Share this post
How butyrate modulates inflammation and overall health
Our gut depends on trillions of bacteria to facilitate digestion, immunity, and many other functions. Until recently, however, the mechanisms by which the microbiome regulates so many aspects of human health have remained elusive.
There are at least three nutritional strategies to support the microbiome and overall health.
- Probiotics are live bacteria that confer a health benefit if consumed in adequate amounts.
- Prebiotics are compounds in food that induce the growth of beneficial bacteria. They include fermentable fibers that generate butyrate (and other short-chain fatty acids) in the colon.
- Postbiotics are soluble factors secreted by live bacteria, providing physiological benefits to the host. They include vitamins, peptides, proteins, enzymes, fatty acids (including butyrate, acetate, and propionate) and other bioactive molecules that have beneficial effects within the gut and throughout the body.,
Of all the postbiotic substances, butyrate is among the most commonly celebrated for its effects on health. It is produced by indigenous bacteria that ferment dietary fibers in the colon. Healthy microbiomes have abundant populations of butyrate-producing species.,
Aging, infections, antibiotic use, and low-fiber diets all cause a decline in butyrate production. This decline can trigger inflammation, damage the colon lining, and increase the risk of various diseases.,, In fact, low butyrate levels are associated with asthma, colorectal cancer, diabetes, fatty liver, inflammatory bowel disease, kidney disease, and other ailments.,,,,,,
It’s no wonder that scientists are investigating whether supplemental butyrate may reduce the risk of these and other diseases.
Butyrate promotes colon health
Butyrate helps protect the lining of the colon, reduce inflammatory tone, and improve the microbiome.
Butyrate is necessary to support the health of colonocytes, cells that line the surface of the large intestine (colon). Unlike other cells in the body that metabolize glucose, colonocytes rely on butyrate for most of their energy.,,
Colonocytes begin to die off if they are deprived of butyrate., Their death damages the intestinal lining, promotes inflammation, and facilitates the expansion of pathogenic bacteria that irritate the bowel.,
Butyrate helps protect the lining of the colon, reduce inflammatory tone, and improve the microbiome. Specifically, butyrate has been shown to:
- Stimulate the growth and survival of normal colon epithelial cells
- Selectively inhibit the growth of cancer cells
- Reduce excessive inflammation
- Boost innate defenses against bacterial pathogens
- Reduce oxidative stress
- Strengthen the intestinal barrier (more below)
- Support regular bowel movements and alleviate constipation,
- Increase sodium and water absorption in the colon, thereby reducing the risk of diarrhea. [In a placebo-controlled trial with 60 adults, supplementation with sodium butyrate (1500 mg/day) and other short-chain fatty acids reduced the incidence of traveler’s diarrhea by more than 80% as compared to a placebo.]
Butyrate helps reduce gut inflammation
Butyrate reduces inflammation in part by strengthening the intestinal barrier.
Diverticulitis is the inflammation of pouches that can form in the intestines. In a randomized controlled trial of sodium butyrate (300 mg/day) in 52 people with diverticular disease, less than 7% of those in the butyrate group experienced clinical symptoms of diverticulitis, compared with slightly more than 31% in the placebo group.
Butyrate reduces inflammation in part by strengthening the intestinal barrier. This barrier comprises a layer of cells that block pathogens, toxins, and other waste products in the gut from penetrating the gut wall and entering the circulation.
Butyrate has been shown to work in multiple ways. It stimulates the innate immune response; enhances the production of mucin, which protects the intestinal tract;, and has a beneficial effect on “tight junctions,” the connections between gut cells.,,
In animal models, butyrate supplementation has been shown to ameliorate a variety of disease conditions including diabetes, fatty liver, inflammatory bowel disease, lung inflammation, and kidney disease.,,,,,, All of these conditions are associated with low butyrate levels in humans, so correcting this problem could potentially improve outcomes.
Can butyrate inhibit colon cancer?
