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Article | Open Access

Dietary oxidized cholesterol causes mucus barrier thinner via decreasing Muc2 expression in the proximal colon and increasing the abundance of mucus-degrading bacteria

Chi Yan, Shouhe Huang, Zixing Chen, Huafang Ding(), Zhenyu Chen()
School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Hong Kong 999077, China

Peer review under responsibility of Beijing Academy of Food Sciences.

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Highlights

• Intake of oxidized cholesterol (OXC) induced the thinness of colonic mucus layer.

• OXC promoted mucus layer erosion and bacteria infiltration in DSS-induced colitis mice.

• OXC down-regulated the expression of proximal Muc2 and increased the mucus-degrading bacteria.

• Antibiotics-treated experiments proved OXC-induced mucus layer thinness was mediated by gut microbiota dysbiosis.

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Abstract

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 2 mucus-degrading 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.

Keywords

Dietary oxidized cholesterolGut microbiotaColonic inflammationMucus barrierWestern dietsInflammatory bowel diseases

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Food Science and Human Wellness
Volume 14 Issue 4,
April 2025
Article number: 9250200
DOI: 10.26599/FSHW.2024.9250200
Cite this article:
Yan C, Huang S, Chen Z, et al. Dietary oxidized cholesterol causes mucus barrier thinner via decreasing Muc2 expression in the proximal colon and increasing the abundance of mucus-degrading bacteria. Food Science and Human Wellness, 2025, 14(4): 9250200. https://doi.org/10.26599/FSHW.2024.9250200
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