Microbial translocation in type 2 diabetes: when bacterial invaders overcome host defence in human obesity

Metabolic endotoxemia, characterised by systemic influx of bacterial components, impairs lipid handling and glucoregulation.1 Early preclinical studies showed that high fat diet feeding facilitates bacterial translocation to metabolic tissues coinciding with dendritic cell (DC)-mediated inflammation.2 This process was aggravated in mice lacking either the canonical adaptor for inflammatory signalling pathways downstream of Toll-like receptor (TLR) families, MyD882 or the intracellular microbial pattern recognition receptor, NOD2.3 The first conceptual evidence for bacterial translocation in human type 2 diabetes (T2D) was reported in 2011 when Amar et al showed that 16S rDNA gene content in blood was associated with future T2D risk.4 These seminal papers pioneered the concept of bacterial translocation in metabolic diseases. Yet, it remains intensely debated whether bacterial translocation to extraintestinal tissues is a true phenomenon or a result of spurious data, as it is notoriously difficult to robustly distinguish biologically relevant bacterial DNA sequences in very low microbial biomass tissues from environmental contaminants.5 6 Indeed, low bacteria:host cell ratio obviously increases the risk of contamination during surgical procedures, biobanking and wet-laboratory processing of tissue samples. This has revivified the tenet that internal organs are sterile and casted doubt on emerging reports of tissue microbial signatures in a number of diseases, arguing that such findings may be confounded by sample contamination. In GUT, Massier et al challenge again the dogma of sterile internal organs …