Gut Microbiome Alteration after Reboxetine Administration in Type-1 Diabetic Rats.
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ABSTRACT:
SUBMITTER: Aydin S
PROVIDER: S-EPMC8465486 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This study was undertaken to determine whether aqueous blackcurrant extracts (BC) improve glucose metabolism and gut microbiomes in non-obese type 2 diabetic animals fed a high-fat diet and to identify the mechanism involved. Partially pancreatectomized male Sprague-Dawley rats were provided a high-fat diet containing 0% (control), 0.2% (L-BC; low dosage), 0.6% (M-BC; medium dosage), and 1.8% (H-BC; high dosage) blackcurrant extracts; 0.2% metformin (positive-C); plus 1.8%, 1.6%, 1.2%, 0%, and 1.6% dextrin, specifically indigestible dextrin, daily for 8 weeks. Daily blackcurrant extract intakes were equivalent to 100, 300, and 900 mg/kg body weight (bw). After a 2 g glucose or maltose/kg bw challenge, serum glucose and insulin concentrations during peak and final states were obviously lower in the M-BC and H-BC groups than in the control group (p < 0.05). Intraperitoneal insulin tolerance testing showed that M-BC and H-BC improved insulin resistance. Hepatic triglyceride deposition, TNF-α expression, and malondialdehyde contents were lower in the M-BC and H-BC groups than in the control group. Improvements in insulin resistance in the M-BC and H-BC groups were associated with reduced inflammation and oxidative stress (p < 0.05). Hyperglycemic clamp testing showed that insulin secretion capacity increased in the acute phase (2 to 10 min) in the M-BC and H-BC groups and that insulin sensitivity in the hyperglycemic state was greater in these groups than in the control group (p < 0.05). Pancreatic β-cell mass was greater in the M-BC, H-BC, and positive-C groups than in the control group. Furthermore, β-cell proliferation appeared to be elevated and apoptosis was suppressed in these three groups (p < 0.05). Serum propionate and butyrate concentrations were higher in the M-BC and H-BC groups than in the control group. BC dose-dependently increased α-diversity of the gut microbiota and predicted the enhancement of oxidative phosphorylation-related microbiome genes and downregulation of carbohydrate digestion and absorption-related genes, as determined by PICRUSt2 analysis. In conclusion, BC enhanced insulin sensitivity and glucose-stimulated insulin secretion, which improved glucose homeostasis, and these improvements were associated with an incremental increase of the α-diversity of gut microbiota and suppressed inflammation and oxidative stress.
| S-EPMC8150986 | biostudies-literature
Project description:Background & aimsAccumulating research has addressed the linkage between the changes to gut microbiota structure and type 2 diabetes (T2D). Inulin is one type of soluble dietary fiber that can alleviate T2D. As a prebiotic, inulin cannot be digested by humans, but rather is digested by probiotics. However, whether inulin treatment can benefit the entire gut bacteria community remains unknown. In this study, we evaluated the differences in gut microbiota composition among diabetic, inulin-treated diabetic, normal control, and inulin-treated normal control rats.MethodsA diabetic rat model was generated by a high-fat diet and streptozotocin injections (HF/STZ). Inulin was orally administered to normal and diabetic rats. To determine the composition of the gut microbiota, fecal DNA extraction and 16S rRNA gene 454 pyrosequencing were performed.ResultsWe found that inulin treatment reduced fasting blood glucose levels and alleviated glucose intolerance and blood lipid panels in diabetic rats. Additionally, inulin treatment increased the serum glucagon-like peptide-1 (GLP-1) level, reduced serum IL-6 level, Il6 expression in epididymal adipose tissue, and Pepck, G6pc expression in liver of diabetic rats. Pyrophosphate sequencing of the 16s V3-V4 region demonstrated an elevated proportion of Firmicutes and a reduced abundance of Bacteroidetes at the phylogenetic level in diabetic rats compared to normal control rats. The characteristics of the gut microbiota in control and inulin-treated rats were similar. Inulin treatment can normalize the composition of the gut microbiota in diabetic rats. At the family and genus levels, probiotic bacteria Lactobacillus and short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae, Phascolarctobacterium, and Bacteroides were found to be significantly more abundant in the inulin-treated diabetic group than in the non-treated diabetic group. In addition, inulin-treated rats had a lower abundance of Desulfovibrio, which produce lipopolysaccharide (LPS). The abundance of Lachnospiraceae was negatively correlated with the blood glucose response after a glucose load.ConclusionIn summary, diabetic rats have different gut microbiota from control rats. Inulin treatment can alleviate gut microbiota dysbiosis in T2D model rats. Moreover, inulin treatment enhanced serum GLP-1 level to suppress IL-6 secretion and production and hepatic gluconeogenesis, resulted in moderation of insulin tolerance.
