Abstract
Accumulating evidence suggests that the gut microbiota is an important factor in mediating the development of obesity-related metabolic disorders, including type 2 diabetes. Metformin and berberine, two clinically effective drugs for treating diabetes, have recently been shown to exert their actions through modulating the gut microbiota. In this study, we demonstrated that metformin and berberine similarly shifted the overall structure of the gut microbiota in rats. Both drugs showed reverting effects on the high-fat diet-induced structural changes of gut microbiota. The diversity of gut microbiota was significantly reduced by both berberine- and metformin-treatments. Nearest shrunken centroids analysis identified 134 operational taxonomic units (OTUs) responding to the treatments, which showed close associations with the changes of obese phenotypes. Sixty out of the 134 OTUs were decreased by both drugs, while those belonging to putative short-chain fatty acids (SCFA)-producing bacteria, including Allobaculum, Bacteriodes, Blautia, Butyricoccus, and Phascolarctobacterium, were markedly increased by both berberine and, to a lesser extent, metformin. Taken together, our findings suggest that berberine and metformin showed similarity in modulating the gut microbiota, including the enrichment of SCFA-producing bacteria and reduction of microbial diversity, which may contribute to their beneficial effects to the host.
Highlights
Chinese medicine), berberine has long been used to treat intestinal infection-related diarrhea in China[16], and has recently been proven to be clinically effective in treating type 2 diabetes (T2D), dyslipidemia and hypercholesterolemia[13,17]
This study provides a direct comparison for the modulations of gut microbiota structure by the treatments of berberine and metformin, which may help to improve our understanding on the host-microbe interactions during the treatment of metabolic diseases and the mechanisms of the two drugs
We found that the fecal microbiota of high-fat diet (HFD)-fed rats obviously changed during the treatments of berberine and metformin, which is in agreement with previous individual studies for these two drugs[10,15]
Summary
Chinese medicine), berberine has long been used to treat intestinal infection-related diarrhea in China[16], and has recently been proven to be clinically effective in treating T2D, dyslipidemia and hypercholesterolemia[13,17]. Introduction of the Akkermansia spp. into the gut of diet-induced obese mice improved the host glucose homeostasis[10], suggesting that the modulation of the gut microbiota may be one of the mechanisms contributing to the antidiabetic effects of metformin. Napolitano et al demonstrated that the human gut microbiome in T2D patients was modified by the treatments of metformin, and these changes were closely associated with the alterations of entero-hepatic recirculation of bile acids and gut hormones[22] These findings suggest that the gastrointestinal tract is an important target of metformin. This study provides a direct comparison for the modulations of gut microbiota structure by the treatments of berberine and metformin, which may help to improve our understanding on the host-microbe interactions during the treatment of metabolic diseases and the mechanisms of the two drugs
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