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Gut-Brain Inflammation and Disrupted Homeostasis Due to Activation of Mast Cells and Microglia

Pejman Katiraei1, Richard E Frye2, Theoharis C Theoharides3,4

  • 1Wholistic Kids and Families, Santa Monica, CA 90403, USA.

International Journal of Molecular Sciences
|February 27, 2026
PubMed

Insights

Autism Spectrum Disorder (ASD) incidence is rising, potentially linked to environmental toxins disrupting the gut-brain axis. This review explores gut-brain inflammation and epigenetic factors in ASD development.

Area of Science:

  • Neuroscience
  • Immunology
  • Environmental Health

Background:

  • Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with increasing incidence, affecting 1 in 31 children.
  • Individuals with ASD experience a range of neurological, behavioral, sensory, feeding, gastrointestinal, and immunological issues.
  • While genetics play a role, environmental and pathogenic toxins may contribute to ASD pathogenesis.

Purpose of the Study:

  • To discuss how environmental, pathogenic, and stress factors disrupt gut-brain homeostasis in ASD.
  • To explore the role of gut-blood barrier (GBB) and blood-brain barrier (BBB) disruption in ASD.
  • To suggest potential interventions for key pathogenetic processes in ASD.

Main Methods:

  • Review of current data on ASD incidence and contributing factors.
  • Discussion of the mechanisms involving mast cells (MCs) and microglia in gut-brain inflammation.
  • Exploration of epigenetic effects and gut-brain axis disruption.

Main Results:

  • Environmental toxins can activate mast cells and microglia, disrupting the GBB and BBB.
  • This disruption can lead to chronic gut-brain inflammation, a potential factor in ASD development.
  • Gut-brain axis dysregulation and epigenetic changes are implicated in ASD susceptibility.

Conclusions:

  • Environmental factors and gut-brain axis disruption are significant contributors to ASD pathogenesis.
  • Addressing inflammation and barrier integrity may offer therapeutic avenues for ASD.
  • Further research into environmental impacts and epigenetic modifications is warranted for ASD.

Keywords:
brainflavonoidsfolinic acidgutinflammationluteolinmast cellsmicrobiomemicrogliatoxins

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