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Published on: February 3, 2016
Food Allergy-Induced Autism-Like Behavior is Associated with Gut Microbiota and Brain mTOR Signaling
Li-Hua Cao1, Hong-Juan He1, Yuan-Yuan Zhao2
1Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan Province, People's Republic of China.
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.
Insights
Gut microbiota and mTOR signaling may drive autism-like behaviors in cow's milk allergy (CMA). This study in mice suggests these factors play a role in the development of autism spectrum disorder (ASD) symptoms. Further research is needed.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Autism Spectrum Disorder (ASD) is complex, with increasing association to food allergies.
- The precise mechanisms linking food allergies to ASD-like behaviors remain unclear.
- Cow's milk allergy (CMA) is a common food allergy with potential neurological implications.
Purpose of the Study:
- To investigate the role of gut microbiota and mammalian/mechanistic target of rapamycin (mTOR) signaling in cow's milk allergy (CMA)-induced autism pathogenesis.
- To identify biomarkers associated with CMA-induced autism-like behavior.
Main Methods:
- Induction of experimental CMA in mice via intragastric and intraperitoneal sensitization and challenge.
- Assessment of food allergic immune responses, ASD-like behaviors, brain mTOR signaling, and gut microbial community structure.
- Analysis of specific biomarkers including 5-hydroxymethylcytosine (5-hmC) and c-Fos expression.
Main Results:
- CMA mice displayed autism-like behaviors and distinct biomarkers, including altered hypothalamic 5-hmC and differential c-Fos localization in the prefrontal cortex (PFC).
- Reduced serotonin 1A levels were observed in the amygdala and PFC of CMA mice.
- A specific gut microbiota signature, with altered abundance of genera like *Lactobacillus*, was identified, accompanied by enhanced brain mTOR signaling.
Conclusions:
- Disease-associated gut microbiota and mTOR activation may contribute to the pathogenesis of intestinal, immunological, and psychiatric symptoms in CMA-associated autism.
- These findings suggest a potential link between gut dysbiosis, mTOR pathway activation, and ASD-like phenotypes in the context of food allergies.
- Further investigation is required to elucidate the precise mechanisms underlying these associations.
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