The potential role of gut microbiota and its modulators in the management of propionic and methylmalonic acidemia

ABSTRACT

Introduction: Propionic and methylmalonic acidemia (PA/MMA) are rare inborn errors of metabolism characterized by accumulation of propionyl CoA and/or methylmalonyl CoA, resulting in potentially serious metabolic crises and clinical complications. The gut microbiota contributes a significant proportion of total propionate production and provides a potentially modifiable target. Empiric use of oral antibiotics to reduce propionate production is a common approach but is hampered by possible drug resistance, perturbation of normal gut microbiota, and toxicity. Moreover, constipation, associated with low fiber intake, inadequate fluid intake, low gut motility, and other factors, is a chronic problem in this patient population and may influence propionate production. Newer management techniques that reduce the burden of propionate and address these clinical challenges are needed.

Areas covered: This paper summarizes the potential contribution of gut-related factors in PA/MMA and considers modifying gut microbiota as a management approach.

Expert opinion: Dietary management of PA/MMA may be improved by specific prebiotics that modify gut microbiota to stabilize or possibly reduce PA production.

KEYWORDS:

• Propionic acid
• methylmalonic acid
• prebiotic
• probiotic
• microbiota

Article highlights

• Gut microbiota is a major contributor to propionate production in propionic acidemia.

• Gut microbiota is a potentially modifiable target for propionate production.

• Propiogenic prebiotics should be avoided to stabilize PA production.

• Specific prebiotics may reduce propionate production in the gut.

This box summarizes key points contained in the article.

Declaration of interest

A MacDonald received research funding and honoraria from Nutricia, Vitaflo International and Merck Serono; is a member of the European Nutritionist Expert Panel (Biomarin), member of Sapropterin Advisory Board (Biomarin), member of the Advisory Board entitled ELEMENT (Danone-Nutricia), and member of an Advisory Board for Arla and Applied Pharma Research. AP Burlina has received speaker honoraria for presentations and board meetings from Amicus Therapeutics, Merck-Serono, Nutricia, and Sanofi Genzyme. S Tims, M Rakhshandehroo and M Kuhn and J Knol are employees of Nutricia Research. Editorial support was provided by Tim Kelly (Medi-Kelsey Limited). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was supported by Nutricia Research.