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-α (TNF-α), 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.
Highlights
type 2 diabetes mellitus (T2DM) and obesity are both representative chronic systemic disorders of overweight and hyperglycemia mainly resulting from the genetic and environmental risk factors, including the relative lack of insulin caused by insulin resistance, high-fat and highsugar diet, and lack of exercise [1,2,3,4]
In order to investigate if the combination of OFS and MET affects the metabolism of animals, we treated the diet-induced obesity (DIO) rats with placebo, 150 mg/kg of MET, 10% OFS, and 10% OFS+150 mg/kg of MET, respectively, for 8 consecutive weeks, using the healthy rats treated with saline as normal group
Compared to the control group, weight gain and final body weight of DIO rats were significantly decreased in both MET (P < 0.05) and OFS+MET (P < 0.01) groups; the effect was not significant, though the result had the same situation in the OFS group
Summary
T2DM and obesity are both representative chronic systemic disorders of overweight and hyperglycemia mainly resulting from the genetic and environmental risk factors, including the relative lack of insulin caused by insulin resistance, high-fat and highsugar diet, and lack of exercise [1,2,3,4]. Metformin (MET), an oral blood glucose-lowering non-metabolizable compound, becomes the mainstay therapy for T2DM patients, its mechanism of action remained unclear [7, 8]. Administration of MET obviously improves the blood glucose levels and insulin resistance of individuals with T2DM by the inhibition of hepatic gluconeogenesis and opposing the action of glucagon [9]. At least 30% of T2DM patients report adverse effects including diarrhea, nausea, vomiting, and bloating, with underlying mechanisms poorly understood. These side effects severely limit the wide application prospects of MET [13,14,15]
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