosal immune system in response to the invasion of bacterial pathogen.
