We all know that gut bacteria are great, right? Right. Well, they’re great as long as they keep their distance from our intestinal epithelial cells. New research shows that the closer bacteria get to gut epithelial cells in humans, the more likely people are to develop metabolic diseases.
According to study author Andrew Gewirtz, “previous studies in mice have indicated that bacteria that are able to encroach upon the epithelium might be able to promote inflammation that drives metabolic diseases, and now we've shown that this is also a feature of metabolic disease in humans, specifically type 2 diabetics who are exhibiting microbiota encroachment."
They collected samples from patients at the Veterans Administration Hospital in Atlanta, Georgia, who were undergoing a routine colonoscopy. Colon biopsies were used to investigate the relationship between “microbiota-mucus-epithelial juxtaposition” and risk factors for metabolic disease. The study subjects were middle-aged, 86% were overweight, 45% were obese, and 33% had diabetes.
Although the standard preparation for a colonoscopy - consumption of polyethylene glycol - removes many intestinal bacteria, the researchers were able to use the remaining bacteria to calculate the average distance of the bacteria from the epithelium. In healthy subjects (those without diabetes and who were not obese) the gut bacteria were found in the outer layer of mucus. In obese people with diabetes, however, the bacteria were found in much closer proximity to the epithelial cell layer.
Interestingly, the microbiota-epithelial distance was inversely correlated with specific markers of metabolic syndrome, including body-mass index, fasting blood glucose level, and A1C. In subjects with type 2 diabetes, the microbiota-epithelial distance was reduced by nearly 3-fold! This decrease remained even if the obese subjects were removed from the analysis.
Next, the researchers were curious about whether there was a correlation between the presence of specific immune cells in the gut and the microbiota-epithelial distance. They found more B cells in subjects with diabetes, but there were no changes in the number of dendritic cells or macrophages (compared to people without diabetes). These findings suggest that a decrease in microbiota-epithelial distance may activate mucosal B cells.
According to the study authors, “we envision that defining the interrelationship between microbiota encroachment, B-cell responses, and metabolic disease may elucidate the pathophysiology of metabolic syndrome and perhaps eventuate in novel strategies to treat and/or prevent this condition.”