Gut Microbiota In Diabetic Mice Research Articles

Polysaccharide extracted from Sarcandra glabra residue attenuate cognitive impairment by regulating gut microbiota in diabetic mice

Diabetic encephalopathy (DE), characterized by cognitive impairment, currently lacks targeted treatment. Previous studies have shown that Sarcandra glabra extracted residue polysaccharide (SERP) exhibited hypoglycemic effects either in vitro or in streptozotocin-induced diabetes mice. However, the therapeutic effect of SERP on DE was not elucidated. This study investigated the therapeutic effect of SERP on DE and its underlying mechanism. Our results revealed that SERP regulates glucose and lipid metabolism, improves cognitive function, and exhibits diminished activity post-antibiotic intervention. Importantly, we discovered a novel mechanism by which SERP modulates the gut microbiota, specifically enriching Bacteroidales S24-7, resulting in elevated levels of butyric acid in the intestine. This regulation modulates the intestinal endocrine cell lipid metabolism level, restores damaged intestinal barriers and neural epithelial circuits, thus exhibiting cure effects. Our findings suggest that SERP could become a candidate for treating DE, potentially involving the regulation mechanism of the “microbiota-gut-brain axis”. This study underscores the unique therapeutic efficacy of SERP in managing DE, offering fresh drug candidates and innovative treatment strategies for this challenging condition.

Hypoglycemic Effects of Gynura divaricata (L.) DC Polysaccharide and Action Mechanisms via Modulation of Gut Microbiota in Diabetic Mice.

Aiming to provide a basis for the application of Gynura divaricata (L.) DC polysaccharide (GDP) in functional foods, the hypoglycemic effects of GDP, and action mechanisms, were investigated. Results showed that GDP effectively inhibited α-glucosidase and remarkably increased the glucose absorption, glycogen content, and pyruvate kinase and hexokinase activities of insulin-resistant HepG2 cells, indicating its potent in vitro hypoglycemic effect. In streptozotocin-induced type 2 diabetes mice, GDP significantly improved various glycolipid metabolism-related indices in serum and liver, e.g., fasting blood glucose, oral glucose tolerance, glycosylated serum protein content, serum insulin level, antioxidant enzyme activities, TG, TC, LDL-C, and HDL-C levels, and hepatic glycogen content, and recovered the structure of gut microbiota to the normal level. It was also found that GDP significantly affected the expression of related genes in the PI3K/Akt, AMPK, and GS/GSK-3β signaling pathways. Therefore, GDP regulates blood glucose possibly by directly inhibiting α-glucosidase, exerting antioxidant activity, and regulating intestinal microbiota.

Investigating the contribution of mulberry leaf Fu tea to ameliorating metabolic disorders and remodeling gut microbiota in diabetic mice

AbstractDysbiosis of the gut microbiota and metabolic disorders contributes to the occurrence of diabetes mellitus. Polyphenols reduce the risk of type II diabetes mellitus (T2DM) by inhibiting α‐glucosidase. Mulberry leaf Fu tea (FM) is a kind of tea obtained by the fermentation of Eurotium cristatum, which is polyphenol‐enriched and has a distinctive aroma, but its antidiabetic mechanism is unclear. In this study, we investigated the polyphenols in the aqueous extract of FM through HRLC‐MS and verified its inhibitory effect on α‐glucosidase in vitro test and finally studied its effect on gut microbiota and short‐chain fatty acids (SCFAs) in diabetic mice. The findings demonstrated that FM supplementation considerably altered gut microbiota abnormalities in diabetic mice, maintained the balance of microflora, encouraged the growth of beneficial microorganisms (Coriobacteriaceae UCG‐002, Dubosiella, Lactobacillus, and Bifidobacterium), and increased levels of acetic acid, propionic acid, and butyric acid. In conclusion, FM can regulate gut microbiota and SCFAs to ameliorate or alleviate T2DM caused by HFD‐STZ. Therefore, FM can also be used as postbiotics to improve T2DM.

