Soy protein β-conglycinin ameliorates pressure overload-induced heart failure by increasing short-chain fatty acid (SCFA)-producing gut microbiota and intestinal SCFAs
Nozomi Furukawa, Miku Kobayashi, Mikako Ito, Hiroki Matsui, Koji Ohashi, Toyoaki Murohara, Jun‐ichi Takeda, Jun Ueyama, Masaaki Hirayama, Kinji Ohno
Abstract
BACKGROUND AND AIMS: Soybeans and their ingredients have antioxidant and anti-inflammatory effects on cardiovascular diseases. β-Conglycinin (β-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 β-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 β-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 β-CG-fed mice. RESULTS: β-CG ameliorated impaired cardiac contractions, cardiac hypertrophy, and myocardial fibrosis in TAC-operated mice. As β-CG is a highly glycosylated protein, we examined the effects of GlcNAc. GlcNAc had similar but less efficient effects on LV remodeling compared to β-CG. β-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 β-CG in TAC-operated mice by markedly reducing SCFA-producing intestinal bacteria and fecal SCFAs. In contrast, oral administration of sodium propionate, one of SCFAs, ameliorated LV remodeling in TAC-operated mice to a similar extent as β-CG. CONCLUSIONS: β-CG was protective against TAC-induced LV remodeling, which was likely to be mediated by increased SCFA-producing gut microbiota and increased intestinal SCFAs. Modified β-CG and/or derivatives arising from β-CG are expected to be developed as prophylactic and/or therapeutic agents to ameliorate devastating symptoms in heart failure.