We tested the hypothesis that alterations in the intestinal microbiota are linked with the progression of type 1 diabetes (T1D). Herein, we present results from a study performed in subjects with islet autoimmunity living in the U.S. High-throughput sequencing of bacterial 16S rRNA genes and adjustment for sex, age, autoantibody presence, and HLA indicated that the gut microbiomes of seropositive subjects differed from those of autoantibody-free first-degree relatives (FDRs) in the abundance of four taxa. Furthermore, subjects with autoantibodies, seronegative FDRs, and new-onset patients had different levels of the Firmicutes genera Lactobacillus and Staphylococcus compared with healthy control subjects with no family history of autoimmunity. Further analysis revealed trends toward increased and reduced abundances of the Bacteroidetes genera Bacteroides and Prevotella, respectively, in seropositive subjects with multiple versus one autoantibody. Canonical discriminant analysis suggested that the gut microbiomes of autoantibody-positive individuals and seronegative FDRs clustered together but separate from those of new-onset patients and unrelated healthy control subjects. Finally, no differences in biodiversity were evident in seropositive versus seronegative FDRs. These observations suggest that altered intestinal microbiota may be associated with disease susceptibility.
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