Theasinensin A attenuated diabetic development by restoring glucose homeostasis, improving hepatic steatosis and modulating gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice

Theasinensin A (TSA), a dimer of epigallocatechin gallate, has been preliminarily demonstrated to have hypoglycemia and anti-inflammatory effects. However, little information is available on its potential mechanisms of anti-diabetes. Therefore, the present study aimed to investigate the influence of TSA on glucose and lipid metabolism and gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice. As result, TSA improved polydipsia, polyphagia and impaired glucose tolerance of diabetic mice, declined the fasting blood glucose and hepatic triglyceride level, and enhanced the expression at mRNA level of insulin receptor substrate, phosphoinositide 3-kinase, protein kinase B and glucagon-like peptide 1 receptor (GLP-1R) in the diabetic liver. Moreover, TSA could restore the disorder of gut microbiota of diabetic mice. High-dose (100 mg/kg) TSA showed better beneficial effects from the blood biochemical parameters, hepatic function and gut microbiota. In general, high-dose TSA significantly modulated gut microbiota by increasing the relative abundance of Akkermansia and decreasing the relative abundances of Acetatifactor, Anaerotruncus, Pseudoflavonifactor, Oscillibacter and Clostridium clusters. The results indicated that TSA could exert an anti-diabetes effect in diabetic mice through restoring glucose homeostasis, declining hepatic steatosis, activating insulin and GLP-1 signaling pathways, and ameliorating gut microbiota dysbiosis.

Rutin alleviates colon lesions and regulates gut microbiota in diabetic mice

Diabetes is a common metabolic disorder that has become a major health problem worldwide. In this study, we investigated the role of rutin in attenuating diabetes and preventing diabetes-related colon lesions in mice potentially through regulation of gut microbiota. The rutin from tartary buckwheat as analyzed by HPLC was administered intragastrically to diabetic mice, and then the biochemical parameters, overall community structure and composition of gut microbiota in diabetic mice were assayed. The results showed that rutin lowered serum glucose and improved serum total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride concentrations, tumor necrosis factor-α, interleukin-6, and serum insulin in diabetic mice. Notably, rutin obviously alleviated colon lesions in diabetic mice. Moreover, rutin also significantly regulated gut microbiota dysbiosis and enriched beneficial microbiota, such as Akkermansia (p < 0.05). Rutin selectively increased short-chain fatty acid producing bacteria, such as Alistipes (p < 0.05) and Roseburia (p < 0.05), and decreased the abundance of diabetes-related gut microbiota, such as Escherichia (p < 0.05) and Mucispirillum (p < 0.05). Our data suggested that rutin exerted an antidiabetic effect and alleviated colon lesions in diabetic mice possibly by regulating gut microbiota dysbiosis, which might be a potential mechanism through which rutin alleviates diabetes-related symptoms.

Regulatory mechanisms of the edible alga Ulva lactuca polysaccharide via modulation of gut microbiota in diabetic mice

In this study, Ulva lactuca polysaccharide (ULP) antihyperglycemic effect was assessed by monitoring changes in the gut microbiota of aging diabetic mice. The results showed that ULP alleviated type 2 diabetes by improving insulin tolerance, increasing SOD and CAT activities, and thus lowering blood glucose level. Moreover, ULP regulated the expressions of INSR and AMPK concurrent with inhibition the expression of JNK, JAK, STAT3, p16 and p38 to improve glucose metabolism dysfunction. Interestingly, the abundance of Alloprevotella and Pediococcus change might the key factor for ULP antihyperglycemic effectiveness in aging-related diabetes. These results suggest that ULP can exert a mechanism of blood glucose regulation by improving intestinal diversity composition asides from direct insulin mimetic actions.

