TY - JOUR
T1 - Microbiota Induced Changes in the Immune Response in Pregnant Mice
AU - Faas, Marijke M.
AU - Liu, Yuanrui
AU - Borghuis, Theo
AU - van Loo-Bouwman, Carolien A.
AU - Harmsen, Hermie
AU - de Vos, Paul
N1 - Copyright © 2020 Faas, Liu, Borghuis, van Loo-Bouwman, Harmsen and de Vos.
PY - 2020/1/9
Y1 - 2020/1/9
N2 - Pregnancy is associated with adaptations of the immune response and with changes in the gutmicrobiota. We hypothesized the gut microbiota are involved in inducing (part of) the immunological adaptations during pregnancy. To test this hypothesis, we collected feces from pregnant conventional mice before and during pregnancy (days 7, 14, and 18) and microbiota were measured using 16S RNA sequencing. At day 18, mice were sacrificed and splenic (various Th cell populations) and blood immune cells (monocyte subsets) were measured by flow cytometry. The data were compared with splenic and blood immune cell populations from pregnant (day 18) germfree mice and non-pregnant conventional and germfree mice. Finally, the abundances of the individual gut bacteria in the microbiota of each conventional pregnant mouse were correlated to the parameters of the immune response of the same mouse. The microbiota of conventional mice were significantly different at the end of pregnancy (day 18) as compared with pre-pregnancy (Permanova, p <0.05). The Shannon index was decreased and the Firmicutes/Bacteroidetes ratio was increased (Friedman followed by Dunn's test, p <0.05), while abundances of various species (such as Allobaculum stercoricanis, Barnesiella intestihominis, and Roseburia faecis) were significantly different at day 18 compared with pre-pregnancy. In pregnant conventional mice, the percentage of Th1 cells was decreased, while the percentages of Treg cells and Th2 cells were or tended to be increased vs. non-pregnant mice. In germfree mice, only the percentage of Th1 cells was decreased in pregnant vs. non-pregnant mice, with no effect of pregnancy on Treg and Th2 cells. The percentages of monocyte subsets were affected by pregnancy similarly in conventional and germfree mice. However, the activation status of monocytes (expression of CD80 and MHCII) was affected by pregnancy mainly in conventional mice, and not in germfree mice. Correlation (Spearman's coefficient) of pregnancy affected microbiota with pregnancy affected immune cells, i.e., immune cells that were only affected differently in conventional mice and germfree mice, showed 4 clusters of bacteria and 4 clusters of immune cells, some of these clusters were correlated with each other. For instance, the microbiota in cluster 1 and 2 (in which there were various short chain fatty acid producing microbiota) are positively correlated with immune cells in cluster B, containing Treg cells and Th2 cells. Microbiota and immune cells are affected by pregnancy in mice. The different immunological adaptations to pregnancy between conventional and germfree mice, such as the increase in Treg and tendency to an increase in Th2 cells in conventional pregnant mice only, may suggest that the microbiota may play a role in adapting the maternal immune response to pregnancy.
AB - Pregnancy is associated with adaptations of the immune response and with changes in the gutmicrobiota. We hypothesized the gut microbiota are involved in inducing (part of) the immunological adaptations during pregnancy. To test this hypothesis, we collected feces from pregnant conventional mice before and during pregnancy (days 7, 14, and 18) and microbiota were measured using 16S RNA sequencing. At day 18, mice were sacrificed and splenic (various Th cell populations) and blood immune cells (monocyte subsets) were measured by flow cytometry. The data were compared with splenic and blood immune cell populations from pregnant (day 18) germfree mice and non-pregnant conventional and germfree mice. Finally, the abundances of the individual gut bacteria in the microbiota of each conventional pregnant mouse were correlated to the parameters of the immune response of the same mouse. The microbiota of conventional mice were significantly different at the end of pregnancy (day 18) as compared with pre-pregnancy (Permanova, p <0.05). The Shannon index was decreased and the Firmicutes/Bacteroidetes ratio was increased (Friedman followed by Dunn's test, p <0.05), while abundances of various species (such as Allobaculum stercoricanis, Barnesiella intestihominis, and Roseburia faecis) were significantly different at day 18 compared with pre-pregnancy. In pregnant conventional mice, the percentage of Th1 cells was decreased, while the percentages of Treg cells and Th2 cells were or tended to be increased vs. non-pregnant mice. In germfree mice, only the percentage of Th1 cells was decreased in pregnant vs. non-pregnant mice, with no effect of pregnancy on Treg and Th2 cells. The percentages of monocyte subsets were affected by pregnancy similarly in conventional and germfree mice. However, the activation status of monocytes (expression of CD80 and MHCII) was affected by pregnancy mainly in conventional mice, and not in germfree mice. Correlation (Spearman's coefficient) of pregnancy affected microbiota with pregnancy affected immune cells, i.e., immune cells that were only affected differently in conventional mice and germfree mice, showed 4 clusters of bacteria and 4 clusters of immune cells, some of these clusters were correlated with each other. For instance, the microbiota in cluster 1 and 2 (in which there were various short chain fatty acid producing microbiota) are positively correlated with immune cells in cluster B, containing Treg cells and Th2 cells. Microbiota and immune cells are affected by pregnancy in mice. The different immunological adaptations to pregnancy between conventional and germfree mice, such as the increase in Treg and tendency to an increase in Th2 cells in conventional pregnant mice only, may suggest that the microbiota may play a role in adapting the maternal immune response to pregnancy.
KW - pregnancy
KW - gut microbiota
KW - immune response
KW - monocytes
KW - lymphocytes
KW - NATURAL-KILLER-CELLS
KW - CHAIN FATTY-ACIDS
KW - T-HELPER-CELLS
KW - CYTOKINE PRODUCTION
KW - GUT MICROBIOTA
KW - MONONUCLEAR-CELLS
KW - FOLLICULAR PHASE
KW - MONOCYTES
KW - BLOOD
KW - TH2
U2 - 10.3389/fimmu.2019.02976
DO - 10.3389/fimmu.2019.02976
M3 - Article
C2 - 31998293
VL - 10
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 2976
ER -