Abstract
Introduction Pregnancy is associated with maternal immunological adaptations in order to tolerate and support the development of the semi-allogeneic fetus. Hypothesis Since intestinal microbiota are linked to immune modulations, we hypothesized that intestinal microbiota are altered during pregnancy to support maternal immune adaptations. Methods Pregnant (day 18) and non-pregnant C57BL/6 and BALB/c mice were sacrificed and feces and colonic tissue were harvested. Fecal microbiota composition (MITchip) and intestinal gene expression (microarray (Affymetrix)) were evaluated. Results Pregnancy influenced intestinal microbiota diversity and composition in a mouse strain dependent way. Pregnant BALB/c mice had, among others, a higher abundance of various Lactobacillus species (e.g. L. paracasei et rel. and L. plantarum), Allobaculum et rel, Roseburia intestinalis et rel. and Eubacterium hallii et rel., as compared to non-pregnant BALB/c mice. The microbiota composition in C57BL/6 mice hardly changed during pregnancy. Additionally, intestinal immunological pathways were changed during pregnancy, again in a mouse strain dependent way. For example, pathways related to B cell development and CD28 signaling in T helper cells were only affected in C57BL/6 mice, while IL-10 signaling was only affected in BALB/c mice. Using advanced statistics, we combined microarray data with microbiota composition data from BALB/c mice and found many correlations between the presence of various pregnancy affected intestinal bacteria and immunological genes. Various bacteria with a higher abundance in pregnant mice (such as Allobaculum et rel.) correlated with clusters of genes, with many genes involved in immune responses (for instance T cell development). Conclusion Our data support a role for the microbiome in adapting immune responses in pregnancy. However, also other factors are involved, since in C57BL/6 mice many immunological changes take place in the absence of microbiome changes. Follow up studies are needed to study the exact relationship between intestinal bacteria and maternal immune responses in pregnancy.
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