Butyric acid#History

Butyric acid was first observed in an impure form in 1814 by the French chemist Michel Eugène Chevreul. By 1818, he had purified it sufficiently to characterize it. However, Chevreul did not publish his early research on butyric acid; instead, he deposited his findings in manuscript form with the secretary of the Academy of Sciences in Paris, France. Henri Braconnot, another French chemist, was also researching the composition of butter and was publishing his findings and this led to disputes about priority. As early as 1815, Chevreul claimed that he had found the substance responsible for the smell of butter.Chevreul (1815) [https://books.google.com/books?id=tZU5AAAAcAAJ&pg=PA73 "Lettre de M. Chevreul à MM. les rédacteurs des Annales de chimie"] (Letter from Mr. Chevreul to the editors of the Annals of Chemistry), Annales de chimie, 94 : 73–79; in a footnote spanning pp. 75–76, he mentions that he had found a substance that is responsible for the smell of butter. By 1817, he published some of his findings regarding the properties of butyric acid and named it.Chevreul (1817) [https://books.google.com/books?id=y1E3AAAAYAAJ&pg=PA79 "Extrait d'une lettre de M. Chevreul à MM. les Rédacteurs du Journal de Pharmacie"] (Extract of a letter from Mr. Chevreul to the editors of the Journal of Pharmacy), Journal de Pharmacie et des sciences accessoires, 3 : 79–81. On p. 81, he named butyric acid: "Ce principe, que j'ai appelé depuis acid butérique, … " (This principle [i.e., constituent], which I have since named "butyric acid", … ) However, it was not until 1823 that he presented the properties of butyric acid in detail.E. Chevreul, Recherches chimiques sur les corps gras d'origine animale [Chemical researches on fatty substances of animal origin] (Paris, France: F.G. Levrault, 1823), [https://archive.org/details/rechercheschimi00chevgoog/page/n144 pages 115–133]. The name butyric acid comes from {{wikt-lang|grc|βούτῡρον}}, meaning "butter", the substance in which it was first found. The Latin name butyrum (or buturum) is similar.

Triglycerides of butyric acid make up 3–4% of butter. When butter goes rancid, butyric acid is liberated from the glyceride by hydrolysis.{{cite journal |doi=10.3168/jds.S0022-0302(83)82052-9 |title=Stepwise Discriminant Analysis of Free Fatty Acid Profiles for Identifying Sources of Lipolytic Enzymes in Rancid Butter |year=1983 |last1=Woo |first1=A.H. |last2=Lindsay |first2=R.C. |journal=Journal of Dairy Science |volume=66 |issue=10 |pages=2070–2075 |doi-access=free }} It is one of the fatty acid subgroup called short-chain fatty acids. Butyric acid is a typical carboxylic acid that reacts with bases and affects many metals.[http://www.inchem.org/documents/icsc/icsc/eics1334.htm ICSC 1334 – Butyric acid]. Inchem.org (23 November 1998). Retrieved on 2020-10-27.

It is found in animal fat and plant oils, bovine milk, breast milk, butter, parmesan cheese, body odor, vomit and as a product of anaerobic fermentation (including in the colon).{{cite journal|pmc=5748798|year=2017|last1=McNabney|first1=S. M.|title=Short Chain Fatty Acids in the Colon and Peripheral Tissues: A Focus on Butyrate, Colon Cancer, Obesity and Insulin Resistance|journal=Nutrients|volume=9|issue=12|pages=1348|last2=Henagan|first2=T. M.|pmid=29231905|doi=10.3390/nu9121348|doi-access=free}}{{cite journal|pmc=4939913|year=2016|last1=Morrison|first1=D. J.|title=Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism|journal=Gut Microbes|volume=7|issue=3|pages=189–200|last2=Preston|first2=T.|pmid=26963409|doi=10.1080/19490976.2015.1134082}} It has a taste somewhat like butter and an unpleasant odor. Mammals with good scent detection abilities, such as dogs, can detect it at 10 parts per billion, whereas humans can detect it only in concentrations above 10 parts per million. In food manufacturing, it is used as a flavoring agent.{{cite web |url=http://www.thegoodscentscompany.com/data/rw1003411.html |title=Butyric acid |website=The Good Scents Company |access-date=2020-10-26}}

