Imbalance of Fecal Microbiota at Newly Diagnosed Type 1 Diabetes in Chinese Children

Abstract

Background: Recent studies have indicated that an imbalance of gut microbiota is associated with the development of type 1 diabetes mellitus (T1DM) and there is no literature regarding it in Chinese children yet. The aim of this study was to evaluate the alteration of gut microbiota between children with newly diagnosed T1DM and healthy controls and to determine if gut microbiota could partly explain the etiology of this disease.

Methods: A case-control study was carried out with 15 children with T1DM and 15 healthy children. The fecal bacteria composition was investigated by high-throughput sequencing of the V3-V4 region of the 16S rDNA gene and analyzed by the estimators of community richness (Chao) indexes.

Results: There was a notable lower richness of fecal bacteria in T1DM group than controls (156.53 ± 36.96 vs. 130.0 ± 32.85, P = 0.047). At the genus level, the composition of Blautia was increased in T1DM group than control group whereas the composition of Haemophilus, Lachnospira, Dialister, and Acidaminococcus was decreased. In addition, we found that the percentage of Blautia was correlated positively with HbA1c (ρ = 0.40, P = 0.031), the numbers of T1DM autoantibodies (ρ = 0.42, P = 0.023), and the titers of tyrosine phosphatase autoantibodies (IA-2) (ρ = 0.82, P = 0.000) in the study.

Conclusions: This study showed that gut microbiota was associated with the development of T1DM by affecting the autoimmunity, and the results suggested a potential therapy for T1DM via modulating the gut microbiota.

Figure 1

Principal coordinate analysis plots based on unweighted UniFrac metrics in controls (C) and type 1 diabetes mellitus (D) children (n = 15 in each group).

Figure 2

Relative abundance (%) of fecal microbiota in each sample at the phylum level (n = 15 in each group). C: Controls; D: Type 1 diabetes mellitus children.

Figure 3

(a) Taxonomic representation of statistically and biologically consistent differences between control and type 1 diabetes mellitus (T1DM) groups. Differences are represented by the color of the most abundant class (red: T1DM group; yellow: nonsignificant; and green: control group). The diameter of each circle is proportional to the taxon's abundance. (b) Histogram of the linear discriminant analysis scores for differentially abundant genera. Linear discriminant analysis scores were calculated by linear discriminant analysis effect size, which is a metagenome analysis approach, using the linear discriminant analysis to assess effect size of each differentially abundant taxon or operational taxonomic unit. Moreover, before this, the differentially abundant taxons were found out by the Mann-Whitney U-test; the cladogram is displayed according to effect size.

Figure 4

Correlation analyses between relative abundance (%) of Blautia sequences and HbA1c, using Spearman's correlation analyses (n = 30). HbA1c: Glycated hemoglobin.

Figure 5

Correlation analyses between relative abundance (%) of Blautia sequences and the number of type 1 diabetes mellitus (T1DM) autoantibodies, using Spearman's correlation analyses (n = 30).

Figure 6

Correlation analyses between relative abundance (%) of Blautia sequences and the titers of IA-2, using Spearman's correlation analyses (n = 15). IA-2: Tyrosine phosphatase autoantibodies.