Abstract
Gut microbiota-derived metabolites, in particular short chain fatty acids (SCFAs) and their receptors, are linked to hypertension. Fructose and antibiotics are commonly used worldwide, and they have a negative impact on the gut microbiota. Our previous study revealed that maternal high-fructose (HF) diet-induced hypertension in adult offspring is relevant to altered gut microbiome and its metabolites. We, therefore, intended to examine whether minocycline administration during pregnancy and lactation may further affect blood pressure (BP) programmed by maternal HF intake via mediating gut microbiota and SCFAs. Pregnant Sprague-Dawley rats received a normal diet or diet containing 60% fructose throughout pregnancy and lactation periods. Additionally, pregnant dams received minocycline (50 mg/kg/day) via oral gavage or a vehicle during pregnancy and lactation periods. Four groups of male offspring were studied (n = 8 per group): normal diet (ND), high-fructose diet (HF), normal diet + minocycline (NDM), and HF + minocycline (HFM). Male offspring were killed at 12 weeks of age. We observed that the HF diet and minocycline administration, both individually and together, causes the elevation of BP in adult male offspring, while there is no synergistic effect between them. Four groups displayed distinct enterotypes. Minocycline treatment leads to an increase in the F/B ratio, but decreased abundance of genera Lactobacillus, Ruminococcus, and Odoribacter. Additionally, minocycline treatment decreases plasma acetic acid and butyric acid levels. Hypertension programmed by maternal HF diet plus minocycline exposure is related to the increased expression of several SCFA receptors. Moreover, minocycline- and HF-induced hypertension, individually or together, is associated with the aberrant activation of the renin–angiotensin system (RAS). Conclusively, our results provide a new insight into the support of gut microbiota and its metabolite SCAFs in the developmental programming of hypertension and cast new light on the role of RAS in this process, which will help prevent hypertension programmed by maternal high-fructose and antibiotic exposure.
Highlights
Hypertension is considered to be an increasingly common driver of the epidemic of non-communicable disease around the world [1]
As we previously reported, offspring born to dams exposed to a 60% high-fructose diet develop hypertension in adulthood, which is associated with reshaping microbiota and alterations of its metabolite short chain fatty acids (SCFAs) [13,14]
We examined four groups of male offspring born to mother rats that received a normal diet (ND), a high-fructose diet (HF), a normal diet and minocycline administration (NDM), Int
Summary
Hypertension is considered to be an increasingly common driver of the epidemic of non-communicable disease around the world [1]. Accumulative evidence demonstrates that adverse in utero environments can increase the risk of developing hypertension in later life [3,4,5] Today, this theory is called the Developmental Origins of Health and Disease (DOHaD) [6]. Reshaping microbiota during the critical phases of development is reported to have a lifelong influence on offspring health outcomes [8]. As reviewed elsewhere, such programming is beneficial or harmful depending on the circumstances [9,10]. Offspring from pregnancies where maternal diets are high in fructose are at greater risk for adverse health outcomes [12]. As we previously reported, offspring born to dams exposed to a 60% high-fructose diet develop hypertension in adulthood, which is associated with reshaping microbiota and alterations of its metabolite short chain fatty acids (SCFAs) [13,14]
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