Bacteroides fragilis strain ZY-312 facilitates colonic mucosa regeneration in colitis via motivating STAT3 signaling pathway induced by IL-22 from ILC3 secretion.
Bacteroides fragilis strain ZY-312 facilitates colonic mucosa regeneration in colitis via motivating STAT3 signaling pathway induced by IL-22 from ILC3 secretion.
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DOI：
10.3389/fimmu.2023.1156762
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
益生菌在缓解炎症性肠病（IBD）中起着关键作用。然而，脆弱拟杆菌菌株ZY-312（B. fragilis）对IBD中结肠粘膜再生的影响尚不清楚。以体重减轻、疾病活动指数（DAI）、结肠长度和病理组织学相关指数（HAI）为指标评价B的疗效。在DSS诱导的结肠炎小鼠模型中，组织学染色检测结肠黏膜增殖、凋亡水平及粘液密度。通过16 srRNA分析对肠道微生物群进行测序。检测B组结肠黏膜信号转导和转录激活因子3（STAT 3）磷酸化的表达。fragilis治疗的小鼠结肠炎。B。通过ELISA和流式细胞术筛选激发下游STAT 3磷酸化的脆弱性调节的免疫因子。最后，B。通过小鼠STAT 3（Stat 3 △IEC）和IL-22（IL-22-/-）的敲除以及共培养模型中STAT 3和IL-22的抑制剂，验证了fragilis介导的结肠粘膜再生作用。 B。fragilis减轻DSS诱导的小鼠结肠炎，体重减轻、DAI、结肠长度缩短和HAI较少。结果表明，B.通过Stat 3 △IEC小鼠模型和体外添加STAT 3的模型，证实了在结肠粘膜中，脆弱型STAT 3蛋白磷酸化可上调增殖指数Ki-67和粘液密度，下调细胞凋亡水平，并调节肠道菌群。与此同时，我们发现，B。fragilis促进IL-22的产生，并增加结肠炎中分泌IL-22的3型先天淋巴细胞（ILC 3）的百分比。因此，我们确定了B。在IL-22 -/-小鼠中，fragilis没有增加pSTAT 3的表达，无论是增殖水平、粘液密度还是改变肠道微生物群。 B。fragilis可能间接刺激ILC 3分泌IL-22，随后IL-22诱导STAT 3磷酸化，从而促进结肠炎中的结肠粘膜再生。这表明B. fragilis具有成为IBD治疗的生物制剂的潜力。
Probiotics play critical roles in relieving inflammatory bowel disease (IBD). However, the underlying mechanism of Bacteroides fragilis strain ZY-312 (B. fragilis) for colonic mucosa regeneration in IBD remains unclear. The weight loss, disease activity index (DAI), colon length, and histopathology-associated index (HAI) were evaluated the therapeutic effects of B. fragilis in a DSS-induced colitis mouse model. Colonic mucosa proliferation and apoptosis level, and mucus density were detected by histological stain. Gut microbiota was sequenced by 16srRNA analysis. The expression of signal transducer and activator of transcription 3 (STAT3) phosphorylation in colonic mucosa was detected in B. fragilis-treated mice in colitis. B. fragilis-regulated immunity factors of motivating downstream STAT3 phosphorylation were screened by ELISA and flow cytometry. Lastly, B. fragilis-mediated colonic mucosa regeneration effects were verified though the knockout of STAT3 (Stat3 △IEC) and IL-22 (IL-22-/-) in mice, and inhibitor of STAT3 and IL-22 in co-culture model. B. fragilis alleviated DSS-induced colitis in mice with less weight loss, DAI, colon length shortening, and HAI. Further the results showed that B. fragilis motivated STAT3 phosphorylation in colonic mucosa with the upregulation of proliferation index Ki-67 and mucus density, the downregulation of apoptosis level, and the modulation of gut microbiota through a Stat3 △IEC mice model and STAT3 inhibitor-added model in vitro. Meanhwhile we found that B. fragilis promoted IL-22 production, and increased the percentage of IL-22-secreting type 3 innate lymphocytes (ILC3) in colitis. Consequently, We identified that B. fragilis did not increase the expression of pSTAT3, either proliferation level, mucus density, or alter gut microbiota in IL-22 -/- mice. B. fragilis may indirectly motivate ILC3 to secrete IL-22, followed by IL-22-induced STAT3 phosphorylation, hence promoting colonic mucosa regeneration in colitis. It indicates that B. fragilis has the potential to be a biological agent for IBD therapy.
DOI：
10.1080/14756366.2021.2001805
发表时间：
2022-12
影响因子：
5.6
作者：
Xu S;Fan R;Wang L;He W;Ge H;Chen H;Xu W;Zhang J;Xu W;Feng Y;Fan Z
通讯作者：
Fan Z