Nutrition-dependent development of the Oral Microbiome in Early Pregnancy

Finkelstein, S.; Frishman, S.; Turjeman, S.; Shtossel, O.; Riumin, A.; Tikhonov, E.; Ohayon, M. N.; Pinto, Y.; Popova, P.; Tkachuk, A.; Vasukova, E.; Anopova, A.; Pustozerov, E.; Pervunina, T.; Grineva, E.; Hod, M.; Schwartz, B.; Hadar, E.; Koren, O.; Louzoun, Y.

doi:10.1101/2025.09.29.679276

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bioRxiv · 10.1101/2025.09.29.679276

Nutrition-dependent development of the Oral Microbiome in Early Pregnancy

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Abstract

BackgroundMost studies of the oral microbiome during pregnancy have focused on the second and third trimesters (T2, T3, respectively). Findings remain inconsistent-some report shifts in specific taxa, whereas others observe little change in diversity. To date, no large-scale longitudinal study has examined oral microbiome development across all three trimesters, leaving early gestational dynamics (during the first trimester; T1) largely unexplored. MethodsWe conducted a longitudinal analysis of the oral microbiome in 346 pregnant women from Israel and validated key findings in an independent cohort of 154 pregnant women from Russia. In Israel, saliva samples were collected during T1 (11-14 weeks), T2 (24-28 weeks), and T3 (32-38 weeks) trimesters; in Russia, samples were collected during T2 and T3 with similar ranges of gestational weeks. Alongside sample collection, participants completed dietary and health questionnaires to assess maternal factors that could influence microbial composition. Microbial profiles were analyzed to test for (i) differential abundance across trimesters and (ii) the influence of maternal nutrition and lifestyle factors on these dynamics. ResultsSignificant shifts in oral microbial composition were observed as early as the transition from T1 to T2. Alpha diversity decreased progressively across pregnancy (Shannon index: T1 = 3.261, T2 = 3.173, T3 = 3.109; Kruskal-Wallis p = 0.0023). Notable taxonomic changes included a significant reduction in Verrucomicrobiota (particularly Akkermansia muciniphila) and an increase in Synergistota from T1 to T2 (adjusted p < 0.01), alongside an increase in Gammaproteobacteria and a decrease in Erysipelotrichia, suggesting an ecological shift towards potentially pro-inflammatory communities. Despite these systematic population-level changes, within-subject microbial distances across trimesters were smaller than between-subject distances, indicating that individual women maintained relatively stable microbial profiles over time. Among 54 maternal variables examined, gluten-free diet showed the strongest and most consistent associations with oral microbiome composition across all trimesters, followed by smoking history and conception method. Key findings were validated in an independent cohort of 154 Russian women. ConclusionsThis study provides the first large-scale evidence of significant oral microbiome changes beginning in early pregnancy, characterized by reduced diversity and a directional shift toward potentially pro-inflammatory communities. The strong associations with gluten consumption and smoking suggest a large-scale effect of lifestyle on the pregnancy oral microbiome. The alteration in the microbial composition highlights the oral microbiome as a sensitive marker of gestational physiology.

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Finkelstein, S., Frishman, S., Turjeman, S., Shtossel, O., Riumin, A., Tikhonov, E., Ohayon, M. N., Pinto, Y., Popova, P., Tkachuk, A., Vasukova, E., Anopova, A., Pustozerov, E., Pervunina, T., Grineva, E., Hod, M., Schwartz, B., Hadar, E., Koren, O., Louzoun, Y.. 2025-09-29. Nutrition-dependent development of the Oral Microbiome in Early Pregnancy. https://doi.org/10.1101/2025.09.29.679276

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