In humans, butyric acid is one of two primary endogenous agonists of human hydroxycarboxylic acid receptor 2 ({{chem2|HCA2}}), a {{nowrap|G_i/o-coupled}} G protein-coupled receptor.{{cite journal | vauthors = Offermanns S, Colletti SL, Lovenberg TW, Semple G, Wise A, IJzerman AP | title = International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B) | journal = Pharmacological Reviews | volume = 63 | issue = 2 | pages = 269–290 | date = June 2011 | pmid = 21454438 | doi = 10.1124/pr.110.003301 | doi-access = free}}{{cite web |vauthors = Offermanns S, Colletti SL, IJzerman AP, Lovenberg TW, Semple G, Wise A, Waters MG |title=Hydroxycarboxylic acid receptors |url=http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=48 |website=IUPHAR/BPS Guide to Pharmacology |publisher=International Union of Basic and Clinical Pharmacology |access-date=13 July 2018}}

Butyric acid is present as its octyl ester in parsnip (Pastinaca sativa){{cite journal|doi=10.1023/A:1021093114663|pmid=12523562|year=2002|last1=Carroll|first1=Mark J.|title=Behavioral responses of the parsnip webworm to host plant volatiles|journal=Journal of Chemical Ecology|volume=28|issue=11|pages=2191–2201|last2=Berenbaum|first2=May R.|bibcode=2002JCEco..28.2191C |s2cid=23512190}}

and in the seed of the ginkgo tree.{{cite book|last1=Raven|first1=Peter H.|author-link1=Peter H. Raven|last2=Evert|first2=Ray F.|last3=Eichhorn|first3=Susan E.|title=Biology of Plants|url=https://archive.org/details/biologyofplants00rave_0|url-access=registration|access-date=11 October 2018|year=2005|publisher=W. H. Freemanand Company|isbn=978-0-7167-1007-3|pages=[https://archive.org/details/biologyofplants00rave_0/page/429 429]–431}}

In industry, butyric acid is produced by hydroformylation from propene and syngas, forming butyraldehyde, which is oxidised to the final product.

: {{chem2|H2 + CO + CH3CH\dCH2 → CH3CH2CH2CHO}}{{overset|oxidation|→}}butyric acid

It can be separated from aqueous solutions by saturation with salts such as calcium chloride. The calcium salt, {{chem2|Ca(C4H7O2)2 · H2O}}, is less soluble in hot water than in cold.

File:ButyrateBisyn.svg

Butyrate is produced by several fermentation processes performed by obligate anaerobic bacteria.{{cite journal|doi=10.1073/pnas.0711093105|pmid=18218779|pmc=2542871|title=The Genome of Clostridium kluyveri, a Strict Anaerobe with Unique Metabolic Features|journal=Proceedings of the National Academy of Sciences|volume=105|issue=6|pages=2128–2133|year=2008|last1=Seedorf|first1=H.|last2=Fricke|first2=W. F.|last3=Veith|first3=B.|last4=Bruggemann|first4=H.|last5=Liesegang|first5=H.|last6=Strittmatter|first6=A.|last7=Miethke|first7=M.|last8=Buckel|first8=W.|last9=Hinderberger|first9=J.|last10=Li|first10=F.|last11=Hagemeier|first11=C.|last12=Thauer|first12=R. K.|last13=Gottschalk|first13=G.|bibcode=2008PNAS..105.2128S|doi-access=free}}

This fermentation pathway was discovered by Louis Pasteur in 1861. Examples of butyrate-producing species of bacteria:

• Clostridium butyricum
• Clostridium kluyveri
• Clostridium pasteurianum
• Faecalibacterium prausnitzii
• Fusobacterium nucleatum
• Butyrivibrio fibrisolvens
• Eubacterium limosum

