Editors' ChoiceAutism

Treating the Brain Through the Gut

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Science Translational Medicine  08 Jan 2014:
Vol. 6, Issue 218, pp. 218ec6
DOI: 10.1126/scitranslmed.3008244

A mechanistic understanding of the rising incidence of autism spectrum disorders (ASDs) (in the United States, 1 in 88 live births) might require a little help from our friends—gut bacteria. In a recent paper, Hsiao et al. demonstrate that alterations in the gut microbiota can modulate behavioral and physiological abnormalities associated with a mouse model of ASD. These findings suggest an intriguing mechanistic link between the intestinal flora and neurodevelopmental disorders.

Studies have shown that patients with ASD are at increased risk for gastrointestinal problems, particularly abnormal intestinal permeability. This so-called “leaky gut” is often associated with an altered immune response, which has been implicated in the pathogenesis of ASD. The authors used an established mouse model—the maternal immune activation (MIA) model—to investigate the relationship between gastrointestinal abnormalities and ASD. MIA model offspring displayed typical ASD behavioral features (such as anxiety, stereotyped behaviors, deficits in sociability, and reduced vocalizations) as well as increased intestinal permeability and altered intestinal microbial flora. Moreover, the offspring exhibited altered cytokine composition in the colon and changes in concentrations of more than 20 metabolites in the blood. Treating the mice with cultures of the bacterium Bacillus fragilis corrected all of the ASD-related behavioral features mentioned above except deficits in sociability and normalized many of the blood metabolic changes. One of the normalized metabolites, 4-ethylphenylsufate, was particularly interesting because it induced anxiety-like behavior similar to that in MIA offspring when administered to naïve wild-type mice.

The study by Hsiao et al. is important because it suggests a possible causal relationship between the intestinal microbiota and ASD. The discovery that probiotic intervention reduces some behavioral abnormalities is particularly promising and justifies further investigations using similar treatments for human patients.

E. Y. Hsiao et al., Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451–1463 (2013). [PubMed]

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