Rutin alleviates colon lesions and regulates gut microbiota in diabetic mice

Rutin alleviates colon lesions and regulates gut microbiota in diabetic mice

Fermented Psidium guajava leaves regulate the gut microbiota and improve metabolic alterations in diabetic mice

The phenolic extract from fermented Psidium guajava leaves (PFGL) helps to improve diabetes; however, its hypoglycemic and hypolipidemic mechanisms remain unclear. In this study, gut microbiota modulation and glucose-lipid metabolism was investigated. The results showed that dietary supplement of PFGL enriched in quercetin glucosides significantly improved serum glucose-lipid profiles as well as insulin resistance in diabetic mice. The gut microbiota of diabetic mice was modulated by PFGL (200 mg/kg), causing an abundance of Bacteroidetes, Prevotellaceae, and Alistipes and a reduced the presence of Firmicutes and Streptococcus. Increased levels of short-chain fatty acids (SCFA) activated G protein-coupled receptor signaling that induced peptide YY release to promote insulin secretion. Diabetes-induced serum metabolite disorders that are involved in glycerophospholipid metabolism and tryptophan metabolism were restored by PFGL. The protein expression of metabolic enzymes including phospho-adenosine 5’-monophosphate-activated protein kinase, fatty acid synthase, acyl-coenzyme A oxidase, and diacylglycerol aeyltransferase 2 were also regulated to promote glucose-lipid metabolism. In particular, gut microbiota enriched with Alistipes genera and SCFA metabolic regulation were closely correlated with diabetes-related indicators. These findings provide a theoretical support for the development and application of PFGL for the treatment of diabetes.

Rutin alleviates colon lesions and regulates gut microbiota in diabetic mice

Rutin alleviates colon lesions and regulates gut microbiota in diabetic mice

The Preventive Effects of Fermented and Germinated Foxtail Millet Whole Grain on Kidney Damage in a Diabetic Mouse Model.

Diabetic kidney disease (DKD) is an important complication of diabetes. The prevention of DKD can effectively reduce the mortality rate of diabetic patients and improve their quality of life. The present study examined the effects of fermented and germinated foxtail millet whole grain (FG-FM) on kidney lesions in a diabetic mouse model (Db/Db mice). The results proved that the FG-FM consumption significantly alleviated the kidney tissue damage in the diabetic mouse model. The transcriptome analysis of kidney tissues demonstrated that the overactivation of signaling pathways related to inflammation and immunity in the diabetic mouse model was significantly inhibited with the FG-FM intake. Moreover, the consumption of the FG-FM diet effectively elevated the bacterial diversity, increased the relative abundance of probiotics and decreased the relative abundance of previously reported DKD-related bacteria in the gut microbiota of diabetic mice. Our study confirmed foxtail millet as a potential source of functional food for the non-pharmacological intervention of DKD.

Tangnaikang Alleviates Hyperglycemia and Improves Gut Microbiota in Diabetic Mice.

Dysregulation of gut microbiota contributes to the development of type 2 diabetes. To investigate the antidiabetic effect of Tangnaikang and its regulation of gut microbiota in diabetic KKAy mice, a type 2 diabetes mouse model was established by feeding KKAy mice with a high-fat diet (HFD) for 2 weeks. The diabetic KKAy mice were treated with vehicle, Acarbose, or different doses of Tangnaikang once a day for 8 weeks. The fasting plasma glucose (FPG) levels and bodyweights were measured weekly. The fecal and blood samples were collected 8 weeks after treatment. The 16s rRNA sequencing and bioinformatics analysis were conducted to explore the effects of Tangnaikang treatment on the richness, diversity, and relative abundance of gut microbiota. Compared with other treatments, high-dose Tangnaikang (4.68 g/kg) significantly reduced FPG levels while elevating bodyweights in model mice. Compared with saline treatment, different doses of Tangnaikang significantly increased gut microbial species richness and diversity. Linear discriminant analysis effect size identified potential bacterial biomarkers associated with Tangnaikang treatment. Relative abundance analysis revealed that Tangnaikang treatment modulated the abundance of gut bacteria at the class and genus levels, such as Bacilli, Lactobacillus, and Alistipes. The principal component analysis demonstrated that, compared with the samples of the high-dose group, the samples of medium-dose and low-dose groups were closer to those of the model group. Tangnaikang alleviated hyperglycemia and improved the composition and abundance of gut microbiota in diabetic KKAy mice.

Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets.

