The microbiome and neuroinflammation in youth with pans/pandas

The significance of the microbiome in neurodevelopmental, neuropsychiatric, and neuroimmune disorders has greatly expanded over the last decade, identifying new models of mechanisms of the gut-brain axis and highlighting opportunities for novel interventions for patient care. Systemic inflammation/neuroinflammation are impacted by the intestinal microbiome, particularly in the context of dysbiosis. Neuroinflammation is implicated in postinfectious neuropsychiatric conditions of childhood such as PANS, and small studies have identified measurable differences in the microbiome/metabolome of patients with PANS prior to interventions. We aim to evaluate the microbiome/metabolome of treatment-naïve subjects identified with PANS to identify potential targets for treatment at 2 sites where research-based PANS clinics are held (University of Arizona, Dartmouth). Serial measurement of microbiome/metabolomics from fecal samples in subjects with PANS were captured prior to treatments and in remission and relapse of neuropsychiatric illness compared to controls. Targeted analysis (16s) and metagenomics/metabolomics were performed. We used a murine fecal transplant model employing stool from subjects/controls with measurement of inflammation (cytokines, activation of microglia). Ongoing enrollment at both sites continues, and results are pending. Pilot data (University of Arizona, Kiela P) from 18 subjects with PANDAS and 23 healthy controls identified significant differences in overall community composition and key taxa of the gut microbiome (but no difference in oropharyngeal or nasal microbiome between groups). Fecal metabolomics identified an altered profile in subjects with PANDAS in patterns mirroring other systemic autoimmune conditions. Further results are pending. The intestine and its microbiome are a substantial nidus for immunity, inflammation, and neurotransmitters and are implicated in neurodevelopment and a plethora of neuropsychiatric conditions. Subjects with immune-mediated neuropsychiatric conditions such as PANS/PANDAS have measurable patterns in the microbiome/metabolome associated with onset of symptoms that are likely able to be leveraged for diagnostics, clarification of underlying mechanisms, and novel targets for interventions.