Authors
Arpan Dhungel, Rinchi Bora
Published in
The European journal of neuroscience. Volume 64. Issue 2. Pages e70637.
Abstract
Autism spectrum disorder manifests through dysbiosis across the microbiota-gut-brain-immune axis, characterized by depletion of short-chain fatty acid (SCFA)-producing taxa like Bifidobacterium, Faecalibacterium, and Roseburia, along with an increase in endotoxin-producing taxa like Desulfovibrio and Bacteroides. SCFA emerge as one of the regulators of neuroimmune homeostasis by governing microglial maturation through GPR43/GPR109A-dependent histone deacetylase inhibition, modulating astrocytic tryptophan-aryl hydrocarbon receptor signaling, and preserving tight junction integrity at blood-brain and blood-CSF barriers. SCFA insufficiency constitutes the upstream metabolic defect linking gut dysbiosis to ASD neuropathology, such as impaired microglial priming and brain-resident CD4+ T cell differentiation, reactive astrocytosis with kynurenine neurotoxicity superseding protective signaling, barrier breakdown enabling LPS-driven TLR4-NF-κB neuroinflammation, and excitatory/inhibitory imbalance from reduced glutamate decarboxylase and astrocyte glutamate dysregulation. This review advances an integrative SCFA-centric framework repositioning ASD as metabolite-dependent neuroimmune dysregulation during brain development. Preclinical and early clinical data demonstrate that SCFA restoration through prebiotic fiber/resistant starch, probiotics, or direct SCFA supplementation normalizes gastrointestinal symptoms, behavioral deficits, microglial morphology, and neurotransmitter ratios. This guides mechanistically targeted microbiota interventions with fecal/plasma SCFA profiling as stratification biomarkers, establishing precision therapeutic regimens for ASD.
PMID:
42470181
Bibliographic data and abstract were imported from PubMed on 18 Jul 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 3
- Comments 0