Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring
Open accessAbstract
Maternal immune activation (MIA) contributes to behavioural abnormalities associated with neurodevelopmental disorders in both primate and rodent offspring. In humans, epidemiological studies suggest that exposure of fetuses to maternal inflammation increases the likelihood of developing autism spectrum disorder. In pregnant mice, interleukin-17a (IL-17a) produced by T helper 17 (T H 17) cells (CD4+ T helper effector cells involved in multiple inflammatory conditions) induces behavioural and cortical abnormalities in the offspring exposed to MIA. However, it is unclear whether other maternal factors are required to promote MIA-associated phenotypes. Moreover, the underlying mechanisms by which MIA leads to T cell activation with increased IL-17a in the maternal circulation are not well understood. Here we show that MIA phenotypes in offspring require maternal intestinal bacteria that promote T H 17 cell differentiation. Pregnant mice that had been colonized with mouse commensal segmented filamentous bacteria or human commensal bacteria that induce intestinal T H 17 cells were more likely to produce offspring with MIA-associated abnormalities. We also show that small intestine dendritic cells from pregnant, but not from non-pregnant, females secrete IL-1β, IL-23 and IL-6 and stimulate T cells to produce IL-17a upon exposure to MIA. Overall, our data suggest that defined gut commensal bacteria with a propensity to induce T H 17 cells may increase the risk of neurodevelopmental disorders in the offspring of pregnant mothers undergoing immune system activation owing to infections or autoinflammatory syndromes.
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Provision of IL-17 promoting segmented filamentous bacteria to MIA mothers further enhances behavioral abnormalities in MIA offspring.
“Provision of IL-17 promoting segmented filamentous bacteria to MIA mothers further enhances behavioral abnormities in MIA offspring (Kim et al., 2017).”
From Microbiome–microglia connections via the gut–brain axis (2019) · cites this paper as Kim et al., 2017
Offsprings of pregnant female mice that harbor certain gut bacteria with propensity to induce Th17 response are at increased risk of developing neurodevelopmental disorders.
“Offsprings of pregnant female mice that harbor certain gut bacteria with a propensity to induce T helper 17 response are at increased risk of developing neurodevelopmental disorders.246”
From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [246]
Increased systemic IL-17 during pregnancy leads to autism-like behaviors in pup offspring, which can be regulated by maternal microbiota.
“Increased systemic IL-17 during pregnancy leads to development of autism-like behaviors in pup offspring (Choi et al., 2016), which can also be regulated by maternal microbiota (Kim et al., 2017).”
From The IL-17 Family of Cytokines in Health and Disease (2019) · cites this paper as Kim et al., 2017
MIA phenotypes require maternal intestinal bacteria that promote Th17 cell differentiation.
“The MIA phenotypes require maternal intestinal bacteria that promote Th17 cell differentiation [63].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [63]
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Cites
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129 · see citing works
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 · see citing works
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554 · see citing works
Self-citationCommensal <i>Bifidobacterium</i> promotes antitumor immunity and facilitates anti–PD-L1 efficacy
Sivan, A., Corrales, L., Hubert, N., Williams, J. B., Aquino-Michaels, K., Earley, Z. M., Benyamin, F. W., Man Lei, Y., Jabri, B., Alegre, M.-L., et al. (2015) · Science · doi:10.1126/science.aac4255 · Cited by 3,888 · see citing works
Host microbiota constantly control maturation and function of microglia in the CNS
Erny, D., Hrabě de Angelis, A. L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4030 · Cited by 3,569 · see citing works
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 · see citing works
Ivanov, I. I., Frutos, R. D. L., Manel, N., Yoshinaga, K., Rifkin, D. B., Sartor, R. B., Finlay, B. B., & Littman, D. R. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.09.009 · Cited by 1,770 · see citing works
Self-citationMaternal Immune Activation Alters Fetal Brain Development through Interleukin-6
