DIETARY FIBER PROVIDES PROTECTION AGAINST KIDNEY ISCHEMIA REPERFUSION INJURY THROUGH MODULATION OF THE GUT MICROBIOTA
Huiling Wu1,2, Yik Wen Loh1, Weiping Zhu1, Julian Singer1,2, Steven Chadban1,2 1University of Sydney, Sydney, NSW, Australia2Royal Prince Alfred Hospital, Sydney, NSW, Australia
Abstract
Aim: To investigate the impact of dietary fiber on kidney IRI in a murine model.
Background: Short-chain fatty acids (SCFAs) derived from gut microbial fermentation of fiber exert anti-inflammatory effects in acute kidney disease.
Methods: Mice were fed a high fiber (HF) diet and controls received normal chow (NC) for 2 weeks. Kidney ischemia was induced for 22 min followed by reperfusion. Samples were collected 24 hours after reperfusion. Kidney histology and gene expression was examined. Stool was assessed by 16S rRNA sequencing (gut microbiome) and 1H NMR spectroscopy (SCFAs).
Results: HF mice were protected against kidney IRI, with lower serum creatinine, less tubular damage and tubulo-interstitial neutrophil and macrophage accumulation versus NC controls (p<0.01). HF significantly reduced proinflammatory cytokine (IL6), chemokine (CCL2) and fibrosis (TGF related gene expression within IRI-kidney compared with NC controls (p<0.05-0.01). Kidney IRI-associated dysbiosis and significant expansion of pathobionts was evident in NC IRI mice compared to NC sham-operated controls (p<0.05-0.001), however this was attenuated in HF-IRI mice (p<0.05-0.001). HF-IRI mice also exhibited significant expansion of SCFA-producing bacteria compared to NC controls. Pearson correlation analyses showed that at a family level, Enterobacteriaceae and Clostridia_vadinBB60_group were most strongly associated with kidney injury. In contrast, SCFA producers were associated with better kidney histology and function. Consistent with changes in the gut microbiome, HF mice had significantly higher serum acetate and fecal SCFA concentrations.
Conclusions: Dietary fiber protects against IRI through modulation of the gut microbiota, enrichment of SCFA-producing bacteria, and increased SCFA production, ameliorating IRI-associated dysbiosis.
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