Changes in Gut Microbiome Seen in Pregnant Women With T1D

During pregnancy, women with type 1 diabetes (T1D) exhibit a shift toward a more pro-inflammatory gut microbiome, which may be modifiable through dietary means, according to study findings published in Microbiome. This shift is also associated with evidence of intestinal inflammation, while the change could contribute to the increased risk of pregnancy complications women with T1D experience.

The gut microbiome, with its essential metabolites and vitamins, plays an important role in the developments of the immune system. Although some research has been conducted assessing changes in women’s gut microbiota compositions during pregnancy, findings are contrary and limited.

However, “alterations in the bacterial gut microbiome have been reported in T1D, mainly in children at high risk and at diagnosis,” the authors explained, while “in pregnancy, T1D is associated with systemic and intra-uterine markers of sub-clinical inflammation and higher risks of complications for mother and fetus.”

To determine a consensus around gut microbiome composition in pregnant women with T1D, the researchers applied shotgun whole metagenomic sequencing to individuals enrolled in the Australia-wide Environmental Determinants of Islet Autoimmunity (ENDIA) study.

Between February 2013 and October 2017, investigators collected fecal samples from 35 women (36 pregnancies) with T1D and 31 women (34 pregnancies) without T1D. Each participant provided 1 to 3 samples across their pregnancy, for a total of 134 samples. As inclusion criteria, each unborn child had to have a first-degree relative with T1D.

A mean (SD) total of 44,940,628 (10,572,188) paired-end reads per sample were obtained, the authors wrote, and across pregnancy, women with and without T1D exhibited compositional and functional changes in their gut microbiomes.

Analyses revealed:

• Profiles in women with T1D had an increase in bacteria that produce lipopolysaccharides (LPS) and a decrease in those that produce short-chain fatty acids, especially in the third trimester
• Women with T1D had elevated concentrations of fecal calprotectin, a marker of intestinal inflammation, and serum intestinal fatty acid-binding protein, a marker of intestinal epithelial damage
• Across all trimesters, the species Bacteroides caccae (false discovery rate [FDR], 0.03) and its unique strain (unclassified) in the dataset (FDR, 0.03), as well as the order Enterobacteriales (FDR, 0.07), were increased in women with T1D
• Species Bacteroidales bacterium ph8 (FDR, 0.034) and its strain (GCF000311925) (FDR, 0.03), the genus (FDR 0.08) and family (FDR, 0.08) to which Bacteroidales bacterium ph8 belongs, and the order Bifidobacteriales (FDR, 0.07), were decreased in women with T1D

“We observed no differences across pregnancy in alpha diversity but found differences in beta diversity at the strain and species levels in women without T1D and at all taxonomic levels in women with T1D,” the researchers said. “In addition, particularly in women with T1D, we saw changes in the relative abundance of specific taxa across pregnancy with progression to a more pro-inflammatory microbiome.”

Based on these findings, they hypothesized systemic inflammation—secondary to changes in the gut microbiome—may contribute to the increased risk of pregnancy complications among women with T1D, while a pro-inflammatory gut microbiome in the mother may also impact infants postnatally. Dietary interventions, aimed at promoting a less pro-inflammatory gut microbiome may benefit both the mother and baby.

Overall, the decrease in bacteria that synthesize essential vitamins and those with anti-inflammatory properties—seen in the current study—in addition to the increase in pro-inflammatory bacteria “together may lead to low-grade gut inflammation, epithelial barrier dysfunction, increased epithelial permeability, and low-grade systemic inflammation,” the authors concluded.

“These are features of the gut microbiome ‘dysbiosis’ observed in a wide range of diseases some of which have shown clinical benefit in response to probiotic and other dietary interventions. The relationship of these changes to the increased risk to mother and fetus in the T1D pregnancy requires further investigation.”

Reference

Roth-Schulze AJ, Penno MAS, Ngui KM, et al; ENDIA Study Group.. Type 1 diabetes in pregnancy is associated with distinct changes in the composition and function of the gut microbiome. Microbiome. Published online August 6, 2021. doi:10.1186/s40168-021-01104-y