Alterations in the gastrointestinal (GI) microbiome and gut-brain axis have been demonstrated in a range of neuropsychiatric disorders, likely through gene-environment interactions. Anorexia nervosa (AN) is a life-threatening mental illness with strong genetic underpinnings, and is characterized by dysregulated psychologic, metabolic and weight-regulation processes. The GI microbiome is implicated in many of these processes, affecting weight loss/gain, energy extraction from the diet, and communication with the brain via the gut-brain axis. The oropharynx represents the sole entry-point of the GI tract, lying in close proximity to the brain and cranial nerves. Evidence has shown that the microbial community residing in the oral cavity is a close representation of that in the upper GI tract, suggesting a role for the salivary microbiome as a diagnostic and prognostic tool for diseases affecting the GI tract. The oropharynx may represent a site of AN pathology, e.g. decreased taste sensation. Preliminary research suggests intestinal dysbiosis in AN, but the salivary microbiome has not been investigated. We characterized the salivary microbiome of females (age 11-21 years) with AN restrictive-type at the outset of treatment, in comparison to healthy controls (HC) and patients with anxiety (AX), a common comorbid diagnosis. Morning pre- and post-prandial salivary samples, and AN post-treatment samples, were collected (n=70). RNA sequencing was used to compare differences in taxa activity (at multiple taxonomic ranks), as well as alpha diversity (within sample) and beta diversity (between sample) among AN, AX, and HC groups. For global analysis, microbiome activity differences between groups were evaluated via permutational analysis of variance (PERMANOVA). The Wilcoxon rank sum test was used to identify differential activity of each individual taxon between groups and across pre/post-treatment AN samples. There was a significant difference in the global microbiome activity between AN and HC groups (p=0.004) as reflected by both alpha-diversity and beta-diversity comparisons, indicating salivary dysbiosis in AN. Six genera showed significantly different abundances between AN and HC samples, four of which were more abundant in AN and two of which were less abundant in AN. Rhodobacter, a genus more abundant in AN, includes species which possess an extensive range of metabolic capabilities. Leptospira, also more abundant in AN, is a spirochete bacteria that causes generalized symptoms such as vomiting, jaundice, abdominal pain, and diarrhea. Individual taxa comparisons between AN and AX/HC identified 13 taxa which uniquely characterized AN microbial samples, including enrichment in Proteobacteria and depletion in Firmicutes. Pre- and post-treatment comparison demonstrated a shift in activity of these 13 taxa towards a healthier state after treatment. This study presents evidence of upper GI microbiome dysbiosis in AN, consistent with previous gut microbiome findings. Several of the genera differentially expressed in AN are implicated in functional pathways that are characteristically dysregulated in the disease state of AN. Additionally, the salivary microbiome appears to improve to a healthier state following treatment. Future directions include uncovering the differential effects of nutrition/weight restoration and psychological improvement.