| S-EPMC5835350 | biostudies-literature
Project description:The aim of the present was to ameliorate the protective effect of exogenous melatonin and insulin against the diabetes induced alterations in the different hematological variables. Albino rats were administrated streptozotocin at the dose of 15?mg/kg for 6 days. Total 54 rats were randomly selected for the experimental purpose and were divided into two major groups. Group-1 consisting twenty four (24) and were further sub-divided into four (4) different groups viz. group-I served as normal control, group-II served as melatonin treated, group-III served as insulin treated and group-IV served as glibenclamide treated. Group-2 consisting thirty (30) rats were given streptozotocin (STZ) injection (15?mg/kg) for 6 days. After confirmation of diabetes by measuring blood glucose level, animals having blood glucose level above 250?mg/dl) confirmed as diabetic. Thirty (30) Diabetic rats were further subdivided into following sub-groups and were given different therapeutic treatments, Viz group-I served as Diabetic control, group-II treated with melatonin, group-III treated with insulin, group-IV given treatment of melatonin and insulin and group-V were given treatment of glibenclamide respectively. Diabetic rats showed modulation in all the studied hematological variables. Diabetic rats displayed significant decline in RBCs count, HB level and its associated indices (HCT, RDW, MCV, MCH, MCHC), WBCs and its related indices (polymorphs and lymphocytes) and platelet distribution width (PDW %) whereas platelet count showed significant increase. Nonetheless alone as well as combined treatment of exogenous melatonin and insulin restored all altered hematological parameters. However, significant recovery was found in the group in which combined dose of melatonin and insulin was administrated. Therefore, it might be concluded that combined administration of melatonin and insulin will be better remedy to normalize the altered blood profile during the diabetic condition.
| S-EPMC7033445 | biostudies-literature
Project description:In this study, we examined the metabolic and gut microbiome responses to paraquat (PQ) in male Wistar rats, focusing on oxidative stress effects. Rats received a single intraperitoneal injection of PQ at 15 and 30 mg/kg, and various oxidative stress parameters (i.e., MDA, SOD, ROS, 8-isoprostanes) were assessed after three days. To explore the omic profile, GC-qTOF and UHPLC-qTOF were performed to assess the plasma metabolome; 1H-NMR was used to assess the urine metabolome; and shotgun metagenomics sequencing was performed to study the gut microbiome. Our results revealed reductions in body weight and tissue changes, particularly in the liver, were observed, suggesting a systemic effect of PQ. Elevated lipid peroxidation and reactive oxygen species levels in the liver and plasma indicated the induction of oxidative stress. Metabolic profiling revealed changes in the tricarboxylic acid cycle, accumulation of ketone body, and altered levels of key metabolites, such as 3-hydroxybutyric acid and serine, suggesting intricate links between energy metabolism and redox reactions. Plasma metabolomic analysis revealed alterations in mitochondrial metabolism, nicotinamide metabolism, and tryptophan degradation. The gut microbiome showed shifts, with higher PQ doses influencing microbial populations (e.g., Escherichia coli and Akkermansia muciniphila) and metagenomic functions (pyruvate metabolism, fermentation, nucleotide and amino acid biosynthesis). Overall, this study provides comprehensive insights into the complex interplay between PQ exposure, metabolic responses, and gut microbiome dynamics. These findings enhance our understanding of the mechanisms behind oxidative stress-induced metabolic alterations and underscore the connections between xenobiotic exposure, gut microbiota, and host metabolism.
