Clostridioides difficile aggravates dextran sulfate solution (DSS)-induced colitis by shaping the gut microbiota and promoting neutrophil recruitment.
Clostridioides difficile aggravates dextran sulfate solution (DSS)-induced colitis by shaping the gut microbiota and promoting neutrophil recruitment.
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DOI：
10.1080/19490976.2023.2192478
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发表时间：
2023-01
期刊：
影响因子：
12.2
通讯作者：
中科院分区：
文献类型：
--
作者：
艰难梭状芽胞杆菌是炎症性肠病(IBD)患者发病率和死亡率增加的病原体。为了确定艰难梭菌如何影响结肠炎的严重程度，我们构建了一种艰难梭菌挑战的葡聚糖硫酸盐溶液诱导的结肠炎模型。在没有给予抗生素的情况下，艰难梭菌导致了结肠炎小鼠的短暂定植，但根据体重减轻、组织病理学损害和炎性细胞因子浓度的评估，仍显著增加了疾病的严重性。由于这种影响独立于毒素的产生，如感染非产毒菌株所显示的那样，我们专注于肠道微生物区系的变化。艰难梭菌改变的微生物群以g_Prevoteaceae_UCG-001和g_Muribaculaceae的比例减少为特征，通过粪便微生物群移植证实对结肠炎小鼠的疾病严重程度有贡献。流式细胞术和髓过氧化物酶免疫组织化学染色显示炎性结肠有中性粒细胞聚集。RNA测序分析表明，在白细胞趋化或迁移过程中，上调基因的表达明显增强。从艰难梭菌感染的结肠炎小鼠分离的中性粒细胞表现出强大的迁移能力，并增强了细胞因子和趋化因子的表达。我们观察到中性粒细胞通过使用CXCR2抑制剂SB225002阻碍中性粒细胞募集而在疾病进展中起到有害的作用。此外，中性粒细胞募集似乎受白细胞介素1β的调节，因为抑制白细胞介素1β的产生可明显减轻炎症反应，减少中性粒细胞聚集和中性粒细胞衍生趋化因子的表达。总之，我们的研究为艰难梭菌诱导的结肠炎小鼠炎症中微生物区系和免疫反应之间的复杂相互作用提供了信息。我们的发现有助于确定IBD合并艰难梭菌感染患者的潜在治疗目标。
Clostridioides difficile is a pathogen contributing to increased morbidity and mortality of patients with inflammatory bowel disease (IBD). To determine how C. difficile affects the severity of colitis, we constructed a dextran sulfate solution-induced colitis model challenged with C. difficile. Without antibiotic administration, C. difficile led to transient colonization in mice with colitis, but still significantly enhanced disease severity as assessed by weight loss, histopathological damages, and inflammatory cytokine concentrations. Because this effect is independent of toxin production as shown by infection with a non-toxigenic strain, we focused on changes in the gut microbiota. The microbiota altered by C.difficile, featured with reduced proportions of g_Prevotellaceae_UCG-001 and g_Muribaculaceae, were confirmed to contribute to disease severity in colitis mice via fecal microbiota transplantations. The inflamed colon showed neutrophil accumulation by flow cytometric analysis and myeloperoxidase immunochemical staining. There was enrichment of upregulated genes in leukocyte chemotaxis or migration as shown by RNA sequencing analysis. The isolated neutrophils from C. difficile-infected mice with colitis showed a robust migratory ability and had enhanced expression of cytokines and chemokines. We observed a detrimental role of neutrophils in the progress of disease by hindering neutrophil recruitment with the CXCR2 inhibitor SB225002. Furthermore, neutrophil recruitment appeared to be regulated by interleukin (IL)-1β, as inhibition of IL-1β production by MCC950 markedly ameliorated inflammation with decreased neutrophil accumulation and neutrophil-derived chemokine expression. In conclusion, our study provides information on the complicated interaction between microbiota and immune responses in C. difficile-induced inflammation in mice with colitis. Our findings could help determine potential therapeutic targets for patients with IBD concurrent with C. difficile infection.
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肠道微生物群形成短链脂肪酸及其对人代谢的影响。
影响因子：
12.2
作者：
Morrison DJ;Preston T
通讯作者：
Preston T
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
6.4
作者：
Lee, Yeon Joo;Arguello, Esther S.;Taur, Ying
通讯作者：
Taur, Ying
DOI：
10.1084/jem.20111453
发表时间：
2012-08-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coccia M;Harrison OJ;Schiering C;Asquith MJ;Becher B;Powrie F;Maloy KJ
通讯作者：
Maloy KJ
影响因子：
20.3
作者：
Hayashi, F;Means, TK;Luster, AD
通讯作者：
Luster, AD