The type 2 diabetes drug metformin is thought to reduce hepatic glucose production. Here, Bauer and colleagues propose a novel mechanism for this, involving the gut microbiome and its regulation of the sodium glucose co-transporter 1 (SGLT1).

In rats, a glucose load infused into the lumen of the upper small intestine reduced glucose production. This effect was dependent upon SGLT1. Three days of a high-fat diet (HFD) reduced SGLT1 expression in the intestinal mucosa, and thus impaired glucose sensing. Both were restored with metformin pretreatment.

At the same time, the team characterised the microbiome of the upper small intestine. Compared with normal diet, an HFD reduced levels of the Lactobacillaceae family, and increased abundance of the Clostridiaceae, Enterobacteriaceae and Pseudomonadaceae families, amongst others. Metformin pretreatment changed the population, increasing the abundance of some Lactobacillus species.

When transplanted into HFD recipients, the microbiome of metformin-pretreated donors was associated with increased SGLT1 expression and improved glucose sensing, compared with salinepretreated donors. This effect was lost when small intestine SGLT1 was knocked down. Here are more reasons to take care of your microbiome!

Read the full article in Cell Metabolism 27 101–117