| S-EPMC10812659 | biostudies-literature
Project description:Emerging evidence has suggested the association of the gut microbiome with some human diseases, including type 2 diabetes (T2D). In this study, we analyzed the gut microbiota from a cohort of healthy and diabetic Chinese individuals from Northern China. Pyrosequencing of the V4V5 region of 16S rRNA genes revealed a significant decrease in the gut microbiota diversity of diabetic patients as compared to healthy individuals. Butyrate-producing bacteria such as Bifidobacterium and Akkermansia were significantly decreased in diabetic patients. Furthermore, the abundance of Dorea was significantly increased in T2D individuals and negatively correlated with the abundance of butyrate-producing bacteria. The increase of Dorea could play a role in the development of T2D and has been previously overlooked. Importantly, functional analysis of the gut microbiome revealed for the first time that increased levels of butyrate production via transferases and the degradation of several amino acids due to gut microbial metabolism have strong correlations with T2D in Northern China. Moreover, the potential of gut microbiota-based classifiers to identify individuals with a high risk for T2D has been demonstrated in this study. Taken together, our findings have revealed a previously unappreciated association of the gut microbiome with T2D and have also suggested that changes in gut microbiota may be used to identify individuals at high risk for T2D.
| S-EPMC7096501 | biostudies-literature
Project description:Leptin has been shown to reduce hyperglycemia in rodent models of type 1 diabetes. We investigated the effects of leptin administration in University of California, Davis, type 2 diabetes mellitus (UCD-T2DM) rats, which develop adult-onset polygenic obesity and type 2 diabetes. Animals that had been diabetic for 2 mo were treated with s.c. injections of saline (control) or murine leptin (0.5 mg/kg) twice daily for 1 mo. Control rats were pair-fed to leptin-treated animals. Treatment with leptin normalized fasting plasma glucose and was accompanied by lowered HbA1c, plasma glucagon, and triglyceride concentrations and expression of hepatic gluconeogenic enzymes compared with vehicle (P < 0.05), independent of any effects on body weight and food intake. In addition, leptin-treated animals exhibited marked improvement of insulin sensitivity and glucose homeostasis compared with controls, whereas pancreatic insulin content was 50% higher in leptin-treated animals (P < 0.05). These effects coincided with activation of leptin and insulin signaling pathways and down-regulation of the PKR-like endoplasmic reticulum (ER) kinase/eukaryotic translation inhibition factor 2? (PERK-eIF2?) arm of ER stress in liver, skeletal muscle, and adipose tissue as well as increased pro-opiomelanocortin and decreased agouti-related peptide in the hypothalamus. In contrast, several markers of inflammation/immune function were elevated with leptin treatment in the same tissues (P < 0.05), suggesting that the leptin-mediated increase of insulin sensitivity was not attributable to decreased inflammation. Thus, leptin administration improves insulin sensitivity and normalizes fasting plasma glucose in diabetic UCD-T2DM rats, independent of energy intake, via peripheral and possibly centrally mediated actions, in part by decreasing circulating glucagon and ER stress.
| S-EPMC3167517 | biostudies-literature
Project description:Gut bacterial microbiome dysbiosis in type 2 Diabetes Mellitus (T2DM) has been reported, but such an association with Diabetic Retinopathy (DR) is not known. We explored possible link between gut bacterial microbiome dysbiosis and DR. Using fecal samples of healthy controls (HC) and people with T2DM with/without DR, gut bacterial communities were analysed using 16S rRNA gene sequencing and data analysed using QIIME and R software. Dysbiosis in the gut microbiomes, at phyla and genera level, was observed in people with T2DM and DR compared to HC. People with DR exhibited greater discrimination from HC. Microbiomes of people with T2DM and DR were also significantly different. Both DM and DR microbiomes showed a decrease in anti-inflammatory, probiotic and other bacteria that could be pathogenic, compared to HC, and the observed change was more pronounced in people with DR. This is the first report demonstrating dysbiosis in the gut microbiome (alteration in the diversity and abundance at the phyla and genera level) in people with DR compared to HC. Such studies would help in developing novel and targeted therapies to improve treatment of DR.
