Comparative analysis of gut microbiome alterations in early- and late-onset preeclampsia: A case control study

Preeclampsia (PE) is a complication during pregnancy characterized by hypertension, organ damage, and systemic inflammation. Increasing evidence suggests that the gut microbiome may play a role in the pathophysiology of PE. However, previous studies on the gut microbiome have generally overlooked the distinction between subgroups of PE, although clinical manifestations may differ. Also, most studies have not used deep sequencing techniques. Therefore, this study aimed to explore further potential differences in gut dysbiosis in different PE subgroups compared to controls using shotgun metagenomics. We studied the bacterial gut microbiome using shotgun metagenomic sequencing in 37 pregnant patients in the third trimester from a Swedish cohort, separating patients according to subtype (healthy controls N = 21, late-onset PE N = 8, early-onset PE N = 8). Differential relative abundances and alpha diversity were evaluated using Wilcoxon rank sum test, and beta diversity was evaluated using PERMANOVA. Multiple linear regression was used to study associations between gut microbiome composition differences and clinical parameters. Late-onset PE and early-onset PE were both associated with significantly different beta diversity compared to controls. Differences remained significant after adjusting for age, and were not affected by gestational age, BMI or parity. Alpha diversity was lower in late-onset PE compared to controls. While no significant differences in taxonomic abundances were seen after correcting for multiple testing, several interesting leads were identified, including a higher abundance of genus Blautia in late-onset PE, and lower abundance of Coprococcus catus and unclassified Lachnospiraceae in early-onset PE. Functional analysis did not reveal any significant differences after false discovery rate (FDR) correction. In conclusion, our results showed subgroup-specific gut microbiome differences in PE with more pronounced associations in late-onset PE, despite limited power due to the observational design and small cohort. Accordingly, our results highlight the importance of subgroup analysis when studying PE.