The Role of Short-Chain Fatty Acids in Inflammatory Bowel Disease

December 6, 2025 •

3 min read

Approximately 10% of our daily caloric needs can be provided by short-chain fatty acids (SCFAs) produced by gut bacteria through the fermentation of undigested dietary fiber. In inflammatory bowel disease (IBD), however, the delicate balance of these metabolites is often disrupted, with significant implications for the intestinal lining and overall health.

Quick Summary

This article examines the function and importance of short-chain fatty acids (SCFAs), including butyrate, propionate, and acetate, in maintaining a healthy gut. It details their roles in supporting the gut barrier, modulating immune responses, and mitigating inflammation, particularly in the context of inflammatory bowel disease (IBD).

Key Points

SCFA Production: Gut bacteria ferment dietary fiber to produce short-chain fatty acids, primarily acetate, propionate, and butyrate.
IBD Connection: IBD patients often have lower levels of SCFAs and reduced populations of SCFA-producing bacteria, contributing to inflammation.
Butyrate's Role: Butyrate is a key anti-inflammatory agent and the main energy source for colon cells, supporting gut barrier integrity.
Dietary Modulation: Increasing intake of fermentable fiber from foods like legumes, oats, and resistant starches can boost SCFA production.
Microbial Regulation: Probiotic and prebiotic supplementation can promote the growth of beneficial bacteria, thereby enhancing SCFA levels.
Immune Modulation: SCFAs regulate immune function by influencing T-cell differentiation and inhibiting inflammatory pathways.

What are short-chain fatty acids (SCFAs)?

Short-chain fatty acids are organic acids with a carbon chain of fewer than six atoms. They are primarily produced in the colon when beneficial gut bacteria ferment dietary fibers and resistant starches. The most abundant SCFAs in the gut are acetate (C2), propionate (C3), and butyrate (C4), typically found in a ratio of about 3:1:1. These metabolites are a key link between diet, gut bacteria, and the body's overall health.

The crucial role of SCFAs in gut health

SCFAs are vital for maintaining a healthy gut, performing functions that are often impaired in inflammatory bowel disease. They act by activating G-protein coupled receptors (GPCRs) and inhibiting histone deacetylase (HDAC) activity, which affects gene expression.

Functions of SCFAs:

Provide energy for colon cells: Butyrate is the main energy source for the cells lining the colon, helping them grow and maintain the gut barrier.
Maintain intestinal barrier function: SCFAs strengthen the gut barrier against harmful substances by boosting mucus production and improving the connections between gut lining cells.
Modulate immune responses: SCFAs help regulate the immune system by influencing immune cell development and reducing excessive inflammation, promoting immune tolerance.
Anti-inflammatory effects: They inhibit pro-inflammatory signals and increase anti-inflammatory ones. Butyrate is particularly effective at reducing inflammation by blocking a key inflammatory pathway.

SCFA levels in inflammatory bowel disease

Studies show that people with IBD often have lower levels of SCFAs and fewer diverse SCFA-producing bacteria in their gut, a condition called dysbiosis. This reduction is a major contributor to the ongoing inflammation and weakened gut barrier seen in Crohn's disease and ulcerative colitis. Specific butyrate-producing bacteria like Faecalibacterium prausnitzii and Roseburia spp. are often less abundant in these patients. This lack of SCFAs weakens the gut lining and its anti-inflammatory defenses.

Specific roles of butyrate, propionate, and acetate in IBD

Each of the main SCFAs plays a different role in gut health, and an imbalance can specifically impact IBD.

The three main SCFAs contrasted in IBD


Feature	Butyrate	Propionate	Acetate
Primary Role	Main energy source for colon cells.	Used by the liver to produce glucose.	Most abundant; involved in cholesterol synthesis and gut barrier integrity.
Mechanism	Inhibits HDAC and activates GPR109A.	Activates GPR41 and GPR43; helps regulate appetite.	Activates GPR43; involved in regulating immune cells.
IBD Impact	Reduces inflammation, helps repair the gut barrier, and promotes healthy gut cell development.	Modulates immune responses and strengthens the gut barrier.	Protects the gut barrier and regulates immune responses.
Dietary Source	Mainly produced from resistant starch.	Produced from various fibers, including mucin.	Produced from different types of fermentable fibers.

