The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
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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In the citing paper
“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
In the citing paper
“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]
In the citing paper
“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
In the citing paper
“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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Metadata
- 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
- 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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