scholarly journals The Impact of Rhodiola Rosea On Biomarkers of Diabetes, Inflammation, and Gut Microbiota in a Leptin Receptor-Knockout Mouse Model

2022 ◽  
Author(s):  
Mahtab Jafari ◽  
Jasmin Grace Juanson Arabit ◽  
Robert Courville ◽  
Dara Kiani ◽  
John M. Chaston ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Leptin Receptor ◽  
Insulin Response ◽  
Rhodiola Rosea ◽  
Root Extract ◽  
Receptor Knockout Mouse ◽  
The Impact

Abstract Type 2 diabetes is the most prevalent endocrine disease in the world, and recently the gut microbiota have become a potential target for its management. Recent studies have illustrated that this disease may predispose individuals to certain microbiome compositions, and treatments like metformin have been shown to change gut microbiota and their associated metabolic pathways. However, given the limitations and side effects associated with pharmaceuticals currently being used for therapy of diabetes, there is a significant need for alternative treatments. In this study, we investigated the effects of a root extract from Rhodiola rosea in a Leptin receptor knockout (db/db) mouse model of type 2 diabetes. Our previous work showed that Rhodiola rosea had anti-inflammatory and gut microbiome-modulating properties, while extending lifespan in several animal models. In this study, treatment with Rhodiola rosea improved the insulin response, and significantly decreased serum lipopolysaccharide and C-reactive protein levels. We hypothesize that these changes may in part reflect the modulation of the microbiota, resulting in improved gut barrier integrity and decreasing the translocation of inflammatory biomolecules into the bloodstream. These findings indicate that Rhodiola rosea is an attractive candidate for further research in the management of type 2 diabetes.

scholarly journals Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model

2021 ◽  
Author(s):  
Yoichiro Kashiwagi ◽  
Syunsuke Aburaya ◽  
Naoyuki Sugiyama ◽  
Yuki Narukawa ◽  
Yuta Sakamoto ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Porphyromonas Gingivalis ◽  
Alveolar Bone ◽  
Periodontal Pathogens ◽  
Periodontal Infection ◽  
Related Enzyme ◽  
Diabetes Mouse

Abstract Periodontal infection is thought to generate systemic inflammation, thus aggravating diabetes. Furthermore, orally administered periodontal pathogens may directly alter the gut microbiota. To elucidate this, using an obese db/db diabetes mice, orally treated with Porphyromonas gingivalis (Pg), we screened for Pg-specific peptides in intestinal fecal specimens and examined whether Pg localization affected the intestinal microbiota profile altering gut metabolite levels. Finally, we screened whether deterioration of fasting hyperglycemia was related to changes in intrahepatic glucose metabolism, using proteome and metabolome analyses. As results; (1) Oral Pg treatment aggravated both fasting and postprandial hyperglycemia (P < 0.05) with a significant (P < 0.01) increase in dental alveolar bone resorption. (2) Pg-specific peptides were identified in fecal specimens after oral Pg treatment and intestinal Pg profoundly altered gut microbiome profiles at the phylum, family, and genus levels. Prevotella showed the largest increase in abundance. Furthermore, Pg-treatment significantly altered intestinal metabolite levels. (3) Fasting hyperglycemia was associated with increases in gluconeogenesis-related enzyme and metabolite levels without changes in proinflammatory cytokine expressions and insulin resistance. This work reveals that oral Pg administration induced gut microbiota changes, leading to entero-hepatic metabolic derangements, thereby aggravating hyperglycemia in an obese type 2 diabetes mouse model.

scholarly journals Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoichiro Kashiwagi ◽  
Shunsuke Aburaya ◽  
Naoyuki Sugiyama ◽  
Yuki Narukawa ◽  
Yuta Sakamoto ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Porphyromonas Gingivalis ◽  
Alveolar Bone ◽  
Postprandial Hyperglycemia ◽  
Periodontal Pathogens ◽  
Periodontal Infection ◽  
Diabetes Mouse

AbstractPeriodontal infection induces systemic inflammation; therefore, aggravating diabetes. Orally administered periodontal pathogens may directly alter the gut microbiota. We orally treated obese db/db diabetes mice using Porphyromonas gingivalis (Pg). We screened for Pg-specific peptides in the intestinal fecal specimens and examined whether Pg localization influenced the intestinal microbiota profile, in turn altering the levels of the gut metabolites. We evaluated whether the deterioration in fasting hyperglycemia was related to the changes in the intrahepatic glucose metabolism, using proteome and metabolome analyses. Oral Pg treatment aggravated both fasting and postprandial hyperglycemia (P < 0.05), with a significant (P < 0.01) increase in dental alveolar bone resorption. Pg-specific peptides were identified in fecal specimens following oral Pg treatment. The intestinal Pg profoundly altered the gut microbiome profiles at the phylum, family, and genus levels; Prevotella exhibited the largest increase in abundance. In addition, Pg-treatment significantly altered intestinal metabolite levels. Fasting hyperglycemia was associated with the increase in the levels of gluconeogenesis-related enzymes and metabolites without changes in the expression of proinflammatory cytokines and insulin resistance. Oral Pg administration induced gut microbiota changes, leading to entero-hepatic metabolic derangements, thus aggravating hyperglycemia in an obese type 2 diabetes mouse model.