Smith, S. E. P., Li, J., Garbett, K., Mirnics, K., & Patterson, P. H. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2178-07.2007 · Cited by 1,605 · see citing works
Gut-Residing Segmented Filamentous Bacteria Drive Autoimmune Arthritis via T Helper 17 Cells
Wu, H.-J., Ivanov, I. I., Darce, J., Hattori, K., Shima, T., Umesaki, Y., Littman, D. R., Benoist, C., & Mathis, D. (2010) · Immunity · doi:10.1016/j.immuni.2010.06.001 · Cited by 1,577 · see citing works
Self-citationProinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis
Lee, Y. K., Menezes, J. S., Umesaki, Y., & Mazmanian, S. K. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000082107 · Cited by 1,323 · see citing works
The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring
Choi, G. B., Yim, Y. S., Wong, H., Kim, S., Kim, H., Kim, S. V., Hoeffer, C. A., Littman, D. R., & Huh, J. R. (2016) · Science · doi:10.1126/science.aad0314 · Cited by 1,214 · see citing works
Self-citationTh17 cell induction by adhesion of microbes to intestinal epithelial cells
Atarashi, K., Tanoue, T., Ando, M., Kamada, N., Nagano, Y., Narushima, S., Suda, W., Imaoka, A., Setoyama, H., Nagamori, T., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.058 · Cited by 1,071 · see citing works
Self-citationNakae, S., Komiyama, Y., Nambu, A., Sudo, K., Iwase, M., Homma, I., Sekikawa, K., Asano, M., & Iwakura, Y. (2002) · Immunity · doi:10.1016/s1074-7613(02)00391-6 · Cited by 1,053 · see citing works
Maternal Infection Requiring Hospitalization During Pregnancy and Autism Spectrum Disorders
Atladóttir, H. Ó., Thorsen, P., Østergaard, L., Schendel, D. E., Lemcke, S., Abdallah, M., & Parner, E. T. (2010) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-1006-y · Cited by 916 · see citing works
Patches of Disorganization in the Neocortex of Children with Autism
Stoner, R., Chow, M. L., Boyle, M. P., Sunkin, S. M., Mouton, P. R., Roy, S., Wynshaw-Boris, A., Colamarino, S. A., Lein, E. S., & Courchesne, E. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1307491 · Cited by 722 · see citing works
Malkova, N. V., Yu, C. Z., Hsiao, E. Y., Moore, M. J., & Patterson, P. H. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.01.011 · Cited by 662 · see citing works
Persson, E. K., Uronen‐Hansson, H., Semmrich, M., Rivollier, A., Hägerbrand, K., Marsal, J., Guðjónsson, S., Håkansson, U., Reizis, B., Kotarsky, K., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.03.009 · Cited by 591 · see citing works
Lewis, K. L. T., Caton, M. L., Bogunovic, M., Greter, M., Grajkowska, L. T., Ng, D., Klinakis, A., Charo, I. F., Jung, S., Gommerman, J. L., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.08.013 · Cited by 538 · see citing works
Focused specificity of intestinal TH17 cells towards commensal bacterial antigens
Yang, Y., Torchinsky, M. B., Gobert, M., Xiong, H., Xu, M., Linehan, J. L., Alonzo, F., Ng, C., Chen, A., Lin, X., et al. (2014) · Nature · doi:10.1038/nature13279 · Cited by 520 · see citing works
Self-citationTan, T. G., Sefik, E., Geva-Zatorsky, N., Kua, L., Naskar, D., Teng, F., Pasman, L., Ortiz-Lopez, A., Jupp, R., Wu, H.-J. J., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617460113 · Cited by 427 · see citing works
Self-citationElevated maternal C-reactive protein and autism in a national birth cohort
Brown, A. S., Sourander, A., Hinkka-Yli-Salomäki, S., McKeague, I. W., Sundvall, J., & Surcel, H.-M. (2014) · Molecular Psychiatry · doi:10.1038/mp.2012.197 · Cited by 343 · see citing works
Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders
Lee, B. K., Magnusson, C., Gardner, R. M., Blomström, Å., Newschaffer, C. J., Burstyn, I., Karlsson, H., & Dalman, C. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.09.001 · Cited by 337 · see citing works
Viladomiu, M., Kivolowitz, C., Abdulhamid, A., Dogan, B., Victorio, D., Castellanos, J. G., Woo, V., Teng, F., Tran, N. L., Sczesnak, A., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf9655 · Cited by 314 · see citing works
Self-citationReversing behavioural abnormalities in mice exposed to maternal inflammation
Shin Yim, Y., Park, A., Berrios, J., Lafourcade, M., Pascual, L. M., Soares, N., Yeon Kim, J., Kim, S., Kim, H., Waisman, A., et al. (2017) · Nature · doi:10.1038/nature23909 · Cited by 303 · see citing works
Self-citationBauman, M. D., Iosif, A.-M., Smith, S. E. P., Bregere, C., Amaral, D. G., & Patterson, P. H. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.06.025 · Cited by 294 · see citing works