In animals, supplemental butyrate has been shown to interfere with the development and progression of colorectal cancer.
Patients with colorectal cancer, or with colorectal adenoma (polyps), have lower levels of butyrate compared to healthy controls.,,, In one study of colorectal cancer patients, butyrate levels were reduced by nearly a half as compared to a control group. Low butyrate production is correlated with a greater potential for malignancy.
Interestingly, many of the beneficial effects of fiber are attributable to its ability to increase butyrate production. Direct supplementation with butyrate has thus been considered as a possible preventive strategy. In animals, supplemental butyrate has been shown to interfere with the development and progression of colorectal cancer.,,, These results obviously need to be confirmed in human studies.
Dietary sources of butyrate
The main way to increase butyrate is to consume more dietary fiber from a variety of sources.
Butyrate (as butyric acid) is found in the diet, with butter being the main source. In fact, the name comes from the Greek word for butter, the substance in which butyrate was first found.
One tablespoon of butter provides about 560 mg of butyric acid. It is quite possible for an individual to consume in excess of one gram of butyrate in a day from butter along with other high-fat dairy products. However, butter is high in saturated fat and calories, so thankfully there are other sources of butyrate besides eating butter.
The majority of butyrate in the body is derived from dietary fibers that are fermented in the colon. Healthy individuals can produce up to 10 grams of butyrate per day. While levels can drop to 1 gram per day in extreme cases, the average is about 5 to 7 grams per day. The amount of butyrate that is produced depends on the amount of dietary fiber that is consumed, and on the composition of the gut microbiome, which varies widely among individuals.,
The main way to increase butyrate is to consume more dietary fiber from a variety of sources (fruits, vegetables, whole grains and legumes.) Increasing dietary fiber helps protect against colorectal cancer and many other conditions.56, Experts recommend that adults consume at least 21 to 38 grams of fiber daily, depending on age and gender.
It’s worth noting that some individuals experience bloating and abdominal cramps when they ramp up fiber intake, and they may not tolerate certain foods for this reason., It’s important to figure out what works best for your own digestive comfort.
The effects of probiotics and prebiotics on butyrate
Probiotic supplementation can enhance butyrate levels and improve the microbiome.
Probiotic supplementation can help enhance butyrate levels and improve the microbiome overall. Supplemental Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus, and/or Lactobacillus paracasei, were all shown to increase fecal butyrate levels after a month or more of daily supplementation.,,
In studies of prebiotics, supplemental xylo-oligosaccharides (XOS) and arabinoxylan-oligosaccharides (AXOS) were shown to increase butyrate production as well.,, The magnitude of the effect, however, depends on the individual’s microbiome: if butyrate-producing species have declined, prebiotics will be less effective at boosting butyrate levels.
Results with supplemental fructo-oligosaccharides (FOS) have been mixed, with some studies showing an increase in butyrate production and other studies showing a decrease., Further studies are needed.
Human trials of butyrate supplementation
Butyrate supplementation may expand the populations of butyrate-producing bacteria.
As mentioned, oral butyrate supplementation is of great interest. In two randomized, double-blind, placebo-controlled trials of diabetic adults, supplementation with sodium butyrate (600 mg/day for 45 days) significantly reduced blood markers of inflammation and oxidative stress as compared with placebo.,
In one study of 60 diabetic adults who were overweight or obese, butyrate supplementation significantly decreased blood pressure as compared to a placebo. In the same study, butyrate decreased circulating levels of high-sensitive C-reactive protein (hs-CRP). This protein is a marker for cardiovascular disease, so by reducing hs-CRP, butyrate may reduce this risk. Taken together, the results suggest that orally administered butyrate can have beneficial physiological effects at fairly low doses of 600 mg/day.,
Butyrate supplementation may even improve the overall health of the microbiota by expanding the populations of butyrate-producing bacteria.,, This newly-discovered property of butyrate has been described as a “virtuous circle” – wherein butyrate increases the abundance of butyrate-producing species, which then produce more butyrate, and so on. In one study there was even an increase in A. muciniphila, a valuable bacterial species that assists with blood glucose control.,
In sum, butyrate may be one of the most valuable postbiotic substances yet discovered, with significant implications for the microbiome and overall health. If you are contemplating butyrate supplementation, consider formulations comprising calcium butyrate and magnesium butyrate. They are sodium-free, and they provide essential calcium and magnesium along with butyrate.Click here to see References
 Koh A, et al. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. 2016 Jun 2;165(6):1332-45.
