Targeting on Gut Microbial Metabolite Trimethylamine-N-Oxide (TMAO) and Short Chain Fatty Acid to Prevent Maternal High-Fructose Diet-Induced Developmental Programming of Hypertension in Adult Male Offspring.

Abstract

SCOPE\nAlterations of gut metabolites, like short-chain fatty acids (SCFAs) and trimethylamine (TMA), and microbial composition are associated with the development of hypertension. We examined whether maternal 3,3-dimethyl-1-butanol (DMB, an inhibitor for TMA formation) treatment or the predominant SCFA acetate supplementation can prevent programmed hypertension induced by high-fructose diet (HFD) exposure during pregnancy and lactation in adult male offspring.\n\n\nMETHODS AND RESULTS\nMale offspring were divided into 4 groups: ND: normal diet; HFD: 60% HF diet; ACE: HFD plus 200\xa0mmol/L magnesium acetate in drinking water; and DMB: HFD plus 1% DMB in drinking water. Maternal HFD induced programmed hypertension in adult male offspring, which was prevented by maternal acetate supplementation or DMB treatment. HFD-induced hypertension is relevant to increased plasma levels of TMA and acetate, and alterations of gut microbial composition. The protective effects of acetate supplementation are associated with decreased plasma TMA level and TMA-to-trimethylamine-N-oxide (TMAO) ratio, and increased renal expression of SCFA receptors. Maternal DMB treatment reduced plasma TMA, TMAO, acetate, and propionate levels.\n\n\nCONCLUSION\nEarly intervention targeting on gut microbiota-derived metabolites TMAO and SCFAs to reprogram hypertension may have significant impact to reduce the burden of hypertension. This article is protected by copyright. All rights reserved.