Low-grade inflammation in insulin resistance associates with bacterial load in adipose tissue

Compositional and functional alterations of intestinal microbiota are known to contribute to host pathologies including obesity and type 2 diabetes (T2D). Studies in animal models support the “leaky gut” hypothesis suggesting that increased intestinal permeability leads to transmucosal bacterial translocation to blood and adipose tissue (AT) contributing to chronic low-grade inflammation and insulin resistance. Obesity-associated tissue inflammation is a key factor in altering insulin sensitivity. The aim of the present study was to examine the correlation between bacterial load in subcutaneous, omental and epiploic AT with various inflammatory markers, including macrophages infiltration. We collected AT biopsies and blood samples from 27 subjects with morbid obesity (BMI: 48.09 ± 5.81 kg/m²) who underwent bariatric surgery. Adipose tissue samples were stained for adipocytes and macrophages, largest adipocytes were found in subcutaneous AT and most ATMs in omental AT. Both parameters correlated positively with HOMA-IR (Homeostasis model assessment – insulin resistance) and HbA1c (Glycated hemoglobin levels).These correlations were also observed for further inflammatory markers such as circulating TNF-α (Tumor necrosis factor-α) and AT specific TNFA gene expression. Most importantly, a positive correlation between ATMs and the bacterial load in omental AT was observed, supporting the “leaky gut” hypothesis.

In conclusion, our data support presence of bacteria in human AT and their role in obesity-associated tissue inflammation.