BUTYRATE IS A SHORT-CHAIN FATTY ACID THAT IS BIOLOGICALLY ACTIVE IN THE GUT MICROBIOME AND IN ULCERATIVE COLITIS

Pandolfi F, Lauri A. Butyrate is a short-chain fatty acid that is biologically active in the gut microbiome and in ulcerative colitis. International Journal of Infection. 2025;9(3):97-101.

F. Pandolfi¹ and A. Lauri^2*

¹ Immunology and Allergy, Internal Medicine Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy;
² Department of Gastroenterology and Endoscopy, Santo Spirito Civil Hospital, Pescara, Italy.

*Correspondence to:
Adriano Lauri, MD,
Department of Gastroenterology and Endoscopy,
Santo Spirito Civil Hospital,
Pescara 65124, Italy.
e-mail: adrianolauri1@gmail.com

Received: 06 October, 2025 Accepted: 24 November, 2025

ISSN 3103-6678 [online] Copyright 2025 © by Biolife-publisher This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

ABSTRACT

Short-chain fatty acids (SCFAs) have approximately 1-6 carbon atoms, and this category includes butyrate, a molecule that provides energy to various tissues, including the intestinal lining. Butyrate plays an important role in human health by regulating the immune system, reducing inflammation, and improving cell binding to insulin, and additionaly, in ulcerative colitis. The intestinal microbiota produces a significant amount of butyrate from specific bacteria, which plays a beneficial role in the colon. In the intestine, butyrate produces energy, strengthens the intestinal barrier, and has anti-inflammatory and antitumor effects by inducing apoptosis. Dysbiosis reduces the amount of butyrate in the intestine, leading to increased tissue permeability, vulnerability to infections, and neurological disorders. Butyrate is metabolized in the mitochondria and is an important source of energy. It stimulates the expression of tight junction proteins that are important for the occlusion and narrowing of the intercellular spaces of the endothelium. Butyrate inhibits pro-inflammatory cytokines through the inhibition of NF-kB. An alteration of the intestinal microbiota is a risk factor for potentially lethal ulcerative colitis. Treatment with anti-inflammatory drugs and anti-inflammatory cytokines is useful.

KEYWORDS: Butyrate, short-chain fatty acid, SCFA, ulcerative colitis, microbiome

INTRODUCTION

Bacteria produce short-chain fatty acids (SCFAs) that support various pathophysiological processes (1).  Most fatty acids consist of 16-18 carbons, but SCFAs have 1-6 carbons. Among these molecules is butyrate, which provides energy to various tissues, including the epithelial cells lining the intestine (2). Butyrate reduces inflammation and improves the cells’ ability to capture insulin and plays an important role in human health and in some intestinal diseases, such as ulcerative colitis (3).

The human body produces a good amount of butyrate through its microbes (4). Butyrate is produced mostly by the gut microbiota and is derived from the bacterial flora of the colon, where it plays beneficial roles for both the colon and systemic health (5). Butyrate is produced by specific bacteria, such as Aceratherium prausnitzii, Enterobacterium rectal, and Roseburia spp (6,7). These bacteria ferment soluble fiber and resistant starch to produce SCFAs, including acetate, propionate, and butyrate (8).

DISCUSSION        

Butyrate plays a key role in maintaining colon health (9). At the intestinal level, butyrate is a primary energy source for colonocytes, strengthens the intestinal barrier, and reduces colon inflammation (9). Butyrate also has an anti-tumor effect by inducing apoptosis in tumor cells (10).  Systemic effects include its action on metabolism, affecting insulin production, and its interaction with the gut-brain axis (11).

In dysbiosis, the microbiota is altered, resulting in a reduction of butyrate-producing bacteria (12) (Fig.1).  Butyrate deficiency causes increased intestinal permeability, increased susceptibility to inflammation, and increased neurological and metabolic disorders (13). A diet rich in soluble fiber, starches, or probiotics can promote the production of butyrate (14).

Fig. 1. Pro-inflammatory cytokines such as IL-1, TNF, IL-6, and IFNs are produced during the immune response, increasing intestinal permeability and disrupting the tight junctions between epithelial cells. In dysbiosis, some pathogenic or opportunistic bacteria produce pro-inflammatory metabolites and further activate the immune system. This leads to increased inflammation and damage to colonocytes.

Butyrate is the most important source of energy for colonic epithelial cells (15). It is metabolized in the mitochondria to produce ATP (16). Butyrate stimulates the expression of tight junction proteins such as claudin, occludin, and zoulin (17), which is important for the occluding and narrow tight junctions that form a barrier regulating the flow of liquid substances in the spaces between the cells of epithelial and endothelial tissues, preventing the leakage of molecules while maintaining cell polarity (18). Zoulin induces the synthesis of protective mucin by goblet cells (19).

Butyrate inhibits NF-kB, a crucial transcription factor for the production of inflammatory cytokines such as TNF, IL-6, and IL-1b (20). These reactions are important for controlling intestinal inflammation that occurs in certain diseases such as Crohn’s disease and ulcerative colitis (21) (Fig.2).

Fig. 2. Dietary fiber is used by the gut microbiota, which produces metabolites with anti-inflammatory effects such as butyrate. Butyrate helps maintain the intestinal barrier and produce the anti-inflammatory cytokine IL-10. The liver produces ATP in response to immune activation and the production of pro-inflammatory cytokines.

Ulcerative colitis is a chronic inflammatory bowel disease that primarily affects the colon and rectum (22).  In this disease, inflammation affects the intestinal mucosa, often resulting in bleeding ulcers (23). It differs from Crohn’s disease, which can affect any part of the gastrointestinal tract and even the deeper layers of the intestinal wall (24).

Ulcerative colitis affects the colon and rectum, where it begins and spreads steadily upward (25). It is characterized by inflammation affecting only the superficial layer of the mucosa (26). Symptoms include chronic abdominal diarrhea, fecal urgency, weight loss, and, in severe cases, fever (27). The cause of ulcerative colitis is unknown, although it is often attributed to a dysfunction of the immune system, which can overwork the intestinal flora (28). Genetic and environmental factors, such as diet, pollution, and excessive use of antibiotics, are also implicated (29). Furthermore, alterations in the intestinal microbiota may also be involved (30).

People with ulcerative colitis may experience colon cancer, erythematous arthritis, uveitis, liver dysfunction, anaemia, and potentially life-threatening colon dilation (31). Treatment is performed with local nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressants, biologics (anti-TNF, anti-IL1 receptor antagonist), and probiotics (30).  Additionally, the anti-inflammatory cytokines IL-37 and IL-38 are under consideration for treating ulcerative colitis and other chronic inflammatory diseases. In severe cases, surgical removal of the colon may be necessary (32). A high-fiber diet can increase the production of butyrate, which is important in ulcerative colitis (33).  Butyrate can also be administered topically in enemas for therapeutic effects (34).

CONCLUSIONS

Butyrate is a SCFA that provides energy to various tissues, including the intestinal mucosa. Butyrate improves cellular binding to insulin and reduces inflammation. The gut microbiota generates butyrate from bacteria, supporting the physiological functioning of the colon. Butyrate is metabolized by mitochondria and reduced by dysbiosis, resulting in vulnerability to infections and neurological disorders. Butyrate inhibits inflammatory cytokines through the NF-kB pathway and can be used in combination with other anti-inflammatory drugs to alleviate chronic inflammatory diseases, such as ulcerative colitis.

Conflict of interest

The authors declare that they have no conflict of interest.

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