Soy protein beta-conglycinin ameliorates pressure overload-induced heart failure by increasing short-chain fatty acid (SCFA)-producing gut microbiota and intestinal SCFAs

Background: Soybeans and their ingredients have antioxidant and anti-inflammatory effects on cardiovascular diseases. beta-Conglycinin (beta-CG), a major constituent of soy proteins, is protective against obesity, hypertension, and chronic kidney disease, but its effects on heart failure remain to be elucidated. We tested the effects of beta-CG on left ventricular (LV) remodeling in pressure overload-induced heart failure. Methods: A transverse aortic constriction (TAC)-induced pressure overload was applied to the heart in 7-week-old C57BL6 male mice that were treated with beta-CG, GlcNAc, or sodium propionate. Gut microbiota was analyzed by 16S rRNA sequencing. Fecal short chain fatty acids (SCFAs) were quantified by GC-MS. The effects of oral antibiotics were examined in beta-CG-fed mice. Results: beta-CG ameliorated impaired cardiac contractions, cardiac hypertrophy, and myocardial fibrosis in TAC-operated mice. GlcNAc had similar but less efficient effects on LV remodeling compared to beta-CG. beta-CG increased three major SCFA-producing intestinal bacteria, as well as fecal concentrations of SCFAs, in sham- and TAC-operated mice. Oral administration of antibiotics nullified the effects of beta-CG in TAC-operated mice by markedly reducing SCFA-producing intestinal bacteria and fecal SCFAs. In contrast, oral administration of sodium propionate ameliorated LV remodeling in TAC-operated mice to a similar extent as beta-CG. Conclusion: beta-CG was protective against TAC-induced LV remodeling, which was likely to be mediated by increased SCFA-producing gut microbiota and increased intestinal SCFAs. Three mechanisms were postulated to explain the effects of SCFAs on the heart failure: (i) SCFAs served as a energy source for the heart better than ketone bodies; (ii) GLP-1 released from the enteroendocrine L cells by SCFAs directly worked on the heart; and (iii) SCFAs directly worked on the heart, the vagal nerve, and/or the other organs. Modified beta-CG and/or derivatives arising from beta-CG are expected to be developed as prophylactic or therapeutic agents to ameliorate devastating symptoms in heart failure.