Early pregnancy is characterized by a significant decrease in the diversity of the oral microbiome and strong associations with lifestyle and conception method

Background: Most studies of the oral microbiome during pregnancy have focused on the second and third trimesters (T2, T3, respectively). To date, no large-scale longitudinal study has examined oral microbiome development across all three trimesters, leaving early gestational dynamics largely unexplored. Methods: We conducted a longitudinal analysis of 346 pregnant Israeli women, validated in an independent cohort of 154 Russian women. In Israel, saliva samples were collected during T1 (11–14 weeks), T2 (24–28 weeks), and T3 (32–38 weeks); in Russia, samples were collected during T2 and T3 at similar gestational ages. Microbial profiles were analyzed for differential abundance and associations with maternal nutrition and lifestyle. Results: Significant shifts in oral microbial composition were observed as early as the transition from T1 to T2. Alpha diversity decreased progressively across pregnancy. Taxonomic changes included a reduction in Verrucomicrobiota and an increase in Synergistota. Gluten-free diet showed the strongest associations with microbiome composition across all trimesters, followed by smoking history and conception method. Conclusions: This study provides the first large-scale evidence of significant oral microbiome changes beginning in early-mid pregnancy, characterized by reduced diversity and a directional shift toward inflammation-associated communities. Strong associations between gluten consumption and smoking suggest a lifestyle effect on the oral microbiome.