Resveratrol Butyrate Esters Inhibit BPA-Induced Liver Damage in Male Offspring Rats by Modulating Antioxidant Capacity and Gut Microbiota

Resveratrol can affect the physiology or biochemistry of offspring in the maternal–fetal animal model. However, it exhibits low bioavailability in humans and animals. Fifteen-week SD pregnant female rats were orally administered bisphenol A (BPA) and/or resveratrol butyrate ester (RBE), and the male offspring rats (n = 4–8 per group) were evaluated. The results show that RBE treatment (BPA + R30) compared with the BPA group can reduce the damage caused by BPA (p < 0.05). RBE enhanced the expression of selected genes and induced extramedullary hematopoiesis and mononuclear cell infiltration. RBE increased the abundance of S24-7 and Adlercreutzia in the intestines of the male offspring rats, as well as the concentrations of short-chain fatty acids (SCFAs) in the feces. RBE also increased the antioxidant capacity of the liver by inducing Nrf2, promoting the expression of HO-1, SOD, and CAT. It also increased the concentration of intestinal SCFAs, enhancing the barrier formed by intestinal cells, thereby preventing BPA-induced metabolic disruption in the male offspring rats, and reduced liver inflammation. This study identified a potential mechanism underlying the protective effects of RBE against the liver damage caused by BPA exposure during the peri-pregnancy period, and the influence of the gut microbiota on the gut–liver axis in the offspring.

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Altered Gut Microbiota and Its Metabolites in Hypertension of Developmental Origins: Exploring Differences between Fructose and Antibiotics Exposure

International Journal of Molecular Sciences ◽

10.3390/ijms22052674 ◽

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 ◽

...

Keyword(s):

Gut Microbiota ◽

Negative Impact ◽

Short Chain Fatty Acids ◽

Normal Diet ◽

Male Offspring ◽

Sprague Dawley ◽

Minocycline Treatment ◽

High Fructose ◽

Induced Hypertension ◽

Pregnancy And Lactation

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.

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The Influence of Diet and Sex on the Gut Microbiota of Lean and Obese JCR:LA-cp Rats

Microorganisms ◽

10.3390/microorganisms9051037 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1037

Author(s):

Craig Resch ◽

Mihir Parikh ◽

J. Alejandro Austria ◽

Spencer D. Proctor ◽

Thomas Netticadan ◽

...

Keyword(s):

Gut Microbiota ◽

Control Diet ◽

Bacterial Species ◽

Alpha Diversity ◽

Short Chain Fatty Acids ◽

Female Rats ◽

Dependent Manner ◽

Male And Female ◽

Ground Flaxseed ◽

The Impact

There is an increased interest in the gut microbiota as it relates to health and obesity. The impact of diet and sex on the gut microbiota in conjunction with obesity also demands extensive systemic investigation. Thus, the influence of sex, diet, and flaxseed supplementation on the gut microbiota was examined in the JCR:LA-cp rat model of genetic obesity. Male and female obese rats were randomized into four groups (n = 8) to receive, for 12 weeks, either (a) control diet (Con), (b) control diet supplemented with 10% ground flaxseed (CFlax), (c) a high-fat, high sucrose (HFHS) diet, or (d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. Illumine MiSeq sequencing revealed a richer microbiota in rats fed control diets rather than HFHS diets. Obese female rats had lower alpha-diversity than lean female; however, both sexes of obese and lean JCR rats differed significantly in β-diversity, as their gut microbiota was composed of different abundances of bacterial types. The feeding of an HFHS diet affected the diversity by increasing the phylum Bacteroidetes and reducing bacterial species from phylum Firmicutes. Fecal short-chain fatty acids such as acetate, propionate, and butyrate-producing bacterial species were correspondingly impacted by the HFHS diet. Flax supplementation improved the gut microbiota by decreasing the abundance of Blautia and Eubacterium dolichum. Collectively, our data show that an HFHS diet results in gut microbiota dysbiosis in a sex-dependent manner. Flaxseed supplementation to the diet had a significant impact on gut microbiota diversity under both flax control and HFHS dietary conditions.

