Rethinking Short-Chain Fatty Acids: A Closer Look at Propionate in Inflammation, Metabolism, and Mucosal Homeostasis

Area of Science:

• Microbiology
• Metabolic Science
• Immunology

Background:

• Propionate is a short-chain fatty acid (SCFA) produced by gut bacteria from dietary fiber fermentation.
• While butyrate is well-studied, propionate's roles in immune modulation, metabolism, and gut health are less understood.
• Propionate influences host physiology via FFAR2/FFAR3 receptors.

Purpose of the Study:

• To review the multifaceted effects of propionate on metabolism, inflammation, gut microbiota, and gastrointestinal diseases.
• To highlight propionate's dual role as both a beneficial and potentially harmful compound.
• To emphasize the need for context-specific and personalized therapeutic strategies involving propionate.

Main Methods:

• This study is a narrative review of existing literature.
• It synthesizes findings on propionate's mechanisms of action and physiological impacts.
• The review examines evidence from various studies on metabolic disorders, inflammatory conditions, and neurodevelopmental contexts.

Main Results:

• Propionate modulates immunity, energy metabolism, and gut-brain axis communication.
• Beneficial effects are observed in metabolic disorders, inflammatory bowel disease (IBD), and alcohol-related liver disease (ALD).
• Excessive propionate is associated with neurotoxicity, autism spectrum disorder (ASD), and mitochondrial dysfunction, indicating dose and tissue-specific effects.

Conclusions:

• Propionate's physiological impact is complex and context-dependent, exhibiting both protective and detrimental properties.
• Therapeutic applications of propionate require careful consideration of dosage, pathological context, and individual host microbiota.
• Personalized approaches are crucial for harnessing propionate's benefits while mitigating potential adverse effects.