Abstract
Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that affect communication and social behavior. Besides social deficits, systemic inflammation, gastrointestinal immune-related problems, and changes in the gut microbiota composition are characteristic for people with ASD. Animal models showed that these characteristics can induce ASD-associated behavior, suggesting an intimate relationship between the microbiota, gut, immune system and the brain in ASD. Multiple factors can contribute to the development of ASD, but mutations leading to enhanced activation of the mammalian target of rapamycin (mTOR) are reported frequently. Hyperactivation of mTOR leads to deficits in the communication between neurons in the brain and to immune impairments. Hence, mTOR might be a critical factor linking the gut-brain-immune axis in ASD. Pharmacological inhibition of mTOR is shown to improve ASD-associated behavior and immune functions, however, the clinical use is limited due to severe side reactions. Interestingly, studies have shown that mTOR activation can also be modified by nutritional stimuli, in particular by amino acids. Moreover, specific amino acids are demonstrated to inhibit inflammation, improve gut barrier function and to modify the microbiota composition. In this review we will discuss the gut-brain-immune axis in ASD and explore the potential of amino acids as a treatment option for ASD, either via modification of mTOR activity, the immune system or the gut microbiota composition.
Highlights
Reviewed by: Arturo Ortega, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Mexico Elena Gonzalez-Rey, Instituto de Parasitología y Biomedicina López-Neyra (IPBLN), Spain
Multiple factors can contribute to the development of Autism spectrum disorder (ASD), but mutations leading to enhanced activation of the mammalian target of rapamycin are reported frequently
In this review we will discuss the gut-brain-immune axis in ASD and explore the potential of amino acids as a treatment option for ASD, either via modification of mammalian target of rapamycin (mTOR) activity, the immune system or the gut microbiota composition
Summary
Rapamycin treatment increased the expression of Treg cell-associated cytokines, including IL-10 and TGF-β in the small intestine of CMA mice [82] Till this day, the effects of targeting mTOR on possible immune dysregulations found in the rodent ASD models mentioned above remain understudied. Besides its involvement in intestinal barrier function, Gln is widely known as an anti-inflammatory agent, likely via inhibition of the activation of nuclear factor kappa B (NF-κB) and signal transducers and activators of transcription (STAT) [129] This inhibition leads to suppression of the production of inflammatory cytokines such as IL-6, TNFα and IL-8 as shown for various immune cells in vitro, in animal immune models and in immune-compromised human [129,130,131].
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