Type 2 diabetes is a common metabolic disorder related to insulin resistance, or deficiency of insulin secretion, caused by decreased insulin sensitivity and destruction of islet structure and function. As the second human genome, the microbiota has been observed to have a growing relationship with diabetes in recent years. Microbiota imbalance has been hypothesized to be involved in the regulation of energy metabolism and the inflammatory immune response in diabetes. The present study aimed to investigate whether fecal microbiota transplantation (FMT) could alleviate the symptoms associated with type 2 diabetes. To this end, a type 2 diabetes mouse model was first established through the consumption of a high-fat diet combined with streptozotocin (100 mg/kg), and FMT was used to rebuild the gut microbiota of diabetic mice. Fasting blood glucose, oral glucose tolerance tests, and HbA1c levels were monitored, while the hypoglycemic effects of FMT were also observed. Insulin levels were tested by ELISA and related indexes such as HOMA-IR, HOMA-IS, and HOMA-β were calculated. We found that insulin resistance and pancreatic islet β-cells were improved after FMT treatment. Meanwhile, the markers of inflammation in the pancreatic tissue were detected by ELISA and immunohistochemistry, which indicated that inflammatory response decreased following FMT treatment. Furthermore, flow cytometry and western blot results revealed that FMT inhibited the β-cell apoptosis. Here, the effect of FMT on hypoglycemia in type 2 diabetes was addressed by improving insulin resistance and repairing impaired islets, thereby providing a potential treatment strategy for type 2 diabetes.

Hypoglycemic effects and modulation of gut microbiota of diabetic mice by saponin from Polygonatum sibiricum.

Polygonatum sibiricum is a medicinal and homologous plant grown in China, which is commercially available without the provision of medical prescription. Saponin is one of the biologically active components of Polygonatum sibiricum. This study aimed to extract saponin from Polygonatum sibiricum (PSS) and to investigate its hypoglycemic effect and effect on gut micorbiota in diabetic mice. Through single factor and orthogonal experiments, the extraction conditions of saponin were optimized, and the content of saponin in the extract was 3.07 ± 0.02 mg g-1. During the experiment evaluating the hypoglycemic ability, it was found that PSS could inhibit the activity of α-amylase and α-glucosidase at first. Then, HepG2 was used to observe the effect of the saponin on insulin resistance. The results showed that PSS could significantly improve the state of insulin resistance in IR-HepG2 cells, increase the glucose consumption and intracellular glycogen content of cells, and the activity of hexokinase (0.455 ± 0.007 μmol min-1 g-1) and pyruvate kinase (0.174 ± 0.038 U per g prot). Finally, it was found that PSS could alleviate the symptoms of polyphagia and polydipsia in diabetic mice, regulate the gut microbiota of diabetic mice, increase the number of probiotics, and reduce the number of harmful bacteria. In summary, PSS may play an important role in regulating diabetes and can be developed as a promising natural material for diabetes prevention and treatment.

BuZangTongLuo decoction improved hindlimb ischemia by activating angiogenesis and regulating gut microbiota in diabetic mice.

Seven traditional medicinal plants (including Astragalus membranaceus, Dioscorea hemsleyi, Salvia miltiorrhiza, Scrophularia ningpoensis, Ophiopogon japonicus, Panax ginseng and Fritillariae cirrhosae) and one insect leech (Whitmania pigra Whitman) were combined into BuZangTongLuo formula (BZTLF) under the guidance of traditional Chinese medicine. BZTLF is potentially effective against diabetic vascular complications. Previous studies failed to clarify the molecular mechanism through which BZTLF suppressed diabetic ischemia. In this study, we aimed to explore whether BZTLF treatment could prevent the occurrence of type 2 diabetic (T2D) hindlimb ischemia in mice. Further, we investigated the regulatory effect of BZTLF on angiogenesis-related VEGF signaling pathway and gut microbiota dysfunction in diabetic ischemia mice. C57BL/6J mice fed with high-fat diet (HFD) received STZ injection and femoral artery ligation to build T2D diabetic hindlimb ischemia model. Mice were gavaged with BZTLF (5 g [raw materials]/kg/d) or with metformin plus atorvastatin for three weeks. Laser doppler imaging system was utilized for the visualization of blood flow. Histochemistry analysis was performed for microvascular vessel staining. Western blot was applied to detect the protein changes of signaling molecules responsible for VEGF pathway. Finally, 16S rDNA gene sequencing was conducted for analysis of gut microbiota structure. BZTLF treatment remarkably restored blood flow and capillary density of diabetic hindlimb ischemia. And the protein changes of VEGF signaling molecules were reversed in BZTLF-treated diabetic ischemia mice, including the decreased VEGF and HIF-1α, and the increased NO, eNOS and p-ERK1/2. The gut microbiota analysis suggests that BZTLF treatment increased the abundances of several beneficial bacteria (Akkermansia, Bifidobacterium and Bacteroides), while decreased the populations of some harmful bacteria(Blautia, Weissella, Escherichia Shigella and Kurthia). By using Spearman's correlation analysis, these changed gut flora were positively/negatively correlated with VEGF signaling pathway or glycometabolic parameters. BZTLF displayed beneficial effects on diabetic hindlimb ischemia by reshaping the gut microbiota structure and stunning the VEGF/HIF-1α pathway.

