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Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders

Hsiao, Elaine Y. and McBride, Sara W. and Hsien, Sophia and Sharon, Gil and Hyde, Embriette R. and McCue, Tyler and Codelli, Julian A. and Chow, Janet and Reisman, Sarah E. and Petrosino, Joseph F. and Patterson, Paul H. and Mazmanian, Sarkis K. (2013) Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders. Cell, 155 (7). pp. 1451-1463. ISSN 0092-8674. PMCID PMC3897394. https://resolver.caltech.edu/CaltechAUTHORS:20131205-105756544

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Abstract

Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.cell.2013.11.024DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897394/PubMed CentralArticle
ORCID:
AuthorORCID
Hsiao, Elaine Y.0000-0002-1633-588X
Sharon, Gil0000-0002-4605-9943
Hyde, Embriette R.0000-0002-9370-0051
Reisman, Sarah E.0000-0001-8244-9300
Petrosino, Joseph F.0000-0002-4046-6898
Mazmanian, Sarkis K.0000-0003-2713-1513
Alternate Title:The microbiota modulates gut physiology and behavioral abnormalities associated with autism
Additional Information:© 2013 Elsevier Inc. Received: August 20, 2013; Revised: October 3, 2013; Accepted: November 18, 2013; Published: December 5, 2013. We acknowledge Reyna Sauza, Jaime Rodriguez, and Taren Thron for caring for the animals; Dr. Michael Fischbach (UCSF) for advising on pathways of 4EPS and indolepyruvate synthesis; Dr. Nadim Ajami (Baylor) for providing helpful comments on the manuscript; Greg Donaldson (Caltech) for conducting experiments on microbial viability; Dr. Kym Faull (UCLA) for conducting pilot GC/MS experiments; Dr. Alessio Fasano (Massachusetts General) for conducting pilot microbiota sequencing experiments; and Dr. Jerrold Turner (U Chicago) for providing histological analysis of intestinal sections. This work was supported by a Caltech Innovation Fellowship (to E.Y.H.), Autism Speaks Weatherstone Fellowship (to E.Y.H.), NIH/NRSA Predoctoral Fellowship (to E.Y.H.), Human Frontiers Science Program Fellowship (to G.S.), DOD Graduate Fellowship (to J.A.C.), NSF Graduate Research Fellowship (to J.A.C.), Autism Speaks Trailblazer Award (to P.H.P. and S.K.M.), Caltech Innovation Initiative (to P.H.P. and S.K.M.), Caltech Grubstake Awards (to P.H.P. and S.K.M), Congressionally Directed Medical Research Award (to P.H.P. and S.K.M.), Weston Havens Award (to P.H.P. and S.K.M.), Callie D. McGrath Charitable Foundation awards (to P.H.P.) and NIMH grant MH100556 (to P.H.P. and S.K.M.).
Funders:
Funding AgencyGrant Number
Autism SpeaksUNSPECIFIED
NIH Predoctoral FellowshipUNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
National Defense Science and Engineering Graduate (NDSEG) FellowshipUNSPECIFIED
NSF Graduate Research FellowshipUNSPECIFIED
Caltech Innovation Initiative (CI2)UNSPECIFIED
Caltech Grubstake AwardsUNSPECIFIED
Congressionally Directed Medical Research AwardUNSPECIFIED
Weston Havens FoundationUNSPECIFIED
Callie D. McGrath Charitable FoundationUNSPECIFIED
NIHMH100556
Issue or Number:7
PubMed Central ID:PMC3897394
Record Number:CaltechAUTHORS:20131205-105756544
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20131205-105756544
Official Citation:Elaine Y. Hsiao, Sara W. McBride, Sophia Hsien, Gil Sharon, Embriette R. Hyde, Tyler McCue, Julian A. Codelli, Janet Chow, Sarah E. Reisman, Joseph F. Petrosino, Paul H. Patterson, Sarkis K. Mazmanian, Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders, Cell, Volume 155, Issue 7, 19 December 2013, Pages 1451-1463, ISSN 0092-8674, http://dx.doi.org/10.1016/j.cell.2013.11.024. (http://www.sciencedirect.com/science/article/pii/S0092867413014736)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:42857
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:05 Dec 2013 19:39
Last Modified:24 Feb 2020 21:22

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