Genetic risk for autoimmunity is associated with distinct changes in the human gut microbiome

Jordan T Russell,Jorma Ilonen,Desmond A Schatz,Mark A Atkinson,Luiz F W Roesch,Johnny Ludvigsson,Eric W Triplett,Malin Ördberg

doi:10.1038/s41467-019-11460-x

Abstract

Susceptibility to many human autoimmune diseases is under strong genetic control by class II human leukocyte antigen (HLA) allele combinations. These genes remain by far the greatest risk factors in the development of type 1 diabetes and celiac disease. Despite this, little is known about HLA influences on the composition of the human gut microbiome, a potential source of environmental influence on disease. Here, using a general population cohort from the All Babies in Southeast Sweden study, we report that genetic risk for developing type 1 diabetes autoimmunity is associated with distinct changes in the gut microbiome. Both the core microbiome and beta diversity differ with HLA risk group and genotype. In addition, protective HLA haplotypes are associated with bacterial genera Intestinibacter and Romboutsia. Thus, general population cohorts are valuable in identifying potential environmental triggers or protective factors for autoimmune diseases that may otherwise be masked by strong genetic control.

Highlights

Susceptibility to many human autoimmune diseases is under strong genetic control by class II human leukocyte antigen (HLA) allele combinations
The aim of the All Babies in Southeast Sweden (ABIS) cohort, in part, is to identify the importance of environmental factors in autoimmune diseases and how genetic and environmental factors may interact in such diseases
HLA gene alleles appear to have a significant effect on the bacterial composition of the late infant gut based on our findings from children in the ABIS cohort

Summary

Introduction

Susceptibility to many human autoimmune diseases is under strong genetic control by class II human leukocyte antigen (HLA) allele combinations These genes remain by far the greatest risk factors in the development of type 1 diabetes and celiac disease. Using a general population cohort from the All Babies in Southeast Sweden study, we report that genetic risk for developing type 1 diabetes autoimmunity is associated with distinct changes in the gut microbiome. Kubinak et al were able to demonstrate that the inability to present class II antigens led to distinct changes in gut microbial composition and structure, namely a decrease in Lactobacillus species and an enrichment of segmented filamentous bacteria[8] They showed that gut microbial communities of the congenic mice were distinct based on MHC II polymorphisms that control T follicular helper cell influence on antibody response to commensal bacteria and that the effect of these polymorphisms was most potent at the mucosal interface of the gut vs the feces[8]. In the multinational Environmental Determinants of Diabetes in the Young (TEDDY)

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