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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

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.
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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.

Mentions: We postulated that alterations in the intestinal microbiome would be involved in the progression of human T1D. To test this possibility, we sequenced the V4 region of 16S rRNA genes (primers 534F–805R [9,10]) from fecal samples of seropositive individuals with one to four autoantibodies (n = 21) compared with seronegative FDRs (n = 32). Comparisons were also made between the gut bacterial content of autoantibody-positive individuals and seronegative FDRs to that of new-onset patients (n = 35) and autoantibody-free healthy control subjects with no family history of autoimmunity (n = 23). A median of 131,000 (range 8,100–313,000) high-quality 16S rRNA gene sequences were obtained for each sample. The data presented in Fig. 1A demonstrate that similar overall gut bacterial profiles were observed among the subject cohorts. Furthermore, comparable Shannon bacterial diversity indices were measured in seropositive versus seronegative FDRs (Fig. 1B) (P = 0.44). These observations suggest that islet autoimmunity is probably not associated with altered bacterial diversity or striking differences in the intestinal microbiota.


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

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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.
Mentions: We postulated that alterations in the intestinal microbiome would be involved in the progression of human T1D. To test this possibility, we sequenced the V4 region of 16S rRNA genes (primers 534F–805R [9,10]) from fecal samples of seropositive individuals with one to four autoantibodies (n = 21) compared with seronegative FDRs (n = 32). Comparisons were also made between the gut bacterial content of autoantibody-positive individuals and seronegative FDRs to that of new-onset patients (n = 35) and autoantibody-free healthy control subjects with no family history of autoimmunity (n = 23). A median of 131,000 (range 8,100–313,000) high-quality 16S rRNA gene sequences were obtained for each sample. The data presented in Fig. 1A demonstrate that similar overall gut bacterial profiles were observed among the subject cohorts. Furthermore, comparable Shannon bacterial diversity indices were measured in seropositive versus seronegative FDRs (Fig. 1B) (P = 0.44). These observations suggest that islet autoimmunity is probably not associated with altered bacterial diversity or striking differences in the intestinal microbiota.

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