Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats - PubMed (original) (raw)

Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats

Xu Zhang et al. Sci Rep. 2015.

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.

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Figures

Figure 1

Figure 1. Anti-obesity effects of berberine and metformin in high-fat diet-induced obese rats.

(a) Body weight; (b) Adiposity index, calculated according to the following formula: 100 × (epididymal fat weight + perirenal fat weight)/body weight. Differences were assessed by one-way ANOVA, *P < 0.05, **P < 0.01, **P < 0.001.

Figure 2

Figure 2. Diversity and richness of the gut microbiota in rats.

(a–c) shows the Rarefaction curves at 0th, 8th and 18th week, respectively; (e–g) shows the Shannon curves at 0th, 8th and 18th week, respectively; (d,h) shows the Rarefaction OTU estimates and Shannon index of each group at the 18th week after rarefying the sequencing depth to 1500 for all the samples. Values are expressed as means ± standard error. Differences were assessed by ANOVA and denoted as follows: ***P < 0.001; NS not significant.

Figure 3

Figure 3. Responses of the structure of the gut microbiota to berberine and metformin during the treatments of obesity in rats.

(a) PCA score plot; PCoA score plot based on unweighted (b) and weighted (c) UniFrac metrics. Clustering of the group means based on the Mahalanobis distances calculated using MANOVA based on the PCA (d), unweighted UniFrac PCoA (e) and weighted UniFrac PCoA (f). P values were indicated as: *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 4

Figure 4. Heatmap of 134 most predictive OTUs.

The color of the spot corresponds to the normalized and log-transformed relative abundance of the OTUs. The OTUs are organized according to their phylogenetic positions. The taxonomic assignment of each OTU was determined by RDP classifier and the genus name was labeled in the graph.

Figure 5

Figure 5. Modulations of Allobaculum by berberine and metformin.

Each spot of the heatmap corresponds to the normalized and log-transformed relative abundance of the OTU in each sample. The OTUs are organized according to their phylogenetic positions. The home-defined subgroup names (A1, A2, A3, A4 and A5) were labeled according to their phylogenetic positions and distributions among groups.

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