The Possible Role of the Microbiota-Gut-Brain-Axis in Autism Spectrum Disorder

Piranavie Srikantha, M Hasan Mohajeri, Piranavie Srikantha, M Hasan Mohajeri

Abstract

New research points to a possible link between autism spectrum disorder (ASD) and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites, or leaky gut in autistic people are described. Various altered metabolite levels were observed in the blood and urine of autistic children, many of which were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides (LPS). A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients, triggering new body responses or an altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in cells, altered tight junctions in the blood-brain barrier and structural changes in the cortex, hippocampus, amygdala and cerebellum were also detected. Moreover, this paper suggests that ASD is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between ASD and gut microbiota is not yet well established, the consumption of specific probiotics may represent a side-effect free tool to re-establish gut homeostasis and promote gut health. The diagnostic and therapeutic value of bacterial-derived compounds as new possible biomarkers, associated with perturbation in the phenylalanine metabolism, as well as potential therapeutic strategies will be discussed.

Keywords: ASD; Autism; gut-brain-axis; microbiota; microbiota-gut-brain-axis; prebiotics; probiotics.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Methodical approach of this systematic review due to PRISMA criteria [39].
Figure 2
Figure 2
Co-occurring pathologies found in Autism Spectrum disorder (ASD). Red shows gut-related comorbidities found in ASD, purple shows brain-related comorbidities and orange other comorbidities. Chapter 3 gives more information to the mentioned comorbidities.
Figure 3
Figure 3
Taxonomic classification of dysbiotic bacteria found in autistic individuals. All bacterial taxa mentioned within this chapter are found in this figure. Green indicates elevated taxa in the gut microbiota of ASD individuals. Red indicates decreased taxa in the gut microbiota ASD individuals. Additionally, black surrounded boxes show significant results in at least one study. Significance levels are taken from the original literature.
Figure 4
Figure 4
Process of Clostridium tetani infection in the gut. Occurrence of the bacterium Clostridium tetani in the GI tract of autistic population could lead to altered behaviour. [43].
Figure 5
Figure 5
Metabolic pathways of tryptophan. The purple pathways show human metabolism of tryptophan and the orange pathways are observed in bacterial degradation. Green surrounded boxes show elevated metabolites and red surrounded boxes show decreased metabolites in the autistic metabolome [101].

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Source: PubMed

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