Shotgun metagenomic and transcriptomic profiling of a rodent model of renal ischemia reperfusion injury preconditioned with fasting mimicking, sulfur amino acid restricted, or calorie-restricted diets to investigate how diet-induced changes in gut microbiota relate to 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, dietary interventions 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 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 expended in response to renal IRI in dietary-preconditioned mice. Further functional profiling of gut microbiota in our model revealed an increase in 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.