The Guts of Autism

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Microbes living in the gut of MIA mice may affect behavioral symptoms associated with neurodevelopmental disorders such as autism (Image source: http://www.npr.org)

A new study out of the California Institute of Technology has found an unlikely connection between the microbes that live in the gastrointestinal (GI) tract and neurodevelopmental disorders like Autism Spectrum Disorder (ASD). The study, published last month in Cell, found that by simply treating affected mice with the bacterium Bacteroides fragilis, researchers could correct a number of behaviors associated with ASD via the bacterium’s effect on the GI tract.

The group used what are called MIA mice (Maternal Immune Activation mice), whose neurodevelopmental symptoms mirror those of human disorders like ASD and schizophrenia. These symptoms are not limited to behavior, as both MIA mice and ASD patients often have serious GI tract problems, such as irritable bowel disease and other GI disorders. A number of recent studies have established a strong correlation between GI issues and autism in humans, as the authors of the study point out.

This study found that these GI problems may be rooted in changes to the gut’s microbiota that the disorder itself causes. If you’re curious, microbiota refers to the diverse species of commensal microbes that live inside the gut in a wide variety of organisms (including humans’ intestines) and aid in digestion. They often break down those compounds that the host’s body cannot process and funnel their products, called metabolites, into the host’s bloodstream.

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Bacteroides fragilis (picture above) helps repair the integrity of the barrier between the gut and the bloodstream, blocking metabolites that could otherwise induce anxiety (Image source: en.wikipedia.org)

The study’s results show that the gut microbiota of adult MIA mice is quite different from that of normal mice. In particular, MIA mice had much less diversity in the Clostridia and Bacteroides classes of bacteria. According to the study, similar differences in microbe diversity have been reported in ASD patients.

Treating MIA mice with B. fragilis helped to restore some normalcy to the microbiota’s composition, but more importantly it repaired the barrier between the gut and the bloodstream. MIA’s changes to the gut’s microbes had weakened the integrity of that barrier, which allowed more metabolites to escape into the bloodstream. The group found that 8% of all metabolites found in healthy mice showed significant increases in MIA mice as a result of the leaky gut barrier. Treatment with B. fragilis also corrected a number of behavioral abnormalities associated with both MIA and autism, such as anxiety, sensory and motor processes, and problems communicating.

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A diagram describing the process that researchers at CalTech established that connects the gut’s microbiota with neurodevelopmental disorders (Image source: http://www.cell.com)

The group began to look for a connection between the changes that B. fragilis caused in the gut and the changes it caused in behavior. They found their connection in a metabolite called 4-ethylphenylsulphate (or 4EPS for short). The group found 46 times more 4EPS in the serum of MIA mice than in normal mice, whereas MIA mice treated with B. fragilis had normal 4EPS levels. The group found that 4EPS could induce anxiety-like behavior when given to healthy mice, and thus cemented the connection between B. fragilis and the changes seen in behavior. By repairing the barrier between the gut and the bloodstream, B. fragilis blocked 4EPS from escaping into the bloodstream and causing anxiety.

The study shows how a metabolite produced by the gut’s microbiota and regulated by the presence of B. fragilis can cause behavioral symptoms associated with both MIA and ASD, which is a pretty exciting find. This is just one of a large number of studies finding remarkable connections between the gut’s microbiome and a variety of disorders and diseases, which include, among others, such heavy hitters as cancer and heart disease. The gut’s microbiome is an often forgotten and little understood microcosm that we are quickly finding has a lot more influence over our bodies than we ever thought.

Original Article:

http://www.cell.com/abstract/S0092-8674(13)01473-6#Summary

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