Th17 cells: from precursors to players in inflammation and infection
Awasthi, A., & Kuchroo, V. K. (2009) · International Immunology · doi:10.1093/intimm/dxp021 · Cited by 241 · see citing works
Schwartzer, J. J., Careaga, M., Onore, C. E., Rushakoff, J. A., Berman, R. F., & Ashwood, P. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.16 · Cited by 227 · see citing works
Focal cortical dysplasias in autism spectrum disorders
Casanova, M. F., El-Baz, A. S., Kamat, S. S., Dombroski, B. A., Khalifa, F., Elnakib, A., Soliman, A., Allison-McNutt, A., & Switala, A. E. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-67 · Cited by 150 · see citing works
Maternal immune activation in nonhuman primates alters social attention in juvenile offspring
Machado, C. J., Whitaker, A. M., Smith, S. E. P., Patterson, P. H., & Bauman, M. D. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.07.035 · Cited by 136 · see citing works
Yee, N., Schwarting, R. K. W., Fuchs, E., & Wöhr, M. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.05.010 · Cited by 71 · see citing works
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Interaction between microbiota and immunity in health and disease
Zheng, D., Liwinski, T., & Elinav, E. (2020) · Cell Research · doi:10.1038/s41422-020-0332-7 · Cited by 3,947 · see citing works
The gut microbiota–brain axis in behaviour and brain disorders
Morais, L. H., Schreiber, H. L., & Mazmanian, S. K. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-00460-0 · Cited by 2,149 · see citing works
The IL-17 Family of Cytokines in Health and Disease
McGeachy, M. J., Cua, D. J., & Gaffen, S. L. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.021 · Cited by 1,443 · see citing works
The gut microbiome in neurological disorders
Cryan, J. F., O'Riordan, K. J., Sandhu, K., Peterson, V., & Dinan, T. G. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30356-4 · Cited by 1,336 · see citing works
Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice
Sharon, G., Cruz, N. J., Kang, D.-W., Gandal, M. J., Wang, B., Kim, Y.-M., Zink, E. M., Casey, C. P., Taylor, B. C., Lane, C. J., et al. (2019) · Cell · doi:10.1016/j.cell.2019.05.004 · Cited by 1,182 · see citing works
The gut microbiome: Relationships with disease and opportunities for therapy
Durack, J., & Lynch, S. V. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20180448 · Cited by 955 · see citing works
Signaling inflammation across the gut-brain axis
Agirman, G., Yu, K. B., & Hsiao, E. Y. (2021) · Science · doi:10.1126/science.abi6087 · Cited by 846 · see citing works
The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology
Rutsch, A., Kantsjö, J. B., & Ronchi, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.604179 · Cited by 821 · see citing works
Long-term benefit of microbiota transfer therapy on autism symptoms and gut microbiota
Kang, D.-W., Adams, J. B., Coleman, D. M., Pollard, E. L., Maldonado, J., McDonough-Means, S., Caporaso, J. G., & Krajmalnik-Brown, R. (2019) · Scientific Reports · doi:10.1038/s41598-019-42183-0 · Cited by 749 · see citing works
Maternal immune activation and neuroinflammation in human neurodevelopmental disorders
Han, V. X., Patel, S., Jones, H. F., & Dale, R. C. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00530-8 · Cited by 683 · see citing works
Cytokine Regulation and Function in T Cells
Dong, C. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-061020-053702 · Cited by 594 · see citing works
Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development
Yockey, L. J., & Iwasaki, A. (2018) · Immunity · doi:10.1016/j.immuni.2018.07.017 · Cited by 567 · see citing works
The maternal microbiome modulates fetal neurodevelopment in mice
Vuong, H. E., Pronovost, G. N., Williams, D. W., Coley, E. J. L., Siegler, E. L., Qiu, A., Kazantsev, M., Wilson, C. J., Rendon, T., & Hsiao, E. Y. (2020) · Nature · doi:10.1038/s41586-020-2745-3 · Cited by 564 · see citing works
Surgery, neuroinflammation and cognitive impairment
Alam, A., Hana, Z., Jin, Z., Suen, K. C., & Ma, D. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.10.021 · Cited by 483 · see citing works
Microbiome–microglia connections via the gut–brain axis
Abdel-Haq, R., Schlachetzki, J. C. M., Glass, C. K., & Mazmanian, S. K. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180794 · Cited by 471 · see citing works
“Provision of IL-17 promoting segmented filamentous bacteria to MIA mothers further enhances behavioral abnormities in MIA offspring (Kim et al., 2017).”
