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Mol Brain. 2017 Apr 20;10(1):14. doi: 10.1186/s13041-017-0292-0.

Modeling environmental risk factors of autism in mice induces IBD-related gut microbial dysbiosis and hyperserotonemia.

Lim JS1,2, Lim MY1,2,3, Choi Y1, Ko G4,5,6,7.

Author information

1
Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
2
Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea.
3
Research Group of Gut Microbiome, Korea Food Research Institute, Seongnam, Gyeonggi-do, Republic of Korea.
4
Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea. gko@snu.ac.kr.
5
Center for Human and Environmental Microbiome, Seoul National University, Seoul, Republic of Korea. gko@snu.ac.kr.
6
N-Bio, Seoul National University, Seoul, Republic of Korea. gko@snu.ac.kr.
7
KoBioLabs, Inc., 1-Gwanak-ro, Gwanak-gu, Bldg 220, Rm 630, Seoul, 151-746, Republic of Korea. gko@snu.ac.kr.

Abstract

Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that are sharply increasing in prevalence worldwide. Intriguingly, ASD is often accompanied by an array of systemic aberrations including (1) increased serotonin, (2) various modes of gastrointestinal disorders, and (3) inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. Also, accumulating number of studies report that the gut microbial composition is significantly altered in children with ASD or patients with IBD. Surprisingly, when we analyzed the gut microbiota of poly I:C and VPA-induced mouse models of ASD, we found a distinct pattern of microbial dysbiosis that highly recapitulated those reported in clinical cases of ASD and IBD. Moreover, we report that such microbial dysbiosis led to notable perturbations in microbial metabolic pathways that are known to negatively affect the host, especially with regards to the pathogenesis of ASD and IBD. Lastly, we found that serum level of serotonin is significantly increased in both poly I:C and VPA mice, and that it correlates with increases of a bacterial genus and a metabolic pathway that are implicated in stimulation of host serotonin production. Our results using animal model identify prenatal environmental risk factors of autism as possible causative agents of IBD-related gut microbial dysbiosis in ASD, and suggest a multifaceted role of gut microbiota in the systemic pathogenesis of ASD and hyperserotonemia.

PMID:
28427452
PMCID:
PMC5399341
DOI:
10.1186/s13041-017-0292-0
[Indexed for MEDLINE]
Free PMC Article

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