APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland.
School of Biochemistry and Cell Biology, University College Cork, T12 YT20 Cork, Ireland.
Int J Mol Sci. 2021 Aug 3;22(15):8336. doi: 10.3390/ijms22158336.
Interactions between the intestinal microbiota, immune system and nervous system are essential for homeostasis in the gut. Inflammasomes contribute to innate immunity and brain-gut interactions, but their role in microbiota-neuro-immune interactions is not clear. Therefore, we investigated the effect of the inflammasome on visceral pain and local and systemic neuroimmune responses after antibiotic-induced changes to the microbiota. Wild-type (WT) and caspase-1/11 deficient (Casp1 KO) mice were orally treated for 2 weeks with an antibiotic cocktail (Abx, Bacitracin A and Neomycin), followed by quantification of representative fecal commensals (by qPCR), cecal short chain fatty acids (by HPLC), pathways implicated in the gut-neuro-immune axis (by RT-qPCR, immunofluorescence staining, and flow cytometry) in addition to capsaicin-induced visceral pain responses. Abx-treatment in WT-mice resulted in an increase in colonic macrophages, central neuro-immune interactions, colonic inflammasome and nociceptive receptor gene expression and a reduction in capsaicin-induced visceral pain. In contrast, these responses were attenuated in Abx-treated Casp1 KO mice. Collectively, the data indicate an important role for the inflammasome pathway in functional and inflammatory gastrointestinal conditions where pain and alterations in microbiota composition are prominent.
肠道微生物群、免疫系统和神经系统之间的相互作用对于肠道内的稳态至关重要。炎性体有助于先天免疫和脑-肠相互作用，但它们在微生物群-神经-免疫相互作用中的作用尚不清楚。因此，我们研究了炎性体在抗生素诱导的微生物群变化后对内脏疼痛以及局部和全身神经免疫反应的影响。野生型 (WT) 和半胱天冬酶-1/11 缺陷型 (Casp1 KO) 小鼠经口接受抗生素鸡尾酒 (Abx、杆菌肽 A 和新霉素) 治疗 2 周，随后通过 qPCR 定量代表性粪便共生菌，通过 HPLC 定量盲肠短链脂肪酸，通过 RT-qPCR、免疫荧光染色和流式细胞术定量肠道-神经-免疫轴中涉及的途径，此外还评估了辣椒素诱导的内脏疼痛反应。在 WT 小鼠中，Abx 处理导致结肠巨噬细胞、中枢神经-免疫相互作用、结肠炎性体和伤害性受体基因表达增加，以及辣椒素诱导的内脏疼痛减轻。相比之下，这些反应在 Abx 处理的 Casp1 KO 小鼠中减弱。总的来说，这些数据表明炎性体途径在功能性和炎症性胃肠道疾病中具有重要作用，这些疾病的特征是疼痛和微生物群组成的改变。
