Depletion of gut microbiota protects the kidney against ischemia/reperfusion injury

An accumulating body of evidence shows that gut microbiota play an important role in health and disease by modulating local and systemic immunity. Peptidoglycan, known to be turned over from the microbiota and translocated into the circulation, might play a central role in this immunomodulation via interaction with its receptors NOD1 and NOD2 present on leukocytes. The importance of the microbiome in several inflammatory diseases is known but its role in kidney disease is limited. To further study this, we performed renal ischemia reperfusion injury (IRI) in Wt and Nod1/2 KO mice with or without depleted gut microbiota using broad-spectrum antibiotics. Our results showed that in Wt mice, depletion of microbiota significantly attenuated renal damage, dysfunction and granulocyte influx after renal IRI. Isolated granulocytes from antibiotic treated Wt mice were less responsive to several TLR/NOD ligands compared to untreated Wt mice while migration and oxidative burst were similar. No evidence was found for bacterial translocation during renal injury, intestinal permeability was present but unaffected by the severity of kidney damage. Nod1/2 KO mice displayed similar renal dysfunction and damage compared to Wt mice following renal IR. In conclusion, we show that depletion of gut microbiota reduced renal IRI in a NOD1/2-independent way.