A Pragmatic Study of the Gut Microbiota Across Varying Weight Presentations in Adolescents with Anorexia Nervosa and Atypical Anorexia Nervosa

Background: Eating disorders (EDs) including anorexia nervosa (AN) and atypical anorexia nervosa (AAN) are characterized by restriction of energy intake and associated nutritional disturbances, which can substantially alter the intestinal microbial environment. Using a pragmatic sampling design, we compared gut microbial composition and function between adolescent females receiving treatment for AN or AAN and healthy controls (HCs). We further examined whether stratification by percentage treatment goal weight (%TGW) could provide additional clinical context for interpreting microbial variation during treatment. Methods: Stool samples were collected from female adolescents with EDs (n = 61) and age-matched HCs (n = 18; 11–17 years). Microbial diversity and composition were assessed using 16S rRNA gene (V3–V4) sequencing, and fecal short-chain (SCFA) and branched-chain fatty acid (BCFA) concentrations were measured by gas chromatography. Secondary analyses compared these microbial outcomes among ED participants stratified by %TGW (< 80%, n = 21; 80–90%, n = 20; >90%, n = 20) and HCs. Results: Microbial community diversity and composition were altered in the ED cohort compared to HCs, as indicated by reduced α-diversity (e.g. evenness), altered β-diversity (i.e. Aitchison, Bray-Curtis), and greater inter-individual microbial variability (β-dispersion). Differential abundance analysis identified differences in several low-abundance genera, including higher Ruminococcus gnavus group and lower Eubacterium siraeum group and Subdoligranulum in EDs compared with HCs. Fecal SCFA concentrations were also reduced in the ED cohort, indicating altered microbial metabolic output alongside compositional differences. Community-level microbial differences were evident within each %TGW category, whereas fecal SCFA concentrations were not significantly reduced relative to HCs among participants at > 90% TGW. Conclusions: Our findings indicate that adolescents receiving treatment for AN or AAN exhibited compositional and functional differences in the gut microbiota compared with HCs. Stratification by %TGW provided additional clinical context to our heterogenous clinical cohort, by demonstrating that compositional and functional features of the gut microbiota in EDs may not normalize in parallel during nutritional rehabilitation. These findings extend our understanding of the intestinal microbial environment during ED treatment beyond taxonomic characterization alone.