 Wegh CAM, et al. Postbiotics and their potential applications in early life nutrition and beyond. Int J Mol Sci. 2019 Sep 20;20(19):4673.
 Rivière A, et al. Bifidobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut. Front Microbiol. 2016 Jun 28;7:979.
 Barnes D, et al. Competitively selected donor fecal microbiota transplantation: butyrate concentration and diversity as measures of donor quality. J Pediatr Gastroenterol Nutr. 2018 Aug;67(2):185-7.
 Salazar N, et al. Age-associated changes in gut microbiota and dietary components related with the immune system in adulthood and old age: a cross-sectional study. Nutrients. 2019 Jul 31;11(8):1765.
 Hippe B, et al. Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age. FEMS Microbiol Lett. 2011 Mar;316(2):130-5.
 Palleja A, et al. Recovery of gut microbiota of healthy adults following antibiotic exposure. Nat Microbiol. 2018 Nov;3(11):1255-65.
 Chen HM, et al. Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma. Am J Clin Nutr. 2013 May;97(5):1044-52.
 Wu N, et al. Dysbiosis signature of fecal microbiota in colorectal cancer patients. Microb Ecol. 2013 Aug;66(2):462-70.
 Noureldein MH, et al. Butyrate modulates diabetes-linked gut dysbiosis: epigenetic and mechanistic modifications. J Mol Endocrinol. 2020 Jan;64(1):29-42.
 Lloyd-Price J, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 2019 May;569(7758):655-62.
 Wang S, et al. Quantitative reduction in short-chain fatty acids, especially butyrate, contributes to the progression of chronic kidney disease. Clin Sci (Lond). 2019 Sep 10;133(17):1857-70.
 Qin J, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012 Oct 4;490(7418):55-60.
 Liu W, et al. A bridge for short-chain fatty acids to affect inflammatory bowel disease, type 1 diabetes, and non-alcoholic fatty liver disease positively: by changing gut barrier. Eur J Nutr. 2020 Nov 12:1-4.
 Litvak Y, et al. Colonocyte metabolism shapes the gut microbiota. Science. 2018 Nov 30;362(6418):eaat9076.
 Donohoe DR, et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011 May 4;13(5):517-26.
 Gasaly N, et al. Butyrate and the fine-tuning of colonic homeostasis: implication for inflammatory bowel diseases. Int J Mol Sci. 2021 Mar 17;22(6):3061.
 Hamer HM, et al. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19.
 Luciano L, et al. Withdrawal of butyrate from the colonic mucosa triggers “mass apoptosis” primarily in the G0/G1 phase of the cell cycle. Cell Tissue Res. 1996 Oct;286(1):81-92.
 Haq S, et al. Autophagy: roles in intestinal mucosal homeostasis and inflammation. J Biomed Sci. 2019 Feb 14;26(1):19.
 Bedford A, Gong J. Implications of butyrate and its derivatives for gut health and animal production. Anim Nutr. 2018 Jun;4(2):151-9.
 Hague A, et al. Butyrate acts as a survival factor for colonic epithelial cells: further fuel for the in vivo versus in vitro debate. Gastroenterology. 1997 Mar;112(3):1036-40.
