For patients with ulcerative colitis, developing an effective management strategy can be a major challenge. Symptoms vary widely between patients, and many of the most common therapeutics—including aminosalicylates, corticosteroids, antibiotics, and methotrexate—have side effects that can be just as disruptive to the patient’s quality of life as the condition itself. Because ulcerative colitis has no cure, scientists have spent decades searching for therapeutic options that can offer effective relief. Today, a growing body of evidence suggests that short chain fatty acids are a promising option.
The benefits of short chain fatty acids for patients with ulcerative colitis are numerous and wide-ranging. After early observations of the effectiveness of topical supplementation of short chain fatty acids for ulcerative colitis patients, researchers have successfully identified multiple means through which short chain fatty acids may be able to help alleviate symptoms in patients with ulcerative colitis.
Short Chain Fatty Acids: Basic Information and Early Research in Ulcerative Colitis Patients
Short chain fatty acids are metabolites produced by the fermentation of dietary fiber by bacteria. These metabolites have a distinctive chemical structure—a carboxylic acid “head” with a saturated hydrocarbon “tail.” There are several different chemicals that fall into this category, and they are distinguished from each other by the number of carbon atoms in their “tails.” The three most common short chain fatty acids in the human gut are acetic acid (2 carbons in the tail), propionic acid (3 carbons in the tail), and butyric acid (4 carbons in the tail). Together, they make up about 95 percent of all the short chain fatty acids in the GI tract.
Researchers first became interested in the possible benefits of short chain fatty acids for ulcerative colitis patients when they observed that the concentrations of these chemicals in patients’ fecal samples was significantly lower than the concentrations in healthy controls. To examine the clinical relevance of these observations, researchers in the late 1980s and early 1990s conducted studies on the use of topical short chain fatty acid therapies (such as enemas and rectal irrigation treatments) for patients with distal ulcerative colitis. The results indicated that these treatments—which directly introduce short chain fatty acids into the colon—could effectively reduce common symptoms, including rectal bleeding and urgency.
While the benefits of short chain fatty acids were clearly observed in ulcerative colitis patients, researchers could only hypothesize as to why patients were experiencing a reduction in symptoms upon the introduction of these acids. Only after years of work have researchers finally been able to formulate a more complete picture of how short chain fatty acids can improve the health of patients with ulcerative colitis.
Improving the Function of the Colon
One of the benefits of short chain fatty acids is that they can help improve the structural integrity of the colon. Most patients with ulcerative colitis have a “leaky gut,” which means the intestinal wall is highly permeable to bacteria and other toxins. When these substances enter the bloodstream, they can wreak havoc throughout the body. However, studies suggest that short chain fatty acids can encourage the proliferation of colonocytes, which can help build a stronger intestinal barrier with a lower level of permeability. The short chain fatty acid with the most significant role in this process is butyric acid, since it is the major energy substrate for epithelial cells.
Butyric acid also plays a role in the development of the mucosal barrier in the colon, which is also involved in leaky gut. In patients with ulcerative colitis, the thickness of the mucosal barrier is reduced, and its composition (which includes a wide range of proteins, carbohydrates, lipids and antimicrobial compounds) is different from that of healthy patients. In experimental models of ulcerative colitis, butyric acid can promote mucus production and help restore the optimal level of mucosal permeability.
Another hallmark of ulcerative colitis is the inefficiency with which cells in the colon absorb fluid. Not only can this disrupt electrolyte balances in the body, but it can also contribute to debilitating symptoms like chronic diarrhea. Short chain fatty acids in the colon directly stimulate sodium and fluid absorption, which can lead to a reduction in symptoms.
Short Chain Fatty Acid Benefits for Fighting Inflammation
In addition to the direct impact of short chain fatty acids on the structure and function of the colon, one particular short chain fatty acid—butyric acid—has also been shown to directly combat the intestinal inflammation that underpins ulcerative colitis. There are several key mechanisms through which butyric acid can exert this effect:
Inducing T regulatory cell differentiation in the colon. T regulatory cells play an important role in the regulation of the immune system by suppressing the inflammatory response when necessary. By promoting the differentiation of T regulatory cells in the colon, butyric acid can help dampen gut inflammation in patients with ulcerative colitis.