Changes in Intestinal Microbiota of Type 2 Diabetes in Mice in Response to Dietary Supplementation With Instant Tea or Matcha.

Gut microbiota plays a key role in metabolism and health in diabetes patients with gastrointestinal microbiota dysbiosis. Thus, regulating the ecological balance of gut microbiota may provide a pathway toward improvement for these patients. Our previous study showed that functional ingredients in tea may inhibit cornstarch digestion invitro. A cornstarch-tea diet was developed, and in this study we investigated the effects of such a diet on blood glucose and gut microbiota in diabetic mice. Diabetes resulted in significant weight loss, hyperphagia and hyperglycemia. 16S rDNA sequencing revealed that in diabetes there is significantly increased Bacteroidaceae, Helicobacteraceae, Ruminococcaceae, Enterobacteriaceae, Rikenellaceae and Saccharibacteria_genera_incertae_sedis, and significantly decreased Lactobacillaceae, Prevotellaceae, Coriobacteriaceae, Verrucomicrobiaceae and Bifidobacteriaceae. The cornstarch‒tea diet resulted in a trend toward reduced blood glucose, with particularly increased levels of Coriobacteriaceae, Lactobacillaceae, Prevotellaceae and Bifidobacteriaceae, and decreased Bacteroidaceae, Ruminococcaceae, Helicobacteraceae and Enterobacteriaceae. Instant tea and matcha supplementation had beneficial effects on regulation of blood glucose and gut microbiota, reversing the changes in microbiota caused by alloxan injection. The cornstarch‒tea regulation pathway is involved in bacterium group regulation rather than single-species regulation, which suggests that cornstarch combined with tea may be used as a functional food supplement for diabetes patients.

Edgeworthia gardneri (Wall.) Meisn. water extract improves diabetes and modulates gut microbiota

Ethnopharmacological relevanceIn Chinese folk medicine, the flower of Edgeworthia gardneri (Wall.) Meisn. is used to treat various metabolic diseases, such as hyperglycemia, hypertension, and hyperlipidemia. Aim of the studyThis study aimed to explore the antidiabetes potential of the flower of E. gardneri and investigate whether it can benefit the entire gut bacteria community. Materials and methodsChemical constituents of the extract were analyzed by UHPLC-Q Exactive Mass Spectrometer (UHPLC-QE-MS). The antidiabetes effect of the water extract (WAE) of the flower of E. gardneri was evaluated in diabetic mice induced by high-fat diet (HFD) and streptozotocin (STZ) (six groups, n = 8) daily at doses of 1, 2, and 3 g/kg for 4 weeks. The gut microbiota was analyzed using high-throughput 16S rRNA gene sequencing. Short-chain fatty acids (SCFAs) in the fecal were also investigated. ResultsUHPLC-QE-MS analysis identified 29 compounds, including five alkaloids, six coumarins, four flavonoids, 11 organic acids, and three additional compounds, in the WAE. Results showed that the high dose of WAE considerably decreased the blood glucose level by 30.0%. Furthermore, E. gardneri significantly ameliorated insulin resistance and lipid metabolism dysfunction and repaired islet, hepatic, and white fat and colon histology in diabetic mice. Diabetic mice treated with WAE showed apparent changes in the structure and composition of the gut microbiota. WAE reversed the changes in Clostridiales, Lachnospiraceae, S24-7, Rikenellaceae, and Dorea in diabetic mice. The correlation analysis indicated that key OTUs were related to diabetes indices. The amounts of SCFAs, including acetic, propionic, and valeric acids, were significantly high in WAE-treated diabetic groups. ConclusionsE. gardneri treatment improved the glucose metabolism and reshaped the unbalanced gut microbiota of diabetic mice. Our study provides evidence for application of E. gardneri to treatment of diabetes mellitus.

