Type 2 Diabetes, Insulin Resistance and your Gut Microbiota
I found the connection to Type 2 diabetes (T2D) and dysbiosis interesting! Therefore this blog is a bit lengthy because I wanted to dive some more into this, as I find it fascinating. (Also my mom is dealing with T2D so I also partially researched it for her too!)
A study by Han et. al indicated that intestinal microbiota does have a role in the pathogenesis of T2D. “Intestinal microbiota may play an important role in the pathogenesis of T2DM by influencing body weight, bile acid metabolism, proinflammatory activity and insulin resistance, and modulation of gut hormones” (Han & Lin, 2014). Researchers have found that the ratio of Firmicutes and Bacteroidetes and also some showed dysbiosis in the levels of Clostridia. Patients in the pre-diabetic group had a significantly increased level of Betaproteobacteria compared to the normal glucose group. Across the board people with T2D demonstrate having a reduction in butyrate producing bacteria, increase in opportunistic pathogens, and interesting an overgrowth of Lactobacillus (Han & Lin, 2014). Researchers also detected to rate of live gut bacteria to be higher in the T2D group than control, which may indicate bacterial translocation. Elevated plasma LPS concentration in mice induced by high-fat feeding is defined as metabolic endotoxemia. Consequently, a high-fat diet (as seen in mice) can significantly alters intestinal microbiota composition, induce metabolic endotoxemia, increase blood glucose and insulin that contribute to weight gain. LPS can also stimulate NF-KB transcription factors and increase expression of numerous mediators of inflammation that can stimulate insulin resistance. “Therefore, the metabolic endotoxemia induced by LPS derived from the gut microbiota is associated with inflammation and insulin resistance” (Han & Lin, 2014).
Over the past decade, a growing body of evidence has shown that bile acids play an important role in glucose metabolism. Therefore, patients with T2D should be evaluated for their bile acid production which can be detected through various stool tests. I found it interesting that bile acids contribute to suppression of bacterial colonization and have a strong antimicrobial function in the gut.
Since increasing endotoxemia is correlated with increased gut permeability, modulating gut microbiota with probiotics and prebiotics can improve gut permeability, reduce metabolic endotoxemia, lower inflammation and alleviate glucose intolerance. Modulation of the intestinal microbiota with specific strains of probiotics can also upregulate CB2 receptor expression as seen in mice. A specific strain Akkermansia muciniphila (A. muciniphila), a mucin degrading bacterium that colonizes the gut can reduce body fat, metabolic endotoxemia, low-grade inflammation, and insulin resistance. Ways to increase this strain is through fasting and also prebiotics such as inulin and those found in certain foods such as kiwifruit. Other probiotics such as VSL#3 and prebiotics demonstrated the ability to stimulate short chain fatty acids that produce gut hormones such as GLP-1. “Many investigations have demonstrated that prebiotics increase release of GLP-1 and improve the metabolic inflammation and insulin resistance induced by a high-fat diet” (Han & Lin, 2014). Changes of microbiota from ingestion of prebiotics, as seen in laboratory studies, also promoted a significant release of other gut hormones such as GPL-2 and Peptide YY which has also been shown to enhance insulin sensitivity. “Rats receiving a diet supplemented with oligofructose, oligofructose-enriched inulin or high-molecular weight inulin demonstrated an increase in portal serum levels of GLP-1 and PYY” (Han & Lin, 2014). In an animal study, researchers observed that a fermented milk product containing probiotic bacteria significantly delayed the onset of glucose intolerance, hyperglycemia, and hyperinsulinemia in diabetic rats induced by high fructose concentration.
And finally, antimicrobials seem to have a positive role in modulating gut bacteria in favor of insulin sensitivity. The enhanced insulin sensitivity was independent of food intake, weight loss, or adiposity. Berberine, one of the main ingredients of a Chinese traditional herb used to treat bacterial diarrhea, improves glycemia. “Berberine is a potent oral hypoglycemic agent with modest effect on lipid metabolism” (Yin, Xing, & Ye, 2008). The antimicrobial activity of berberine and its modulation of the gut microbiota may play a role in the antidiabetic effect of this herb. The hypoglycemic effect of berberine was reported in 1988 when it was used to treat diarrhea in diabetic patients in China (Yin et al., 2008). Since then, berberine has often been used as an antihyperglycemic agent by many physicians in China. In a pilot study, berberine significantly decreased HbA1c levels in diabetic patients, as compared to metformin. Berberine also decreased serum triglyceride and total cholesterol significantly. In combination with other agents, berberine exhibited consistent activities in improvement of glycemic and lipid parameters in diabetic patients, such as improved insulin sensitivity. It is thought that berberine has an insulin sensitizing effect. “Berberine enhancing glucose metabolism may be due to stimulation of glycolysis, which is related to inhibition of oxidation in mitochondria” (Yin et al., 2008)
Han, J. L., & Lin, H. L. (2014). Intestinal microbiota and type 2 diabetes: from mechanism insights to therapeutic perspective. World J Gastroenterol, 20(47), 17737-17745. doi:10.3748/wjg.v20.i47.17737
Yin, J., Xing, H., & Ye, J. (2008). Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism, 57(5), 712-717. doi:10.1016/j.metabol.2008.01.013