Gut microbiota and blood glucose control

The intestinal microbiota, the set of microorganisms that inhabit our intestine, controls several aspects related to human metabolism and eating behavior. It is also closely linked to the development of metabolic pathologies such as diabetes or obesity. A new study now reveals that some intestinal bacteria produce substances with an identical function to the human enzyme DPP-4, responsible for the degradation of incretins, the hormones that control blood glucose.

This discovery opens the door to developing drugs against enzymes of bacterial origin and improving treatments for type 2 diabetes.

The study was led by the Institute of Agrochemistry and Food Technology (IATA) of the Spanish National Research Council (CSIC).

Incretins are the hormones responsible for the secretion of insulin by the pancreas when food is ingested and, therefore, responsible for the decrease in blood glucose levels. The two main incretins are gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), hormones with which DPP-4 interacts directly. IATA research shows that enzymes produced by bacteria, with identical behaviour to DPP-4, also interact with these hormones.

“Until now, we knew that the activity of dipeptidyl peptidase-4 or DPP-4 produced by human cells worsened the response to glucose, because it breaks down and inactivates the incretins responsible for the release of insulin after eating. Now we have detected that some intestinal bacteria produce a homologue of DPP-4. This is a mechanism through which the microbiota can worsen our metabolic health,” explains Marta Olivares, a CSIC researcher at IATA and one of the authors of the study.

Pharmaceutical research for the treatment of type 2 diabetes has focused on the interaction between DPP-4 and incretins, attempting to increase the lifespan of these by inhibiting the activity of the DPP-4 enzyme. “These drugs have been designed to act on human DPP-4, but we did not know that some intestinal bacteria produce enzymes that act in an identical way,” says Alfonso Benítez, a CSIC scientist at IATA and co-author of the study.

The results of the study show that, while some drugs are effective in preventing the action of the enzymes homologous to DPP-4 of the bacteria of the genus Parabacteroides merdae, other drugs have no effect on their behaviour. In other words, the inhibitors commonly used in antidiabetic therapies vary in their capacity to act against bacterial enzymes.

The research team highlights the importance of developing treatments that act against enzymes of bacterial origin. “Our discovery shows the need to incorporate this factor to achieve more effective therapies against type 2 diabetes,” concludes Benítez.

The gut microbiota influences many aspects of human health. (Illustration: Amazings / NCYT)

Gut hormones in diabetes

The overindulgence of foods rich in carbohydrates or sugars, often associated with overweight and obesity, is related to higher blood glucose levels. Glucose, our main source of energy, enters the cells thanks to insulin, a hormone released by the pancreas after eating.

Overweight and obese subjects have excess glucose in their blood as a result of consuming unhealthy diets, and require greater insulin secretion so that glucose, after food intake, enters the interior of the cells and blood glucose is reduced.

Obesity is the main risk factor for developing type 2 diabetes, which accounts for 90% of diabetes cases. It is a metabolic disorder characterized by hyperglycemia, a high level of sugar in the blood.

Various studies have shown an increase in DPP-4 activity in individuals with obesity and type 2 diabetes, which causes the inactivation of the hormones responsible for the release of insulin by the pancreas and, consequently, an increase in blood glucose.

“Our study provides scientific evidence on the possible causal role of the microbiota in the development of type 2 diabetes, and highlights the need to address not only dietary factors, but also the composition and functionality of intestinal bacteria in this disease,” the research team highlights. Research staff from the Prince Felipe Research Centre in Valencia (CIPF) also participated in the study.

The study is titled “Gut microbiota DPP4-like enzymes are increased in type-2 diabetes and contribute to incretin inactivation.” It has been published in the academic journal Genome Biology. (Source: Isidoro García / CSIC)