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

• Published in: Molecular nutrition & food research Vol. 63; no. 18; pp. e1900073 - n/a
• Main Authors: Hsu, Chien‐Ning, Chang‐Chien, Guo‐Ping, Lin, Sufan, Hou, Chih‐Yao, Tain, You‐Lin
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-09-2019
• Subjects: Acetic acid; Butanol; Composition effects; developmental origins of adult health and disease (DOHaD); Diet; Dietary supplements; Drinking water; Fatty acids; Fructose; Hypertension; Intestinal microflora; Lactation; Levels; Magnesium; Metabolites; Microbiota; Microorganisms; Offspring; Plasma levels; Pregnancy; Propionic acid; Receptors; short‐chain fatty acids; Trimethylamine; trimethylamine‐N‐oxide; trimethylamine-N-oxide; fructose; developmental origins of adult health and disease (DOHaD); short-chain fatty acids; hypertension
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201900073

Scope
Alterations of gut metabolites, such as SCFAs and trimethylamine (TMA), and microbial composition are associated with the development of hypertension. Whether maternal 3,3‐dimethyl‐1‐butanol (DMB, an inhibitor for TMA formation) treatment or the predominant SCFA acetate supplementation can prevent programed hypertension induced by a high‐fructose diet (HFD) exposure during pregnancy and lactation in adult male offspring is examined.
Methods and results
Male offspring are divided into four groups: ND, normal diet; HFD, 60% HFD; ACE, HFD plus 200 mmol L–1 magnesium acetate in drinking water; and DMB: HFD plus 1% DMB in drinking water. Maternal HFD induces programed hypertension in adult male offspring, which is 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 reduces plasma TMA, TMAO, acetate, and propionate levels.
Conclusion
Early intervention targeting on gut‐microbiota‐derived metabolites TMAO and SCFAs to reprogram hypertension may have significant impact to reduce the burden of hypertension.
Maternal high‐fructose diet (HFD) induces developmental programing of hypertension in adult offspring, which is associated with alterations of gut microbiota compositions and their metabolites: trimethylamine (TMA), trimethylamine‐N‐oxide (TMAO), and SCFAs. 3,3‐Dimethyl‐1‐butanol (an inhibitor for TMA formation) or the predominant SCFA acetate supplementation can prevent maternal HFD‐induced programed hypertension.