BackgroundAn Inflammation-Centric View of Neurological Disease: Beyond the Neuron
Skaper, S. D., Facci, L., Zusso, M., & Giusti, P. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00072 · Cited by 461 · see citing works
Immunoneuropsychiatry — novel perspectives on brain disorders
Pape, K., Tamouza, R., Leboyer, M., & Zipp, F. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0174-4 · Cited by 455 · see citing works
Dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus
Wang, J., Zheng, J., Shi, W., Du, N., Xu, X., Zhang, Y., Ji, P., Zhang, F., Jia, Z., Wang, Y., et al. (2018) · Gut · doi:10.1136/gutjnl-2018-315988 · Cited by 452 · see citing works
Microbiota modulate sympathetic neurons via a gut–brain circuit
Muller, P. A., Schneeberger, M., Matheis, F., Wang, P., Kerner, Z. J., Ilanges, A., Pellegrino, K., del Mármol, J. I., Castro, T. B. R., Furuichi, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2474-7 · Cited by 449 · see citing works
Self-citationMicroglia and early brain development: An intimate journey
Thion, M. S., Ginhoux, F., & Garel, S. (2018) · Science · doi:10.1126/science.aat0474 · Cited by 440 · see citing works
Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS
Faust, T. E., Gunner, G., & Schafer, D. P. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00507-y · Cited by 440 · see citing works
The microbiota–gut–brain axis and neurodevelopmental disorders
Wang, Q., Yang, Q., & Liu, X. (2023) · Protein & Cell · doi:10.1093/procel/pwad026 · Cited by 407 · see citing works
Aburto, M. R., & Cryan, J. F. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00890-0 · Cited by 391 · see citing works
Neuromodulation by the immune system: a focus on cytokines
Salvador, A. F., de Lima, K. A., & Kipnis, J. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00508-z · Cited by 389 · see citing works
Prenatal developmental origins of future psychopathology: mechanisms and pathways
Monk, C., Lugo-Candelas, C., & Trumpff, C. (2019) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-050718-095539 · Cited by 388 · see citing works
Recognizing Depression from the Microbiota–Gut–Brain Axis
Liang, S., Wu, X., Hu, X., Wang, T., & Jin, F. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061592 · Cited by 387 · see citing works
Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders
Kang, D.-W., Ilhan, Z. E., Isern, N. G., Hoyt, D. W., Howsmon, D. P., Shaffer, M., Lozupone, C. A., Hahn, J., Adams, J. B., & Krajmalnik-Brown, R. (2018) · Anaerobe · doi:10.1016/j.anaerobe.2017.12.007 · Cited by 381 · see citing works
Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition
Pasciuto, E., Burton, O. T., Roca, C. P., Lagou, V., Rajan, W. D., Theys, T., Mancuso, R., Tito, R. Y., Kouser, L., Callaerts-Vegh, Z., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.026 · Cited by 368 · see citing works
Microbiomes as sources of emergent host phenotypes
Lynch, J. B., & Hsiao, E. Y. (2019) · Science · doi:10.1126/science.aay0240 · Cited by 339 · see citing works
Meningeal γδ T cell-derived IL-17 controls synaptic plasticity and short-term memory
Ribeiro, M., Brigas, H. C., Temido-Ferreira, M., Pousinha, P. A., Regen, T., Santa, C., Coelho, J. E., Marques-Morgado, I., Valente, C. A., Omenetti, S., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aay5199 · Cited by 335 · see citing works
The Impact of Systemic Inflammation on Neurodevelopment
Jiang, N. M., Cowan, M. N., Moonah, S. N., & Petri, W. A. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.06.008 · Cited by 330 · see citing works
The neuroendocrinology of the microbiota-gut-brain axis: a behavioural perspective
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“Indeed, pre-treatment of MIA mothers with the antibiotic vancomycin prevents the development of behavioural deficits in the offspring (Kim et al., 2017).”