Signaling through G-protein coupled receptors. Butyric acid can interact with a wide range of proteins in the highly diverse signaling protein family of G-protein coupled receptors (GPCRs). In one study, researchers demonstrated that the interaction between butyric acid and a specific type of GPCR could significantly reduce gut inflammation in mouse models of ulcerative colitis.
Acting as an epigenetic regulator. Butyric acid can interact with DNA and DNA storage molecules to determine when and where particular genes are expressed. In this way, it can influence the expression of multiple pro-inflammatory mediator proteins, such as NF-KB.
Minimizing oxidative damage in the colon. Studies suggest that the presence of butyric acid is associated with increased levels of glutathione (GSH), an antioxidant that can prevent inflammatory responses by limiting oxidative damage.
Capitalizing on Short Chain Fatty Acid Benefits: Treatment Ideas for Patients and Providers
Although early research focused on topical short chain fatty acid therapy for ulcerative colitis patients—that is, through enema or rectal irrigation—more recent studies have suggested that oral supplementation may be effective in animal models. Comprehensive clinical studies on patients with ulcerative colitis are needed to provide more concrete evidence, but the strong biochemical research results have prompted some patients and providers to start considering oral supplementation options. Highly bioavailable butyric acid supplements show the most promise since butyric acid is the short chain fatty acid with the largest body of evidence indicating potential efficacy for ulcerative colitis patients.
Foundational Medicine Review provides thorough analyses of research behind a wide range of treatment options for gastrointestinal and neurological disorders. Join our mailing list to stay up to date on the latest news on ulcerative colitis and other challenging medical conditions.
Barkas F., Liebropoulos E, Kei A, Elisaf M. 2013. Electrolyte and acid-base disorders in inflammatory bowel disease. Annals of Gastroenterology. 26(1):23-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959504/
Breuer RI, Buto SK, Christ ML, Bean J, Vernia P, et al. 1991. Rectal irrigation with short-chain fatty acids for distal ulcerative colitis: Preliminary report. Digestive Diseases and Sciences. 36(2):185-7. https://www.ncbi.nlm.nih.gov/pubmed/1988261
Kim YI. 1998. Short-chain fatty acids in ulcerative colitis. Nutrition Reviews. 56(1 Pt 1):17-24. https://academic.oup.com/nutritionreviews/article-abstract/56/1/17/1834981?redirectedFrom=fulltext
Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, et al. 2009. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 461(7268):1282-6. https://www.ncbi.nlm.nih.gov/pubmed/19865172/
Michielan A, D’Inca R. 2015. Intestinal permeability in inflammatory bowel disease: Pathogenesis, clinical evaluation, and therapy of leaky gut. Mediator of Inflammation. 2015:628157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637104/
Ogawa H, Rafiee P, Fisher PJ, Johnson NA, Otterson MF, et al. 2011. Butyrate modulates gene and protein expression in human intestinal endothelial cells. Biochemical and Biophysical Research Communications. 309(3):512-9. https://www.ncbi.nlm.nih.gov/pubmed/12963019
Rios-Covian D, Ruas-Madiedo P, Margolles A, Guiemonde M, Reyes-Gavilan CG, et al. Intestinal short chain fatty acids and their link with diet and human health. Frontiers in Microbiology. 7:185. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756104/
Scheppach W. 1994. Effects of short chain fatty acids on gut morphology and function. Gut. 35(1 Suppl):S35-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498258/
Vernia P, Marcheggiano A, Caprilli R, Frieri G, Corrao G et al. 1995. Short-chain fatty acid topical treatment in distal ulcerative colitis. Alimentary Pharmacology & Therapeutics. 9(3):309-13. https://www.ncbi.nlm.nih.gov/pubmed/7654893