Alterations in gut microbiota composition in children with methylmalonic acidemia, propionic acidemia, and maple...

Methylmalonic acidemia (MMA), propionic acidemia (PA), and maple syrup urine disease (MSUD) are rare monogenic disorders that are described as intoxication-type inborn errors of metabolism (IEMs). They usually present in early life, and long-term management requires strict dietary protein restriction, which may significantly alter gut microbiota composition. Despite growing interest in microbiome research, limited data exist on gut microbiota in these disorders, and no study is available for MMA and MSUD. We aimed to describe the gut microbiota compositions in children with MMA, PA, and MSUD.

A total of eight patients (Five MMA, one PA, and two MSUD), and 11age-matched healthy controls were enrolled. All patients were following a medically supervised, protein-restricted diet. Fecal sample was collected from each participant, and gut microbiota composition was evaluated with 16S rRNA sequencing.

Patients with MMA, PA, and MSUD exhibited significantly altered gut microbiota composition compared to healthy controls. Alpha diversity analysis revealed reduced microbial richness in patients, with significantly lower Chao1 and observed OTU indices (p < 0.05). Beta diversity metrics demonstrated distinct clustering between groups, indicating significantly different microbial community structures. Higher relative abundances of opportunistic or dysbiotic taxa have been seen in patient group, while controls were enriched in beneficial taxa like Faecalibacterium prausnitzii, Ruminococcus, and Lactobacillus. LEfSe analysis identified 17 taxa enriched in patients-including members of Proteobacteria, Sphingobacteriia, and Streptococcus anginosus-and 6 taxa enriched in controls, notably Faecalibacterium prausnitzi.

This is the first descriptive study of the gut microbiota composition of MMA, PA, and MSUD patients. These findings indicate an association between long-term dietary management and altered microbiota composition, although causality cannot be inferred due to the cross-sectional study design. The observed alterations suggest that the gut microbiota may represent a novel therapeutic target in the management of IEMs.