Microbiota alterations and Diabetes Development

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Microbiota encroachment into the normally sterile inner colonic mucus layer is a feature of metabolic disease in humans, particularly insulin resistance–associated diabetes.

That’s the matter of a study published on the “Journal of Cellular and Molecular Gastroenterology and Hepatology”.

Gewirtz and his collaborators used a confocal microscopy to explore the concept that a perturbed host – microbiota relationship might be a feature of metabolic syndrome.

The goal was to estimate the microbiota-mucus-epithelial juxtaposition in a cohort of middle-aged Americans (58.1 ± 10.1 years old) undergoing routine cancer-screening colonoscopies (major diseases excluded, as outlined in Methods).

As one would expect in such a cohort, most (86%) were overweight, many (45%) were obese, and a third (14 out of 42) had diabetes.

After the standard pre-colonoscopy used to clean the colon, the researchers could observe the remaining bacteria, were, in healthy (ie, nonobese, nondiabetic) subjects, almost exclusively observed in outer regions of the mucus layer.

In obese persons with diabetes instead, bacteria could be found in the dense inner mucus and in close proximity to the epithelium.

Among all subjects, the researchers observed an inverse correlation between such microbiota-epithelial distance and parameters that mark metabolic syndrome:

– Body mass index (BMI),
– Fasting blood glucose levels, and
– Hemoglobin A1C.

In accord with dysglycemia correlating with microbiota encroachment, stratifying subjects with and without diabetes indicated that microbiota-epithelial distance was reduced by almost 3-fold in patients with type 2 diabetes.

This pattern held true, and remained statistically significant, even if all obese subjects were removed from the analysis, although only a few non-obese subjects had diabetes.

The researchers concluded that “the passage of the microbiota is a feature of dysglicemia associated with insulin resistance in humans,” and added that their findings could eventually contribute to new treatment and prevention strategies for metabolic syndrome.

“The data is impressive and could have opened a new field of investigation into metabolic and type 2 diabetes,” said Samuel Klein, head of the Geriatrics Division and Nutrition Sciences at the Diabetes Research Center.

According to the press release, follow-up studies are underway to identify bacterium passage and explore prevention strategies.