Increased Abundance of Lactobacillales in the Colon of Beta-Adrenergic Receptor Knock Out Mouse Is Associated With Increased Gut Bacterial Production of Short Chain Fatty Acids and Reduced IL17 Expression in Circulating CD4+ Immune Cells

Abstract

Emerging evidence suggests an associative link between gut dysbiosis, the autonomic nervous system (ANS) and the immune system in pathophysiology of neurogenic hypertension (HTN). However, the close interplay between these three systems presents us with difficulties in deciphering the cause-effect relationship in disease. The present study utilized beta 1 and 2 adrenergic receptor knock out (AdrB1tm1BkkAdrB2tm1Bkk/J KO) mice to isolate the effects of reduced overall sympathetic drive on gut microbiota and systemic immune system. We observed the following: (i) Diminished beta adrenergic signaling mainly reflects in shifts in the Firmicutes phyla, with a significant increase in abundance of largely beneficial Bacilli Lactobacillales in the KO mice; (ii) This was associated with increased colonic production of beneficial short chain fatty acids (SCFAs) butyrate, acetate and propionate, confirming functional microbiota shifts in the KO mice; (iii) Dampened systemic immune responses in the KO mice reflected in reduction on circulating CD4+.IL17+ T cells and increase in young neutrophils, both previously associated with shifts in the gut microbiota. Taken together, these observations demonstrate that reduced expression of beta adrenergic receptors may lead to beneficial shifts in the gut microbiota and dampened systemic immune responses. Considering the role of both in hypertension, this suggests that dietary intervention may be a viable option for manipulation of blood pressure via correcting gut dysbiosis.

Neuroimmune Interactions in the Gut and Their Significance for Intestinal Immunity

“…Yang et al made use of a new bone marrow chimera mouse model that lacked the β-adrenergic receptor 1 or 2 and showed a significant shift in the Bacilli class of Firmicutes in the colon, more specifically in the family of Lactobacillaceae. This was in line with the findings that were published by Bartley et al [117] that showed reduced β-adrenergic signaling leads to beneficial shifts in the gut microbiota. However, no significant change was found in the F/B ratio.…”

“…An increased F/B ratio has been associated with obesity [115] and IBD [116]. Therefore, currently it is being used as marker for pathological conditions [117]. Yang et al made use of a new bone marrow chimera mouse model that lacked the β-adrenergic receptor 1 or 2 and showed a significant shift in the Bacilli class of Firmicutes in the colon, more specifically in the family of Lactobacillaceae.…”

Probiotics Prevent Dysbiosis and the Rise in Blood Pressure in Genetic Hypertension: Role of Short‐Chain Fatty Acids

“…In fact, butyrate has been shown to attenuate angiotensin II‐induced hypertension in mice, and both, acetate supplementation or a diet rich in fiber, which substantially increases the production of SCFAs such as acetate, prevented the development of hypertension in deoxycorticosterone acetate (DOCA)‐salt . Increased bacterial production of SCFAs is associated with reduced circulating CD4+ immune cells . Bacterial LPS, through toll‐like receptor (TLR)4 activation, contributes to the low‐grade vascular inflammation and, ultimately, the increased blood pressure present in SHR …”

Probiotic Bifidobacterium breve prevents DOCA‐salt hypertension

“…17 In fact, butyrate attenuates angiotensin II-induced hypertension in mice 19 and SHR, 8 acetate supplementation or a diet rich in fiber, which significantly raises SCFAs production by gut bacteria, such as acetate, prevented the development of hypertension in DOCA-salt mice, 5 and propionate supplementation exhibited antihypertensive effects in angiotensin II-infused mice. 20 Increased bacterial production of SCFAs has been linked to lower numbers of circulating CD4+ immune cells 21 and its antihypertensive effects were Treg-dependent. 8,20 Bacterial LPS, through tolllike receptor (TLR)-4 activation, contributes to high blood pressure and low-grade vascular inflammation in the SHR model.…”