The Interplay between Gut Microbiota and Diet-Induced Kidney Protection

Background: On the one hand, dietary interventions are known for their pivotal role in regulating diversity, composition as well as function of the gut microbiome. On the other hand, specific diets show an immense potential in preventing kidney injury from various damaging stimuli in rodents and recent findings, in turn, highlight a central role of gut microbiota in kidney health and disease. Methods: Three protective dietary regimens - a fasting mimicking diet, a diet depleted in sulfur containing amino acids and caloric restriction - were examined in parallel in a rodent model of ischemia-reperfusion injury. To delineate the diet-induced effect on gut microbiota in response to ischemic kidney damage we used comparative shotgun metagenomics for taxonomic as well as functional profiling. We further examined the renal metabolic response using comparative transcriptomics to unravel the interplay between gut microbiota and kidney protection. Results: Beneficial dietary preconditioning strategies changed the composition of gut microbiota in an IRI-dependent manner. Using ternary plots to investigate the role of dietary interventions over time before and after ischemic insult, we detected a central role of Lachnospiraceae that commonly expanded in response to renal IRI in dietary-preconditioned mice. Further functional profiling of gut microbiota in our model revealed an increase in plasma levels of bacterial derived short chained fatty acids in diet-induced kidney protection. Comparative bulk transcriptomics in our model, in turn, pointed towards the metabolic use of these bacterial derived short-chained fatty acids in kidneys of protected mice. Conclusions: As proximal tubules lack sufficient glycolytic capacity, products of microbial metabolism may serve as an additional energy source to fulfill their high demands when withstanding ischemic damage. Our data shed light on a close interplay between gut microbiota and diet-induced kidney protection calling for further research at the crossroads of microbiology, metabolism and molecular nephrology.