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Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain
Open accessAbstract
The neonate is exposed to the maternal vaginal microbiota during parturition, providing the primary source for normal gut colonization, host immune maturation, and metabolism. These early interactions between the host and microbiota occur during a critical window of neurodevelopment, suggesting early life as an important period of cross talk between the developing gut and brain. Because perturbations in the prenatal environment such as maternal stress increase neurodevelopmental disease risk, disruptions to the vaginal ecosystem could be a contributing factor in significant and long-term consequences for the offspring. Therefore, to examine the hypothesis that changes in the vaginal microbiome are associated with effects on the offspring gut microbiota and on the developing brain, we used genomic, proteomic and metabolomic technologies to examine outcomes in our mouse model of early prenatal stress. Multivariate modeling identified broad proteomic changes to the maternal vaginal environment that influence offspring microbiota composition and metabolic processes essential for normal neurodevelopment. Maternal stress altered proteins related to vaginal immunity and abundance of Lactobacillus, the prominent taxa in the maternal vagina. Loss of maternal vaginal Lactobacillus resulted in decreased transmission of this bacterium to offspring. Further, altered microbiota composition in the neonate gut corresponded with changes in metabolite profiles involved in energy balance, and with region- and sex-specific disruptions of amino acid profiles in the developing brain. Taken together, these results identify the vaginal microbiota as a novel factor by which maternal stress may contribute to reprogramming of the developing brain that may predispose individuals to neurodevelopmental disorders.
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“Animal models demonstrate that microbiome changes in response to maternal stress are passed onto offspring at birth, setting in motion microbial dysbiosis that persists into adulthood (105–107).”
From Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder (2017) · cites this paper as [106]
In the citing paper
“Prenatal stress induced depressive-like behavior in adulthood mice, which led to a long-lasting change of the enteric microbiota composition associated with an exaggerated HPA axis response to stress [353][354][355].”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [353]
In the citing paper
“Jašarević et al. demonstrated changes in the microbiome of these offspring, as well as alterations in the metabolome of the gut and brain (343).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [343]
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Citations
Cites
The gut microbiota shapes intestinal immune responses during health and disease
Round, J. L., & Mazmanian, S. K. (2009) · Nature Reviews Immunology · doi:10.1038/nri2515 · Cited by 5,029
Dominguez-Bello, M. G., Costello, E. K., Contreras, M., Magris, M., Hidalgo, G., Fierer, N., & Knight, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002601107 · Cited by 4,774
Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Cryan, J. F., & Dinan, T. G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3346 · Cited by 4,572
Vaginal microbiome of reproductive-age women
Ravel, J., Gajer, P., Abdo, Z., Schneider, G. M., Koenig, S. S. K., McCulle, S. L., Karlebach, S., Gorle, R., Russell, J., Tacket, C. O., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002611107 · Cited by 4,254
Hsiao, E. Y., McBride, S. W., Hsien, S., Sharon, G., Hyde, E. R., McCue, T., Codelli, J. A., Chow, J., Reisman, S. E., Petrosino, J. F., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.024 · Cited by 3,283
Normal gut microbiota modulates brain development and behavior
Heijtz, R. D., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., Hibberd, M. L., Forssberg, H., & Pettersson, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010529108 · Cited by 3,228
Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X., Kubo, C., & Koga, Y. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.063388 · Cited by 2,735
Succession of microbial consortia in the developing infant gut microbiome
Koenig, J. E., Spor, A., Scalfone, N., Fricker, A. D., Stombaugh, J., Knight, R., Angenent, L. T., & Ley, R. E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000081107 · Cited by 2,540
