Fiber derived microbial metabolites protect against maladaptive repair in AKI through G-protein coupled receptors and HDAC inhibition

Incomplete recovery from acute kidney injury (AKI) may lead to chronic kidney disease (CKD). Gut dysbiosis is associated with inflammation and adverse outcomes in experimental models of AKI. This paper describes the influence of dietary fibre on the gut microbiota and kidney pathology in the murine folic-acid nephropathy model of AKI and subsequent CKD. Here, a high-fiber diet attenuated AKI, enhanced recovery and minimised subsequent development of CKD. Protection was mediated by inhibition of histone deacetylase activity and activation of metabolite-sensing G protein–coupled receptors GPR41 and GPR109A by gut-derived short chain fatty acids. Dietary manipulation of the microbiome to protect against AKI, subsequent maladaptive repair and progression to CKD may be a viable therapeutic strategy.