Microbial Derived Short Chain Fatty‐Acids and Autonomic Regulation of Cardiovascular Function

Abstract

Elevated sympathetic outflow is an important contributor to the salt‐sensitive hypertension (SSH). It’s been established that the paraventricular nucleus (PVN) of the hypothalamus regulates autonomic control of cardiovascular function, and increased PVN activity contributes to the elevated sympathetic nerve activity (SNA) in SSH. Accumulating evidence indicates a correlation between gut microbial composition and hypertension. Interestingly, data also suggests there is an increased neural communication between the gastrointestinal (GI) tract and PVN neurons in hypertensive animals. Moreover, it’s been reported high salt diet significantly increased the production of short chain fatty‐acids (SCFAs), microbiota‐derived metabolites. We have shown microinjection of acetate, a SCFA, into the central nucleus of amygdala, significantly increased SNA and arterial blood pressure (ABP). The objective is to determine the role of microbiota‐produced SCFAs, acetate and lactate in the PVN, in regulating SNA and ABP. In anesthetized rats, microinjection with acetate or lactate (0.2 μmol/100nl, n=3~4) into the PVN produced significant increases in splanchnic SNA and ABP (p <0.05~0.01), respectively. Also, pre‐treatment of kynurenic acid (KYN, 7.2 nmole/100 nl), an ionotropic EAA receptor antagonist, significantly (p <0.05) attenuated the sympathoexcitatory responses evoked by either acetate or lactate. These data suggested that activation of glutamate receptors in the PVN contribute to sympathoexcitatory and pressor responses elicited by SCFAs.Alterations microbiota communities’ impact human host physiology and pathophysiology but a clear cause/effect relationship has yet to be established. Often researchers use fecal matter to determine a subject microbiome profile to make health inferences. While the mucosa associated bacterial communities may be more informative regarding the impact on the host, little investigation into differences between fecal and mucosal bacterial communities has occurred. Gathering information about the microbiome from feces and making inferences to the host’s health may not be an optimal method. Our next aim is to test the hypothesis that shifts in mucosa associated bacteria induce changes in SCFAs concentrations in circulation which may underlie the neural mechanisms of increased sympathetic outflow in hypertension. We extracted feces and mucosa tissue from the small intestine (SI), the location within the GI where absorption occurs. Bacterial composition was determined using 16S rRNA sequencing. Analysis of rat mucosal tissue from the SI (n=6) and feces (n=6) confirmed the bacterial community composition was significantly different (p =5.4×10−5) between the two locations. Collectively, this data supports the continuation into the investigation of mucosa bacteria‐derived SCFA involvement in the increase in sympathetic outflow and SSH.Support or Funding InformationSonger Research Award, Jessica R. Bruning, MTU Potage Health Foundation, Qing‐Hui Chen).