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. 2015 Oct;64(10):3510-20.
doi: 10.2337/db14-1847. Epub 2015 Jun 11.

Alterations in Intestinal Microbiota Correlate With Susceptibility to Type 1 Diabetes

Aimon K Alkanani  1 , Naoko Hara  1 , Peter A Gottlieb  1 , Diana Ir  2 , Charles E Robertson  3 , Brandie D Wagner  4 , Daniel N Frank  3 , Danny Zipris  5
Affiliations

Alterations in Intestinal Microbiota Correlate With Susceptibility to Type 1 Diabetes

Aimon K Alkanani et al. Diabetes. 2015 Oct.

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 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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Figures

Figure 1
Figure 1
A: Stacked bar chart of median percent counts of OTUs representing bacterial genera with a frequency of ≥1% of total counts in the stool from subjects with and without islet autoimmunity as indicated in the figure. The relative abundances are inferred from 16S rRNA sequence counts in datasets. The x and y axes represent the sample name and percentages of bacterial taxa, respectively. B: The distribution of Shannon indices across groups is displayed using box plots. The area inside the box represents the interquartile range (25th to 75th percentiles), and the median and mean are denoted by a line and a circle, respectively. The whiskers extend 1.5 interquartile range from the box; the observations outside of this range are displayed as points. Seroneg., seronegative; Seropos., seropositive.
Figure 2
Figure 2
Median percent abundance of bacterial communities in subjects with and without islet autoimmunity. The plot displays those taxa that were significantly different across groups after adjustment for covariates (statistical significance and numeric values are shown in Table 2 and Supplementary Table 1, respectively).
Figure 3
Figure 3
Plot from canonical discriminant analysis used to discriminate between seropositive and seronegative subjects. The weights attributed to the taxa that contributed the most to the components are displayed as vectors in the plot.
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