Pregnancy-specific shifts in the maternal microbiome and metabolome in the BPH/5 mouse model of superimposed preeclampsia.

Preeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy with an incidence rate of up to 8% worldwide. However, the complete pathogenesis is still unknown. Obesity increases the risk of developing PE threefold. To better understand the relationship of maternal risk factors, the BPH/5 mouse was described as a model of superimposed PE. Previous research demonstrated that adult BPH/5 female mice have an adverse cardiometabolic phenotype characterized by hypertension, obesity with increased white adipose tissue, and dyslipidemia, exaggerated by pregnancy. We hypothesize that BPH/5 mice have gut dysbiosis characterized by changes in alpha and beta diversity of bacterial community structure as well as perturbed short-chain fatty acids (SCFAs) compared with controls in pregnancy. Fecal samples were used for Illumina sequencing of 16S v4 rRNA amplicons. Microbial community composition of the pregnant BPH/5 mice compared with C57 controls was different using permutational multivariate analysis of variance (PERMANOVA) with Bray-Curtis dissimilarity. Alpha diversity was increased in pregnant BPH/5 dams compared with controls. and were increased, whereas , and were decreased compared with controls. Fecal SCFAs were not different between groups, but BPH/5 serum acetic and butyric acids were decreased, whereas isobutyric and isovaleric acids were increased specifically in pregnancy. BPH/5 pregnant colons had decreased expression of free fatty acid receptor, . In conclusion, the BPH/5 maternal fecal microbiome demonstrates microbial dysbiosis characterized by community structure and diversity changes before and after the onset of pregnancy. Gut dysbiosis may be a key mechanism linking SCFA signaling and obesity to the BPH/5 PE-like phenotype. This is the first time the pregnant fecal microbiome has been identified in the BPH/5 spontaneous mouse model of superimposed PE. Community composition changed with the onset of pregnancy in this model. BPH/5 showed an altered colonic signaling with decreased GPR41 expression, suggesting that gut dysbiosis may link SCFA signaling to the PE phenotype. This data highlights the importance of the maternal obesogenic gut microbiome in pregnancy.