Host–Microbiota Interactions in Adolescents with Severe Anorexia Nervosa: Linking Gut Dysbiosis, Intestinal Barrier Function and Microbial Metabolism

Background: Anorexia nervosa (AN) is increasingly recognized as a multisystem disorder involving complex host–microbiota interactions, yet prospective pediatric studies with a comprehensive, longitudinal characterization of host–microbiota interactions remain scarce. Methods: In this prospective longitudinal study, 26 adolescents with severe AN were evaluated at hospital admission (T0), after one month (T1), and after three months of inpatient nutritional rehabilitation (T2). Gut microbiota composition was assessed by 16S rRNA sequencing and compared with healthy controls (HC) at the baseline; predicted functional profiling was performed using PICRUSt2. Serum and urinary biomarkers of intestinal barrier integrity and microbial metabolism, routine clinical and biochemical parameters, and psychometric scores (CDI-2, MASC-2) were evaluated longitudinally using linear mixed-effects models. Results: At the baseline, adolescents with AN showed reduced bacterial richness compared with healthy controls, with significantly lower Chao1 diversity (p = 0.00013), whereas the Shannon and Simpson indices did not differ significantly (p = 0.54 and p = 0.27, respectively). Microbial community composition differed significantly between groups based on Bray–Curtis (R2 = 0.0724, FDR-adjusted p = 0.001) and unweighted UniFrac (R2 = 0.0540, FDR-adjusted p = 0.001) distances. LEfSe identified 19 differentially abundant taxa; among the strongest discriminators, Blautia_A_141781, Romboutsia_B, and Clostridium_T were enriched in AN, whereas Akkermansia, Phocaeicola_A_858004, and Bacteroides_H were enriched in the healthy controls. Nutritional rehabilitation was associated with partial microbiota remodeling, alongside significant improvements in BMI and heart rate. Several host-derived biomarkers, including urinary indican, serotonin, nitric oxide, and serum occludin, changed significantly over time, whereas bile acids, short-chain fatty acids, IgA, lipopolysaccharide, and haptoglobin remained stable. Conclusions: Gut microbiota and host-derived biomarkers evolve dynamically during nutritional rehabilitation in adolescents with severe AN, supporting their potential role as complementary tools for monitoring biological recovery.