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高脂饮食通过改变肠道微生物群落增加了胶原诱导性关节炎在小鼠中的严重程度。

High fat diet increases the severity of collagen-induced arthritis in mice by altering the gut microbial community.

机构信息

The First Hospital of China Medical University, Shenyang, 110002, Liaoning, China.

Liaoning University of Traditional Chinese Medicine, Shenyang, 110001, Liaoning, China.

出版信息

Adv Rheumatol. 2024 May 30;64(1):44. doi: 10.1186/s42358-024-00382-y.

DOI:10.1186/s42358-024-00382-y
PMID:38816873
Abstract

OBJECTIVES

Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, gut microbiota and its metabolites contribute to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear. In this study, we aimed to investigate whether gut microbiota and their metabolites alter the effects of high fat diet (HFD) on the severity of collagen-induced arthritis (CIA) in mice.

METHODS

Briefly, mice were divided into normal group (N), CIA model group (C), HFD group (T), and HFD CIA group (CT). Hematoxylin and Eosin staining(HE) and Safranin O-fast green staining were conducted, and levels of blood lipid and inflammatory cytokines were measured. 16S rDNA sequencing technique and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics were performed to explore changes in the microbiota structure to further reveal the pathomechanism of HFD on CIA.

RESULTS

HFD aggravated the severity of CIA in mice. The CT group had the highest proportion of microbial abundance of Blautia, Oscillibacter, Ruminiclostridium-9, and Lachnospiraceae UCG 006 at the genus level, but had a lower proportion of Alistipes. Additionally, the fecal metabolic phenotype of the combined CT group shows significant changes, with differential metabolites enriched in 9 metabolic pathways, including primary bile acid biosynthesis, arginine biosynthesis, sphingolipid metabolism, purine metabolism, linoleic acid metabolism, oxytocin signaling pathway, aminoacyl-tRNA biosynthesis, the pentose phosphate pathway, and sphingolipid signaling pathway. Correlation analysis revealed that some of the altered gut microbiota genera were strongly correlated with changes in fecal metabolites, total cholesterol (TC), triglyceride (TG), and inflammatory cytokine levels.

CONCLUSIONS

This study shows that HFD may aggravate inflammatory reaction in CIA mice by altering the gut microbiota and metabolic pathways.

摘要

目的

研究表明肥胖可能与类风湿关节炎(RA)有关。此外,肠道微生物群及其代谢物有助于 RA 和肥胖的发生和发展。然而,肥胖影响 RA 的机制尚不清楚。在这项研究中,我们旨在研究肠道微生物群及其代谢物是否会改变高脂肪饮食(HFD)对胶原诱导关节炎(CIA)小鼠严重程度的影响。

方法

简要地说,将小鼠分为正常组(N)、CIA 模型组(C)、HFD 组(T)和 HFD CIA 组(CT)。进行苏木精和伊红染色(HE)和番红 O-快绿染色,并测量血脂和炎症细胞因子水平。采用 16S rDNA 测序技术和基于液相色谱-质谱(LC-MS)的代谢组学技术,探索微生物群落结构的变化,进一步揭示 HFD 对 CIA 的发病机制。

结果

HFD 加重了 CIA 小鼠的严重程度。CT 组在属水平上具有最高比例的微生物丰度 Blautia、Oscillibacter、Ruminiclostridium-9 和 Lachnospiraceae UCG 006,但 Alistipes 的比例较低。此外,联合 CT 组的粪便代谢表型显示出显著变化,差异代谢物富集在 9 条代谢途径中,包括初级胆汁酸生物合成、精氨酸生物合成、鞘脂代谢、嘌呤代谢、亚油酸代谢、催产素信号通路、氨基酸酰-tRNA 生物合成、戊糖磷酸途径和鞘脂信号通路。相关性分析表明,一些改变的肠道微生物属与粪便代谢物、总胆固醇(TC)、甘油三酯(TG)和炎症细胞因子水平的变化密切相关。

结论

本研究表明,HFD 通过改变肠道微生物群和代谢途径可能加重 CIA 小鼠的炎症反应。

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Collinsella is associated with cumulative inflammatory burden in an established rheumatoid arthritis cohort.科林斯氏菌与既定类风湿关节炎队列中的累积炎症负担有关。
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Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa).
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The Gut Microbiome and Metabolites Are Altered and Interrelated in Patients With Rheumatoid Arthritis.类风湿关节炎患者的肠道微生物组和代谢物发生改变且相互关联。
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Individuals at risk for rheumatoid arthritis harbor differential intestinal bacteriophage communities with distinct metabolic potential.类风湿关节炎风险个体具有不同代谢潜能的差异化肠道噬菌体群落。
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