Abstract
Berberine (BBR) has the beneficial effects of anti-inflammation, anti-bacteria, and anti-diabetes. The clinical application of BBR has been hindered by its poor gastrointestinal absorption. Stachyose (Sta), a prebiotic agent, improves the composition of gut microbiota and benefits for diabetes. We therefore investigated whether Sta improves the anti-diabetic actions of BBR using KKAy mice. Here, we find that the combination of BBR and Sta is more effective than BBR alone in blood glucose control, improvement of insulin resistance and islet functions, inflammatory mediators decrease, and maintenance of intestinal barrier integrity. Gut microbiota analysis demonstrates that both BBR and combined administration enhance the abundance of Bacteroidaceae and Akkermansiaceae and decrease Lachnospiraceae levels, whereas Akkermansiaceae elevation due to the administration of BBR with Sta is more significant than BBR alone. Interestingly, the proportion of Lactobacillaceae increases with combination treatment, but is diminished by BBR. Additionally, BBR with Sta significantly reduces the concentrations of fecal short-chain fatty acids compared to BBR. Collectively, these results indicate that the combination of BBR and Sta imparts better effects on the maintenance of glycemia and intestinal homeostasis than BBR alone by modulating gut microbiota and short-chain fatty acids, thereby providing a novel approach for the treatment of type 2 diabetes mellitus.
Highlights
Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by obesity, insulin resistance, chronic hyperglycemia, low-grade inflammation, alteration of gut microbiota, and islet β cell dysfunction (Schwarz et al, 2013)
This study aimed to investigate the effects and mechanisms of BBR combined with Sta on glucose metabolism, inflammation modulation, intestinal integrity, fecal short-chain fatty acids (SCFAs), and gut microbiota in diabetic KKAy mice
We found that the levels of blood glucose and HbA1c in mice treated with either BBR or BBR+Sta were significantly decreased compared to control mice (Figures 1A,B)
Summary
Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by obesity, insulin resistance, chronic hyperglycemia, low-grade inflammation, alteration of gut microbiota, and islet β cell dysfunction (Schwarz et al, 2013). Several studies have shown that BBR has many advantageous biological roles in preclinical and clinical research, such as antiinflammation, anti-insulin resistance, anti-hyperglycemia, antihyperlipidemia, anti-bacteria, and anti-diabetes (Chang et al, 2015b; Li et al, 2019; Neag et al, 2018). BBR ameliorates liver, cardiovascular, and renal disease that are associated with diabetes (Chang et al, 2015b; Neag et al, 2018). This evidence suggests that BBR is a potential drug for the treatment of T2DM (Belwal et al, 2020). BBR may result in gastrointestinal reactions (including diarrhea and constipation) in some patients due to its poor absorption, thereby limiting its long-term and wide application in T2DM management (Chang et al, 2015b; Imenshahidi and Hosseinzadeh, 2019)
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