The pathway starts with the glycolytic cleavage of glucose to two molecules of pyruvate, as happens in most organisms. Pyruvate is oxidized into acetyl coenzyme A catalyzed by pyruvate:ferredoxin oxidoreductase. Two molecules of carbon dioxide ({{chem2|CO2}}) and two molecules of hydrogen ({{chem2|H2}}) are formed as waste products. Subsequently, {{abbr|ATP|adenosine triphosphate}} is produced in the last step of the fermentation. Three molecules of ATP are produced for each glucose molecule, a relatively high yield. The balanced equation for this fermentation is

: {{chem2|C6H12O6 → C4H8O2 + 2CO2 + 2H2}}

Other pathways to butyrate include succinate reduction and crotonate disproportionation.

Several species form acetone and n-butanol in an alternative pathway, which starts as butyrate fermentation. Some of these species are:

• Clostridium acetobutylicum, the most prominent acetone and butanol producer, used also in industry
• Clostridium beijerinckii
• Clostridium tetanomorphum
• Clostridium aurantibutyricum

These bacteria begin with butyrate fermentation, as described above, but, when the pH drops below 5, they switch into butanol and acetone production to prevent further lowering of the pH. Two molecules of butanol are formed for each molecule of acetone.

The change in the pathway occurs after acetoacetyl CoA formation. This intermediate then takes two possible pathways:

• acetoacetyl CoA → acetoacetate → acetone
• acetoacetyl CoA → butyryl CoA → butyraldehyde → butanol

For commercial purposes Clostridium species are used preferably for butyric acid or butanol production.

The most common species used for probiotics is the Clostridium butyricum.{{Cite journal |last1=Zigová |first1=Jana |last2=Šturdı́k |first2=Ernest |last3=Vandák |first3=Dušan |last4=Schlosser |first4=Štefan |date=October 1999 |title=Butyric acid production by Clostridium butyricum with integrated extraction and pertraction |url=https://linkinghub.elsevier.com/retrieve/pii/S0032959299000072 |journal=Process Biochemistry |language=en |volume=34 |issue=8 |pages=835–843 |doi=10.1016/S0032-9592(99)00007-2|url-access=subscription }}

Highly-fermentable fiber residues, such as those from resistant starch, oat bran, pectin, and guar are transformed by colonic bacteria into short-chain fatty acids (SCFA) including butyrate, producing more SCFA than less fermentable fibers such as celluloses.{{cite journal | vauthors = Lupton JR | title = Microbial degradation products influence colon cancer risk: the butyrate controversy | journal = The Journal of Nutrition | volume = 134 | issue = 2 | pages = 479–482 | date = February 2004 | pmid = 14747692 | doi=10.1093/jn/134.2.479| doi-access = free}} One study found that resistant starch consistently produces more butyrate than other types of dietary fiber.{{cite journal | vauthors = Cummings JH, Macfarlane GT, Englyst HN | title = Prebiotic digestion and fermentation | journal = The American Journal of Clinical Nutrition | volume = 73 | issue = 2 Suppl | pages = 415S–420S | date = February 2001 | pmid = 11157351 | doi = 10.1093/ajcn/73.2.415s | doi-access = free}} The production of SCFA from fibers in ruminant animals such as cattle is responsible for the butyrate content of milk and butter.{{cite journal | vauthors = Grummer RR | title = Effect of feed on the composition of milk fat | journal = Journal of Dairy Science | volume = 74 | issue = 9 | pages = 3244–3257 | date = September 1991 | pmid = 1779073 | doi = 10.3168/jds.S0022-0302(91)78510-X | doi-access = free }}