BackgroundWang, Y., Tong, Q., Ma, S.-R., Zhao, Z.-X., Pan, L.-B., Cong, L., Han, P., Peng, R., Yu, H., Lin, Y., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00456-5 · Cited by 319 · see citing works
Reversing behavioural abnormalities in mice exposed to maternal inflammation
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Self-citationControl of Immunity by the Microbiota
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Maternal Immune Activation and Neuropsychiatric Illness: A Translational Research Perspective
Brown, A. S., & Meyer, U. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.17121311 · Cited by 285 · see citing works
IL-17a promotes sociability in mouse models of neurodevelopmental disorders
Reed, M. D., Yim, Y. S., Wimmer, R. D., Kim, H., Ryu, C., Welch, G. M., Andina, M., King, H. O., Waisman, A., Halassa, M. M., et al. (2020) · Nature · doi:10.1038/s41586-019-1843-6 · Cited by 274 · see citing works
Self-citationImmune cells and CNS physiology: Microglia and beyond
Norris, G. T., & Kipnis, J. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180199 · Cited by 274 · see citing works
Beyond Host Defense: Emerging Functions of the Immune System in Regulating Complex Tissue Physiology
Rankin, L. C., & Artis, D. (2018) · Cell · doi:10.1016/j.cell.2018.03.013 · Cited by 271 · see citing works
Evolutionary and Ecological Consequences of Gut Microbial Communities
Moran, N. A., Ochman, H., & Hammer, T. J. (2019) · Annual Review of Ecology Evolution and Systematics · doi:10.1146/annurev-ecolsys-110617-062453 · Cited by 271 · see citing works
Gut-Brain Psychology: Rethinking Psychology From the Microbiota–Gut–Brain Axis
Liang, S., Wu, X., & Jin, F. (2018) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2018.00033 · Cited by 269 · see citing works
Brain changes in a maternal immune activation model of neurodevelopmental brain disorders
Bergdolt, L., & Dunaevsky, A. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.002 · Cited by 266 · see citing works
The fetal origins of mental illness
al-Haddad, B. J. S., Oler, E., Armistead, B., Elsayed, N. A., Weinberger, D. R., Bernier, R., Burd, I. D., Kapur, R. P., Jacobsson, B., Wang, C., et al. (2019) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2019.06.013 · Cited by 265 · see citing works
The Role of Microbiota in Infant Health: From Early Life to Adulthood
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Innate immunity at the crossroads of healthy brain maturation and neurodevelopmental disorders
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Zhang, Z., Tang, H., Chen, P., Xie, H., & Tao, Y. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0074-5 · Cited by 251 · see citing works
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Kentner, A. C., Bilbo, S. D., Brown, A. S., Hsiao, E. Y., McAllister, A. K., Meyer, U., Pearce, B. D., Pletnikov, M. V., Yolken, R. H., & Bauman, M. D. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0185-7 · Cited by 245 · see citing works
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Fung, T. C. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104714 · Cited by 228 · see citing works
Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring
Lim, A. I., McFadden, T. E., Link, V. M., Han, S., Karlsson, R., Stacy, A., Farley, T. K., Lima-Junior, D. S., Harrison, O. J., Desai, J. V., et al. (2021) · Science · doi:10.1126/science.abf3002 · Cited by 226 · see citing works
The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders
Hughes, H. K., Rose, D., & Ashwood, P. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0887-6 · Cited by 225 · see citing works
Neurodevelopmental Resilience and Susceptibility to Maternal Immune Activation
Meyer, U. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.08.001 · Cited by 222 · see citing works
Neuroimmune circuits in inter-organ communication
Huh, J. R., & Veiga‐Fernandes, H. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0247-z · Cited by 216 · see citing works
