Monitored food intake in early pregnancy modulates the maternal microbiome in the obese BPH/5 mouse model of superimposed preeclampsia.

Preeclampsia (PE) is a life-threatening pregnancy disorder strongly associated with maternal obesity, yet the mechanistic links between diet, microbiome, and disease risk remain unclear. The obese BPH/5 mouse, which spontaneously develops PE-like features, provides a model to investigate how maternal nutrition influences microbial and metabolic profiles. Here, we tested the effects of modest caloric restriction [pair-fed (PF)] initiated at embryonic day 0.5 (e0.5) on maternal microbiota and circulating metabolites at embryonic day 7.5 (e7.5). Microbial communities were profiled by 16S rRNA sequencing across fecal, oral, and vaginal niches, and serum short-chain fatty acids (SCFAs) were quantified by gas chromatography mass spectrometry. The PF BPH/5 dams exhibited a markedly reduced Firmicutes-to-Bacteroidetes ratio and increased abundance of Bacteroides and Lactobacillus in fecal samples, which are taxa associated with improved metabolic balance and gut barrier support. In contrast, PF increased Proteobacteria abundance in BPH/5 vaginal and oral sites, a shift linked to inflammation and barrier dysfunction. Serum acetic acid was significantly decreased in PF BPH/5 dams and their offspring, suggesting that restricted intake lowers systemic SCFA availability. These findings demonstrate that early pregnancy caloric restriction produces both beneficial and adverse microbial shifts, suggesting that high-fiber dietary interventions that enhance SCFA production may better support maternal-fetal health than caloric restriction alone.NEW & NOTEWORTHY Caloric restriction via monitored food intake in early pregnancy reshaped the maternal microbiome in obese BPH/5 mice, lowering fecal F/B ratios and enriching Bacteroides and Lactobacillus, while simultaneously reducing systemic acetic acid and increasing Proteobacteria in vaginal and oral sites. These findings reveal that diet-microbiome interactions in early gestation exert both beneficial and detrimental effects, underscoring the need for alternative interventions, potentially high-fiber, to support SCFA production and maternal-fetal health.