The gut microbiome dysbiosis is recovered by restoring a normal diet in hypercholesterolemic pigs.

BACKGROUND
Gut microbiota is thought to modulate cardiovascular risk. However, the effect of cardiovascular primary prevention strategies on gut microbiota remains largely unknown. This study investigates the impact of diet and rosuvastatin interventions on gut microbiota composition in hypercholesterolemic pigs and associated potential changes in host metabolic pathways.


METHODS
Diet-induced hypercholesterolemic pigs (n=32) were randomly distributed to receive one of the following 30-day interventions: I) continued hypercholesterolemic diet (HCD; n=9), II) normocholesterolemic diet (NCD; n=8), III) continued HCD plus 40mg rosuvastatin/daily (n=7), or IV) NCD plus 40mg rosuvastatin/daily (n=8). Feces were collected at study endpoint for characterization of the gut microbiome and metabolic profile prediction (PICRUSt2). TMAO levels and biochemical parameters were determined.


RESULTS
Principal coordinate analyses (beta diversity) showed clear differences in the microbiota of NCD vs HCD pigs (PERMANOVA, p=0.001). NCD-fed animals displayed significantly higher alpha-diversity which inversely correlated with total cholesterol and LDL-cholesterol levels (p<0.0003). NCD and HCD animals differed in the abundance of 12 genera (ANCOM; p=0.001 vs HCD) and PICRUSt2 analysis revealed detrimental changes in HCD-related microbiota metabolic capacities. These latter findings were associated with a significant 5-fold increase in TMAO levels in HCD-fed pigs (p<0.0001 vs NCD). The addition of a 30-day rosuvastatin treatment to either of the diets exerted no effects in microbiota nor lipid profile.


CONCLUSION
In hypercholesterolemic animals, the ingestion of a low-fat diet for 30 days modifies gut microbiota composition in favor of alpha-diversity and towards a healthy metabolic profile, whereas rosuvastatin treatment for this period exerts no effects.