Exploring the Link between Superimposed Preeclampsia and the Gut Microbiome
Authors: Akinleye Adesanya A , Johnson Ashley C , Garrett Michael R. , Sasser Jennifer M 
Published: June 2021

Preeclampsia, a hypertensive disorder of pregnancy, is a leading cause of maternal and fetal morbidity and mortality worldwide. Despite the rising prevalence and severity of this disease, the initiating factors responsible for the development of preeclampsia remain unknown. Recent evidence suggests an association of gut microbiome changes with certain forms of hypertension, but the effects of differences in the microbiome during preeclampsia are unknown. We hypothesized that gut dysbiosis contributes to the development of the preeclamptic phenotype in the Dahl salt‐sensitive rat (Dahl S) model of preeclampsia superimposed on hypertension and chronic kidney disease. Sprague Dawley (SD) rats were used for comparison as a model of healthy pregnancy, and comparisons were made to age matched virgin littermates in both strains. All rats were housed in the same room and maintained on a 0.3% NaCl diet (TD7034) for 5 months prior to study. Fecal samples were obtained on two separate days for baseline measures, and then half of the rats in each strain were mated (n=7–9/group). Samples were collected on days 6, 13, and 20 of pregnancy and then one week postpartum (Day ~29). Microbial DNA was isolated from fecal matter, and the V3‐V4 region of 16S ribosomal RNA was PCR amplified and processed through the Illumina 16S sequencing pipeline. A single library was generated (n=191) and run on Illumina MiSeq instrument. The sequencing reads were processed via QIIME application (Illumina Cloud BaseSpace) which provided an initial analysis of sequencing reads by quality filtering, operational taxonomic unit (OTU) picking, and taxonomic assignment. The web‐based Microbiome Analyst was used for statistical analysis to establish differences in microbiota diversity, composition, and tools for visualization. A preliminary analysis of the fecal microbiota between SD and Dahl S showed a distinct diversity (alpha and beta) in the microbiome between Dahl S and SD rats at baseline. The microbiome diversity stayed relatively constant over the course of pregnancy for SD (versus virgin control), whereas in Dahl S there was a significant difference at day 20 compared to virgin controls. Dahl S microbiome diversity at each time point in pregnancy (day 6, 13, and 20) trended higher than SD. Both pregnant Dahl S and SD (versus virgin) demonstrated a significant change at the Phylum level for several taxa. However, the ratio of Firmicutes:Bacteroidetes (F:B) ratio remained relatively constant across pregnancy for both Dahl S (average ratio 1.34) and SD (1.37), with the exception of day 20 in pregnant Dahl S which demonstrated a significant change in F:B ratio from 1.30 (virgin) to 0.78 (pregnant). Currently, we are working to perform a more systematic analysis, including potential changes in bacterial populations that produce beneficial short‐chain fatty acids (SCFA) that have been identified in other models of hypertension to place the differences in context of physiological changes. Future studies will determine if manipulation of the microbiota in the Dahl S strain will improve the preeclamptic phenotype and offspring outcomes.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.