Hypertension can originate in early life caused by perinatal high-fat (HF) consumption. Gut microbiota and their metabolites short chain fatty acids (SCFAs), trimethylamine (TMA), and trimethylamine N-oxide (TMAO) are involved in the development of hypertension. Despite the beneficial effects of prebiotic/probiotic on human health, little is known whether maternal use of prebiotics/probiotics could protect offspring against the development of hypertension in adulthood. We investigated whether perinatal HF diet-induced programmed hypertension in adult offspring can be prevented by therapeutic uses of prebiotic inulin or probiotic Lactobacillus casei during gestation and lactation. Pregnant Sprague–Dawley rats received regular chow or HF diet (D12331, Research Diets), with 5% w/w long chain inulin (PRE), or 2 × 108 CFU/day Lactobacillus casei via oral gavage (PRO) during pregnancy and lactation. Male offspring (n = 8/group) were assigned to four groups: control, HF, PRE, and PRO. Rats were sacrificed at 16 weeks of age. Maternal prebiotic or probiotic therapy prevents elevated blood pressure (BP) programmed by perinatal HF consumption. Both prebiotic and probiotic therapies decreased the Firmicutes to Bacteroidetes ratio and renal mRNA expression of Ace, but increased abundance of genus Lactobacillus and Akkermansia. Additionally, prebiotic treatment prevents HF-induced elevation of BP is associated with reduced fecal propionate and acetate levels, while probiotic therapy restored several Lactobacillus species. Maternal probiotic or prebiotic therapy caused a reduction in plasma TMAO level and TMAO-to-TMA ratio. The beneficial effects of prebiotic or probiotic therapy on elevated BP programmed by perinatal HF diet are relevant to alterations of microbial populations, modulation of microbial-derived metabolites, and mediation of the renin-angiotensin system. Our results cast a new light on the use of maternal prebiotic/probiotic therapy to prevent hypertension programmed by perinatal HF consumption. The possibility of applying gut microbiota-targeted therapies as a reprogramming strategy for hypertension warrants further clinical translation.

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 × 108 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.

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 chronic kidney disease (CKD) during pregnancy causes adverse fetal programming. Nitric oxide (NO) deficiency, gut microbiota dysbiosis, and dysregulated renin-angiotensin system (RAS) during pregnancy are linked to the development of hypertension in adult offspring. We examined whether maternal adenine-induced CKD can program hypertension and kidney disease in adult male offspring. We also aimed to identify potential mechanisms, including alterations of gut microbiota composition, increased trimethylamine-N-oxide (TMAO), reduced NO bioavailability, and dysregulation of the RAS. To construct a maternal CKD model, female Sprague-Dawley rats received regular chow (control group) or chow supplemented with 0.5% adenine (CKD group) for 3 weeks before pregnancy. Mother rats were sacrificed on gestational day 21 to analyze placentas and fetuses. Male offspring (n = 8/group) were sacrificed at 12 weeks of age. Adenine-fed rats developed renal dysfunction, glomerular and tubulointerstitial damage, hypertension, placental abnormalities, and reduced fetal weights. Additionally, maternal adenine-induced CKD caused hypertension and renal hypertrophy in adult male offspring. These adverse pregnancy and offspring outcomes are associated with alterations of gut microbiota composition, increased uremic toxin asymmetric and symmetric dimethylarginine (ADMA and SDMA), increased microbiota-derived uremic toxin TMAO, reduced microbiota-derived metabolite acetate and butyrate levels, and dysregulation of the intrarenal RAS. Our results indicated that adenine-induced maternal CKD could be an appropriate model for studying uremia-related adverse pregnancy and offspring outcomes. Targeting NO pathway, microbiota metabolite TMAO, and the RAS might be potential therapeutic strategies to improve maternal CKD-induced adverse pregnancy and offspring outcomes.

This study aimed to determine the efficacy of seven predominant wine terpenoids (i.e. α-pinene, limonene, myrcene, geraniol, linalool, nerol, and terpineol) against foodborne pathogenic bacteria, as well as to observe their antioxidant activities. Antibacterial activities were observed against foodborne pathogenic bacteria. MIC 50 and MBC values for Escherichia coli, Salmonella enterica, and Staphylococcus aureus were in the ranges of 0.420-1.598 mg/mL and 0.673-3.432 mg/mL, respectively. The terpenoid α-pinene showed the strongest DPPH free radical scavenging (IC 50 value = 12.57 ± 0.18 mg/mL) and the highest reducing power (213.7 ± 5.27 μg/mL of L-ascorbic acid equivalents). However, the DPPH free radical scavenging of the terpenoids was found to be lower than that of butylated hydroxytoluene, which is known to be a strong reducing agent. The seven predominant terpenoids in wines that were identified in this study could be new potential sources of natural antibacterial and antioxidant agents for use in the food industry. ARTICLE HISTORY