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The earliest predictors of future autoimmune diseases are a series of autoantibodies that are rarely evaluated and very within and between diseases. In addition, autoantibodies often appear just prior to disease onset. All of these factors make it difficult to apply interventions that might prevent disease. Earlier predictors of disease are needed. Here, a general population cohort was used to assess whether gut bacterial biomarkers could be identified prior to disease. Gut microbiome analysis on 1741 one-year old Swedish children was performed on samples collected in the late 1990s. These children were then followed for 18 years for the incidence of five autoimmune diseases and autism. Specific bacterial strains in the gut microbiome of one-year-old children have been identified as exclusive to the 96 subjects (cases) who acquired type 1 diabetes, celiac disease, hypothyroidism, Crohn’s disease, juvenile idiopathic arthritis, or autism over their next 18 years. None of these strains were found in the 1645 children (controls) who did not acquire any of these diseases. Ten other strains were exclusive to those who remained disease-free. In most cases, the presence or absence of these bacteria were strongly associated with: 1) high-risk class II human leukocyte antigen (HLA) alleles; 2) dietary factors; or 3) a combination of HLA genetics and diet. These results have three significant implications: 1) certain class II HLA haplotypes may serve as bacterial gatekeepers early in life, altering microbiome composition thereby creating the potential for dysbiosis and inflammation; 2) the gut microbiome dysbiosis and inflammation during infancy, largely derived from host HLA genetics and diet, may be a common precedent to all five autoimmune diseases and autism; and 3) HLA gatekeeping may prevent gut colonization of beneficial bacteria in those genetically at-risk individuals who could most benefit from probiotic therapy.FundingJDRF, Swedish Child Diabetes Foundation, Swedish Council for Working Life and Social Research, Medical Research Council of Southeast Sweden, Regions Östergötland, and Linköping University. |
