Abstract
Hormones and placental factors are thought to underlie the maternal immunological changes during pregnancy. However, as several intestinal microbiota are linked to immune modulations, we hypothesized that the intestinal microbiota are altered during pregnancy in favor of species associated with pregnancy associated immune modulations. We studied the fecal microbiota composition (MITchip) and intestinal and peripheral immune cells (microarray and flow cytometry) in pregnant and non-pregnant C57BL/6 and BALB/c mice. Pregnancy influenced intestinal microbiota diversity and composition, however in a mouse strain dependent way. Pregnant BALB/c mice had, among others, a relative higher abundance of Lactobacillus paracasei et rel., Roseburia intestinalis et rel. and Eubacterium hallii et rel., as compared to non-pregnant BALB/c mice, while the microbiota composition in B6 mice hardly changed during pregnancy. Additionally, intestinal immunological pathways were changed during pregnancy, however again in a mouse strain dependent way. Correlations between various bacteria and immunological genes were observed. Our data do support a role for the microbiome in changing immune responses in pregnancy. However, other factors are also involved, such as for instance changes in SCFA or changes in sensitivity to bacteria, since although immunological changes are observed in B6 mice, hardly any changes in microbiota were found in this strain. Follow up studies are needed to study the exact relationship between these parameters.
Highlights
Pregnancy is associated with immunological adaptations of the mother in order to tolerate and support the development of the semi-allogeneic fetus
Segmented filamentous bacteria for example showed to be able to induce the development of intestinal T helper 17 (Th17) cells[13], while several bacteria species from the genus Clostridium have been shown to promote the accumulation of intestinal Tregs[9,10]
Intestinal microbiota composition changed during pregnancy, but in a mouse strain dependent way
Summary
Pregnancy is associated with immunological adaptations of the mother in order to tolerate and support the development of the semi-allogeneic fetus. One of the mechanisms by which bacteria can modulate immune cells is by producing short chain fatty acids (SCFA), such as butyrate, which has been shown to induce the differentiation of Tregs in the colon[14]. This is true for Clostridium species from the clusters IV and XIVa9. In this study we investigated a possible relationship between microbiota and the immunological adaptations at the end of pregnancy in mice To this end, we studied the effect of pregnancy on the microbiota composition and the effect of pregnancy on both intestinal immune cells and peripheral immune cells with a microarray (colon tissue) and flow cytometry (spleen and mesenteric lymph nodes (MLN)). We used two different mouse strains (C57BL/6 and BALB/c) that were shown to have different microbiota profiles and intestinal immunological responses[15,16], to study the consequences of a different pre-pregnancy starting point in the intestinal microbiota-host interactions
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