The mechanism of berberine alleviating metabolic disorder based on gut microbiome

Abstract

With socioeconomic advances and improved living standards, metabolic syndrome has increasingly come into the attention. In recent decades, a growing number of studies have shown that the gut microbiome and its metabolites are closely related to the occurrence and development of many metabolic diseases, and play an important role that cannot be ignored, for instance, obesity, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cardiovascular disease and others. The correlation between gut microbiota and metabolic disorder has been widely recognized. Metabolic disorder could cause imbalance in gut microbiota, and disturbance of gut microbiota could aggravate metabolic disorder as well. Berberine (BBR), as a natural ingredient, plays an important role in the treatment of metabolic disorder. Studies have shown that BBR can alleviate the pathological conditions of metabolic disorders, and the mechanism is related to the regulation of gut microbiota: gut microbiota could regulate the absorption and utilization of berberine in the body; meanwhile, the structure and function of gut microbiota also changed after intervention by berberine. Therefore, we summarize relevant mechanism research, including the expressions of nitroreductases-producing bacteria to promote the absorption and utilization of berberine, strengthening intestinal barrier function, ameliorating inflammation regulating bile acid signal pathway and axis of bacteria-gut-brain. The aim of our study is to clarify the therapeutic characteristics of berberine further and provide the theoretical basis for the regulation of metabolic disorder from the perspective of gut microbiota.

Keywords: berberine; diabetes; gut microbiota; metabolic disorder; obesity.

Figure 1

Chemical structural formula of Berberine (BBR).

Figure 2

Mechanism of action of Berberine in modulating Gut Microbioata. Increasing of the NR-producing bacteria: BBR can increase th abundance of Bacteroides, Escherichia-Shigella and Bifidobacterium which can produc NRs. Nrs converts BBR into its absorbable form of DhBBR, which has highly polar and easily absorbed into the blood. Increasing of mucin-degrading-producing bacteria: BBR can increase the abundance of A.muciniphila. The increased abundance of A.muciniphila may lead to the reduction in mucin-2 expression in ileum. BBR seemed to protect the intestinal barrier integrity through modulating HMGCT, SREBP2 and CYP7A1 expressions. Decreasing of LPS-producing bacteria: BBR reduced the level of Vibrio desulfuricus and Enterobacter to inhibit the production of LPS. So that inflammatory factors (IL-1β, TNF-a IL-6, CRP in plasma Sta reduced IL-1β levels) were decreased. Increasing of SCFA-producing bacteria: BBR increased the number of SCFA producing bacteria (such as Butyricimonas, Coprococcus, Ruminococcus and Roseburia), raised the expression of pro-inflammatory cytokines, including LPS, TNF-α IL-1β and IL-6. Increasing of BAs-decomposing bacteria: BBR increased the number of BAs-decomposing bacteria (such as phylum Firmicutes, phylum Bacteroidetes, C. scindens and C. hylemonae) and reduced the level of C. hiranosis, decreased the activity of BSH. The possible mechanism is to Up-regulate Na+/H+ antiporter, up-regulate colonic TGR5 expression and GLP secretion and to increase CYP7A1 and CYP27A1 expression. Regulating microbiota-gut-brain axis: BBR increases the propotion of Bacteroidetes and Firmicutes, increases the expression of serum GLP-1, GLP-2, increase of the number of L.cells.