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Metformin increases A. muciniphila in patients with type 2 diabetes
Metformin was associated with a greater abundance of mucin-degrading Akkermansia muciniphila in the gut, researchers in Colombia found.
The drug was also associated with an increase in several other microbiota.
“Recent studies in animals and humans provide evidence that metformin may partially restore gut dysbiosis associated with type 2 diabetes,” Jacobo de la Cuesta-Zuluaga, of Grupo Empresarial Nutresa, Medellin, Colombia, and colleagues wrote. “In mice fed a high-fat diet, metformin treatment increased the relative abundance of Akkermansia muciniphila, a mucin-degrading bacterium that has been shown to reverse metabolic disorders. In humans, participants with diabetes taking metformin had similar abundance of Subdoligranulum and, to some extent, Akkermansia compared with control subjects without diabetes, suggesting that metformin may help ameliorate a type 2 diabetes-associated gut microbiome.”
Researchers matched 28 Colombian adults with type 2 diabetes, 14 of whom were taking metformin, with 84 participants without diabetes. Cuesta-Zuluaga and colleagues recorded anthropometry, demographic information and blood biochemical data in addition to collecting fecal samples to analyze the participants’ gut microbiota.
When researchers pooled mucin-degrading and butyrate-producing microbes, they reported that patients with diabetes who took metformin had 3.4 times more A. muciniphila (F1, 109 = 9.46; P = .003) and 4.4 times more Butyrivibrio (F1, 109 = 3.03; P = .08) than patients with diabetes who did not take metformin. The metformin group also had higher levels of Bifidobacterium bifidum, Megasphera and an operational taxonomic unit of Prevotella. The same was true for the metformin group when compared with the nondiabetic group, Cuesta-Zuluaga and colleagues wrote.
“In our community-based sample of Colombian adults, we provide evidence consistent with previous literature that the association between gut microbiota and type 2 diabetes is modified by metformin use,” the researchers wrote. “Type 2 diabetes metformin participants had higher relative abundance of purportedly beneficial mucin-degrading and SCFA-producing bacteria compared with type 2 diabetes metformin-negative and nondiabetic participants matched on age, sex and BMI. Our study… provides evidence congruent with the hypothesis that metformin has direct effects on gut microbiota composition through augmentation of mucin-degrading A. muciniphila as well as several SCFA-producing bacteria. Randomized controlled trials are needed to determine whether the anti-diabetes and anti-inflammatory effects of metformin are mediated by the changes to gut microbiota composition.” – by Andy Polhamus
Disclosure: Cuesta-Zuluaga reports being an employee of Grupo Empresarial Nutresa. Please see the full study for a complete list of all other authors’ relevant financial disclosures.
Perspective
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Meghan Jardine
Insulin resistance and type 2 diabetes are associated with an altered microbiota. A Western dietary pattern high in saturated fat and refined carbohydrates is thought to be a major factor contributing to dysbiosis. Low dietary fiber intake provides insufficient substrates for the bacterial production of short-chain fatty acids in the colon, which have an important role in health by improving gut barrier function, glucose metabolism, satiety and fatty acid metabolism. Impaired gut barrier function associated with dysbiosis allows lipopolysaccharide to be absorbed into circulation, initiating endotoxemia and metabolic inflammation.
Metformin, the preferred initial pharmacologic agent for type 2 diabetes, reduces hepatic glucose production, improves insulin sensitivity and reduces the amount of glucose absorbed from food. This study confirms reports that metformin enhances the abundance of Akkermansia muciniphila. Populations of bacteria that produce short-chain fatty acids were also augmented in subjects taking metformin compared with those not on the drug (both those with and without type 2 diabetes). These bacteria populations contribute to a healthier gut barrier, reducing insulin resistance associated with chronic inflammation. In human studies, concentrations of A. muciniphila, a mucin-degrading bacteria, have been found to be inversely associated with obesity and insulin resistance. Might modulation of gut bacteria be a mechanism of metformin’s metabolic effects? There is evidence that intravenous metformin administration does not improve glucose control. An eating pattern that includes sufficient dietary fiber has also been shown to increase populations of both A. muciniphila and short-chain fatty acid–producing bacteria.
According to the 2017 American Diabetes Association Standard of Care, metformin therapy should be the first pharmacologic agent initiated in people with type 2 diabetes. As long as there are no contraindications, metformin is inexpensive and safe, improves glycemic control and reduces cardiovascular events and death. It should be mentioned, the ADA cautions that long-term use of metformin may be associated with vitamin B12 deficiency and periodic testing is recommended, particularly in individuals with anemia and peripheral neuropathy. More studies will reveal the mechanism by which metformin works through modulation of the gut microbiota. In addition to metformin, nutrition therapy plays an important role in gut health, as well as improving diabetes health outcomes. Clinicians should support the adoption of healthy eating patterns, containing nutrient-dense, high-quality foods, including Mediterranean, DASH and plant-based diets for their patients with diabetes.
Disclosure: Jardine reports no relevant financial disclosures.