 Wang W, et al. Sodium butyrate selectively kills cancer cells and inhibits migration in colorectal cancer by targeting thioredoxin-1. Onco Targets Ther. 2020 May 27;13:4691-704.
 Silva JPB, et al. Protective mechanisms of butyrate on inflammatory bowel disease. Curr Pharm Des. 2018;24(35):4154-66.
 Schulthess J, et al. The short chain fatty acid butyrate imprints an antimicrobial program in macrophages. Immunity. 2019 Feb 19;50(2):432-45.
 Hamer HM, et al. Butyrate modulates oxidative stress in the colonic mucosa of healthy humans. Clin Nutr. 2009 Feb;28(1):88-93.
 Canani RB, et al. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011 Mar 28;17(12):1519-28.
 Pituch A, et al. Butyric acid in functional constipation. Prz Gastroenterol. 2013;8(5):295-8.
 Velázquez OC, et al. Butyrate and the colonocyte. Production, absorption, metabolism, and therapeutic implications. Adv Exp Med Biol. 1997;427:123-34.
 Krokowicz L, et al. Sodium butyrate and short chain fatty acids in prevention of travellers’ diarrhoea: a randomized prospective study. Travel Med Infect Dis. Mar-Apr 2014;12(2):183-8.
 Krokowicz L, et al. Microencapsulated sodium butyrate administered to patients with diverticulosis decreases incidence of diverticulitis–a prospective randomized study. Int J Colorectal Dis. 2014 Mar;29(3):387-93.
 Bischoff SC, et al. Intestinal permeability–a new target for disease prevention and therapy. BMC Gastroenterol. 2014 Nov 18;14:189.
 Isobe J, et al. Commensal-bacteria-derived butyrate promotes the T-cell-independent IgA response in the colon. Int Immunol. 2020 Apr 12;32(4):243-58.
 Willemsen LEM, et al. Short chain fatty acids stimulate epithelial mucin 2 expression through differential effects on prostaglandin E(1) and E(2) production by intestinal myofibroblasts. Gut. 2003 Oct;52(10):1442-7.
 Gaudier E, et al. Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose. Am J Physiol Gastrointest Liver Physiol. 2004 Dec;287(6):G1168-74.
 Ma X, et al. Butyrate promotes the recovering of intestinal wound healing through its positive effect on the tight junctions. J Anim Sci. 2012 Dec;90 Suppl 4:266-8.
 Wang RX, et al. Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin. Proc Natl Acad Sci U S A. 2020 May 26;117(21):11648-57.
 Kelly CJ, et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe. 2015 May 13;17(5):662-71.
 Cait A, et al. Microbiome-driven allergic lung inflammation is ameliorated by short-chain fatty acids. Mucosal Immunol. 2018 May;11(3):785-95.
 Chen G, et al. Sodium butyrate inhibits inflammation and maintains epithelium barrier integrity in a TNBS-induced inflammatory bowel disease mice model. EBioMedicine. 2018 Apr;30:317-25.
 Xu YH, et al. Sodium butyrate supplementation ameliorates diabetic inflammation in db/db mice. J Endocrinol. 2018 Sep;238(3):231-44.
 Gao Z, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009 Jul;58(7):1509-17.
 Matheus VA, et al. Butyrate reduces high-fat diet-induced metabolic alterations, hepatic steatosis and pancreatic beta cell and intestinal barrier dysfunctions in prediabetic mice. Exp Biol Med (Maywood). 2017 Jun;242(12):1214-26.
 Baumann A, et al. Oral supplementation of sodium butyrate attenuates the progression of non-alcoholic steatohepatitis. Nutrients. 2020 Mar 30;12(4):951.
 Vieira ELM, et al. Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis. J Nutr Biochem. 2012 May;23(5):430-6.
 Weir TL, et al. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS One. 2013 Aug 6;8(8):e70803.
 Chen W, et al. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS One. 2012;7(6):e39743.