The Effect of Chitooligosaccharides on Gut Microbiota in Diabetic Mice

Chitooligosaccharides (COS) has an effect to reduce blood glucose and blood lipids and is used in adjuvant therapy for diabetes mellitus (DM), which is closely associated with gut microbiota. Therefore, it is worthy investigating whether COS exerts its effect via the gut microbiota. In this paper, we studied the response of gut microbiota in diabetic mice to COS, using the high-throughput sequencing technology. We found that COS had significant effect on the community structure of gut microbiota in mice though it had no significant effect on the α-diversity of gut microbiota; the abundance of Ac-tinobacteria was increased significantly in the gut tract of mice fed with COS (P

A polysaccharide extracted from Astragalus membranaceus residue improves cognitive dysfunction by altering gut microbiota in diabetic mice

A novel polysaccharide named as AERP was extracted from industrial Astragalus membranaceus-extracted waste residue, which was composed of two components coded as AERP1 and AERP2. The structures of AERP1 and AERP2 were determined by HPLC-SEC-RID, HPLC-C18-UV, FT-IR, and NMR. The results showed that AERP1 was an acidic component with a molecular weight of 2.01 × 106 Da and glycosidic bonds of →3/5-α-araf-(1→, T-α-araf, →4,6-β-manp-(1→, →3/3,6-β-galp-(1→, →2/2,4-α-rha-(1→, →-4/4,6-α-glcp-(1→, →4-α-galpA-(1→ and →4)-6-OMe-α-galpA-(1→. AERP2 was a glucan with 2.11 × 103 Da by →4/6-α-glcp-(1→ linkage. In vitro, AERP retarded glucose diffusion significantly than each single component. In vivo, AERP had a hypoglycemic effect on db/db diabetic mice by alleviating the hyperglycemia, tissue impairment, and inhibiting cognitive impairment. AERP could alter the gut microbiota and modulate the composition of SCFAs. This study gives an opportunity for exploring the industrial waste of Astragalus membranaceus in diabetic complication therapy.

Chitosan oligosaccharides improve the disturbance in glucose metabolism and reverse the dysbiosis of gut microbiota in diabetic mice

The aim of this study is to investigate the effect of chitosan oligosaccharides (COS) on type 2 diabetes mellitus. Wild type C57BL/6J mice or diabetic db/db mice were treated with vehicle or COS for three months. COS treatment significantly decreased the blood glucose (P < 0.01) and reversed the insulin resistance (P < 0.05) in db/db mice, which was accompanied by suppressing the inflammation mediators (P < 0.05), down-regulating the lipogenesis (P < 0.01) and inhibiting the adipocyte differentiation (P < 0.05) in white adipose tissue. Additionally, COS treatment inhibited the reduction of occludin (P < 0.01) and relieved the gut dysbiosis in diabetic mice by promoting Akkermansia (P < 0.01) and suppressing Helicobacter (P < 0.05). Spearman's correlation analysis indicates that the COS-modulated bacteria are positively correlated with inflammation, hyperglycemia and dyslipidemia. The functional profiling based on the microbiota composition implicated that COS treatment may regulate the metabolic pathways of gut microbiota. In summary, COS treatment remarkably improved the glucose metabolism and reshaped the unbalanced gut microbiota of diabetic mice. Our study provided the evidence for application of COS to the treatment of diabetes mellitus.