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UPCOMING SEMINAR: Tommi Vatanen, Broad Institute

Posted by on 29 May 2017 | Comments

12.00pm Monday, 29 May
Room 208
2nd floor, Microbiology Building
720 Cumberland St

Tommi Vatanen
Broad Institute

Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans

Type 1 Diabetes (T1D) is an autoimmune disorder affecting millions of individuals world-wide, involving both genetic and environmental risk factors.  In order to study the role of the living environment and specifically the gut microbiota in T1D onset, we performed longitudinal metagenomic characterisation of gut microbiome development from birth until age 3 in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but less prevalent in Russia.  Finnish and Estonian infants harboured both a greater proportion of Bacteroides species and an enrichment in lipopolysaccharide (LPS) biosynthesis-encoding genes, when compared to Russian infants. To link the results from these metagenomic analyses with the identification of novel molecular immune mechanisms, we analysed LPS structure and function from several Bacteroides species. Bacteroides produced a structurally and functionally distinct form of LPS that differed from the dominating form of LPS in the early Russian microbiome, which was almost exclusively derived from Escherichia coli. Indeed, LPS from Bacteroides dorei, a bacterium previously associated with Type 1 Diabetes pathogenesis, harboured tetra- and penta-acylated lipid A structures, as opposed to the hexa-acylated lipid A seen in E. coli. B. dorei LPS was immunologically silent and inhibited innate immune signalling and endotoxin tolerance in human cells. Finally, unlike LPS from E. coli, B. dorei LPS did not decrease the incidence of autoimmune diabetes in non-obese diabetic mice. These findings suggest that differences in microbiota-derived LPS may preclude aspects of immune education in Finnish and Estonian children, uncovering one potential mechanism linking the human gut microbiome to susceptibility to immune-mediated diseases

This seminar is kindly sponsored by: BD Biosciences