 Wu N, et al. Dysbiosis signature of fecal microbiota in colorectal cancer patients. Microb Ecol. 2013 Aug;66(2):462-70.
 Yusuf F, et al. Butyrate acid as a potential marker for diversity of gut microbiota in colorectal cancer patients. Age. 2020;53(13.3):50.
 Sánchez-Alcoholado L, et al. Gut microbiota-mediated inflammation and gut permeability in patients with obesity and colorectal cancer. Int J Mol Sci. 2020 Sep 16;21(18):6782.
 Brenner H, Chen C. The colorectal cancer epidemic: challenges and opportunities for primary, secondary and tertiary prevention. Br J Cancer. 2018 Oct;119(7):785-92.
 Magalhães B, et al. Dietary patterns and colorectal cancer: systematic review and meta-analysis. Eur J Cancer Prev. 2012 Jan;21(1):15-23.
 Donohoe DR, et al. A gnotobiotic mouse model demonstrates that dietary fiber protects against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner. Cancer Discov. 2014 Dec;4(12):1387-97.
 McNabney SM, Henagan TM. Short chain fatty acids in the colon and peripheral tissues: a focus on butyrate, colon cancer, obesity and insulin resistance. Nutrients. 2017 Dec 12;9(12):1348.
 Tian Y, et al. Short-chain fatty acids administration is protective in colitis-associated colorectal cancer development. J Nutr Biochem. 2018 Jul;57:103-9.
 Ma X, et al. Sodium butyrate modulates gut microbiota and immune response in colorectal cancer liver metastatic mice. Cell Biol Toxicol. 2020 Oct;36(5):509-15.
 Cavaleri F, Bashar E. Potential synergies of β-Hydroxybutyrate and butyrate on the modulation of metabolism, inflammation, cognition, and general health. J Nutr Metab. 2018 Apr 1;2018:7195760.
 Banasiewicz T, et al. Determination of butyric acid dosage based on clinical and experimental studies – a literature review. Prz Gastroenterol. 2020;15(2):119-25.
 David LA, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014 Jan 23;505(7484):559-63.
 O’Keefe SJD, et al. Fat, fibre and cancer risk in African Americans and rural Africans. Nat Commun. 2015 Apr 28;6:6342.
 Matt SM, et al. Butyrate and dietary soluble fiber improve neuroinflammation associated with aging in mice. Front Immunol. 2018 Aug 14;9:1832.
 Quagliani D, et al. Closing America’s fiber intake gap: communication strategies from a Food and Fiber Summit. Am J Lifestyle Med. 2016 Jul 7;11(1):80-5.
 Gill PA, et al. Review article: short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders. Aliment Pharmacol Ther. 2018 Jul;48(1):15-34.
 Magge S, Lembo A. Low-FODMAP diet for treatment of irritable bowel syndrome. Gastroenterol Hepatol (NY). 2012 Nov;8(11):739-45.
 Gargari G, et al. Consumption of a Bifidobacterium bifidum strain for 4 weeks modulates dominant intestinal bacterial taxa and fecal butyrate in healthy adults. Appl Environ Microbiol. 2016 Sep 16;82(19):5850-9.
 Ferrari C, et al. Modulation of fecal Clostridiales bacteria and butyrate by probiotic intervention with Lactobacillus paracasei DG varies among healthy adults. J Nutr. 2014 Nov;144(11):1787-96.
 Hibberd AA, et al. Intestinal microbiota is altered in patients with colon cancer and modified by probiotic intervention. BMJ Open Gastroenterol. 2017 Jul 3;4(1):e000145.
 Lecerf JM, et al. Xylo-oligosaccharide (XOS) in combination with inulin modulates both the intestinal environment and immune status in healthy subjects, while XOS alone only shows prebiotic properties. Br J Nutr. 2012 Nov 28;108(10):1847-58.
 May T, et al. Effect of fiber source on short-chain fatty acid production and on the growth and toxin production by Clostridium difficile. Scand J Gastroenterol. 1994 Oct;29(10):916-22.
