scholarly journals Maternal Administration of Probiotic or Prebiotic Prevents Male Adult Rat Offspring against Developmental Programming of Hypertension Induced by High Fructose Consumption in Pregnancy and Lactation

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1229 ◽  
Author(s):  
Chien-Ning Hsu ◽  
Yu-Ju Lin ◽  
Chih-Yao Hou ◽  
You-Lin Tain

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.

2021 ◽  
Vol 22 (5) ◽  
pp. 2674
Author(s):  
Chien-Ning Hsu ◽  
Julie Y. H. Chan ◽  
Kay L. H. Wu ◽  
Hong-Ren Yu ◽  
Wei-Chia Lee ◽  
...  

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.


Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 856 ◽  
Author(s):  
Chien-Ning Hsu ◽  
Chih-Yao Hou ◽  
Guo-Ping Chang-Chien ◽  
Sufan Lin ◽  
You-Lin Tain

Hypertension can come from early life. N-acetylcysteine (NAC), a hydrogen sulfide (H2S) precursor as well as an antioxidant, has antihypertensive effect. We investigated whether maternal NAC therapy can protect spontaneously hypertensive rats (SHR) male offspring against hypertension. The pregnant rats were assigned to four groups: SHRs without treatment; Wistar Kyoto (WKY) without treatment; SHR+NAC, SHRs received 1% NAC in drinking water throughout pregnancy and lactation; and, WKY+NAC, WKY rats received 1% NAC in drinking water during pregnancy and lactation. Male offspring (n = 8/group) were killed at 12 weeks of age. Maternal NAC therapy prevented the rise in systolic blood pressure (BP) in male SHR offspring at 12 weeks of age. Renal cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulphurtransferase (3MST) protein levels and H2S-releasing activity were increased in the SHR+NAC offspring. Maternal NAC therapy increased fecal H2S and thiosulfate levels in the SHR+NAC group. Additionally, maternal NAC therapy differentially shaped gut microbiota and caused a distinct enterotype in each group. The protective effect of maternal NAC therapy against hypertension in SHR offspring is related to increased phylum Actinobacteria and genera Bifidobacterium and Allobaculum, but decreased phylum Verrucomicrobia, genera Turicibacter, and Akkermansia. Several microbes were identified as microbial markers, including genera Bifidobacterium, Allobaculum, Holdemania, and Turicibacter. Our results indicated that antioxidant therapy by NAC in pregnant SHRs can prevent the developmental programming of hypertension in male adult offspring. Our findings highlight the interrelationships among H2S-generating pathway in the kidneys and gut, gut microbiota, and hypertension. The implications of maternal NAC therapy elicited long-term protective effects on hypertension in later life that still await further clinical translation.


Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 448 ◽  
Author(s):  
Wan-Long Tsai ◽  
Chien-Ning Hsu ◽  
You-Lin Tain

High consumption of saturated fats links to the development of hypertension. AMP-activated protein kinase (AMPK), a nutrient-sensing signal, is involved in the pathogenesis of hypertension. We examined whether early intervention with a direct AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR) during pregnancy or lactation can protect adult male offspring against hypertension programmed by high saturated fat consumption via regulation of nutrient sensing signals, nitric oxide (NO) pathway, and oxidative stress. Pregnant Sprague–Dawley rats received regular chow or high saturated fat diet (HFD) throughout pregnancy and lactation. AICAR treatment was introduced by intraperitoneal injection at 50 mg/kg twice a day for 3 weeks throughout the pregnancy period (AICAR/P) or lactation period (AICAR/L). Male offspring (n = 7–8/group) were assigned to five groups: control, HFD, AICAR/P, HFD + AICAR/L, and HFD + AICAR/P. Male offspring were killed at 16 weeks of age. HFD caused hypertension and obesity in male adult offspring, which could be prevented by AICAR therapy used either during pregnancy or lactation. As a result, we demonstrated that HFD downregulated AMPK/SIRT1/PGC-1α pathway in offspring kidneys. In contrast, AICAR therapy in pregnancy and, to a greater extent, in lactation activated AMPK signaling pathway. The beneficial effects of AICAR therapy in pregnancy is related to restoration of NO pathway. While AICAR uses in pregnancy and lactation both diminished oxidative stress induced by HFD. Our results highlighted that pharmacological AMPK activation might be a promising strategy to prevent hypertension programmed by excessive consumption of high-fat food.


2020 ◽  
Vol 21 (15) ◽  
pp. 5488 ◽  
Author(s):  
Chien-Ning Hsu ◽  
Julie Y. H. Chan ◽  
Hong-Ren Yu ◽  
Wei-Chia Lee ◽  
Kay L. H. Wu ◽  
...  