Fructans are another source of prebiotic soluble dietary fibers which can be digested to produce butyrate.{{cite journal |doi=10.3389/fmicb.2016.00979 |title=Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut |year=2016 |last1=Rivière |first1=Audrey |last2=Selak |first2=Marija |last3=Lantin |first3=David |last4=Leroy |first4=Frédéric |last5=De Vuyst |first5=Luc |journal=Frontiers in Microbiology |volume=7 |page=979 |pmid=27446020 |pmc=4923077 |doi-access=free }} They are often found in the soluble fibers of foods which are high in sulfur, such as the allium and cruciferous vegetables. Sources of fructans include wheat (although some wheat strains such as spelt contain lower amounts),{{cite web|url=http://www.med.monash.edu/cecs/gastro/fodmap/diet-and-ibs.html#5|title=Frequently asked questions in the area of diet and IBS|publisher=Department of Gastroenterology Translational Nutrition Science, Monash University, Victoria, Australia |access-date=24 March 2016}} rye, barley, onion, garlic, Jerusalem and globe artichoke, asparagus, beetroot, chicory, dandelion leaves, leek, radicchio, the white part of spring onion, broccoli, brussels sprouts, cabbage, fennel, and prebiotics, such as fructooligosaccharides (FOS), oligofructose, and inulin.{{Cite journal|last1=Gibson|first1=Peter R.|last2=Shepherd|first2=Susan J.|date=1 February 2010|title=Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach|journal=Journal of Gastroenterology and Hepatology|volume=25|issue=2|pages=252–258|doi=10.1111/j.1440-1746.2009.06149.x|issn=1440-1746|pmid=20136989|s2cid=20666740|doi-access=free}}{{Cite journal|last1=Gibson|first1=Peter R.|last2=Varney|first2=Jane|last3=Malakar|first3=Sreepurna|last4=Muir|first4=Jane G.|date=1 May 2015|title=Food components and irritable bowel syndrome|journal=Gastroenterology|volume=148|issue=6|pages=1158–1174.e4|doi=10.1053/j.gastro.2015.02.005|issn=1528-0012|pmid=25680668|doi-access=free}}

Butyric acid reacts as a typical carboxylic acid: it can form amide, ester, anhydride, and chloride derivatives.{{cite book |doi=10.1039/9781847556196-00096 |chapter=Carboxylic acids and derivatives |title=General and Synthetic Methods |year=1985 |last1=Jenkins |first1=P. R. |volume=7 |pages=96–160 |isbn=978-0-85186-884-4}} The latter, butyryl chloride, is commonly used as the intermediate to obtain the others.

Butyric acid is used in the preparation of various butyrate esters. It is used to produce cellulose acetate butyrate (CAB), which is used in a wide variety of tools, paints, and coatings, and is more resistant to degradation than cellulose acetate.{{cite book|last1=Lokensgard|first1=Erik|title=Industrial Plastics: Theory and Applications|date=2015|publisher=Cengage Learning|edition=6th}}{{ISBN?}}{{page?|date=May 2025}} CAB can degrade with exposure to heat and moisture, releasing butyric acid.{{cite news|last1=Williams|first1=R. Scott|title=Care of Plastics: Malignant plastics|volume=24|url=http://cool.conservation-us.org/waac/wn/wn24/wn24-1/wn24-102.html|access-date=29 May 2017|work=WAAC Newsletter|issue=1|publisher=Conservation OnLine}}

Low-molecular-weight esters of butyric acid, such as methyl butyrate, have mostly pleasant aromas or tastes. As a consequence, they are used as food and perfume additives. It is an approved food flavoring in the EU FLAVIS database (number 08.005).

Due to its powerful odor, it has also been used as a fishing bait additive.[http://www.nutrabaits.net/freezer.html Freezer Baits] {{Webarchive|url=https://web.archive.org/web/20100125054429/http://www.nutrabaits.net/freezer.html |date=25 January 2010 }}, nutrabaits.net Many of the commercially available flavors used in carp (Cyprinus carpio) baits use butyric acid as their ester base. It is not clear whether fish are attracted by the butyric acid itself or the substances added to it. Butyric acid was one of the few organic acids shown to be palatable for both tench and bitterling.{{Cite journal | doi = 10.1046/j.1467-2979.2003.00121.x | last1 = Kasumyan | first1 = A.O. | last2 = Døving | first2 = K.B. | year = 2003 | title = Taste preferences in fishes | journal = Fish and Fisheries | volume = 4 | issue = 4| pages = 289–347 | bibcode = 2003AqFF....4..289K | name-list-style = vanc}} The substance has been used as a stink bomb by the Sea Shepherd Conservation Society to disrupt Japanese whaling crews.[http://www.newser.com/story/80755/japanese-whalers-injured-by-acid-firing-activists.html Japanese Whalers Injured by Acid-Firing Activists] {{Webarchive|url=https://web.archive.org/web/20100608193257/http://www.newser.com/story/80755/japanese-whalers-injured-by-acid-firing-activists.html |date=8 June 2010 }}, newser.com, 10 February 2010