Self-citationRole of Gut Microbiome in Autism Spectrum Disorder and Its Therapeutic Regulation
Taniya, M. A., Chung, H.-J., Al Mamun, A., Alam, S., Aziz, M. A., Emon, N. U., Islam, M. M., Hong, S.-T. S., Podder, B. R., Ara Mimi, A., et al. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.915701 · Cited by 207 · see citing works
Comer, A. L., Carrier, M., Tremblay, M., & Cruz‐Martín, A. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00274 · Cited by 204 · see citing works
Maternal inflammation and its ramifications on fetal neurodevelopment
Kwon, H., Choi, G. B., & Huh, J. R. (2022) · Trends in Immunology · doi:10.1016/j.it.2022.01.007 · Cited by 199 · see citing works
Self-citationHaddad, F. L., Patel, S. V., & Schmid, S. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.012 · Cited by 195 · see citing works
Inflammatory memory and tissue adaptation in sickness and in health
Naik, S., & Fuchs, E. V. (2022) · Nature · doi:10.1038/s41586-022-04919-3 · Cited by 185 · see citing works
Lu, S., Zhao, Q., Yu, G., Sun, Z., Li, W., Guo, S., & Zhang, A. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117207 · Cited by 182 · see citing works
Role of the Immune System in the Development of the Central Nervous System
Morimoto, K., & Nakajima, K. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00916 · Cited by 181 · see citing works
An Immunologic Mode of Multigenerational Transmission Governs a Gut Treg Setpoint
Ramanan, D., Sefik, E., Galván-Peña, S., Wu, M., Yang, L., Yang, Z., Kostic, A. D., Golovkina, T. V., Kasper, D. L., Mathis, D. J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.04.030 · Cited by 173 · see citing works
Gut microbiota and pro/prebiotics in Alzheimer’s disease
Pluta, R. M., Ułamek-Kozioł, M., Januszewski, S., & Czuczwar, S. J. (2020) · Aging · doi:10.18632/aging.102930 · Cited by 171 · see citing works
The contribution of the gut microbiome to neurodevelopment and neuropsychiatric disorders
Warner, B. B. (2018) · Pediatric Research · doi:10.1038/s41390-018-0191-9 · Cited by 168 · see citing works
Microglia and Neurodevelopmental Disorders
Lukens, J. R., & Eyo, U. B. (2022) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-110920-023056 · Cited by 165 · see citing works
Doroszkiewicz, J., Groblewska, M., & Mroczko, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221810028 · Cited by 160 · see citing works
The gut vascular barrier: a new player in the gut–liver–brain axis
Brescia, P., & Rescigno, M. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2021.06.007 · Cited by 158 · see citing works
Gialloreti, L. E., Mazzone, L., Benvenuto, A., Fasano, A., García-Alcón, A., Kraneveld, A. D., Moavero, R., Raz, R., Riccio, M. P., Siracusano, M., et al. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8020217 · Cited by 157 · see citing works
Microbiota-modulated CART <sup>+</sup> enteric neurons autonomously regulate blood glucose
Muller, P. A., Matheis, F., Schneeberger, M., Kerner, Z., Jové, V., & Mucida, D. (2020) · Science · doi:10.1126/science.abd6176 · Cited by 154 · see citing works
Maternal immune activation in mice disrupts proteostasis in the fetal brain
Kalish, B. T., Kim, E., Finander, B., Duffy, E. E., Kim, H., Gilman, C. K., Yim, Y. S., Tong, L., Kaufman, R. J., Griffith, E. C., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-00762-9 · Cited by 151 · see citing works
Self-citationGut microbiota changes in children with autism spectrum disorder: a systematic review
Ho, L. K. H., Tong, V. J. W., Syn, N., Nagarajan, N., Tham, E. H., Tay, S. K., Shorey, S., Tambyah, P. A., & Law, E. C. N. (2020) · Gut Pathogens · doi:10.1186/s13099-020-0346-1 · Cited by 149 · see citing works
Beyond the gut: decoding the gut–immune–brain axis in health and disease
Park, J. C., Chang, L., Kwon, H.-K., & Im, S.-H. (2025) · Cellular & Molecular Immunology · doi:10.1038/s41423-025-01333-3 · Cited by 149 · see citing works
