Social defect is seen in many psychiatric diseases such as autism spectrum disorder (ASD), which
shows particularity high prevalence rate—1 of 59 US human population. The loss of proper gut
microbiota has been suggested to lead to the significant systemic defects of neural functions seen
in ASD. Such defects may be the result of reduced circulation of short chain fatty acid (SCFA)—
which is the major metabolite of firmicutes, a major class of gut bacterial microorganism.
Importantly, both SCFA and firmicutes are substantially reduced in ASD patients compared to
healthy individuals. This gut-brain interaction has not been properly implemented in current animal
or human iPSC models. Through a series of our investigations of innate behaviors, gut microbiota
composition, altered gene-expression patterns, genomic survey of divergent variants, and
responses to ASD drugs, the Mexican cavefish, Astyanax mexicanus, stands out as a particularly
well suited system for this study. A. mexicanus comprises two morphotypes, surface-dwelling and
cave-dwelling (cavefish). In this study, we first found that fatty acid and firmicutes are significantly
reduced in cavefish gut compared with the ones of surface fish, drawing a parallel to ASD patients.
We then established new methods to quantify repetitive circling motion and social interaction in
both surface and cavefish in the dark. Note, with our method, we could successfully detect
reciprocal social interaction in surface fish in the dark. Through these assay, cavefish showed 2.5
times higher rate of repetitive motion and almost no social interaction compared with the ones of
surface fish. Systemic SCFA can be supplied by a dietary treatment of a fatty acid-rich diet—
ketogenic diet—, which recovered social interaction but not repetitive motion in ASD patients.
Surprisingly, in cavefish, the ketogenic diet treatment also increased social interaction but had no
effect on repetitive behavior. Surface fish showed minimal shift of behaviors under this diet
treatment. These results suggest A. mexicanus shares a similar SCFA-brain pathway with human.
We are currently developing a method to deplete gut microorganism to investigate gut-brain
interaction in this social deficit model. We will also report the correlation among ASD-like comorbid
behaviors used 431 F2 hybrid.