The gut microbiome and inflammation in the BPH5 preeclamptic like mouse model

Abstract

Preeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy. It occurs in ~10% of pregnant women worldwide and the etiology is still unknown. Obesity increases the risk of developing PE by three-fold and has been associated with adverse fetal outcomes. Short chain fatty acids (SFCAs) are gut microbiome derived metabolites that fuel the host metabolism and have been found to be key mediators between dysbiosis and disease signaling through G protein coupled receptors (GPRs) that regulate appetite and glucose metabolism. We hypothesize that obese mice with a gut dysbiosis have perturbed GPR pathways and increased local inflammatory response. To better understand the relationship of maternal PE risk and outcomes, the obese hypertensive BPH/5 mouse model of superimposed PE was utilized. Previous research demonstrated that adult BPH/5 female mice have an adverse cardiometabolic phenotype: hyperphagia, hypertension, obesity with increased white adipose tissue (WAT), and dyslipidemia that is exaggerated by pregnancy. Fecal samples were collected from pregnant and non-pregnant BPH5 and C57 female controls for Illumina sequencing of 16S v4 rRNA amplicon libraries to examine the PE-like maternal fecal microbiome. SCFAs, GPR41, and IL-15 were measured in the colon of the pregnant dams. Microbial community composition of the pregnant BPH/5 compared to the lean normotensive C57 controls were significantly different using PERMANOVA with Bray-Curtis dissimilarity of 16S Amplicon Sequence Variant’s relative abundance (p<0.05, n=8-15). Alpha diversity was increased in pregnant BPH/5 dams compared to lean C57 dams (p<0.05, n=8-15). Significant differences were also found in the BPH5 model after the onset of pregnancy such as a decrease in Muribaculum spp., Muribaculaceae unclassified, Parabacteroides spp, and Lachnospiraceae_NK4A136 unclassified. SCFAs were not different between groups (p>0.05). BPH5 demonstrate an altered GPR41 pathway with decreased GPR 41 expression in the colon (p<0.05, n=5-9) and increased IL-15 to represent local colonic inflammation (p<0.05, n=3). In conclusion, the maternal fecal microbiome demonstrates microbial dysbiosis characterized by diversity changes in a model of PE and after the onset of pregnancy. The gut dysbiosis may be a key mechanism that affects GPR41 signaling, inflammation, and contributes to the BPH5 phenotype and poor pregnancy outcomes. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.