Abstract: Autism Spectrum Disorder (ASD) involves social interaction
deficit, impaired communication skills, and pervasive and stereotypic behavior. It also
involves co-morbidities such as anxiety, aggressive nature, and epilepsy. Apart from
the above, this disorder also affects physiological co-morbidities that co-exist with
behavioral symptoms, such as immune system and mitochondrial dysfunction, and
gastrointestinal complications, leading to oxidative stress neuroinflammation, further
worsening the behavioral complications. It has been reported that 23%-70% of patients
who have ASD account for gastrointestinal complications, which correlate with
behaviors relevant to autistic endophenotype. A strong gut-brain dysbiosis occurs in
ASD patients due to the enormous production of short-chain fatty acids such as
propanoic acid (PPA) by abnormal gut-flora, worsening the behavioral neurochemical
and mitochondrial dysfunction. This further leads to the generation of free radical
species responsible for synthesizing pro-inflammatory cytokines, which cause
microglia activation. There are various animal models of autism, such as the induced
animal model and transgenic animal model, which could give valuable hints toward
understanding the molecular, cellular, and pathomorphological processes involved in
this neurodevelopmental disorder heterogeneous and has a multifactorial origin.
However, though all animal models focus on establishing the face validity of ASD,
very few focus on construct validity and predictive validity about gut-brain dysbiosis in
ASD patients because of the abnormal gut-flora leaky-gut phenomenon. Thus, in this
chapter, our focus would be to understand the phenomenon of gut-brain cross-talk in
ASD, the role of short-chain fatty acids, and to bring forth the neuropsychopathology
of propanoic acid (PPA)-induced rat model of ASD, which can help in establishing
construct as well as predictive validity with the gut-brain cross-talk and the
neuroimmune as well as behavioral complications occurring as a result of short-chain
fatty acids and abnormal gut flora.
Keywords: Autism, Gut-microbiota, Inflammatory cytokines, Neurobehavior, Propanoic
acid.