| S-EPMC7854632 | biostudies-literature
Project description:Diallyl disulfide (DADS) is one of the primary components of garlic and it exhibits a broad range of biological activities. In the present study, the effects of DADS on lipid metabolism and its potential role in the modulation of the gut microbiome were determined. Hematoxylin and eosin and oil?red O staining were used to assess the liver and intestinal tissues of mice treated with DADS. The expression of lipid metabolism?associated genes was measured using reverse transcription?quantitative PCR (RT?qPCR). The effects of DADS on the gut microbiome were measured using 16S recombinant (r)DNA gene analysis. The results revealed that the serum non?esterified free fatty acids, high density lipoprotein?cholesterol, low density lipoprotein?cholesterol, serum total cholesterol, liver triglyceride and total cholesterol levels of the mice fed with a low?dose of DADS was significantly higher when compared with the control. Hematoxylin and eosin and oil?red O staining demonstrated that DADS induced fatty liver in mice. The results of the RT?qPCR revealed that the expression levels of a number of lipid metabolism?associated genes were altered in the livers of mice treated with DADS. The 16S rDNA gene analysis demonstrated that the mice fed on a normal diet treated with a low?dose of DADS had decreased levels of bacteria from the Bacteroidetes phyla and increased levels of bacteria from the Firmicutes phyla. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the top 20 pathways enriched in the low?dose DADS group of mice fed with a normal diet. In the present study, low?dose DADS induced fatty liver and altered the gut microbiota, similar to the phenotype induced by a high fat diet, by regulating the expression of lipid metabolism associated genes.
| S-EPMC6777666 | biostudies-literature
Project description:BackgroundThe pathogenesis of post-stroke depression (PSD) remains largely unknown. There is growing evidence indicating that gut microbiota participates in the development of brain diseases through the gut-brain axis. Here, we aim to determine whether and how microbial composition and function altered among control, stroke and PSD rats.Materials and methodsAfter the PSD rat model was successfully established, gut microbiome combined with fecal metabolome approach were performed to identify potentially PSD-related gut microbes and their functional metabolites. Then, correlations between behavior indices and altered gut microbes, as well as correlations between altered gut microbial operational taxonomic units (OTUs) with differential metabolites in PSD rats were explored. Enrichment analysis was also conducted to uncover the crucial metabolic pathways related to PSD.ResultsAlthough there were some alterations in the microbiome and metabolism of the control and stroke rats, we found that the microbial and metabolic phenotypes of PSD rats were significantly different. The microbial composition of PSD showed a decreased species richness indices, characterized by 22 depleted OTUs mainly belonging to phylum Firmicutes, genus Blautia and Streptococcus. In addition, PSD was associated with disturbances of fecal metabolomics, among them Glutamate, Maleic acid, 5-Methyluridine, Gallocatechin, 1,5-Anhydroglucitol, L-Kynurenine, Daidzein, Cyanoalanine, Acetyl Alanine and 5-Methoxytryptamine were significantly related to disturbed gut microbiome (P ≤ 0.01). Disordered fecal metabolomics in PSD rats mainly assigned to lipid, amino acid, carbohydrate and nucleotide metabolism. The steroid biosynthesis was particularly enriched in PSD.ConclusionsOur findings suggest that gut microbiome may participate in the development of PSD, the mechanism may be related to the regulation of lipid metabolism.
| S-EPMC8100602 | biostudies-literature
Project description:The potential pharmacokinetic (PK) interaction of conventional western drug, baclofen, and oriental medications Oyaksungisan (OY) and Achyranthes bidentata radix (AB) extract for the treatment of spasticity has been evaluated. Rats were pretreated with distilled water (DW), OY, or AB extract by oral administration every day for 7 days. After 10 min of the final dose of DW or each herbal medication, baclofen (1 mg/kg) was given by oral administration and plasma concentrations of baclofen were determined by LC/MS/MS. The plasma baclofen concentration-time profiles were then analyzed by noncompartmental analysis and a population PK model was developed. Baclofen was rapidly absorbed, showed biexponential decline with elimination half-life of 3.42-4.10 hr, and mostly excreted into urine. The PK of baclofen was not affected by AB extract pretreatment. However, significantly lower maximum plasma concentration (C max) and longer time to reach C max (T max) were observed in OY pretreated rats without changes in the area under the curve (AUC) and the fraction excreted into urine (F urine). The absorption rate (K a ) of baclofen was significantly decreased in OY pretreated rats. These data suggested that repeated doses of OY might delay the absorption of baclofen without changes in extent of absorption, which needs further evaluation for clinical significance.
| S-EPMC4229966 | biostudies-literature