Strategies to increase SCFA production

Increasing SCFA levels is a potential treatment approach for IBD, often involving diet or supplements to support beneficial bacteria.

Dietary interventions

Eating more fermentable fibers and resistant starches provides food for gut bacteria to produce SCFAs. Diets high in these components, like the Mediterranean diet, are linked to higher SCFA levels.

High-fiber food examples:

Legumes (e.g., lentils, chickpeas)
Oats and barley
Green bananas and cooled potatoes (resistant starch)
Onions, garlic, and leeks (prebiotics)
Asparagus

Prebiotic and probiotic supplements

Prebiotics: Non-digestible fibers like inulin and fructooligosaccharides (FOS) feed beneficial gut bacteria, boosting SCFA production.
Probiotics: Live bacteria such as Bifidobacterium and Lactobacillus can increase SCFA levels. Some probiotic mixtures, like VSL#3, have shown effectiveness in maintaining remission for some UC patients.

SCFA producers in the gut

Faecalibacterium prausnitzii: A major producer of butyrate.
Eubacterium rectale: Another important butyrate producer.
Roseburia spp.: Significantly contributes to butyrate production.
Bacteroidetes phylum members: Main producers of propionate.
Bifidobacterium spp.: Can produce acetate and lactate.
Akkermansia muciniphila: Produces propionate and acetate and helps thicken the mucus layer.

Conclusion

Short-chain fatty acids are crucial metabolites produced by gut bacteria, playing essential roles in gut health, immune function, and reducing inflammation. Reduced production and metabolism of SCFAs in IBD significantly contribute to the disease. By supporting the gut barrier, modulating immune responses, and providing energy for colon cells, SCFAs offer a promising area for therapeutic development. While diet, prebiotics, and probiotics can help increase SCFA production, the relationship is complex and requires further research for personalized treatment.

For more in-depth scientific information on this topic, consult the National Institutes of Health website(https://www.mdpi.com/2072-6643/15/20/4466).

Frequently Asked Questions

The three main short-chain fatty acids (SCFAs) are acetate, propionate, and butyrate. They are produced by the fermentation of dietary fiber in the large intestine and constitute up to 95% of the total SCFAs in the gut.

In IBD, SCFAs help strengthen the intestinal barrier by promoting the production of mucus and enhancing tight junctions between epithelial cells. Butyrate is particularly important as it provides the primary energy source for colonocytes, which supports the integrity of the gut lining.

SCFA levels are often lower in IBD patients due to dysbiosis, an imbalance in the gut microbiota. This includes a reduced abundance of specific bacteria, such as Faecalibacterium prausnitzii and Roseburia spp., that specialize in SCFA production.

Diet is a strong modulator of SCFA production. A diet rich in fermentable fibers and resistant starches can increase SCFA levels. However, its effectiveness can vary among individuals, and it may not be sufficient for severe cases.

The 'butyrate paradox' refers to butyrate's ability to promote normal colonocyte growth while inhibiting the proliferation of cancerous colon cells. This is thought to be related to differences in cellular metabolism, with cancer cells relying more on glycolysis rather than butyrate oxidation for energy.

Oral SCFA supplements have shown limited efficacy in clinical trials due to rapid absorption in the small intestine, resulting in low colonic bioavailability. Therapies that promote endogenous SCFA production, such as prebiotics and probiotics, are considered more promising.

Yes, some multi-strain probiotics, like VSL#3, and single-strain supplements, including Bifidobacterium and Lactobacillus species, have been shown to increase SCFA production and improve clinical outcomes in certain IBD patients.