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

Abstract

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 40 mg rosuvastatin/daily (n = 7), or (IV) NCD plus 40 mg rosuvastatin/daily (n = 8). Faeces were collected at study endpoint for characterisation 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 = .001). NCD‐fed animals displayed significantly higher alpha‐diversity, which inversely correlated with total cholesterol and LDL‐cholesterol levels (p < .0003). NCD and HCD animals differed in the abundance of 12 genera (ANCOM; p = .001 vs HCD), and PICRUSt2 analysis revealed detrimental changes in HCD‐related microbiota metabolic capacities. These latter findings were associated with a significant fivefold increase in TMAO levels in HCD‐fed pigs (p < .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 favour of alpha‐diversity and towards a healthy metabolic profile, whereas rosuvastatin treatment for this period exerts no effects.

Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis

“… 112 113 114 The metaorganismal TMAO-pathway was demonstrated to promote arterial thrombus growth via multiple pathways, including the induction of platelet hyperreactivity and vascular endothelial TF expression. 106 115 Of note, in a translational pig model it was recently demonstrated that the reduction of dietary fat for a time period of 30 days, resulting in reduced plasma cholesterol levels, was able to revert dysbiosis of the fecal microbiome and to reduce plasma TMAO levels, 116 a predictive functional marker for adverse cardiac events. 117 Vascular innate immune signaling, triggered by microbial-associated molecular patterns derived from the intestinal microbiota, for instance by the activation of endothelial Toll-like receptor-2 signaling in the liver resulting in enhanced vWF synthesis, is an additional mechanism linking the gut microbiota with enhanced arterial thrombus growth.…”