Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice

Gil Sharon, Nikki Jamie Cruz, Dae Wook Kang, Michael J. Gandal, Bo Wang, Young Mo Kim, Erika M. Zink, Cameron P. Casey, Bryn C. Taylor, Christianne J. Lane, Lisa M. Bramer, Nancy G. Isern, David W. Hoyt, Cecilia Noecker, Michael J. Sweredoski, Annie Moradian, Elhanan Borenstein, Janet K. Jansson, Rob Knight, Thomas O. MetzCarlos Lois, Daniel H. Geschwind, Rosa Krajmalnik-Brown, Sarkis K. Mazmanian

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Autism spectrum disorder (ASD) manifests as alterations in complex human behaviors including social communication and stereotypies. In addition to genetic risks, the gut microbiome differs between typically developing (TD) and ASD individuals, though it remains unclear whether the microbiome contributes to symptoms. We transplanted gut microbiota from human donors with ASD or TD controls into germ-free mice and reveal that colonization with ASD microbiota is sufficient to induce hallmark autistic behaviors. The brains of mice colonized with ASD microbiota display alternative splicing of ASD-relevant genes. Microbiome and metabolome profiles of mice harboring human microbiota predict that specific bacterial taxa and their metabolites modulate ASD behaviors. Indeed, treatment of an ASD mouse model with candidate microbial metabolites improves behavioral abnormalities and modulates neuronal excitability in the brain. We propose that the gut microbiota regulates behaviors in mice via production of neuroactive metabolites, suggesting that gut-brain connections contribute to the pathophysiology of ASD. Repetitive and social behavioral abnormalities in mice with microbiomes from patients with autism spectrum disorder can be corrected by the administration of specific metabolites.

Original languageEnglish (US)
Pages (from-to)1600-1618.e17
JournalCell
Volume177
Issue number6
DOIs
StatePublished - May 30 2019

Fingerprint

Behavioral Symptoms
Metabolites
Microbiota
Brain
Alternative Splicing
Genes
Display devices
Autism Spectrum Disorder
Gastrointestinal Microbiome
Communication
Metabolome
Tissue Donors

Keywords

  • autism
  • autism spectrum disorder
  • bacterial metabolites
  • gut microbiome
  • gut-brain axis
  • metabolome
  • microbiota
  • mouse model

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Sharon, G., Cruz, N. J., Kang, D. W., Gandal, M. J., Wang, B., Kim, Y. M., ... Mazmanian, S. K. (2019). Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice. Cell, 177(6), 1600-1618.e17. https://doi.org/10.1016/j.cell.2019.05.004

Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice. / Sharon, Gil; Cruz, Nikki Jamie; Kang, Dae Wook; Gandal, Michael J.; Wang, Bo; Kim, Young Mo; Zink, Erika M.; Casey, Cameron P.; Taylor, Bryn C.; Lane, Christianne J.; Bramer, Lisa M.; Isern, Nancy G.; Hoyt, David W.; Noecker, Cecilia; Sweredoski, Michael J.; Moradian, Annie; Borenstein, Elhanan; Jansson, Janet K.; Knight, Rob; Metz, Thomas O.; Lois, Carlos; Geschwind, Daniel H.; Krajmalnik-Brown, Rosa; Mazmanian, Sarkis K.

In: Cell, Vol. 177, No. 6, 30.05.2019, p. 1600-1618.e17.

Research output: Contribution to journalArticle

Sharon, G, Cruz, NJ, Kang, DW, Gandal, MJ, Wang, B, Kim, YM, Zink, EM, Casey, CP, Taylor, BC, Lane, CJ, Bramer, LM, Isern, NG, Hoyt, DW, Noecker, C, Sweredoski, MJ, Moradian, A, Borenstein, E, Jansson, JK, Knight, R, Metz, TO, Lois, C, Geschwind, DH, Krajmalnik-Brown, R & Mazmanian, SK 2019, 'Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice', Cell, vol. 177, no. 6, pp. 1600-1618.e17. https://doi.org/10.1016/j.cell.2019.05.004
Sharon G, Cruz NJ, Kang DW, Gandal MJ, Wang B, Kim YM et al. Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice. Cell. 2019 May 30;177(6):1600-1618.e17. https://doi.org/10.1016/j.cell.2019.05.004
Sharon, Gil ; Cruz, Nikki Jamie ; Kang, Dae Wook ; Gandal, Michael J. ; Wang, Bo ; Kim, Young Mo ; Zink, Erika M. ; Casey, Cameron P. ; Taylor, Bryn C. ; Lane, Christianne J. ; Bramer, Lisa M. ; Isern, Nancy G. ; Hoyt, David W. ; Noecker, Cecilia ; Sweredoski, Michael J. ; Moradian, Annie ; Borenstein, Elhanan ; Jansson, Janet K. ; Knight, Rob ; Metz, Thomas O. ; Lois, Carlos ; Geschwind, Daniel H. ; Krajmalnik-Brown, Rosa ; Mazmanian, Sarkis K. / Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice. In: Cell. 2019 ; Vol. 177, No. 6. pp. 1600-1618.e17.
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