UT Microbiome Consortium, Center for Hypertension and Precision Medicine, Department of Physiology & Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH (P.S., B.M., R.M.G., V.R.B., A.A.A., X.M., B.S.Y., B.J., M.V.-K.).
Brown Foundation Institute of Molecular Medicine, University of Texas McGovern Medical School, Houston' TX (P.A.D.).
Hypertension. 2022 Oct;79(10):2239-2249. doi: 10.1161/HYPERTENSIONAHA.122.19307. Epub 2022 Aug 11.
The spontaneously hypertensive rat (SHR) is extensively used to study hypertension. Gut microbiota dysbiosis is a notable feature in SHR for reasons unknown. Immunoglobulin A (IgA) is a major host factor required for gut microbiota homeostasis. We hypothesized that inadequate IgA contributes to gut microbiota dysbiosis in SHR.
IgA was measured in feces, cecum, serum, liver, gut-associated lymphoid tissue, and milk from SHR and Wistar Kyoto rats. IgA regulatory factors like IgM, IgG, and (polymeric immunoglobulin receptor) were analyzed. IgA and IgG antibodies and blood pressure (BP) were measured before and after administrating a bacterial antigen (ie, flagellin).
Compared with Wistar Kyoto rats, SHR displayed remarkably near-deficient IgA levels accompanied by compensatory increases in serum IgM and IgG and gut-liver expression. Inadequate milk IgA in SHR emphasized this immune defect stemmed from the neonatal stage. Reduced IgA B cells in circulation and Peyer patches indicated a possible reason for the lower IgA in SHR. Noteworthy, a genetic insufficiency was unlikely because administering flagellin to SHR induced anti-flagellin IgA antibodies. This immune response surprisingly accelerated hypertension development in SHR, suggesting IgA quiescence may help maintain lower BP.
This study is the first to reveal IgA deficiency in SHR as one host factor associated with gut microbiota dysbiosis and invigorates future research to determine the pathophysiological role of IgA in hypertension.
自发性高血压大鼠（SHR）被广泛用于研究高血压。肠道微生物失调是 SHR 的一个显著特征，但原因尚不清楚。免疫球蛋白 A（IgA）是维持肠道微生物群稳态的主要宿主因素。我们假设，IgA 不足导致 SHR 肠道微生物失调。
测量 SHR 和 Wistar Kyoto 大鼠粪便、盲肠、血清、肝脏、肠道相关淋巴组织和乳汁中的 IgA。分析 IgA 调节因子，如 IgM、IgG 和（多聚免疫球蛋白受体）。在给予细菌抗原（即鞭毛蛋白）前后测量 IgA 和 IgG 抗体和血压（BP）。
与 Wistar Kyoto 大鼠相比，SHR 的 IgA 水平明显接近不足，同时血清 IgM 和 IgG 以及肠道-肝脏 表达代偿性增加。SHR 乳汁中 IgA 不足强调了这种免疫缺陷源于新生儿期。循环和派伊尔斑中 IgA B 细胞减少表明 SHR 中 IgA 减少的可能原因。值得注意的是，遗传不足不太可能，因为给 SHR 给予鞭毛蛋白会诱导抗鞭毛蛋白 IgA 抗体。这种免疫反应出人意料地加速了 SHR 高血压的发展，表明 IgA 静止可能有助于维持较低的 BP。
本研究首次揭示了 SHR 中的 IgA 缺乏是与肠道微生物失调相关的宿主因素之一，并激发了未来研究以确定 IgA 在高血压中的病理生理作用。
