High fibre diet in kidney IRI

Background: Ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury and is associated with significant morbidity and mortality. Modulation of the gut-kidney axis through dietary fibre intervention represents a potential strategy to attenuate kidney IRI and reduce risk of progression to chronic kidney disease. Methods: C57BL/6 mice were randomised to receive either a high-fibre (HF) or normal chow (NC) diet for 2 weeks prior to bilateral kidney IRI. Kidney ischaemia was induced for 22 mins followed by reperfusion. Samples were collected at day 1 or day 28 post-IRI. Results: HF-fed mice were protected against acute and chronic kidney IRI, with reduced serum creatinine, tubular injury and inflammatory cell infiltrates compared to NC controls. HF-fed mice had less proteinuria and interstitial fibrosis at day 28. HF diet reduced inflammatory chemokines, cytokines and fibrosis-related gene expression within IRI kidneys versus NC controls. IRI-induced dysbiosis and expansion of pathobionts was evident in NC-IRI mice compared to NC-sham controls, however this was attenuated by HF diet. Expansion of SCFA-producing bacteria was evident in HF-fed mice compared to NC controls and was associated with better kidney histology and function. Consistent with gut microbiota changes, HF-fed mice had significantly higher serum acetate and caecal SCFA concentrations. GPR43-/- mice exhibited partial protection from a HF diet compared to wild type mice. Conclusions: Dietary fibre protects against acute and chronic kidney injury following IRI. This is associated with enrichment of SCFA-producing gut bacteria, ameliorating IRI-associated dysbiosis. This protection is partially mediated through GPR43.