Dataset Information

Combination of Oligofructose and Metformin Alters the Gut Microbiota and Improves Metabolic Profiles, Contributing to the Potentiated Therapeutic Effects on Diet-Induced Obese Animals.

ABSTRACT: Accumulating studies implicate that the metformin (MET)- and oligofructose (OFS)-altered gut microbiota may play roles in the improvement of type 2 diabetes mellitus (T2DM) and obesity. However, whether the combined administration of OFS and MET could effectively affect the gut microbiota and improve metabolic profiles remains unknown. Here, we randomized diet-induced obesity (DIO) rats to OFS, MET, or MET+OFS for 8 weeks and demonstrated that the combined administration of OFS+MET possessed potentiated effects on the glycemia, body weight, and gut microbiome. In addition, fecal samples from the MET and MET+OFS group were exchanged and transferred to germ-free rats induced by antibiotics. Not surprisingly, the glucose tolerance and serum levels of endotoxin, free fatty acids (FFA), tumor necrosis factor-? (TNF-?), interleukin-2 (IL-2), and interleukin-6 (IL-6) were all sustainably improved among OFS+MET fecal microbiota-treated DIO rats while the MET fecal microbiota-treated ones presented a relatively reverse trend. Furthermore, transfer of fecal samples from the rats after 8 weeks of treatment to antibiotics-treated germ-free mice significantly improved metabolic profiles, including glucose tolerance and weight reduction in mice that received MET+OFS-altered microbiota. In conclusion, the present study illustrated that the effects of OFS and MET combined treatment on gut microbiota, especially for the MET-induced side effect-related ones, and host metabolism were of greater magnitude than individual OFS or MET treatment in obese rats and mice. Therefore, it is likely that combined administration of OFS and MET may offer a novel and promising strategy for reducing side effects induced by MET and improving metabolic outcomes, particularly glycemia control and weight reduction.

SUBMITTER: Li Q

PROVIDER: S-EPMC7052043 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Combination of Oligofructose and Metformin Alters the Gut Microbiota and Improves Metabolic Profiles, Contributing to the Potentiated Therapeutic Effects on Diet-Induced Obese Animals.

Li Qingzhong Q He Rui R Zhang Fengmei F Zhang Jian J Lian Shihai S Liu Hongxia H

Frontiers in endocrinology 20200225

Accumulating studies implicate that the metformin (MET)- and oligofructose (OFS)-altered gut microbiota may play roles in the improvement of type 2 diabetes mellitus (T2DM) and obesity. However, whether the combined administration of OFS and MET could effectively affect the gut microbiota and improve metabolic profiles remains unknown. Here, we randomized diet-induced obesity (DIO) rats to OFS, MET, or MET+OFS for 8 weeks and demonstrated that the combined administration of OFS+MET possessed pot ...[more]

PMID: 32158428

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Project description:Emerging evidence has consistently shown that a very low carbohydrate diet (VLCD) can protect against the development of obesity, but the underlying mechanisms are not fully understood. Here we applied a comprehensive metabonomics approach using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry and gas chromatography-time-of-flight mass spectrometry to study the effects of an 8-week dietary intervention with VLCD on serum metabolic profiles in obese subjects. The VLCD intervention resulted in a weight loss and significantly decreased homeostasis model assessment-insulin resistance. The metabonomics analysis identified a number of differential serum metabolites (p < 0.05) primarily attributable to fatty acids, amino acids including branched chain amino acids, amines, lipids, carboxylic acids, and carbohydrates in obese subjects compared to healthy controls. The correlation analysis among time, VLCD intervention, and clinical parameters revealed that the changes of metabolites correlated with the changes of clinical parameters and showed differences in males and females. Fatty acids, amino acids, and carboxylic acids were increased in obese subjects compared with their normal healthy counterparts. Such increased levels of serum metabolites were attenuated after VLCD intake, suggesting that the health beneficial effects of VLCD are associated with attenuation of impaired fatty acid and amino acid metabolism. It also appears that VLCD induced significant metabolic alterations independent of the obesity-related metabolic changes. The altered metabolites in obese subjects post-VLCD intervention include arachidonate, cis-11,14-eicosadienoate, cis-11,14,17-eicosatrienoate, 2-aminobutyrate, acetyl-carnitine, and threonate, all of which are involved in inflammation and oxidation processes. The results revealed favorable shifts in fatty acids and amino acids after VLCD intake in obese subjects, which should be considered biomarkers for evaluating health beneficial effects of VLCD and similar dietary interventions.

Project description:Background/aimsObesity, which is related to increased oxidative stress in various tissues, is a risk factor for male infertility. Metformin is reported to have an antioxidant effect; however, the precise role of metformin in obesity-induced male infertility remains unknown. The current study is aimed at exploring the effects of metformin and characterizing its underlying mechanism in the fertility of obese males.MethodsAn obese male mouse model was generated by feeding mice with a high-fat diet; then, the mice were administered metformin in water for 8 weeks. Reproductive ability, metabolic parameters, and follicle-stimulating hormone (FSH) were assessed by cohabitation, enzymatic methods, and ELISA, respectively. Damage to the integrity of the blood-testis barrier (BTB), which ensures spermatogenesis, was assessed by transmission electron microscopy and immunofluorescence with a biotin tracer. Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were employed for the assessments of oxidative stress. BTB-related proteins were measured by immunoblotting. Nuclear factor κB (NF-κB) was assessed by immunofluorescence.ResultsHigh-fat-diet-fed mice presented evident lipid metabolic disturbances, disrupted BTB integrity, and decreased reproductive function. Metformin alleviated the decrease in male fertility, decreased ectopic lipid deposition in the testis, and increased serum FSH levels. A further mechanistic analysis revealed that metformin ameliorated the high-fat-diet-induced injury to the BTB structure and permeability and restored the disordered BTB-related proteins, which might be associated with an improvement in oxidative stress and a recovery of NF-κB activity in Sertoli cells (SCs).ConclusionMetformin improves obese male fertility by alleviating oxidative stress-induced BTB damage. These findings provide new insights into the effect of metformin on various diseases and suggest future possibilities in the treatment of male infertility.

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Dataset Information

Combination of Oligofructose and Metformin Alters the Gut Microbiota and Improves Metabolic Profiles, Contributing to the Potentiated Therapeutic Effects on Diet-Induced Obese Animals.

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Combination of Oligofructose and Metformin Alters the Gut Microbiota and Improves Metabolic Profiles, Contributing to the Potentiated Therapeutic Effects on Diet-Induced Obese Animals.

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