The gut microbiota influences blood-brain barrier permeability in mice
Braniste, V., Al-Asmakh, M., Kowal, C., Anuar, F., Abbaspour, A., Tóth, M., Korecka, A., Bakocevic, N., Ng, L. G., Kundu, P., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009759 · Cited by 2,530
Orthogonal projections to latent structures (O‐PLS)
Trygg, J., & Wold, S. (2002) · Journal of Chemometrics · doi:10.1002/cem.695 · Cited by 2,523
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Qansuwa, E. M., Atalah, H. N., Abdelkader, M., Russell, A. E., Dakhlallah, D. A., & Brown, C. M. (2023) · Springer eBooks · doi:10.1007/978-981-19-3949-5_2-1
Heim, C. C. (2023) · Vandenhoeck & Ruprecht eBooks · doi:10.13109/9783666408687.39
O’Callaghan, J. L. (2023) · Queensland University of Technology · doi:10.5204/thesis.eprints.244719
Özdemir, B. G. (2023) · Academic Journal of Health · doi:10.14744/acadjhealth.2023.14632
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Foster, J. A., & Clarke, G. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-12-814800-6.00004-2
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EARLY LIFE STRESS AS A MODEL FOR STUDYING COMPLEX BEHAVIORS IN EXPERIMENTAL ANIMALS
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Arsenault, M., Lillie, B. N., Nadeem, K., Khafipour, E., & Farzan, A. (2024) · Figshare · doi:10.6084/m9.figshare.26725544
Arsenault, M., Lillie, B. N., Nadeem, K., Khafipour, E., & Farzan, A. (2024) · Figshare · doi:10.6084/m9.figshare.25902431
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Iachizzi, M., Zajac, N., Ruiz, J. L., Güller, T., RABIN, R., Schalbetter, S. M., Cillis, F. D., Moccia, M., Cattaneo, A., Cryan, J. F., et al. (2026) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2026.106571
Zhang, F., Xu, W., Zeng, R., Chen, J., & Huang, J. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2649440
Airaksinen, V., Pesonen, M., Bernhardsen, G. P., Chortatos, A., Keski‐Nisula, L., Backman, K., Täubel, M., Kirjavainen, P. V., & Lehto, S. M. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.121828
Compositional maturation of the microbiome and adaptive immunity in the postnatal period
Green, M., Cleary, S. R., Kwiecien-Delaney, B. J., & Foster (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1772425
Alnasser, S. M., Ravikumar, S., Saravanan, J., Selvaraj, D., & Gunasekaran, V. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1778580
Li, Q., Sun, J., Tian, P., Zhao, J., Chen, W. F., Wang, G., & Zhang, H. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.111109
The cervicovaginal gut microbiota axis as a key determinant of systemic physiology
Rosenn, E. H., Zuniga, M., Lipshitz, M., Fox, E., Engel, M., & Pasinetti, G. M. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2726648
Vaginal dysbiosis increases risk of PPROM, neonatal sepsis and is exacerbated by erythromycin
MacIntyre, D. (2020) · ImmPort · doi:10.21430/m31zxg1mzw
Metadata
- Authors
- Jašarević, E., Howerton, C. L., Howard, C. D., & Bale, T. L.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Bale, Tracy L.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2015-06-16
- Volume
- 156
- Issue
- 9
- Pages
- 3265-3276
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC4541625
- OpenAlex
- W1906460723
- Cited by
- 329
- References
- 91
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 32 · 2023: 32 · 2022: 24 · 2021: 39 · 2020: 25 · 2019: 40 · 2018: 33 · 2017: 37 · 2016: 35 · 2015: 8
- FWCI
- 16.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania (P30DK19525)
- National Institutes of Health (5r01mh091258-05, MH104184, DK 19525, MH091258)
- Perelman School of Medicine, University of Pennsylvania (P30-DK19525)
- National Institute of Mental Health (P50MH099910, MH087597, MH 104184, MH 091258, R33MH104184, R01 MH-091258, R21MH104184, R01MH087597)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK 19525, P30DK019525)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Keywords
- maternal stress, vaginal microbiota, prenatal stress, neonatal gut microbiota, Lactobacillus, brain development, brain metabolomics, amino acid metabolism, energy balance, vaginal immunity, neurodevelopmental disorders, host-microbiota interactions
- MeSH terms
- Amino Acids, Animals, Brain, Colon, Female, Male, Mice, Inbred C57BL, Pregnancy, Pregnancy, Animal, Random Allocation, Sex Characteristics, Stress, Psychological, Vagina, Mice, 129 Strain, Microbiota
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