 Baxter NT, et al. Dynamics of human gut microbiota and short-chain fatty acids in response to dietary interventions with three fermentable fibers. mBio. 2019 Jan 29;10(1):e02566-18.
 Tandon D, et al. A prospective randomized, double-blind, placebo-controlled, dose-response relationship study to investigate efficacy of fructo-oligosaccharides (FOS) on human gut microflora. Sci Rep. 2019 Apr 2;9(1):5473.
 Liu F, et al. Fructooligosaccharide (FOS) and galactooligosaccharide (GOS) increase Bifidobacterium but reduce butyrate producing bacteria with adverse glycemic metabolism in healthy young population. Sci Rep. 2017 Sep 18;7(1):11789.
 Roshanravan N, et al. Effects of oral butyrate and inulin supplementation on inflammation-induced pyroptosis pathway in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Cytokine. 2020 Jul;131:155101.
 Roshanravan N, et al. The effects of sodium butyrate and inulin supplementation on angiotensin signaling pathway via promotion of Akkermansia muciniphila abundance in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. J Cardiovasc Thorac Res. 2017;9(4):183-90.
 Facchin S, et al. Microbiota changes induced by microencapsulated sodium butyrate in patients with inflammatory bowel disease. Neurogastroenterol Motil. 2020 Oct;32(10):e13914.
 Zhou D, et al. Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier. World J Gastroenterol. 2017 Jan 7;23(1):60-75.
 Xu Y, et al. Function of Akkermansia muciniphila in obesity: interactions with lipid metabolism, immune response and gut systems. Front Microbiol. 2020 Feb 21;11:219.
 Shih CT, et al. Akkermansia muciniphila is negatively correlated with Hemoglobin A1c in refractory diabetes. Microorganisms. 2020 Sep 5;8(9):1360.
Share this post
Marina MacDonald, MS, PhD
Tips for a Happy Belly This Holiday Season
How to enjoy the season without paying for it later With the winter holidays upon us, holiday gatherings and celebrations with an abundance of food and drink are commonplace. “Worry about it in the new year” is an approach many opt to take with respect to the excess calories consumed this time of year….
Leaky Gut 101
Why intestinal permeability causes so much harm, and what to do about it Brilliantly packed within the body, the intestinal barrier covers a surface area of over 4,000 square feet and requires about 40% of the body’s energy expenditure. But what happens when it starts to break down? What is leaky gut? Hold up…
What is Bowel Tolerance?
A guide to dosing vitamin C, magnesium, and other nutrients We often talk about taking vitamin C and magnesium to “bowel tolerance” – but what does that mean? Dosing a supplement to bowel tolerance means taking the highest dose of that supplement possible without causing loose, watery stools (diarrhea). If you’re taking vitamin C…
Digestives Enzymes – The Fix for Your Digestive Discomfort?
The important role of the pancreas and digestive enzymes on health There are so many supplements out there designed to support digestion, and probiotics seem to be getting all the limelight. However, many are surprised to find that digestive enzymes (also known as pancreatic enzymes) often have a far greater impact on digestive symptoms…
Vaccine Efficacy, Part 1 of 2: Can a Healthy Diet Improve It?
The influence of dietary fiber, prebiotics, beta-glucan, and fucoidan Vaccines are one of the greatest successes of modern medicine, helping to protect entire populations against a wide range of infectious diseases. A vaccine works by training the immune system to recognize and combat pathogens, either viruses or bacteria. To do this, certain molecules (antigens)…
Response to CBS News Report: Do Probiotics Actually Do Anything?
They got a lot right, but we have a few (cited) details to add to the conversation By Mike Grochocki, RD, LDN On June 28th, 2020 the CBS News show 60 MINUTES aired a segment on probiotics, which have become wildly popular in both professional and retail nutritional supplement markets. The main question CBS…