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

Propionate is a short-chain fatty acid (SCFA) produced by gut microbiota through the fermentation of dietary fibers. Among the SCFAs, butyrate stands out and has been extensively studied for its beneficial effects; however, propionate has received less attention despite its relevant roles in immune...

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Main Authors: Sonia Facchin, Matteo Calgaro, Edoardo V. Savarino
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/15/1130
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author Sonia Facchin
Matteo Calgaro
Edoardo V. Savarino
author_facet Sonia Facchin
Matteo Calgaro
Edoardo V. Savarino
author_sort Sonia Facchin
collection DOAJ
description Propionate is a short-chain fatty acid (SCFA) produced by gut microbiota through the fermentation of dietary fibers. Among the SCFAs, butyrate stands out and has been extensively studied for its beneficial effects; however, propionate has received less attention despite its relevant roles in immune modulation, metabolism, and mucosal homeostasis. This narrative review focuses on propionate’s effects on metabolism, inflammation, microbiota, and gastrointestinal diseases. Propionate acts as a signalling molecule through FFAR2/FFAR3 receptors and modulates immunity, energy metabolism, and gut–brain communication. It has beneficial effects in metabolic disorders, inflammatory bowel disease (IBD), and alcohol-related liver disease (ALD). However, excessive accumulation is linked to neurotoxicity, autism spectrum disorder (ASD), and mitochondrial dysfunction. Its effects are dose-dependent and tissue-specific, with both protective and harmful potentials depending on the context. Propionate use requires a personalized approach, considering the pathological context, host microbiota composition, and appropriate dosage to avoid adverse effects.
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spelling doaj-art-89c67a9b60c84a6e94acc7750d2409ca2025-08-20T03:36:03ZengMDPI AGCells2073-44092025-07-011415113010.3390/cells14151130Rethinking Short-Chain Fatty Acids: A Closer Look at Propionate in Inflammation, Metabolism, and Mucosal HomeostasisSonia Facchin0Matteo Calgaro1Edoardo V. Savarino2Department of Surgery, Oncology and Gastroenterology (DISCOG), University Hospital of Padua, 35128 Padua, ItalyDepartment of Biotechnology, University of Verona, 37134 Verona, ItalyDepartment of Surgery, Oncology and Gastroenterology (DISCOG), University Hospital of Padua, 35128 Padua, ItalyPropionate is a short-chain fatty acid (SCFA) produced by gut microbiota through the fermentation of dietary fibers. Among the SCFAs, butyrate stands out and has been extensively studied for its beneficial effects; however, propionate has received less attention despite its relevant roles in immune modulation, metabolism, and mucosal homeostasis. This narrative review focuses on propionate’s effects on metabolism, inflammation, microbiota, and gastrointestinal diseases. Propionate acts as a signalling molecule through FFAR2/FFAR3 receptors and modulates immunity, energy metabolism, and gut–brain communication. It has beneficial effects in metabolic disorders, inflammatory bowel disease (IBD), and alcohol-related liver disease (ALD). However, excessive accumulation is linked to neurotoxicity, autism spectrum disorder (ASD), and mitochondrial dysfunction. Its effects are dose-dependent and tissue-specific, with both protective and harmful potentials depending on the context. Propionate use requires a personalized approach, considering the pathological context, host microbiota composition, and appropriate dosage to avoid adverse effects.https://www.mdpi.com/2073-4409/14/15/1130short-chain fatty acidsmetabolitesmicrobiotaIBDIBS
spellingShingle Sonia Facchin
Matteo Calgaro
Edoardo V. Savarino
Rethinking Short-Chain Fatty Acids: A Closer Look at Propionate in Inflammation, Metabolism, and Mucosal Homeostasis
Cells
short-chain fatty acids
metabolites
microbiota
IBD
IBS
title Rethinking Short-Chain Fatty Acids: A Closer Look at Propionate in Inflammation, Metabolism, and Mucosal Homeostasis
title_full Rethinking Short-Chain Fatty Acids: A Closer Look at Propionate in Inflammation, Metabolism, and Mucosal Homeostasis
title_fullStr Rethinking Short-Chain Fatty Acids: A Closer Look at Propionate in Inflammation, Metabolism, and Mucosal Homeostasis
title_full_unstemmed Rethinking Short-Chain Fatty Acids: A Closer Look at Propionate in Inflammation, Metabolism, and Mucosal Homeostasis
title_short Rethinking Short-Chain Fatty Acids: A Closer Look at Propionate in Inflammation, Metabolism, and Mucosal Homeostasis
title_sort rethinking short chain fatty acids a closer look at propionate in inflammation metabolism and mucosal homeostasis
topic short-chain fatty acids
metabolites
microbiota
IBD
IBS
url https://www.mdpi.com/2073-4409/14/15/1130
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AT edoardovsavarino rethinkingshortchainfattyacidsacloserlookatpropionateininflammationmetabolismandmucosalhomeostasis