Alterations in Intestinal Microbiota Correlate with Susceptibility to

ABSTRACT 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 United States. High-throughput sequencing of bacterial 16S rRNA genes and adjustment for gender, 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 controls with no family history of autoimmunity. Further analysis revealed trends towards increased and reduced abundances of the Bacteroidetes genera Bacteroides and Prevotella , respectively, in seropositive subjects with multiple versus one autoantibody. Canonical discriminant analysissuggested that the gut microbiomes of autoantibody positive individuals and seronegative FDRs clustered together but separate from those of new onset patients and unrelated healthy controls. 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.