Dietary Considerations in Autism Spectrum Disorders: The Potential Role of Protein Digestion and Microbial Putrefaction in the Gut-Brain Axis

Abstract

Children with autism spectrum disorders (ASD), characterized by a range of behavioral abnormalities and social deficits, display high incidence of gastrointestinal (GI) co-morbidities including chronic constipation and diarrhea. Research is now increasingly able to characterize the “fragile gut” in these children and understand the role that impairment of specific GI functions plays in the GI symptoms associated with ASD. This mechanistic understanding is extending to the interactions between diet and ASD, including food structure and protein digestive capacity in exacerbating autistic symptoms. Children with ASD and gut co-morbidities exhibit low digestive enzyme activity, impaired gut barrier integrity and the presence of antibodies specific for dietary proteins in the peripheral circulation. These findings support the hypothesis that entry of dietary peptides from the gut lumen into the vasculature are associated with an aberrant immune response. Furthermore, a subset of children with ASD exhibit high concentrations of metabolites originating from microbial activity on proteinaceous substrates. Taken together, the combination of specific protein intakes poor digestion, gut barrier integrity, microbiota composition and function all on a background of ASD represents a phenotypic pattern. A potential consequence of this pattern of conditions is that the fragile gut of some children with ASD is at risk for GI symptoms that may be amenable to improvement with specific dietary changes. There is growing evidence that shows an association between gut dysfunction and dysbiosis and ASD symptoms. It is therefore urgent to perform more experimental and clinical research on the “fragile gut” in children with ASD in order to move toward advancements in clinical practice. Identifying those factors that are of clinical value will provide an evidence-based path to individual management and targeted solutions; from real time sensing to the design of diets with personalized protein source/processing, all to improve GI function in children with ASD.

Autism in Children Connected with Gastrointestinal Symptoms

“…Given these reports, the hypothesis combining the symptoms of autism with the functioning of the digestive system and its bacterial microflora based on the concept of the gut-brain axis becomes very interesting and credible [54][55][56][57]. Different types of environmental and situational stressors may contribute to the occurrence of gastrointestinal disorders such as irritable bowel syndrome, enteritis, as well as increase intestinal permeability and change their bacterial flora [58][59][60][61][62][63][64][65][66]. Differences were found in intestinal microbiome in children with ASD compared to healthy ones based on the analysis of metabolic products and composition of fecal flora [59,67].…”

Functional Neuroimaging in Psychiatry—Aiding in Diagnosis and Guiding Treatment. What the American Psychiatric Association Does Not Know

“…While as yet poorly studied, many clinicians are utilizing antifungals for depression, anxiety, schizophrenia, behavioral dysregulation, and autism (81,82). While skeptical, the authors have experience with patients whose depression, agitation, irritability, and manic-like mood symptoms improved with elimination of sugars and a course of probiotics and antifungals.…”

Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

“…Some of the discrepancies between these studies are likely due to differences in sample number, tissue analyzed, and methodology. Other sources of variability include differences in environmental factors, such as diet and gut bacteria, which differ between ASD and TD populations (35)(36)(37). Diet is a major source of circulating metabolites, impacting the metabolome directly or indirectly through chemical transformation by the trillions of gut microbes, the microbiome, which has been proposed to modulate complex behaviors in animal models and humans (38)(39)(40).…”