Inflammasome Signaling Regulates the Microbial-Neuroimmune Axis and Visceral Pain in Mice.
Inflammasome Signaling Regulates the Microbial-Neuroimmune Axis and Visceral Pain in Mice.
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DOI：
10.3390/ijms22158336
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发表时间：
2021-08-03
影响因子：
5.6
通讯作者：
Melgar S
中科院分区：
文献类型：
--
作者：
Aguilera M;Rossini V;Hickey A;Simnica D;Grady F;Felice VD;Moloney A;Pawley L;Fanning A;McCarthy L;O'Mahony SM;Cryan JF;Nally K;Shanahan F;Melgar S
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是必不可少的。炎性小体有助于先天免疫和脑-肠相互作用，但它们在微生物-神经-免疫相互作用中的作用尚不清楚。因此，我们研究了抗生素诱导微生物群变化后炎性体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caspase-1/11缺陷型（Casp 1 KO）小鼠用抗生素鸡尾酒口服治疗2周（Abx、杆菌肽A和新霉素），然后定量代表性粪便中的脂肪酸（通过qPCR）、盲肠短链脂肪酸（通过HPLC）、肠-神经-免疫轴中涉及的途径（通过RT-qPCR、免疫荧光染色和流式细胞术）。WT小鼠的Abx治疗导致结肠巨噬细胞、中枢神经免疫相互作用、结肠炎性小体和伤害感受受体基因表达增加，辣椒素诱导的内脏疼痛减少。相反，这些反应在Abx处理的Casp 1 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性胃肠道疾病中的重要作用，其中疼痛和微生物群组成的改变是突出的。
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.
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影响因子：
39.3
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