scholarly journals Functional characterisation of gut microbiota and metabolism in Type 2 diabetes indicates that Clostridiales and Enterococcus could play a key role in the disease

2019 ◽  
Author(s):  
Marina Mora-Ortiz ◽  
Alain Oregioni ◽  
Sandrine P. Claus
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Short Chain Fatty Acid ◽  
Microbial Composition ◽  
Functional Characterisation ◽  
Branched Chain ◽  
Acetate Butyrate

AbstractThere is growing evidence indicating that gut microbiota contributes to the development of metabolic syndrome and Type 2 Diabetes (T2D). The most widely-used model for T2D research is the leptin deficient db/db mouse model. Yet, a characterisation of the gut microbial composition in this model in relationship with the metabolism is lacking. The objectives of this study were to identify metabolomics and microbial modulations associated with T2D in the db/db mouse model. The majority of microbial changes observed included an increase of Enterobacteriaceae and a decrease of Clostridiales in diabetics. The metabolomics interrogation of caecum indicated a lower proteolytic activity in diabetics, who also showed higher Short-Chain Fatty Acid (SCFA) levels. In the case of faeces, the model identified 9 metabolites, the main ones were acetate, butyrate and Branched Chain Amino Acids (BCAAs). Finally, liver was the organ with more metabolic links with gut-microbiota followed by the Gut-Brain Axis (GBA). In conclusion, the interaction between Clostridiales and Enterococcus with caecal metabolism could play a key role in the onset and development of diabetes. Further studies should investigate whether the role of these bacteria is causal or co-occurring.

scholarly journals Leptin signaling and the intervertebral disc: Sex dependent effects of leptin receptor deficiency and Western diet on the spine in a type 2 diabetes mouse model

PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0227527 ◽  
Author(s):  
Devorah M. Natelson ◽  
Alon Lai ◽  
Divya Krishnamoorthy ◽  
Robert C. Hoy ◽  
James C. Iatridis ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Intervertebral Disc ◽  
Leptin Receptor ◽  
Western Diet ◽  
Leptin Signaling ◽  
Diabetes Mouse

scholarly journals Evaluation of Poorly-Bioavailable Cocoa Flavanols and Their Gut Microbial Metabolites in Potentiating Anti-diabetic Activities Through BTBR.Cg-Lepob/ob/WiscJ Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 361-361
Author(s):  
Kathryn Racine ◽  
Lisard Iglesias-Carres ◽  
Lauren Essenmacher ◽  
Gabriella Agnello ◽  
Jeffery Tessem ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Gain ◽  
Gut Microbiota ◽  
Significant Protection ◽  
Peripheral Tissues ◽  
Progressive Type ◽  
Males And Females ◽  
The Impact ◽  
Cocoa Flavanols

Abstract Objectives Cocoa (Theobroma cacao) is a concentrated dietary source of flavanols that have beneficial activities against type-2 diabetes. These compounds have limited small intestinal absorption and are metabolized by the microbiota to bioavailable metabolites that may exert anti-diabetic effects locally and in peripheral tissues. Our objectives were to 1) determine the role of the gut microbiome in facilitating protective effects of cocoa flavanols, and 2) evaluate these effects in a novel mouse model of progressive type-2 diabetes. Methods A small pilot study (n = 3) of male and female BTBR mice (wild-type and homozygous for the Lepob mutation) received either control or cocoa extract-supplemented diet for 10 weeks. Half the animals were administered antibiotics orally to knock down the commensal gut microbiota. Glucose and insulin tolerance tests were conducted at weeks 1 and 5 and 2 and 6, respectively. Weight gain and food intake were monitored weekly. Biomarkers of gut integrity and inflammation were assessed by ELISA. Results Baseline fasting blood glucose (FBG) levels in five-week-old homozygous males and females were measured at 211–271 mg/dL and 112–234 mg/dL, respectively. After five weeks, FBG measured at 281–438 mg/dL and 177–562 mg/dL, respectively. Cocoa provided moderate, yet not significant, protection against weight gain in homozygous males when compared to homozygous males fed control diet. Cocoa provided no significant protection against hypoglycemia in homozygous male or female mice when compared to homozygous controls. In treatment comparisons with and without antibiotics, knocking out the commensal gut microbiota appeared to have minimal effect on weight gain and glycemic control in both males and females. Conclusions Cocoa did provide a moderate level of protection for homozygous males when directly comparing weight gain and FBG across sex. While the microbiome has displayed a promising role in the bioavailability of large flavanols, in this particular model, the impact was minimal. Overall, cocoa was ineffective against the mediation of advanced diabetes and further work must be conducted to understand if this conclusion is isolated to this model of progressive type-2 diabetes. Funding Sources This work was supported by the US Department of Agriculture by AFRI grant 2020–67,017-30,846.