Mirabella, F., Desiato, G., Mancinelli, S., Fossati, G., Rasile, M., Morini, R., Markicevic, M., Grimm, C., Amegandjin, C. A., Termanini, A., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.10.006 · Cited by 148 · see citing works
Kim, E., Paik, D., Ramírez, R. N., Biggs, D. G., Park, Y., Kwon, H., Choi, G. B., & Huh, J. R. (2021) · Immunity · doi:10.1016/j.immuni.2021.11.005 · Cited by 148 · see citing works
Self-citationPerinatal Interactions between the Microbiome, Immunity, and Neurodevelopment
Pronovost, G. N., & Hsiao, E. Y. (2019) · Immunity · doi:10.1016/j.immuni.2018.11.016 · Cited by 146 · see citing works
Carlezon, W. A., Kim, W., Missig, G., Finger, B. C., Landino, S. M., Alexander, A. J., Mokler, E. L., Robbins, J. O., Li, Y., Bolshakov, V. Y., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-53294-z · Cited by 143 · see citing works
Pre/post-natal exposure to microplastic as a potential risk factor for autism spectrum disorder
Zaheer, J., Kim, H., Ko, I. O., Jo, E.-K., Choi, E., Lee, H., Shim, I., Woo, H., Choi, J. H., Kim, G.-H., et al. (2022) · Environment International · doi:10.1016/j.envint.2022.107121 · Cited by 141 · see citing works
Self-citationTranscriptional and Epigenetic Regulation of Microglia in Health and Disease
Yeh, H., & Ikezu, T. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.11.004 · Cited by 135 · see citing works
The role of the microbiome in the neurobiology of social behaviour
Sarkar, A., Harty, S., Johnson, K. V. ‐., Moeller, A. H., Carmody, R. N., Lehto, S. M., Erdman, S. E., Dunbar, R. I. M., & Burnet, P. W. J. (2020) · Biological Reviews · doi:10.1111/brv.12603 · Cited by 135 · see citing works
Li, N., Yang, J., Zhang, J., Liang, C., Wang, Y., Chen, B., Zhao, C., Wang, J., Zhang, G., Zhao, D., et al. (2019) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2019.01.002 · Cited by 135 · see citing works
The NLRP6 inflammasome in health and disease
Ghimire, L., Paudel, S., Jin, L., & Jeyaseelan, S. (2020) · Mucosal Immunology · doi:10.1038/s41385-020-0256-z · Cited by 134 · see citing works
Exposure to Ultraviolet Radiation in the Modulation of Human Diseases
Hart, P. H., Norval, M., Byrne, S. N., & Rhodes, L. E. (2018) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012809 · Cited by 133 · see citing works
The immune system and psychiatric disease: a basic science perspective
Bennett, F. C., & Molofsky, A. V. (2019) · Clinical & Experimental Immunology · doi:10.1111/cei.13334 · Cited by 133 · see citing works
Fujii, Y., Nguyen, T. T. T., Fujimura, Y., Kameya, N., Nakamura, S., Arakawa, K., & Morita, H. (2019) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2019.1644149 · Cited by 133 · see citing works
Tang, B., Tang, L., Li, S., Liu, S., He, J., Li, P., Wang, S., Yang, M. J., Zhang, L., Lei, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36981-4 · Cited by 133 · see citing works
Multi-hit early life adversity affects gut microbiota, brain and behavior in a sex-dependent manner
Rincel, M., Aubert, P., Chevalier, J., Grohard, P. ‐., Basso, L., de Oliveira, C. M., Helbling, J., Lévy, É., Chevalier, G., Leboyer, M., et al. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.03.006 · Cited by 132 · see citing works
The gut microbiome and mental health: advances in research and emerging priorities
Shoubridge, A. P., Choo, J. M., Martin, A. M., Keating, D. J., Wong, M., Licinio, J., & Rogers, G. B. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01479-w · Cited by 130 · see citing works
Microbial transmission in the social microbiome and host health and disease
Sarkar, A., McInroy, C. J. A., Harty, S., Raulo, A., Ibata, N. G. O., Valles‐Colomer, M., Johnson, K. V. ‐., Brito, I., Henrich, J., Archie, E. A., et al. (2024) · Cell · doi:10.1016/j.cell.2023.12.014 · Cited by 130 · see citing works
Inflammation of the Embryonic Choroid Plexus Barrier following Maternal Immune Activation
