Altered gut microbiome diversity and function in patients with propionic acidemia.

Area of Science:

• Metabolic Disorders
• Microbiome Research
• Gastroenterology

Background:

• Propionic acidemia (PA) is an inherited metabolic disorder affecting propionate metabolism.
• The gut microbiota's role in PA pathophysiology is largely unknown, yet it presents a potential therapeutic target.
• PA management involves diet and medication, both known to influence gut microbiota composition.

Purpose of the Study:

• To characterize the gut microbiota composition and metabolic activity in patients with PA.
• To compare fecal microbiota and metabolites between PA patients and healthy household controls.
• To identify potential microbial targets for improving PA clinical outcomes.

Main Methods:

• Fecal samples were collected from PA patients and healthy controls across two centers (UK and Austria) over three months.
• Microbiota composition and diversity were analyzed using sequencing techniques.
• Key microbial metabolites, including short-chain fatty acids like butyrate, were quantified.

Main Results:

• Significant differences in microbial taxa were observed between PA patients and controls, with increased Proteobacteria and decreased butyrate-producing genera (e.g., Roseburia, Faecalibacterium).
• Most measured microbial metabolites were lower in PA patients, with notable butyrate depletion in UK-based patients.
• PA patients displayed reduced gut microbiota diversity, functional diversity, and stability over the study period.

Conclusions:

• This study provides the first comprehensive map of the gut microbiota in PA patients.
• Altered gut microbiota, characterized by reduced diversity and butyrate levels, is associated with PA.
• Findings suggest that targeting microbial propionate and butyrate production, alongside microbiota stability, could inform new therapeutic strategies for PA.