Prebiotics, Probiotics, and Acetate Supplementation Prevent Hypertension in a Model of Obstructive Sleep Apnea.
Prebiotics, Probiotics, and Acetate Supplementation Prevent Hypertension in a Model of Obstructive Sleep Apnea.
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DOI：
10.1161/hypertensionaha.118.11695
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发表时间：
2018-11
期刊：
影响因子：
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通讯作者：
Durgan DJ
中科院分区：
文献类型：
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作者：
Ganesh BP;Nelson JW;Eskew JR;Ganesan A;Ajami NJ;Petrosino JF;Bryan RM Jr;Durgan DJ
肠道微生物群的破坏，称为肠道生态失调，已在高血压动物模型和高血压患者中描述。我们在阻塞性睡眠呼吸暂停（OSA）大鼠模型中发现，肠道生态失调在高血压的发生中起着因果作用。OSA中的生态失调微生物群的功能分析表明产生短链脂肪酸（SCFA）的细菌的损失。然而，缺乏SCFA浓度的测量及其在血压调节中的作用的测试。我们假设肠道中SCFAs的减少是OSA诱导的高血压的原因。OSA在第7天和第14天显著增加SBP（p<0.05），益生菌丁酸梭菌或益生元Hylon VII消除了这种作用。16S rRNA分析鉴定了通过丁酸梭菌和Hylon处理显著增加的许多SCFA产生细菌。盲肠中的乙酸浓度在OSA后降低了48%（p<0.05），丁酸梭菌和Hylon阻止了这种作用。丁酸梭菌和Hylon减少了OSA诱导的生态失调、上皮杯状细胞损失、粘液屏障变薄和脑小胶质细胞活化（各自p<0.05）。为了研究醋酸盐在阻塞性睡眠呼吸暂停引起的高血压中的作用，我们在2周的假手术或阻塞性睡眠呼吸暂停期间将醋酸盐长期注入盲肠。恢复盲肠乙酸盐浓度可预防OSA诱导的肠道炎症和高血压（p<0.05）。这些研究确定醋酸盐是OSA诱导的高血压的关键因素。我们证明了增加盲肠乙酸盐浓度的各种方法可以保护OSA对微生物群，肠道，大脑和血压的不利影响。
Disruption of the gut microbiota, termed gut dysbiosis, has been described in animal models of hypertension and hypertensive patients. We have shown that gut dysbiosis plays a causal role in the development of hypertension in a rat model of obstructive sleep apnea (OSA). Functional analysis of the dysbiotic microbiota in OSA demonstrates a loss of short chain fatty acid (SCFA) producing bacteria. However, measurements of SCFA concentrations and testing of their role in blood pressure regulation is lacking. We hypothesized that reduced SCFAs in the gut are responsible for OSA-induced hypertension. OSA significantly increased SBP at 7 and 14 days (p<0.05), an effect that was abolished by the probiotic Clostridium butyricum or the prebiotic Hylon VII. 16S rRNA analysis identified a number of SCFA producing bacteria that were significantly increased by C.butyricum and Hylon treatment. Acetate concentration in the cecum was decreased by 48% following OSA (p<0.05), an effect that was prevented by C.butyricum and Hylon. C.butyricum and Hylon reduced OSA-induced dysbiosis, epithelial goblet cell loss, mucus barrier thinning, and activation of brain microglia (p<0.05 for each). To examine the role of acetate in OSA-induced hypertension, we chronically infused acetate into the cecum during 2 weeks of sham or OSA. Restoring cecal acetate concentration prevented OSA-induced gut inflammation and hypertension (p<0.05). These studies identify acetate as a key player in OSA-induced hypertension. We demonstrate that various methods to increase cecal acetate concentrations are protective from the adverse effects of OSA on the microbiota, gut, brain, and blood pressure.