Title: Altered gut microbiome diversity and function in patients with propionic acidemia
|Authors:||Sebastian Tims, et al.|
Molecular Genetics and Metabolism
The new exploratory publication “Altered gut microbiome diversity and function in patients with propionic acidemia” is the first study to map the gut microbiota of patients with propionic acidemia (PA).
Propionic acidemia is a rare inborn disorder of propionate metabolism caused by propionyl-coenzyme A (CoA) carboxylase (PCC, EC 126.96.36.199) resulting from mutations in the PCCA or PCCB genes. In PA, propionyl-CoA accumulates to toxic levels, and patients commonly present in infancy with acute sepsis-like metabolic decompensation.
PA is managed with a combination of diet and pharmaceutical treatments aimed at guaranteeing metabolic stability and normal growth by reducing the production of toxic organic acids. Both treatments, likely compounded by the condition itself, influence patient gut microbiota.
Disruptions in gut microbiota composition and activity can contribute to pathologies such as obesity, inflammatory bowel diseases, diabetes and cardiovascular diseases. PA patients commonly suffer from constipation and low gut mobility. Constipation in PA patients leads to longer intestinal transit time, therefore potentially increasing bacterial propionate production. Thus, gut microbiota is a relevant, potentially modifiable therapeutic target in PA.
To characterize gut microbiota of PA patients, the study observes 15 metabolically stable, treated from birth PA patients and 14 healthy same-household controls. Over the course of three months, four total stool samples were collected from each subject. To assess metabolic activity of gut microbiota, the pH, shirt chain fatty acid (SCFA) levels (I.e., acetate, propionate, butyrate, isobutyrate, valerate, and isovalerate), D- and L-lactate, ammonia, and calprotectin of samples were measured.
Outcomes show statistically significant differences in gut microbiota composition between PA patients and controls. Most notably, PA patients showed higher levels of proteobacteria and lower levels of butyrate-producing bacteria, as well as lower diversity of microbiota profile suggesting risk of gut dysbiosis.
First of its kind, this work represents an important step forward for developing new therapeutic strategies for PA management. Results show the need for dietary strategies to not only focus on propionate production, but also butyrate production and microbiota stability.