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Maternal N-Acetylcysteine Therapy Prevents Hypertension in Spontaneously Hypertensive Rat Offspring: Implications of Hydrogen Sulfide-Generating Pathway and Gut Microbiota

Antioxidants ◽

10.3390/antiox9090856 ◽

2020 ◽

Vol 9 (9) ◽

pp. 856 ◽

Cited By ~ 2

Author(s):

Chien-Ning Hsu ◽

Chih-Yao Hou ◽

Guo-Ping Chang-Chien ◽

Sufan Lin ◽

You-Lin Tain

Keyword(s):

Drinking Water ◽

Hydrogen Sulfide ◽

Gut Microbiota ◽

Spontaneously Hypertensive Rat ◽

Later Life ◽

Male Offspring ◽

Protective Effects ◽

Male Adult ◽

Spontaneously Hypertensive ◽

Pregnancy And Lactation

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.

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Prenylated Isoflavonoids-Rich Extract of Erythrinae Cortex Exerted Bone Protective Effects by Modulating Gut Microbial Compositions and Metabolites in Ovariectomized Rats

Nutrients ◽

10.3390/nu13092943 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2943

Author(s):

Hui-Hui Xiao ◽

Xueli Yu ◽

Chen Yang ◽

Chi-On Chan ◽

Lu Lu ◽

...

Keyword(s):

Bone Microarchitecture ◽

Cathepsin K ◽

Short Chain Fatty Acids ◽

Female Rats ◽

Ovariectomized Rats ◽

Protective Effects ◽

Sprague Dawley ◽

Mineral Density ◽

Beneficial Effects ◽

Ovx Rats

Flavonoids, found in a wide variety of foods and plants, are considered to play an important role in the prevention and treatment of osteoporosis. Our previous studies demonstrated that Erythrina cortex extract (EC) rich in prenylated isoflavonoids exerted bone protective effects in ovariectomized (OVX) rats. The present study aimed to investigate the interactions of gut microbiota with the EC extract to explore the underlying mechanisms involved in its beneficial effects on bone. Sprague-Dawley female rats of 3-months-old were ovariectomized and treated with EC extract for 12 weeks. EC extract reversed ovariectomy-induced deterioration of bone mineral density and bone microarchitecture as well as downregulated cathepsin K (Ctsk) and upregulated runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) in the tibia of OVX rats. Its protective effects on bone were correlated with changes in microbial richness and the restorations of several genera. EC increased the serum circulating levels of acetate and propionate in OVX rats. We conclude that the bone protective effects of EC extract were associated with the changes in microbial compositions and serum short chain fatty acids (SCFAs) in OVX rats.

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Resveratrol and the Interaction between Gut Microbiota and Arterial Remodelling

Nutrients ◽

10.3390/nu12010119 ◽

2020 ◽

Vol 12 (1) ◽

pp. 119 ◽

Cited By ~ 4

Author(s):

Andy W.C. Man ◽

Huige Li ◽

Ning Xia

Keyword(s):

Gut Microbiota ◽

Cell Cycle Progression ◽

Vascular Inflammation ◽

Neointimal Hyperplasia ◽

Critical Role ◽

Short Chain Fatty Acids ◽

Cardiovascular Complications ◽

Protective Effects ◽

Vsmc Proliferation ◽

Beneficial Effects

Arterial remodelling refers to the alteration in the structure of blood vessel that contributes to the progression of hypertension and other cardiovascular complications. Arterial remodelling is orchestrated by the crosstalk between the endothelium and vascular smooth muscle cells (VSMC). Vascular inflammation participates in arterial remodelling. Resveratrol is a natural polyphenol that possesses anti-oxidant and anti-inflammatory properties and has beneficial effects in both the endothelium and VSMC. Resveratrol has been studied for the protective effects in arterial remodelling and gut microbiota, respectively. Gut microbiota plays a critical role in the immune system and inflammatory processes. Gut microbiota may also regulate vascular remodelling in cardiovascular complications via affecting endothelium function and VSMC proliferation. Currently, there is new evidence showing that gut microbiota regulate the proliferation of VSMC and the formation of neointimal hyperplasia in response to injury. The change in population of the gut microbiota, as well as their metabolites (e.g., short-chain fatty acids) could critically contribute to VSMC proliferation, cell cycle progression, and migration. Recent studies have provided strong evidence that correlate the effects of resveratrol in arterial remodelling and gut microbiota. This review aims to summarize recent findings on the resveratrol effects on cardiovascular complications focusing on arterial remodelling and discuss the possible interactions of resveratrol and the gut microbiota that modulate arterial remodelling.