Cui, J., Shipley, F. B., Shannon, M. L., Alturkistani, O., Dani, N., Webb, M. D., Sugden, A. U., Andermann, M. L., & Lehtinen, M. K. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.09.020 · Cited by 128 · see citing works
T Cell Responses to the Microbiota
Ivanov, I. I., Tuganbaev, T., Skelly, A. N., & Honda, K. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101320-011829 · Cited by 128 · see citing works
Self-citationGur, T. L., Palkar, A. V., Rajasekera, T., Allen, J., Niraula, A., Godbout, J., & Bailey, M. T. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.06.025 · Cited by 127 · see citing works
Prenatal and postnatal contributions of the maternal microbiome on offspring programming
Jašarević, E., & Bale, T. L. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.100797 · Cited by 127 · see citing works
Histamine, Neuroinflammation and Neurodevelopment: A Review
Carthy, E. R., & Ellender, T. J. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.680214 · Cited by 127 · see citing works
The gut microbiota promotes distal tissue regeneration via RORγ+ regulatory T cell emissaries
Hanna, B. S., Wang, G., Galván-Peña, S., Mann, A. O., Ramirez, R. N., Muñoz-Rojas, A. R., Smith, K., Wan, M., Benoist, C., & Mathis, D. (2023) · Immunity · doi:10.1016/j.immuni.2023.01.033 · Cited by 126 · see citing works
How gut microbes could drive brain disorders
Willyard, C. (2021) · Nature · doi:10.1038/d41586-021-00260-3 · Cited by 124 · see citing works
Environment matters: microglia function and dysfunction in a changing world
Hanamsagar, R., & Bilbo, S. D. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.10.007 · Cited by 122 · see citing works
Regulation of common neurological disorders by gut microbial metabolites
Park, J., & Kim, C. H. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00703-x · Cited by 120 · see citing works
Bacterial Peptidoglycans from Microbiota in Neurodevelopment and Behavior
Gonzalez-Santana, A., & Diaz Heijtz, R. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.05.003 · Cited by 118 · see citing works
Cattane, N., Richetto, J., & Cattaneo, A. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.07.001 · Cited by 118 · see citing works
- Authors
- Kim, S., Kim, H., Yim, Y. S., Ha, S., Atarashi, K., Tan, T. G., Longman, R. S., Honda, K., Littman, D. R., Choi, G. B., & Huh, J. R.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- McGovern Institute for Brain Research (US)
- Keio University (JP)
- Harvard University (US)
- Weill Cornell Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Choi, Gloria B.
- Huh, Jun R.
- ORCID
- Venue
- Nature
- Published
- 2017-09-13
- Volume
- 549
- Issue
- 7673
- Pages
- 528-532
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5870873
- OpenAlex
- W2754172044
- Cited by
- 678
- References
- 30
- Citations by year
- 2026: 49 · 2025: 80 · 2024: 79 · 2023: 81 · 2022: 83 · 2021: 72 · 2020: 77 · 2019: 77 · 2018: 66 · 2017: 11 · 2013: 1
- FWCI
- 21.04
- Type
- journal article
- Language
- en
- Update notices
- expression_of_concern (2026-10-08)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Japan Society for the Promotion of Science (15H05657)
- National Institute of Mental Health (R01MH106497, R01MH115037)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK110559, K08DK099381, R01DK106351)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- maternal immune activation, gut commensal bacteria, neurodevelopmental disorders, autism spectrum disorder, IL-17, Th17 cells, segmented filamentous bacteria, dendritic cells, somatosensory cortex, cortical development, social behavior, pregnancy, maternal inflammation, IL-23, interleukin-6, IL-1β
- MeSH terms
- Gastrointestinal Microbiome, Animals, Behavior, Animal, Dendritic Cells, Female, Inflammation, Intestine, Small, Male, Phenotype, Pregnancy, Prenatal Exposure Delayed Effects, Symbiosis, Interleukin-6, Interleukin-17, Mice, Interleukin-1beta, Interleukin-23, Th17 Cells
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