Could Intestinal Microbes Reduce Insulin Resistance?

The intestinal microbiota can be manipulated to increase insulin sensitivity in people with metabolic syndrome, according to a study published in the October issue of Gastroenterology.

The trillions of microorganisms that reside in the human intestine are important regulators of metabolism. Changes in their composition and metabolic function have been associated with diabetes, as well as other disorders, in animal models. However, little is known about how changes in the human microbiota affect processes such as energy metabolism and insulin sensitivity.

Anne Vrieze et al. studied the effects of transferring intestinal microbiota from healthy, lean men (body mass index <23 kg/m2) to men with metabolic syndrome (obesity, high blood pressure, and increased blood levels of glucose or insulin resistance).

The intestines of 9 obese men were infused, via a duodenal tube, with allogenic microbiota (from feces of lean male donors), and 9 different obese men were infused with autologous microbiota (reinfusion of their own collected feces).

Insulin sensitivity was measured using a hyperinsulinemic euglycemic clamp, to quantify glucose production and hepatic and peripheral insulin sensitivity. The composition of the microbiota in the large intestine (via fecal samples) and small intestine (via duodenal biopsies), and fecal concentrations of short-chain fatty acids, were measured after 6 weeks.

Infusion of microbiota from lean donors reduced the insulin sensitivity of recipients, from a median rate of glucose disappearance of 26.2 at the start of the study to 45.3 μmol/kg/min 6 weeks after the infusion. A trend toward improvement in hepatic insulin sensitivity was observed in the recipients of allogenic transplants.

Vrieze et al. observed significant differences in the composition of the microbiota transferred from lean men, compared with those that received autologous transplants, in the large and small intestine (see below figure).

Heat maps of (A) fecal and (B) small intestinal microbiota with significant differences between groups (red boxes). The color value shows log10 fold changes. The bacteria that differed significantly between groups that received microbiota from lean vs obese donors included the nitric oxide producer Alcaligenes faecalis and Escherichia coli.

In fecal samples (which assess the microbiota of the large intestinal microbiota) there were no changes in the total numbers of bacteria 6 weeks after infusion. However the microbial diversity increased significantly after transfer of microbiota from lean donors, but not in the group that received their own microbiota. In recipients of microbiota from lean donors, bacterial groups that increased significantly included those related to the butyrate-producer Roseburia intestinalis, which increased 2.5-fold, the oxalate-converting Oxalobacter formigenes, and other Firmicutes.

Also, levels of fecal short-chain fatty acids decreased after infusion of microbiota from lean donors, but there were no significant changes in the group that received autologous transplants.

In intestinal samples (collected by duodenal biopsy), a total of 7 bacterial groups changed after the transfer from lean donors, including an increase of the butyrate-producer Eubacterium hallii. In contrast, numbers of E hallii were reduced almost 2-fold in the group that received their own microbiota.

Vrieze et al. propose that butyrate production by intestinal microbes can increase insulin sensitivity.

Butyrate is produced by microbiota in the large and small intestines for energy use and signaling by intestinal epithelial cells. It also regulates the inflammatory response. Orally administrated butyrate has a direct effect on glucose metabolism.

The authors also associate greater intestinal microbiota diversity with less insulin resistance. They don’t know if it is overall diversity or specific changes in bacterial species contribute to this effect, but hope to perform further studies to determine whether oral administration of specific microbiota can have comparable effects on glucose metabolism. These findings could lead to new therapeutic approaches for diabetes.

Read the article online.
Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 2012;143:913–916.e7

About Kristine Novak, PhD, Science Editor

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology, both published by the American Gastroenterological Association. She has worked as an editor at biomedical research journals and as a science writer for more than 12 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.
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