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肠道微生物群失调和胆汁酸分解代谢改变导致银屑病小鼠代谢紊乱。

Gut Microbiota Dysbiosis and Altered Bile Acid Catabolism Lead to Metabolic Disorder in Psoriasis Mice.

作者信息

Hao Yan, Zhou Pei, Zhu Ya-Juan, Zou Song, Zhao Qixiang, Yu Jiadong, Hu Yawen, Li Jiong

机构信息

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.

Department of Biotherapy and Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Front Microbiol. 2022 Apr 14;13:853566. doi: 10.3389/fmicb.2022.853566. eCollection 2022.

Abstract

Patients with psoriasis tend to have significant comorbidities, such as hyperlipemia, diabetes mellitus, and obesity, which belong to metabolic disorders. The specific mechanism through which psoriasis increases the metabolic disorder risk is uncertain. In this study, we demonstrated that the dysbiotic gut microbiota of 6-month-old psoriasis-like model mice (K14-VEGF-A-transgenic) exacerbated psoriasis disease and induced metabolic disorder when transferred into 2-month-old mice. By 16S rRNA gene sequencing, we confirmed that the decreased with age in K14-VEGF mice, and also decreased in the transferred mice. Metabolomic screening identified an altered bile acid profile, including a decrease in chenodeoxycholic acid (CDCA) in the feces of transferred mice. Additionally, CDCA supplements prevented metabolic disorders in K14-VEGF-A-transgenic mice. Consequently, we found that aberrant bile acid metabolism may contribute to metabolic disorder in K14-VEGF-A-transgenic mice, indicating the possibility to prevent and treat the metabolic disorder in psoriasis mice by targeting gut microbial metabolites.

摘要

银屑病患者往往伴有显著的合并症,如高脂血症、糖尿病和肥胖症,这些都属于代谢紊乱。银屑病增加代谢紊乱风险的具体机制尚不确定。在本研究中,我们证明,将6个月大的银屑病样模型小鼠(K14-VEGF-A转基因小鼠)的肠道微生物群失调移植到2个月大的小鼠体内时,会加剧银屑病病情并诱发代谢紊乱。通过16S rRNA基因测序,我们证实K14-VEGF小鼠体内的[此处原文缺失相关内容]随年龄增长而减少,移植小鼠体内的[此处原文缺失相关内容]也减少。代谢组学筛查发现胆汁酸谱发生改变,包括移植小鼠粪便中鹅去氧胆酸(CDCA)减少。此外,补充CDCA可预防K14-VEGF-A转基因小鼠的代谢紊乱。因此,我们发现异常的胆汁酸代谢可能导致K14-VEGF-A转基因小鼠出现代谢紊乱,这表明通过靶向肠道微生物代谢产物预防和治疗银屑病小鼠代谢紊乱具有可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b59c/9048827/40c01a349971/fmicb-13-853566-g0001.jpg

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