Whole grain oat attenuates high-fat and high-cholesterol diet-induced dyslipidemia by modulating non-12OH bile acid ratio via the gut-liver axis

Background: Dyslipidemia is a chronic, metabolic disease characterized by elevated level of serum total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C), and acts as a key contributor to the development of cardiovascular diseases (CVDs). Our previous work has shown that whole grain oat supplementation exerted cholesterol-lowering properties by modulating gut microbiota in individuals with hyperlipidemia. However, it is not clear that whether the cholesterol-lowering effect of whole grain oat depends on gut microbiota and its metabolites. In this study, we leverage a high-fat and high-cholesterol (HFHC) diet induced model of dyslipidemia that exhibits significant remission following whole grain oat intervention, to conduct an animal experiment that integrates clinical parameters, 16S rRNA sequencing, targeted metabolomic profiling and fecal microbiota transplantation (FMT) to investigate the relationship between whole grain oat diet, gut microbiota, and dyslipidemia.

Results: We demonstrated that the improvements in blood circulating TC and LDL-C level induced by a whole grain oat diet is accompanied by alterations in gut microbiota diversity and structure marked by increased abundance of probiotics (e.g., Bifidobacterium and Parabacteroides). Targeted metabolomic profiling analysis showed that whole grain oat supplementation increases the ratio of non-12OH/12-OH bile acid (BA), level of hyodeoxycholic acid (HDCA), glycochenodeoxycholic acid-3S (GCDCA-3S), isodeoxycholic acid (IDCA), and propionate acid. Correlation analysis showed that the alteration in the metabolic profiles is closely related to the changed microbial taxa. Consistently, the expression level of proteins involved in BAs synthesis (especially the alternative pathway) was significantly activated by whole grain oat supplementation. Subsequently, FMT treatment attenuated the abnormal increase of serum lipid in the model rat. Finally, when HDCA was administered to rats for 8 weeks, the circulating TC and LDL-C level were significantly ameliorated.

Conclusions: These data revealed that whole grain oat supplementation ameliorated the dyslipidemia in a gut microbiota-dependent manner, via promoting the production of short-chain fatty acids (SCFAs), activating the alternative pathway of BAs metabolism and increase the ratio of non-12OH/12-OH BAs. Our findings provide a promising, and novel therapeutic strategy for gut microbiota to prevent and treat dyslipidemia.