Type 2 diabetes influences bacterial tissue compartmentalization in human obesity

Visceral obesity is a key risk factor for type 2 diabetes (T2D). While gut dysbiosis appears instrumental for this relationship, it remains elusive if gut-associated signatures translocate to extra-intestinal tissues and how this affects host metabolism. In the present study we provide a comparative analysis of the microbial profile found in plasma, liver and in three distinct adipose tissues (AT) of morbidly obese subjects and explored how these tissue microbial signatures vary between normoglycemic and T2D individuals matched for body mass index. We identified tissue-specific signatures with higher bacterial load in the liver and omental AT. Gut commensals, but also environmental bacteria, showed tissue- and T2D-specific compartmentalization. T2D signatures were most evident in mesenteric AT, where diabetic subjects displayed reduced bacterial diversity concomitant with fewer Gram-positive bacteria, such as Faecalibacterium, as opposed to enhanced levels of typically opportunistic Gram- negative Enterobacteriaceae. Plasma samples of diabetic subjects were similarly enriched in Enterobacteriaceae, including the pathobiont Escherichia-Shigella. Our work provides evidence for the presence of selective plasma and tissue microbial signatures in individuals with severe obesity and identify new potential microbial targets and biomarkers of T2D.