Tumor Necrosis Factor Alpha and the Gastrointestinal Epithelium: Implications for the Gut-Brain Axis and Hypertension

The colonic epithelium is the site of production and transport of many vasoactive metabolites and neurotransmitters that can modulate the immune system, affect cellular metabolism, and subsequently regulate blood pressure. As an important interface between the microbiome and its host, the colon can contribute to the development of hypertension. In this critical review, we highlight the role of colonic inflammation and microbial metabolites on the gut brain axis in the pathology of hypertension, with special emphasis on the interaction between tumor necrosis factor alpha (TNF alpha) and short chain fatty acid (SCFA) metabolites. Here, we review the current literature and identify novel pathways in the colonic epithelium related to hypertension. A network analysis on transcriptome data previously generated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats reveals differences in several pathways associated with inflammation involving TNF alpha (NF-kappa B and STAT Expression Targets) as well as oxidative stress. We also identify down-regulation of networks associated with gastrointestinal function, cardiovascular function, enteric nervous system function, and cholinergic and adrenergic transmission. The analysis also uncovered transcriptome responses related to glycolysis, butyrate oxidation, and mitochondrial function, in addition to gut neuropeptides that serve as modulators of blood pressure and metabolic function. We present a model for the role of TNF alpha in regulating bacterial metabolite transport and neuropeptide signaling in the gastrointestinal system, highlighting the complexity of host-microbiota interactions in hypertension.

Automated summary

The colonic epithelium plays a crucial role in the production and transport of vasoactive metabolites and neurotransmitters that modulate the immune system, affect cellular metabolism, and regulate blood pressure. Inflammation in the colon and microbial metabolites have been highlighted in the pathology of hypertension, particularly the interaction between TNF alpha and SCFA metabolites. This review identifies novel pathways in the colonic epithelium related to hypertension and emphasizes the complexity of host-microbiota interactions in regulating blood pressure and metabolic function.