Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
GIDRU, Queen's University, Kingston, ON, Canada.
Gut Microbes. 2022 Jan-Dec;14(1):2105095. doi: 10.1080/19490976.2022.2105095.
Both mast cells and microbiota play important roles in the pathogenesis of Irritable Bowel Syndrome (IBS), however the precise mechanisms are unknown. Using microbiota-humanized IBS mouse model, we show that colonic mast cells and mast cells co-localized with neurons were higher in mice colonized with IBS microbiota compared with those with healthy control (HC) microbiota. hybridization showed presence of IBS, but not control microbiota, in the and RNAscope demonstrated frequent co-localization of IBS bacteria and mast cells. TLR4 and H receptor expression was higher in mice with IBS microbiota, and in peritoneal-derived and bone marrow-derived mast cells (BMMCs) stimulated with IBS bacterial supernatant, which also increased BMMCs degranulation, chemotaxis, adherence and histamine release. While both TLR4 and H receptor inhibitors prevented BMMCs degranulation, only the latter attenuated their chemotaxis. We provide novel insights into the mechanisms, which contribute to gut dysfunction and visceral hypersensitivity in IBS.
肥大细胞和微生物群在肠易激综合征（IBS）的发病机制中都起着重要作用，但确切的机制尚不清楚。本研究使用微生物群-人源化 IBS 小鼠模型，显示与健康对照（HC）微生物群相比，定植 IBS 微生物群的小鼠结肠肥大细胞和与神经元共定位的肥大细胞更高。杂交显示存在 IBS 微生物群，但不存在对照微生物群，并且 RNAscope 显示 IBS 细菌和肥大细胞频繁共定位。TLR4 和 H 受体表达在具有 IBS 微生物群的小鼠中更高，并且在 IBS 细菌上清液刺激的腹膜衍生和骨髓衍生肥大细胞（BMMC）中更高，这也增加了 BMMC 的脱颗粒、趋化性、黏附和组胺释放。虽然 TLR4 和 H 受体抑制剂均可防止 BMMC 脱颗粒，但只有后者可减轻其趋化性。本研究为 IBS 中导致肠道功能障碍和内脏高敏性的机制提供了新的见解。
