Limits...
Alterations in Intestinal Microbiota Correlate With Susceptibility to Type 1 Diabetes

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

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).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4587635&req=5

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).

Mentions: We next compared the abundance of individual bacterial taxa from autoantibody-positive versus autoantibody-free subjects. Similar numbers of bacterial phyla and genera (i.e., OTU richness) were observed in the subject cohorts (data not shown). Wilcoxon rank-based tests with adjustment for covariates (i.e., age, sex, autoantibody presence, and HLA) and multiple comparisons across groups revealed significant differences in the abundance of nine bacterial taxa, of which four were found to be different in seropositive versus seronegative cohorts (Fig. 2, Table 2, and Supplementary Table 1). Parameter estimates further demonstrated that the level of the majority of the taxa with significant differences across groups was not associated with age, sex, or HLA3/4 (Supplementary Table 2). Only the level of a group of bacteria that belong to the Bacteroidetes phylum and could not be classified to lower levels (termed by us Bacteroidetes other) was observed to be associated with age (P = 0.02). The limited sample size of this study did not provide sufficient power to assess the effect of the autoantibody number on the gut bacterial composition. The covariate-adjusted analysis indicated that a significant increase was detectable in the relative median abundance of the Firmicutes genera Catenibacterium and of the Bacteroidetes family and genus Prevotellaceae and RC9 gut group, respectively, in seropositive compared with seronegative FDRs (adjusted P = 0.02 for all) (Fig. 2, Table 2, and Supplementary Table 1). In contrast, a reduction in the abundance of the taxa classified only to Bacteroidetes (Bacteroidetes other) was evident in seropositive versus seronegative FDRs (adjusted P = 0.09).


Alterations in Intestinal Microbiota Correlate With Susceptibility to Type 1 Diabetes
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).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4587635&req=5

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).
Mentions: We next compared the abundance of individual bacterial taxa from autoantibody-positive versus autoantibody-free subjects. Similar numbers of bacterial phyla and genera (i.e., OTU richness) were observed in the subject cohorts (data not shown). Wilcoxon rank-based tests with adjustment for covariates (i.e., age, sex, autoantibody presence, and HLA) and multiple comparisons across groups revealed significant differences in the abundance of nine bacterial taxa, of which four were found to be different in seropositive versus seronegative cohorts (Fig. 2, Table 2, and Supplementary Table 1). Parameter estimates further demonstrated that the level of the majority of the taxa with significant differences across groups was not associated with age, sex, or HLA3/4 (Supplementary Table 2). Only the level of a group of bacteria that belong to the Bacteroidetes phylum and could not be classified to lower levels (termed by us Bacteroidetes other) was observed to be associated with age (P = 0.02). The limited sample size of this study did not provide sufficient power to assess the effect of the autoantibody number on the gut bacterial composition. The covariate-adjusted analysis indicated that a significant increase was detectable in the relative median abundance of the Firmicutes genera Catenibacterium and of the Bacteroidetes family and genus Prevotellaceae and RC9 gut group, respectively, in seropositive compared with seronegative FDRs (adjusted P = 0.02 for all) (Fig. 2, Table 2, and Supplementary Table 1). In contrast, a reduction in the abundance of the taxa classified only to Bacteroidetes (Bacteroidetes other) was evident in seropositive versus seronegative FDRs (adjusted P = 0.09).

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus