The role of short-chain fatty acids in kidney injury induced by gut-derived inflammatory response

Article ID	Journal	Published Year	Pages	File Type
5588509	Metabolism	2017	40 Pages	PDF

Abstract

It has been found that several circulating metabolites derived from gut microbiota fermentation associate with a systemic immuno-inflammatory response and kidney injury, which has been coined the gut-kidney axis. Recent evidence has suggested that short-chain fatty acids (SCFAs), which are primarily originated from fermentation of dietary fiber in the gut, play an important role in regulation of immunity, blood pressure, glucose and lipid metabolism, and seem to be the link between microbiota and host homeostasis. In addition to their important role as fuel for colonic epithelial cells, SCFAs also modulate different cell signal transduction processes via G-protein coupled receptors, and act as epigenetic regulators by the inhibition of histone deacetylase and as potential mediators involved in the autophagy pathway. Though controversial, an intimate connection between SCFAs and kidney injury has been revealed, suggesting that SCFAs may act as new therapeutic targets of kidney injury. This review is intended to provide an overview of the impact of SCFAs and the potential link to kidney injury induced by gut-derived inflammatory response.

Keywords

PYY MCP-1 SCFAs IκB GPCRs IFN-γ GLP-1 T2D IKK SNS NF-κB NLRP3 NIK FFAR c-Jun. N-terminal kinase IκB kinases β-arrestins NF-κB-inducing kinase JGA IBD LPS Jnk HDAC ERK AKI mTOR MYD88 cAMP G protein-coupled receptors IRI MAPK ROS TLRs Cyclic adenosine monophosphate acute kidney injury Ischemia–reperfusion injury Kidney injury Histone acetylation Short-chain fatty acids inflammation myeloid differentiation primary response 88 interferon-γ interleukin chronic kidney disease ESRD یا end stage renal disease End-stage renal disease Inflammatory bowel disease tumor necrosis factor-α Cin Juxtaglomerular apparatus Type 2 diabetes Intestinal epithelial cells sympathetic nervous system TNF-α nuclear factor-κB lipopolysaccharide inhibitor of NF-κB CKD contrast-induced nephropathy mammalian target of rapamycin monocyte chemoattractant protein-1 mitogen-activated protein kinase peptide YY glucagon-like peptide 1 IECs extracellular signal-regulated kinase Reactive oxygen species free fatty acid receptor Olfactory receptors Toll-like receptors