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人粪便微生物群移植可降低葡聚糖硫酸钠诱导的无菌小鼠结肠炎易感性。

Human Fecal Microbiota Transplantation Reduces the Susceptibility to Dextran Sulfate Sodium-Induced Germ-Free Mouse Colitis.

机构信息

College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.

Center for Translational Medicine, Shanghai Key Laboratory of Diabetes Mellitus and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

出版信息

Front Immunol. 2022 Feb 14;13:836542. doi: 10.3389/fimmu.2022.836542. eCollection 2022.

DOI:10.3389/fimmu.2022.836542
PMID:35237276
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8882623/
Abstract

In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the selection of FMT donors and the mechanism underlying the effect of FMT intervention in IBD require further exploration. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to determine the differences in the protection of colitis symptoms, inflammation, and intestinal barrier, by FMT from two donors. Intriguingly, pre-administration of healthy bacterial fluid significantly relieved the symptoms of colitis compared to the ulcerative colitis (UC) bacteria. In addition, healthy donor (HD) bacteria significantly reduced the levels of inflammatory markers Myeloperoxidase (MPO) and Eosinophil peroxidase (EPO), and various pro-inflammatory factors, in colitis mice, and increased the secretion of the anti-inflammatory factor IL-10. Metagenomic sequencing indicated higher species diversity and higher abundance of anti-inflammatory bacteria in the HD intervention group, including , , , short-chain fatty acids (SCFAs)-producing bacterium , and secondary bile acids (SBAs)-producing bacterium . In the UC intervention group, the SCFA-producing bacterium , IBD-related bacterium , , and the conditional pathogen , were more abundant. Metabolomics analysis showed that the two types of FMT significantly modulated the metabolism of DSS-induced mice. Moreover, compared with the UC intervention group, indoleacetic acid and unsaturated fatty acids (DHA, DPA, and EPA) with anti-inflammatory effects were significantly enriched in the HD intervention group. In summary, these results indicate that FMT can alleviate the symptoms of colitis, and the effect of HD intervention is better than that of UC intervention. This study offers new insights into the mechanisms of FMT clinical intervention in IBD.

摘要

在临床实践中,粪便微生物移植(FMT)已被用于治疗炎症性肠病(IBD),并显示出一定的效果。然而,FMT 供体的选择和 FMT 干预 IBD 的作用机制仍需要进一步探索。在这项研究中,使用葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠来确定来自两个供体的 FMT 在保护结肠炎症状、炎症和肠道屏障方面的差异。有趣的是,与溃疡性结肠炎(UC)细菌相比,预先给予健康细菌液显著缓解了结肠炎的症状。此外,健康供体(HD)细菌显著降低了结肠炎小鼠中炎症标志物髓过氧化物酶(MPO)和嗜酸性粒细胞过氧化物酶(EPO)以及各种促炎因子的水平,并增加了抗炎因子 IL-10 的分泌。宏基因组测序表明,HD 干预组的物种多样性更高,抗炎细菌的丰度更高,包括、、、产生短链脂肪酸(SCFAs)的细菌和产生次级胆汁酸(SBAs)的细菌。在 UC 干预组中,产生 SCFA 的细菌、与 IBD 相关的细菌、和条件致病菌更为丰富。代谢组学分析表明,两种类型的 FMT 显著调节了 DSS 诱导的小鼠代谢。此外,与 UC 干预组相比,具有抗炎作用的吲哚乙酸和不饱和脂肪酸(DHA、DPA 和 EPA)在 HD 干预组中明显富集。综上所述,这些结果表明 FMT 可以缓解结肠炎的症状,HD 干预的效果优于 UC 干预。本研究为 FMT 临床干预 IBD 的机制提供了新的见解。

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