Lately, an increasing number of studies have investigated the relationship between
metformin and gut microbiota, suggesting that
metformin exerts part of its
hypoglycemic effect through the microbes. However, its underlying mechanism remains largely undetermined. In the present study, we investigated the effects of
metformin on gut microbiota and metabolome profiles in serum and compared it with
insulin treatment in rats with
type 2 diabetes mellitus (T2DM). Diabetic rats (DM group) were induced by a combination of
streptozotocin and high-fat diet (HFD). After 7 days, DM rats were treated with
metformin (MET group) or
insulin (INS group) for 3 weeks. The
16S rRNA sequencing of the gut microbiota and non-targeted metabolomics analysis of serum were conducted. A total of 13
bile acids (BAs) in serum were further determined and compared among different groups. The rat model of T2DM was well established with the typical diabetic symptoms, showing significantly increased
blood glucose, AUC of OGTT, HOMA-IR, TC, TG,
LDL-C and TBA.
Metformin or
insulin treatment could ameliorate symptoms of diabetes and partly recover the abnormal biochemical indicators. Compared with DM rats, the relative abundances of 13 genera were significantly changed after
metformin treatment, while only three genera were changed after
insulin treatment. The
metformin and
insulin treatments also exhibited different serum metabolome profiles in T2DM rats. Moreover, 64 differential metabolites were identified between MET and DM groups, whereas 206 were identified between INS and DM groups.
Insulin treatment showed greater influence on
amino acids,
glycerophospholipids/glycerolipids, and
acylcarnitine compared with the
metformin treatment, while
metformin had an important impact on BAs. Furthermore,
metformin could significantly decrease the serum levels of CA, GCA, UDCA, and GUDCA, but increase the level of TLCA in DM rats.
Insulin treatment significantly decreased the levels of CA, UDCA, and CDCA. Besides, several metabolites in serum or microbiota were positively or negatively correlated with some bacteria. Collectively, our findings indicated that
metformin had a stronger effect on gut microbiota than
insulin, while
insulin treatment showed greater influence on serum metabolites, which provided novel insights into the
therapeutic effects of
metformin on diabetes.