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Microbiota and Microglia Interactions in ASD
Marcela Davoli-Ferreira1, Carolyn A Thomson1, Kathy D McCoy1
1Department of Physiology and Pharmacology, Snyder Institute of Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Abstract:
Autism spectrum disorders (ASD) are serious, highly variable neurodevelopmental disorders, commonly characterized by the manifestation of specific behavioral abnormalities, such as stereotypic behaviors and deficits in social skills, including communication. Although the neurobiological basis for ASD has attracted attention in recent decades, the role of microglial cells, which are the main resident myeloid cell population in the brain, is still controversial and underexplored. Microglia play several fundamental roles in orchestrating brain development and homeostasis. As such, alterations in the intrinsic functions of these cells could be one of the driving forces responsible for the development of various neurodevelopmental disorders, including ASD. Microglia are highly sensitive to environmental cues. Amongst the environmental factors known to influence their intrinsic functions, the gut microbiota has emerged as a central player, controlling both microglial maturation and activation. Strikingly, there is now compelling data suggesting that the intestinal microbiota can play a causative role in driving the behavioural changes associated with ASD. Not only is intestinal dysbiosis commonly reported in ASD patients, but therapies targeting the microbiome can markedly alleviate behavioral symptoms. Here we explore the emerging mechanisms by which altered microglial functions could contribute to several major etiological factors of ASD. We then demonstrate how pre- and postnatal environmental stimuli can modulate microglial cell phenotype and function, underpinning the notion that reciprocal interactions between microglia and intestinal microbes could play a crucial role in ASD aetiology.
Insights
Altered microglial cell function, influenced by gut microbiota, may contribute to autism spectrum disorder (ASD) etiology. Environmental factors impact microglia, potentially linking gut health to ASD development and behavioral symptoms.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with poorly understood neurobiological underpinnings.
- Microglia, the brain's resident immune cells, play critical roles in brain development and homeostasis, but their specific involvement in ASD remains unclear.
- The gut microbiota is increasingly recognized for its influence on brain function and behavior, including potential roles in neurodevelopmental disorders.
Purpose of the Study:
- To explore the mechanisms by which microglial dysfunction may contribute to ASD etiology.
- To investigate the role of the gut microbiota in modulating microglial function and its potential impact on ASD.
- To examine how environmental stimuli influence microglial phenotype and function in the context of ASD.
Main Methods:
- Review of current literature on microglial function, gut microbiota, and ASD.
- Analysis of emerging data linking intestinal dysbiosis to ASD behavioral changes.
- Exploration of environmental factors influencing microglial cell phenotype and function.
Main Results:
- Alterations in microglial cell functions are implicated as potential drivers of neurodevelopmental disorders like ASD.
- The gut microbiota significantly influences microglial maturation and activation.
- Intestinal dysbiosis is frequently observed in ASD patients, and microbiome-targeted therapies show promise in alleviating behavioral symptoms.
Conclusions:
- Reciprocal interactions between microglia and the gut microbiota are crucial in ASD etiology.
- Environmental factors, including those affecting the gut microbiome, can modulate microglial function, offering potential therapeutic avenues for ASD.
- Further research into the microglia-gut-brain axis is warranted to understand and treat ASD.
