Gut microbiome composition does not predict pregnancy complications among obese women: a nested case-control study in Sweden

Background Obesity is associated with gut dysbiosis, which has been implicated in the pathogenesis of gestational diabetes, preeclampsia, and gestational hypertension. Its role in obese pregnant women, the population at highest risk, remains largely unexplored. Methods Within the Swedish Maternal Microbiome (SweMaMi) cohort, we conducted a nested case–control study comparing the second-trimester faecal microbiome between obese pregnant women who developed metabolic complications (n = 98) and complication-free controls (n = 113), using shotgun metagenomics. We developed a multi-modal machine learning framework integrating microbial species abundances, functional profiles, community-level features, and registry and questionnaire data to evaluate predictive performance and identify microbial signatures. Results Cases had higher pre-pregnancy BMI and gestational BMI gain. Socioeconomic score, not microbial diversity, was associated with outcomes after adjustment. Models showed limited discriminatory capacity overall, with the highest performance for preeclampsia, where gut metabolic modules emerged as the strongest predictors. Conclusion BMI and socioeconomic status, rather than gut microbiome composition, appear to be the primary drivers of metabolic risk in this population.