Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders

被引：2551

作者：

Hsiao, Elaine Y. ^{[1
,2
]}

McBride, Sara W. ^{[1
]}

Hsien, Sophia ^{[1
]}

Sharon, Gil ^{[1
]}

Hyde, Embriette R. ^{[3
]}

McCue, Tyler ^{[3
]}

Codelli, Julian A. ^{[2
]}

Chow, Janet ^{[1
]}

Reisman, Sarah E. ^{[2
]}

Petrosino, Joseph F. ^{[3
]}

Patterson, Paul H. ^{[1
]}

Mazmanian, Sarkis K. ^{[1
]}

机构：

[1] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA

[2] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA

[3] Baylor Coll Med, Alkek Ctr Metagenom & Microbiome Res, Houston, TX 77030 USA

来源：

CELL | 2013年 / 155卷 / 07期

关键词：

GASTROINTESTINAL DYSFUNCTION; SPECTRUM DISORDERS; GUT MICROBIOTA; AUTISM; CHILDREN; BRAIN; MOUSE; ACTIVATION; MICROFLORA; PREGNANCY;

D O I：

10.1016/j.cell.2013.11.024

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1451 / 1463

页数：13

共 65 条

[1] Amniotic fluid inflammatory cytokines: Potential markers of immunologic dysfunction in autism spectrum disorders [J].

Abdallah, Morsi W. ;

Larsen, Nanna ;

Grove, Jakob ;

Norgaard-Pedersen, Bent ;

Thorsen, Poul ;

Mortensen, Erik L. ;

Hougaard, David M. .

WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY, 2013, 14 (07) :528-538

[2] Gastrointestinal flora and gastrointestinal status in children with autism-comparisons to typical children and correlation with autism severity [J].

Adams, James B. ;

Johansen, Leah J. ;

Powell, Linda D. ;

Quig, David ;

Rubin, Robert A. .

BMC GASTROENTEROLOGY, 2011, 11

[3] Urinary p-cresol is elevated in small children with severe autism spectrum disorder [J].

Altieri, Laura ;

Neri, Cristina ;

Sacco, Roberto ;

Curatolo, Paolo ;

Benvenuto, Arianna ;

Muratori, Filippo ;

Santocchi, Elisa ;

Bravaccio, Carmela ;

Lenti, Carlo ;

Saccani, Monica ;

Rigardetto, Roberto ;

Gandione, Marina ;

Urbani, Andrea ;

Persico, Antonio M. .

BIOMARKERS, 2011, 16 (03) :252-260

[4] BASIC LOCAL ALIGNMENT SEARCH TOOL [J].

ALTSCHUL, SF ;

GISH, W ;

MILLER, W ;

MYERS, EW ;

LIPMAN, DJ .

JOURNAL OF MOLECULAR BIOLOGY, 1990, 215 (03) :403-410

[5] Commensal microbiota is fundamental for the development of inflammatory pain [J].

Amaral, F. A. ;

Sachs, D. ;

Costa, V. V. ;

Fagundes, C. T. ;

Cisalpino, D. ;

Cunha, T. M. ;

Ferreira, S. H. ;

Cunha, F. Q. ;

Silva, T. A. ;

Nicoli, J. R. ;

Vieira, L. Q. ;

Souza, D. G. ;

Teixeira, M. M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (06) :2193-2197

[6] Multivariate dispersion as a measure of beta diversity [J].

Anderson, MJ ;

Ellingsen, KE ;

McArdle, BH .

ECOLOGY LETTERS, 2006, 9 (06) :683-693

[7]

[Anonymous], MED SCI MONIT

[8] Maternal Infection Requiring Hospitalization During Pregnancy and Autism Spectrum Disorders [J].

Atladottir, Hjordis O. ;

Thorsen, Poul ;

Ostergaard, Lars ;

Schendel, Diana E. ;

Lemcke, Sanne ;

Abdallah, Morsi ;

Parner, Erik T. .

JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS, 2010, 40 (12) :1423-1430

[9] Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders [J].

Atladottir, Hjordis O. ;

Pedersen, Marianne G. ;

Thorsen, Poul ;

Mortensen, Preben Bo ;

Deleuran, Bent ;

Eaton, William W. ;

Parner, Erik T. .

PEDIATRICS, 2009, 124 (02) :687-694

[10]

Baio Jon, 2012, Morbidity and Mortality Weekly Report, V61, P1

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