The Dutch branch of Extinction Rebellion has used it as a chemical agent in a clothing store, several people who became unwell were treated on site by ana ambulance crew.{{Cite web |date=2025-01-31 |title=Mensen onwel na actie Extinction Rebellion in kledingwinkel Naaldwijk |url=https://nos.nl/artikel/2554015-mensen-onwel-na-actie-extinction-rebellion-in-kledingwinkel-naaldwijk |access-date=2025-04-10 |website=nos.nl |language=nl}}

Butyric acid (pK_a 4.82) is fully ionized at physiological pH, so its anion is the material that is mainly relevant in biological systems.

It is one of two primary endogenous agonists of human hydroxycarboxylic acid receptor 2 ({{chem2|HCA2}}, also known as GPR109A), a {{nowrap|G_i/o-coupled}} G protein-coupled receptor (GPCR),

Like other short-chain fatty acids (SCFAs), butyrate is an agonist at the free fatty acid receptors FFAR2 and FFAR3, which function as nutrient sensors that facilitate the homeostatic control of energy balance; however, among the group of SCFAs, only butyrate is an agonist of HCA₂.{{cite journal | vauthors = Bourassa MW, Alim I, Bultman SJ, Ratan RR | title = Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health? | journal = Neurosci. Lett. | volume = 625 | pages = 56–63 | date = June 2016 | pmid = 26868600 | pmc = 4903954 | doi = 10.1016/j.neulet.2016.02.009 }} It is also an HDAC inhibitor (specifically, HDAC1, HDAC2, HDAC3, and HDAC8), a drug that inhibits the function of histone deacetylase enzymes, thereby favoring an acetylated state of histones in cells. Histone acetylation loosens the structure of chromatin by reducing the electrostatic attraction between histones and DNA. In general, it is thought that transcription factors will be unable to access regions where histones are tightly associated with DNA (i.e., non-acetylated, e.g., heterochromatin).{{medcn|date=October 2016}} Therefore, butyric acid is thought to enhance the transcriptional activity at promoters, which are typically silenced or downregulated due to histone deacetylase activity.