scholarly journals Author Correction: Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoichiro Kashiwagi ◽  
Shunsuke Aburaya ◽  
Naoyuki Sugiyama ◽  
Yuki Narukawa ◽  
Yuta Sakamoto ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Porphyromonas Gingivalis ◽  
Diabetes Mouse

scholarly journals Glycemic Control by Umbilical Cord-Derived Mesenchymal Stem Cells Promotes Effects of Fasting-Mimicking Diet on Type 2 Diabetes

2021 ◽  
Author(s):  
Na Zhao ◽  
Ying-Feng Gao ◽  
Lei Bao ◽  
Jing Lei ◽  
Huan-Xiao An ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lipid Metabolism ◽  
Glycemic Control ◽  
Umbilical Cord ◽  
Leptin Receptor ◽  
Human Umbilical Cord ◽  
The Impact

Abstract Background Hepatic steatosis is a big hurdle to treat type 2 diabetes (T2D). Fasting-mimicking diet (FMD) has been shown to be an effective intervention in dyslipidemia of T2D. However, fasting might impair the normal glucose metabolism. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) transplantation has been discovered to regulate immune reactions and reduce hyperglycemia in diabetes. However, the effects of UC-MSCs on improving the lipid metabolism disorder are not quite satisfactory. We have investigated the efficacy comparison and interaction between two typical therapies of FMD and UC-MSC infusion, aiming to pave an avenue for their synergistic use, establish effective T2D therapies and explore its mechanism.Methods C57/BL6 mice were fed with high-fat diet (HFD) for 16 weeks to induce a diet-induced obese (DIO) mouse model. Six-week-old leptin-receptor-deficient (db/db) mice were used for follow-up experiments. DIO or db/db mice were divided into 4 groups: PBS, UC-MSCs (1*106), FMD (entails 4-day FMD and 7-day of refeeding (RF)) and UC-MSCs + FMD. At the end of the study period, mice were fasted for 6 h with the measurement of blood glucose and body weight, and then sacrificed. Blood was collected to determine levels of HbA1c, serum insulin, and cytokines. In addition, the fresh liver, skin and white adipose tissue were analyzed by histology.Results FMD restored the lipid metabolism in DIO mice, whereas its capacity to rescue hyperglycemia was uncertain. Infusion of UC-MSCs was effective in T2D glycemic control but the impact on dyslipidemia was insufficient. Furthermore, both the glucose and the lipid alterations of DIO and db/db mice recovered after UC-MSCs combined with FMD. It was proved that UC-MSCs promoted FMD effects on ameliorating hyperglycemia and restoring the lipid metabolism in T2D mice, while FMD had little promotion effect on UC-MSCs. Mechanistically, we discovered that UC-MSC infusion significantly modulated systematic inflammatory microenvironment, which contributed to concerted actions with FMD.Conclusions We established a strategy that combined UC-MSC infusion and FMD were effective in treating T2D, which synergistically attenuated hyperglycemia and improved the lipid metabolism through immunoregulation. The significance of the work is to provide potential approaches for developing novel clinical T2D therapies.

scholarly journals A Pilot Study on the Metabolic Impact of Mediterranean Diet in Type 2 Diabetes: Is Gut Microbiota the Key?

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1228
Author(s):  
Shámila Ismael ◽  
Marta P. Silvestre ◽  
Miguel Vasques ◽  
João R. Araújo ◽  
Juliana Morais ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Pilot Study ◽  
Gut Microbiota ◽  
Mediterranean Diet ◽  
Dietary Intervention ◽  
Model Assessment ◽  
Bacterial Richness ◽  
Diabetes Outcome ◽  
The Impact

The Mediterranean diet (MD) has been recommended for type 2 diabetes (T2D) treatment. The impact of diet in shaping the gut microbiota is well known, particularly for MD. However, the link between MD and diabetes outcome improvement is not completely clear. This study aims to evaluate the role of microbiota modulation by a nonpharmacological intervention in patients with T2D. In this 12-week single-arm pilot study, nine participants received individual nutritional counseling sessions promoting MD. Gut microbiota, biochemical parameters, body composition, and blood pressure were assessed at baseline, 4 weeks, and 12 weeks after the intervention. Adherence to MD [assessed by Mediterranean Diet Adherence Screener (MEDAS) score] increased after the intervention. Bacterial richness increased after 4 weeks of intervention and was negatively correlated with fasting glucose levels and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Prevotella to Bacteroides ratio also increased after 4 weeks. In contrast, glycated haemoglobin (HbA1c) and HOMA-IR were only decreased at the end of study. Alkaline phosphatase activity was assessed in fecal samples and was negatively correlated with HbA1c and positively correlated with bacterial diversity. The results of this study reinforce that MD adherence results in a better glycemic control in subjects with T2D. Changes in gut bacterial richness caused by MD adherence may be relevant in mediating the metabolic impact of this dietary intervention.

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