粪便微生物群移植改善实验性结肠炎的肠道微生物群和 T 细胞调节。
Fecal microbiota transplantation ameliorates experimental colitis gut microbiota and T-cell modulation.
机构信息
Department of Gastroenterology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
出版信息
World J Gastroenterol. 2021 Jun 7;27(21):2834-2849. doi: 10.3748/wjg.v27.i21.2834.
BACKGROUND
Emerging evidence has demonstrated that fecal microbiota transplantation (FMT) has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis (UC), although the mechanism of FMT is unclear.
AIM
To evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota, through association analysis of gut microbiota with colon transcriptome in mice.
METHODS
Dextran sodium sulfate (DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage. Severity of colon inflammation was measured by body weight, disease activity index, colon length and histological score. Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing. The differentially expressed genes (DEGs) in the colon were obtained by transcriptome sequencing. The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry.
RESULTS
Compared with the DSS group, the weight loss, colon length shortening and inflammation were significantly alleviated in the FMT group. The scores of disease activity index and colon histology decreased obviously after FMT. FMT restored the balance of gut microbiota, especially by upregulating the relative abundance of and downregulating the relative abundance of and . In the transcriptomic analysis, 128 DEGs intersected after DSS treatment and FMT. Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation. In the DSS group, there was an increase in colonic T helper CD4 and T cytotoxic CD8 cells by flow cytometry. FMT selectively downregulated the ratio of colonic CD4 and CD8 T cells to maintain intestinal homeostasis. Furthermore, was significantly related to inflammation-related genes including , and .
CONCLUSION
FMT ameliorated DSS-induced colitis in mice regulating the gut microbiota and T-cell modulation.
背景
有新证据表明，粪便微生物群移植（FMT）对实验性结肠炎小鼠和溃疡性结肠炎（UC）患者具有有希望的治疗作用，尽管 FMT 的机制尚不清楚。
目的
通过分析小鼠肠道微生物群与结肠转录组的关联，评估 FMT 对 UC 的保护作用，并阐明其对肠道微生物群的潜在依赖性。
方法
通过灌胃法建立葡聚糖硫酸钠（DSS）诱导的实验性结肠炎模型，并进行粪便微生物群移植。通过体重、疾病活动指数、结肠长度和组织学评分来衡量结肠炎症的严重程度。通过 16S 核糖体核糖核酸测序分析肠道微生物群的变化。通过转录组测序获得结肠中差异表达基因（DEGs）。通过流式细胞术评估固有层结肠 T 淋巴细胞的激活状态。
结果
与 DSS 组相比，FMT 组的体重减轻、结肠缩短和炎症明显缓解。FMT 后疾病活动指数和结肠组织学评分明显降低。FMT 恢复了肠道微生物群的平衡，特别是通过上调相对丰度和下调相对丰度和 。在转录组分析中，DSS 处理和 FMT 后有 128 个 DEGs 相交。功能注释分析表明，这些 DEGs 主要参与 T 淋巴细胞的激活。在 DSS 组中，流式细胞术显示结肠辅助性 T 细胞 CD4 和细胞毒性 T 细胞 CD8 增加。FMT 选择性地下调结肠 CD4 和 CD8 T 细胞的比例，以维持肠道内稳态。此外，与炎症相关基因包括 、 和 显著相关。
结论
FMT 通过调节肠道微生物群和 T 细胞调节，改善了 DSS 诱导的小鼠结肠炎。
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