National Agri-Food Biotechnology Institute (NABI), Knowledge City-Sector 81, SAS Nagar, Punjab, 140306, India; Department of Biotechnology, Panjab University, Sector-25, Chandigarh, 160014, India.
National Agri-Food Biotechnology Institute (NABI), Knowledge City-Sector 81, SAS Nagar, Punjab, 140306, India; Regional Centre for Biotechnology, Faridabad-Gurgaon expressway, Faridabad, Haryana, 121001, India.
Eur J Pharmacol. 2020 Dec 5;888:173567. doi: 10.1016/j.ejphar.2020.173567. Epub 2020 Sep 15.
This study focuses on exploring the role of sensory cation channel Transient Receptor Potential channel subfamily Vanilloid 1 (TRPV1) in gut health, specifically mucus production and microflora profile in gut. We employed resiniferatoxin (ultrapotent TRPV1 agonist) induced chemo-denervation model in rats and studied the effects of TRPV1 ablation on colonic mucus secretion patterns. Histological and transcriptional analysis showed substantial decrease in mucus production as well as in expression of genes involved in goblet cell differentiation, mucin production and glycosylation. 16S metagenome analysis revealed changes in abundance of various gut bacteria, including decrease in beneficial bacteria like Lactobacillus spp and Clostridia spp. Also, TRPV1 ablation significantly decreased the levels of short chain fatty acids, i.e. acetate and butyrate. The present study provides first evidence that systemic TRPV1 ablation leads to impairment in mucus production and causes dysbiosis in gut. Further, it suggests to address mucin production and gut microbiota related adverse effects during the development of TRPV1 antagonism/ablation-based therapeutic and preventive strategies.
本研究旨在探讨感觉阳离子通道瞬时受体电位通道香草素 1 型(TRPV1)在肠道健康中的作用,特别是在肠道中的粘液产生和微生物群特征。我们采用树脂毒素(超高效 TRPV1 激动剂)诱导的化学去神经支配大鼠模型,研究 TRPV1 缺失对结肠粘液分泌模式的影响。组织学和转录分析显示粘液产生以及参与杯状细胞分化、粘蛋白产生和糖基化的基因表达显著减少。16S 宏基因组分析显示各种肠道细菌的丰度发生变化,包括有益细菌如乳杆菌属和梭菌属的减少。此外,TRPV1 缺失还显著降低了短链脂肪酸(如乙酸盐和丁酸盐)的水平。本研究首次提供证据表明,全身性 TRPV1 缺失会导致粘液产生受损,并导致肠道菌群失调。此外,这表明在开发 TRPV1 拮抗/缺失为基础的治疗和预防策略时,需要解决与粘蛋白产生和肠道微生物群相关的不良反应。