Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is an immune-mediated neuropsychiatric disorder characterized by abrupt onset of OCD, anxiety, tics, and behavioral dysregulation, often triggered by infection. This case series describes seven children evaluated at the Dartmouth Neuroimmune Psychiatric Disorders Clinic who exhibited both PANS and either celiac disease (CD) or eosinophilic esophagitis (EoE). All GI autoimmune diagnoses preceded or coincided with PANS onset, suggesting potential immune priming through chronic gut inflammation. Clinical histories revealed symptom escalation with GI flares and improvement following gluten-free diets or EoE-targeted therapies in select cases, raising the possibility of bidirectional gut–brain immune signaling. Mechanistically, increased gut permeability, cytokine release, and dysbiosis may contribute to systemic inflammation and neuroinflammation. Treatment regimens included immunomodulators, antibiotics, cognitive-behavioral therapy, and dietary interventions. Larger prospective studies assessing microbiome composition, permeability biomarkers, and psychiatric outcomes are needed to clarify this emerging autoimmune interplay.