Gut microbiota-dependent metabolites, in particular trimethylamine (TMA), are linked to hypertension. Maternal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure or consumption of food high in fructose (HFR) can induce hypertension in adult offspring. We examined whether 3,3-maternal dimethyl-1-butanol (DMB, an inhibitor of TMA formation) therapy can protect adult offspring against hypertension arising from combined HFR and TCDD exposure. Pregnant Sprague–Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) throughout pregnancy and lactation. Additionally, the pregnant dams received TCDD (200 ng/kg BW orally) or a corn oil vehicle on days 14 and 21 of gestation, and days 7 and 14 after birth. Some mother rats received 1% DMB in their drinking water throughout pregnancy and lactation. Six groups of male offspring were studied (n = 8 for each group): regular chow (CV), high-fructose diet (HFR), regular diet+TCDD exposure (CT), HFR+TCDD exposure (HRT), high-fructose diet+DMB treatment (HRD), and HFR+TCDD+DMB treatment (HRTD). Our data showed that TCDD exacerbates HFR-induced elevation of blood pressure in male adult offspring, which was prevented by maternal DMB administration. We observed that different maternal insults induced distinct enterotypes in adult offspring. The beneficial effects of DMB are related to alterations of gut microbiota, the increase in nitric oxide (NO) bioavailability, the balance of the renin-angiotensin system, and antagonization of aryl hydrocarbon receptor (AHR) signaling. Our findings cast new light on the role of early intervention targeting of the gut microbiota-dependent metabolite TMA, which may allow us to prevent the development of hypertension programmed by maternal excessive fructose intake and environmental dioxin exposure.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1982 ◽  
Author(s):  
Chien-Ning Hsu ◽  
Chih-Yao Hou ◽  
Chien-Te Lee ◽  
Julie Y.H. Chan ◽  
You-Lin Tain

Excessive intake of saturated fat has been linked to hypertension. Gut microbiota and their metabolites, short-chain fatty acids (SCFAs), are known to be involved in the development of hypertension. We examined whether maternal and post-weaning high-fat (HF) diet-induced hypertension in adult male offspring is related to alterations of gut microbiota, mediation of SCFAs and their receptors, and downregulation of nutrient-sensing signals. Female Sprague–Dawley rats received either a normal diet (ND) or HF diet (D12331, Research Diets) during pregnancy and lactation. Male offspring were put on either the ND or HF diet from weaning to 16 weeks of age, and designated to four groups (maternal diet/post-weaning diet; n = 8/group): ND/ND, HF/ND, ND/HF, and HF/HF. Rats were sacrificed at 16 weeks of age. Combined HF/HF diets induced elevated blood pressure (BP) and increased body weight and kidney damage in male adult offspring. The rise in BP is related to a downregulated AMP-activated protein kinase (AMPK)–peroxisome proliferator-activated receptor co-activator 1α (PGC-1α) pathway. Additionally, HF/HF diets decreased fecal concentrations of propionate and butyrate and decreased G protein-coupled receptor 41 (GPR41), but increased olfactory receptor 78 (Oflr78) expression. Maternal HF diet has differential programming effects on the offspring’s microbiota at 3 and 16 weeks of age. Combined HF/HF diet induced BP elevation was associated with an increased Firmicutes to Bacteroidetes ratio, increased abundance of genus Akkermansia and phylum Verrucomicrobia, and reduced abundance in genus Lactobacillus. Maternal gut microbiota-targeted dietary interventions might be reprogramming strategies to protect against programmed hypertension in children and their mothers on consumption of a fat-rich diet.


Author(s):  
G.V. Kozlovskaya ◽  
◽  
M.I. Zinevich ◽  
Y.E. Kozlovsky ◽  
T.I. Khomyakova ◽  
...  

Gut microbiome changes is considered as a basic causative factor of stress-associated diseases. Probiotics are usually used for the correction of disbiosis. The aim of the investigation was the study of the effects of oral probiotic Lactobacillus casei LB 148 use onto the gut microbiota as well as the number and total square of intestinal lymph nodules of rats Sprague Dawley at in health rats and under the cold stress


2020 ◽  
Vol 11 (10) ◽  
pp. 8939-8950
Author(s):  
Keyth Sulamitta de Lima Guimarães ◽  
Valdir de Andrade Braga ◽  
Sylvana I. S. Rendeiro de Noronha ◽  
Whyara Karoline Almeida da Costa ◽  
Kassem Makki ◽  
...  

Lactiplantibacillus plantarum WJL administration during pregnancy and lactation improves gut microbiota diversity.


Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2908 ◽  
Author(s):  
Chien-Ning Hsu ◽  
Chih-Yao Hou ◽  
Julie Y.H. Chan ◽  
Chien-Te Lee ◽  
You-Lin Tain

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.


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