RT Journal Article SR Electronic T1 Chondroitin Sulfate Elicits Systemic Pathogenesis In Mice By Interfering With Gut Microbiota Homeostasis JF bioRxiv FD Cold Spring Harbor Laboratory SP 142588 DO 10.1101/142588 A1 Tao Liao A1 Yan-Ping Chen A1 Shui-Qing Huang A1 Li-Li Tan A1 Chang-Qing Li A1 Xin-An Huang A1 Qin Xu A1 Qi Wang A1 Qing-Ping Zeng YR 2017 UL http://biorxiv.org/content/early/2017/05/27/142588.abstract AB Whether chondroitin sulfate (CS), a common ingredient naturally occurring in livestock and poultry products, improves osteoarthritis remains debating. Here, we show for the first time that CS induces steatogenesis, atherogenesis, and dementia-like pathogenesis in mice. Gut microbiome analysis revealed the sulfatase-secreting bacteria Rikenella and the sulfate-reducing bacteria Desulfovibrio are enriched. Surprisingly, berberine use boosts CS-induced multi-loci inflammatory manifestations by further increasing the abundance of Rikenella and Desulfovibrio, whereas cephalosporin reinforces the colon mucus barrier via flourishing Akkermansia muciniphila and upregulating mucin expression. Mechanistically, berberine aggravates mucus lining injury by prompting mucin degradation, endotoxin leakage, neutralizing antibody induction, pro-inflammatory cytokine burst, lactic acid accumulation and energy currency depletion in multiple organs and tissues. Taken together, CS evokes the early-phase pathogenesis toward steatohepatitis, atherosclerosis, and dementia upon augmenting gut opportunistic infection, and a sustained antibiotic monotherapy does not deprive the risk of CS-driven systemic inflammatory disorders.