Butyrate that is produced in the colon through microbial fermentation of dietary fiber is primarily absorbed and metabolized by colonocytes and the liver{{#tag:ref|Most of the butyrate that is absorbed into blood plasma from the colon enters the circulatory system via the portal vein; most of the butyrate that enters the circulatory system by this route is taken up by the liver.|group="note"}} for the generation of ATP during energy metabolism; however, some butyrate is absorbed in the distal colon, which is not connected to the portal vein, thereby allowing for the systemic distribution of butyrate to multiple organ systems through the circulatory system.{{cite journal |last1=van Hoogdalem |first1=Edward |last2=de Boer |first2=Albertus G. |last3=Breimer |first3=Douwe D. |title=Pharmacokinetics of rectal drug administration, Part I. General considerations and clinical applications of centrally acting drugs |journal=Clinical Pharmacokinetics |date=July 1991 |volume=21 |issue=1 |page=14 |doi=10.2165/00003088-199121010-00002 |pmid=1717195 |url=https://pubmed.ncbi.nlm.nih.gov/1717195/ |access-date=18 March 2024 |issn=0312-5963 |quote=the middle and inferior rectal veins drain the lower part of the rectum and venous blood is returned to the inferior vena cava. Therefore, drugs absorbed in the latter system will be delivered preferentially to the systemic circulation, bypassing the liver and avoiding first-pass metabolism}} Butyrate that has reached systemic circulation can readily cross the blood–brain barrier via monocarboxylate transporters (i.e., certain members of the SLC16A group of transporters).{{cite journal | vauthors = Tsuji A | title = Small molecular drug transfer across the blood–brain barrier via carrier-mediated transport systems | journal = NeuroRx | volume = 2 | issue = 1 | pages = 54–62 | year = 2005 | pmid = 15717057 | pmc = 539320 | doi = 10.1602/neurorx.2.1.54 | quote = Other in vivo studies in our laboratories indicated that several compounds including acetate, propionate, butyrate, benzoic acid, salicylic acid, nicotinic acid, and some β-lactam antibiotics may be transported by the MCT at the BBB.²¹ ... Uptake of valproic acid was reduced in the presence of medium-chain fatty acids such as hexanoate, octanoate, and decanoate, but not propionate or butyrate, indicating that valproic acid is taken up into the brain via a transport system for medium-chain fatty acids, not short-chain fatty acids.}}{{cite journal | vauthors = Vijay N, Morris ME | title = Role of monocarboxylate transporters in drug delivery to the brain | journal = Curr. Pharm. Des. | volume = 20 | issue = 10 | pages = 1487–1498 | year = 2014 | pmid = 23789956 | pmc = 4084603 | doi = 10.2174/13816128113199990462| quote = Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate. ... MCT1 and MCT4 have also been associated with the transport of short chain fatty acids such as acetate and formate which are then metabolized in the astrocytes [78]. ... SLC5A8 is expressed in normal colon tissue, and it functions as a tumor suppressor in human colon with silencing of this gene occurring in colon carcinoma. This transporter is involved in the concentrative uptake of butyrate and pyruvate produced as a product of fermentation by colonic bacteria. }} Other transporters that mediate the passage of butyrate across lipid membranes include SLC5A8 (SMCT1), SLC27A1 (FATP1), and SLC27A4 (FATP4).

Butyric acid is metabolized by various human XM-ligases (ACSM1, ACSM2B, ASCM3, ACSM4, ACSM5, and ACSM6), also known as butyrate–CoA ligase.{{cite encyclopedia|title=Butyric acid|url=http://www.hmdb.ca/metabolites/HMDB00039|website=Human Metabolome Database|publisher=University of Alberta|access-date=15 August 2015}}{{cite web|title=Butanoate metabolism – Reference pathway|url=http://www.genome.jp/kegg-bin/show_pathway?map00650|website=Kyoto Encyclopedia of Genes and Genomes|publisher=Kanehisa Laboratories|date=1 November 2017|access-date=1 February 2018}} The metabolite produced by this reaction is butyryl–CoA, and is produced as follows:

: Adenosine triphosphate + butyric acid + coenzyme A → adenosine monophosphate + pyrophosphate + butyryl-CoA

As a short-chain fatty acid, butyrate is metabolized by mitochondria as an energy (i.e., adenosine triphosphate or ATP) source through fatty acid metabolism. In particular, it is an important energy source for cells lining the mammalian colon (colonocytes). Without butyrates, colon cells undergo autophagy (i.e., self-digestion) and die.{{Cite journal|last1=Donohoe|first1=Dallas R.|last2=Garge|first2=Nikhil|last3=Zhang|first3=Xinxin|last4=Sun|first4=Wei|last5=O'Connell|first5=Thomas M.|last6=Bunger|first6=Maureen K.|last7=Bultman|first7=Scott J.|date=4 May 2011|title=The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian Colon|journal=Cell Metabolism|volume=13|issue=5|pages=517–526|doi=10.1016/j.cmet.2011.02.018|issn=1550-4131|pmc=3099420|pmid=21531334}}

In humans, the butyrate precursor tributyrin, which is naturally present in butter, is metabolized by triacylglycerol lipase into dibutyrin and butyrate through the reaction:{{cite web| title=triacylglycerol lipase – Homo sapiens| url=http://www.brenda-enzymes.org/enzyme.php?ecno=3.1.1.3&Suchword=&organism%5B%5D=Homo+sapiens&show_tm=0| work=BRENDA| publisher=Technische Universität Braunschweig.| access-date=25 May 2015}}

