Selective IgA Deficiency in Spontaneously Hypertensive Rats With Gut Dysbiosis

Abstract

Background: 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. methods: 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 pIgR (polymeric immunoglobulin receptor) were analyzed. IgA and IgG antibodies and blood pressure (BP) were measured before and after administrating a bacterial antigen (ie, flagellin). Results: Compared with Wistar Kyoto rats, SHR displayed remarkably near-deficient IgA levels accompanied by compensatory increases in serum IgM and IgG and gut-liver pIgR 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. Conclusions: 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.

Kidney microbiota dysbiosis contributes to the development of hypertension

“… 18 , 59 Immune responses to serum IgA and secretory IgA are disparate. It was speculated that both renal translocation of secretory IgA-encapsulated bacteria digested by IgA protease found in the present study, and selective deficiency of serum IgA in SHRs reported previously, 58 produce similar consequences during hypertension, but the underlying mechanisms might be quite different. The potential correlations between these findings and hypertension pathogenesis warrant further investigation.…”

“… 58 Serum IgA, which can eliminate a large number of antigens, including bacteria and viruses, and maintain the stability of the internal environment without eliciting inflammation, was determined in SHRs with disordered intestinal flora. 58 Here, we mainly focused on the crucial role of secretory IgA in the translocation of gut microbiota to extraintestinal organs, as IgA is known to selectively bind to specific bacterial species and exert important functions during bacterial colonization in the intestinal tract. 18 , 59 Immune responses to serum IgA and secretory IgA are disparate.…”

Inflammatory Response: A Crucial Way for Gut Microbes to Regulate Cardiovascular Diseases

“…It has become a general agreement that there is a tight connection of gut microbiota with blood pressure regulation under the confirmation of many animal models, including spontaneously hypertensive rats (SHR), Ang II–induced hypertensive rats, and Dahl-salt sensitive rats [ 99 , 100 , 101 , 102 , 103 ]. Studies reported that Bifidobacteria could increase the activity of nitric oxide synthase (eNOS) while decreasing the activity of serum catalase [ 104 ].…”

Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease

“…Specific microbiota, including Romboutsia, Turicibacter, Ileibacterium, and Dubosiella, have affinity to prompt host IgA binding, which may promote the development of hypertension, potentially through the gut-brain axis. [243][244][245] Many of the aforementioned diet-derived and microbemediated metabolites, including TMAO and SCFAs, also play a role in modulating blood pressure. 246 For example, microbe-derived SCFAs bind to olfactory and G-proteincoupled receptors (Olfr78 and Gpr41) in the kidney and vascular endothelium to modulate vasodilation, heart rate, and blood pressure.…”