Altered gut microbiota and metabolites in children with non-organic anorexia: a multi-omics integration study

Gut microbiota alterations have been linked to childhood eating disorders, but the functional and metabolic changes in non-organic anorexia (NOA) remain poorly understood. This study aimed to characterize the gut microbial composition, function, and metabolic profiles in children with NOA using an integrated multi-omics approach. A case-control study was conducted involving 88 children aged 1-5 years (48 NOA, 40 healthy controls). Gut microbiota composition was assessed via 16S rRNA gene sequencing of all fecal samples. Subsequently, the five most representative samples from each group were selected for deep shotgun metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolomics. NOA children showed significantly higher microbial richness and diversity (Chao1, Shannon; P < 0.001). The NOA group had elevated Firmicutes, Bacteroidota, Bacteroides, Faecalibacterium, Subdoligranulum, and Roseburia, but reduced Actobacteriota, Bifidobacterium, and Enterococcus. Metagenomics revealed downregulated riboflavin metabolism and upregulated fat digestion/absorption pathways in NOA (P < 0.05). Metabolomics identified 26 differential fecal metabolites, including decreased L-carnitine derivatives and elevated tyramine glucuronide involved in bile secretion. These metabolites were significantly correlated with altered bacterial genera. Our integrated multi-omics analysis demonstrates that NOA in children is associated with a specific gut ecosystem characterized by altered microbiota structure, perturbed microbial metabolic functions (particularly riboflavin metabolism), and corresponding host-microbiota co-metabolic disturbances. These findings provide novel evidence for the disrupted "microbiota-metabolite" axis in NOA, offering new mechanistic insights.