Purpose: Food allergy-induced autism-like behavior has been increasing for decades, but the causal drivers of this association are unclear. We sought to test the association of gut microbiota and mammalian/mechanistic target of rapamycin (mTOR) signaling with cow’s milk allergy (CMA)-induced autism pathogenesis.
Methods: Mice were sensitized intragastrically with whey protein containing cholera toxin before sensitization on intraperitoneal injection with whey-containing alum, followed by intragastric allergen challenge to induce experimental CMA. The food allergic immune responses, ASD-like behavioral tests and changes in the mTOR signaling pathway and gut microbial community structure were performed.
Results: CMA mice showed autism-like behavioral abnormalities and several distinct biomarkers. These include increased levels of 5-hydroxymethylcytosine (5-hmC) in the hypothalamus; c-Fos were predominantly located in the region of the lateral orbital prefrontal cortex (PFC), but not ventral; decreased serotonin 1A in amygdala and PFC. CMA mice exhibited a specific microbiota signature characterized by coordinate changes in the abundance of taxa of several bacterial genera, including the Lactobacillus . Interestingly, the changes were accompanied by promoted mTOR signaling in the brain of CMA mice.
Conclusion: We found that disease-associated microbiota and mTOR activation may thus play a pathogenic role in the intestinal, immunological, and psychiatric Autism Spectrum Disorder (ASD)-like symptoms seen in CAM associated autism. However, this is only a preliminary study, and their mechanisms require further investigation.
Keywords: cow’s milk allergy, autism-like behavior, gut microbiota, mTOR signaling pathway