Abstract
Excessive intake of fructose is associated with hypertension. Gut microbiota and their metabolites are thought to be associated with the development of hypertension. We examined whether maternal high-fructose (HF) diet-induced programmed hypertension via altering gut microbiota, regulating short-chain fatty acids (SCFAs) and their receptors, and mediating nutrient-sensing signals in adult male offspring. Next, we aimed to determine whether early gut microbiota-targeted therapies with probiotic Lactobacillus casei and prebiotic inulin can prevent maternal HF-induced programmed hypertension. Pregnant rats received 60% high-fructose (HF) diet, with 2 × 10&sup8; CFU/day Lactobacillus casei via oral gavage (HF+Probiotic), or with 5% w/w long chain inulin (HF+prebiotic) during pregnancy and lactation. Male offspring (n = 7⁻8/group) were assigned to four groups: control, HF, HF+Probiotic, and HF+Prebiotic. Rats were sacrificed at 12 weeks of age. Maternal probiotic Lactobacillus casei and prebiotic inulin therapies protect against hypertension in male adult offspring born to fructose-fed mothers. Probiotic treatment prevents HF-induced hypertension is associated with reduced plasma acetate level and decreased renal mRNA expression of Olfr78. While prebiotic treatment increased plasma propionate level and restored HF-induced reduction of Frar2 expression. Maternal HF diet has long-term programming effects on the adult offspring's gut microbiota. Probiotic and prebiotic therapies exerted similar protective effects on blood pressure but they showed different mechanisms on modulation of gut microbiota. Maternal HF diet induced developmental programming of hypertension, which probiotic Lactobacillus casei or prebiotic inulin therapy prevented. Maternal gut microbiota-targeted therapies could be reprogramming strategies to prevent the development of hypertension caused by maternal consumption of fructose-rich diet.