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The Interplay between Maternal and Post-Weaning High-Fat Diet and Gut Microbiota in the Developmental Programming of Hypertension

Nutrients ◽

10.3390/nu11091982 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1982 ◽

Cited By ~ 10

Author(s):

Chien-Ning Hsu ◽

Chih-Yao Hou ◽

Chien-Te Lee ◽

Julie Y.H. Chan ◽

You-Lin Tain

Keyword(s):

Gut Microbiota ◽

Short Chain Fatty Acids ◽

Normal Diet ◽

Nutrient Sensing ◽

Male Offspring ◽

Peroxisome Proliferator ◽

Sprague Dawley ◽

High Fat ◽

Male Adult ◽

Peroxisome Proliferator Activated Receptor

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.

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The Role of the Gut Microbiome in Diabetes and Obesity-Related Kidney Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22179641 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9641

Author(s):

Amgad Zaky ◽

Sarah J. Glastras ◽

May Y. W. Wong ◽

Carol A. Pollock ◽

Sonia Saad

Keyword(s):

Kidney Disease ◽

Gut Microbiota ◽

Renin Angiotensin System ◽

Short Chain Fatty Acids ◽

Therapeutic Effects ◽

Protective Effects ◽

Obesity And Diabetes ◽

Number Of Patients ◽

Diabetes And Obesity

Diabetic kidney disease (DKD) is a progressive disorder, which is increasing globally in prevalence due to the increased incidence of obesity and diabetes mellitus. Despite optimal clinical management, a significant number of patients with diabetes develop DKD. Hence, hitherto unrecognized factors are likely to be involved in the initiation and progression of DKD. An extensive number of studies have demonstrated the role of microbiota in health and disease. Dysregulation in the microbiota resulting in a deficiency of short chain fatty acids (SCFAs) such as propionate, acetate, and butyrate, by-products of healthy gut microbiota metabolism, have been demonstrated in obesity, type 1 and type 2 diabetes. However, it is not clear to date whether such changes in the microbiota are causative or merely associated with the diseases. It is also not clear which microbiota have protective effects on humans. Few studies have investigated the centrality of reduced SCFA in DKD development and progression or the potential therapeutic effects of supplemental SCFAs on insulin resistance, inflammation, and metabolic changes. SCFA receptors are expressed in the kidneys, and emerging data have demonstrated that intestinal dysbiosis activates the renal renin-angiotensin system, which contributes to the development of DKD. In this review, we will summarize the complex relationship between the gut microbiota and the kidney, examine the evidence for the role of gut dysbiosis in diabetes and obesity-related kidney disease, and explore the mechanisms involved. In addition, we will describe the role of potential therapies that modulate the gut microbiota to prevent or reduce kidney disease progression.

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Maternal Dietary Fiber Composition during Gestation Induces Changes in Offspring Antioxidative Capacity, Inflammatory Response, and Gut Microbiota in a Sow Model

International Journal of Molecular Sciences ◽

10.3390/ijms21010031 ◽

2019 ◽

Vol 21 (1) ◽

pp. 31 ◽

Cited By ~ 6

Author(s):

Yang Li ◽

Haoyu Liu ◽

Lijia Zhang ◽

Yi Yang ◽

Yan Lin ◽

...

Keyword(s):

Inflammatory Response ◽

Gut Microbiota ◽

Antioxidant Capacity ◽

Dietary Fiber ◽

High Throughput Sequencing ◽

Short Chain Fatty Acids ◽

Inflammatory Factor ◽

Soluble Fiber ◽

Fiber Composition ◽

Gut Microbiota Composition

To study the effects of maternal dietary fiber composition during gestation on offspring antioxidant capacity, inflammation, and gut microbiota composition, we randomly assigned 64 gilts to four treatments and administered diets with an insoluble/soluble fiber ratio of 3.89 (R1), 5.59 (R2), 9.12 (R3), and 12.81 (R4). Sow samples (blood and feces at gestation 110) and neonatal samples (blood, liver, and colonic contents) were collected. The results showed that sows and piglets in R1 and R2 had higher antioxidant enzyme activity and lower pro-inflammatory factor levels than those in R3 and R4. Moreover, piglets in R1 and R2 had higher liver mRNA expression of Nrf2 and HO-1 and lower NF-κB than piglets in R4. Interestingly, maternal fiber composition not only affected the production of short-chain fatty acids (SCFAs) in sow feces but also influenced the concentrations of SCFAs in the neonatal colon. Results of high-throughput sequencing showed that piglets as well as sows in R1 and R2 had microbial community structures distinct from those in R3 and R4. Therefore, the composition of dietary fiber in pregnancy diet had an important role in improving antioxidant capacity and decreasing inflammatory response of mothers and their offspring through modulating the composition of gut microbiota.

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