The gut microbiome in pregnancy and post-natally in mothers with and without type 1 diabetes

Background: The gut microbiome shapes the development of a healthy immune system and may be altered in children in the pre-clinical stage of type 1 diabetes (T1D). The Environmental Determinants of Islet Autoimmunity (ENDIA; endia.org.au) study investigates environment-gene interactions in the genesis of T1D, from pregnancy through early life in 1,400 infants at genetic risk for T1D. ENDIA offers a unique opportunity to ask how the gut microbiome matures from birth, is influenced by microbiomes of the mother and other family members and, ultimately, how it modifies the risk for T1D. We analysed the gut microbiomes in 373 stool samples from 154 pregnancies of 148 ENDIA women (95 with T1D; 6 women provided samples across two pregnancies). Forty-four women (28 with T1D) provided samples across all trimesters of pregnancy, and 19 (10 with T1D) provided samples post-pregnancy.

Methods: The bacterial 16S rRNA gene V4 amplicon was sequenced with the Illumina MiSeq. Raw sequences were processed in QIIME 2. Data were filtered, de-replicated and sequence variants inferred with q2-dada2 to obtain a feature-per-sample table. Sequences were taxonomically classified using the Silva 16S rRNA database. Diversity and composition were analysed by linear mixed models. Taxonomic relative abundance was determined from log2-transformed cpm with the limma R package.

Results: Although alpha (within-subject) diversity was similar in T1D and non-T1D pregnant women, beta (between-subject) diversity differed at all taxonomic levels (p≤0.003 for each). Women with T1D had lower relative abundance of bacteria with anti-inflammatory properties. Interestingly, in both T1D and non-T1D women there was close clustering of bacterial composition between pregnancy and post-pregnancy samples.

Conclusions: The gut microbiome differs between women with and without T1D and in both is remarkably conserved from pregnancy into the post-natal period.