Extension Region Domain of Soybean 7S Globulin Contributes to Serum Triglyceride‐Lowering Effect via Modulation of Bile Acids Homeostasis

Scope Soybean 7S globulin (β‐conglycinin), a major soybean storage protein, has been demonstrated to exert remarkable triglyceride (TG) and cholesterol‐lowering effects, yet the underlying mechanism remains controversial. Methods and results A comparative investigation is performed to assess the contribution of different structural domains of soybean 7S globulin, including core region (CR) and extension region (ER) domains, to biological effects of soybean 7S globulin using a high‐fat diet rat model. The results show that ER domain mainly contributes to the serum TG‐lowering effect of soybean 7S globulin, but not for CR domain. Metabolomics analysis reveals that oral administration of ER peptides obviously influences the metabolic profiling of serum bile acids (BAs), as well as significantly increased the fecal excretion of total BAs. Meanwhile, ER peptides supplementation reshapes the composition of gut microbiota and impacts the gut microbiota‐dependent biotransformation of BAs which indicate by a significantly increased secondary BAs concentration in fecal samples. These results highlight that TG‐lowering effects of ER peptides mainly stem from their modulation of BAs homeostasis. Conclusion Oral administration of ER peptides can effectively lower serum TG level by regulating BAs metabolism. ER peptides have potential to be used as a candidate pharmaceutical for the intervention of dyslipidemia. Extension region (ER) domain mainly contributes to serum triglyceride (TG)‐lowering effect of soybean 7S globulin, but not for core region (CR) domain. Oral administration of ER peptides can effectively lower serum TG level via modulation of bile acids homeostasis.