Dietary Oxidized Cholesterol Aggravates Chemically Induced Murine Colon Inflammation and Alters Gut Microbial Ecology

Abstract

Western diet with a higher intake of fat and cholesterol has been claimed as an intestinal inflammation trigger. Human diet contains both cholesterol and oxidized cholesterol. Oxidized cholesterol has been claimed to be associated with various inflammation diseases, but its effects on colitis and gut microbiome remain largely unknown. The present study was the first time to investigate the effect of the oxidized cholesterol on gut microbiota and dextran sodium sulfate-induced colitis using mice as a model. The results showed that oxidized cholesterol promoted colitis by exacerbating bleeding, body weight decrease, colon shortening, gut barrier damage, oxidative stress, and gut inflammation, whereas non-oxidized cholesterol had no effect. Meanwhile, oxidized cholesterol could adversely modulate the gut microbiota by increasing the relative abundance of pro-inflammatory bacteria (including <i>Escherichia</i>-<i>Shigella</i> and <i>Bacteroides</i>) and decreasing that of beneficial bacteria (<i>Lachnospiraceae_NK4A136_group</i> and <i>Odoribacter</i>). In addition, oxidized cholesterol significantly reduced the production of fecal short-chain fatty acids in colitis mice. It was concluded that oxidized cholesterol was a potential dietary factor of gut dysbiosis.