: Tributyrin + {{chem2|H2O →}} dibutyrin + butyric acid

{{clear right}}

Butyrate has numerous effects on energy homeostasis and related diseases (diabetes and obesity), inflammation, and immune function (e.g., it has pronounced antimicrobial and anticarcinogenic effects) in humans. These effects occur through its metabolism by mitochondria to generate {{abbr|ATP|adenosine triphosphate}} during fatty acid metabolism or through one or more of its histone-modifying enzyme targets (i.e., the class I histone deacetylases) and G-protein coupled receptor targets (i.e., FFAR2, FFAR3, and Hydroxycarboxylic acid receptor 2).{{cite journal | vauthors = Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I | title = Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation | journal = Nutrients | volume = 7 | issue = 4 | pages = 2839–2849 | year = 2015 | pmid = 25875123 | pmc = 4425176 | doi = 10.3390/nu7042839 | quote = Short-chain fatty acids (SCFAs) such as acetate, butyrate, and propionate, which are produced by gut microbial fermentation of dietary fiber, are recognized as essential host energy sources and act as signal transduction molecules via G-protein coupled receptors (FFAR2, FFAR3, OLFR78, GPR109A) and as epigenetic regulators of gene expression by the inhibition of histone deacetylase (HDAC). Recent evidence suggests that dietary fiber and the gut microbial-derived SCFAs exert multiple beneficial effects on the host energy metabolism not only by improving the intestinal environment, but also by directly affecting various host peripheral tissues.| doi-access = free }}{{cite journal | vauthors = Tilg H, Moschen AR | title = Microbiota and diabetes: an evolving relationship | journal = Gut | volume = 63 | issue = 9 | pages = 1513–1521 | date = September 2014 | pmid = 24833634 | doi = 10.1136/gutjnl-2014-306928| s2cid = 22633025 }}

Butyrate is essential to host immune homeostasis. Although the role and importance of butyrate in the gut is not fully understood, many researchers argue that a depletion of butyrate-producing bacteria in patients with several vasculitic conditions is essential to the pathogenesis of these disorders. A depletion of butyrate in the gut is typically caused by an absence or depletion of butyrate-producing-bacteria (BPB). This depletion in BPB leads to microbial dysbiosis. This is characterized by an overall low biodiversity and a depletion of key butyrate-producing members. Butyrate is an essential microbial metabolite with a vital role as a modulator of proper immune function in the host. It has been shown that children lacking in BPB are more susceptible to allergic disease{{cite journal| last1=Cait| first1= Alissa | last2= Cardenas| first2= Erick| date=December 2019| title=Reduced genetic potential for butyrate fermentation in the gut microbiome of infants who develop allergic sensitization| journal= Journal of Allergy and Clinical Immunology| volume = 144| issue= 6| pages= 1638–1647. E3| doi= 10.1016/j.jaci.2019.06.029| pmid= 31279007 | doi-access= free}} and Type 1 Diabetes.{{cite journal|last1=Vatanen|first1=T.|last2=Franzosa|first2=E.A.|last3=Schwager|first3=R.|display-authors=et al|title=The human gut microbiome in early-onset type 1 diabetes from the TEDDY study|journal=Nature|volume=562|pages=589–594|date=2018|issue=7728|doi=10.1038/s41586-018-0620-2|pmid=30356183|pmc=6296767|bibcode= 2018Natur.562..589V|doi-access=free}} Butyrate is also reduced in a diet low in dietary fiber, which can induce inflammation and have other adverse affects insofar as these short-chain fatty acids activate PPAR-γ.{{cite journal | vauthors=Kumar J, Rani K, Datt C | title=Molecular link between dietary fibre, gut microbiota and health | journal=Molecular Biology Reports | volume=47 | issue=8 | pages=6229–6237 | year=2020 | doi = 10.1007/s11033-020-05611-3 | pmid=32623619| s2cid=220337072 }}

Butyrate exerts a key role for the maintenance of immune homeostasis both locally (in the gut) and systemically (via circulating butyrate). It has been shown to promote the differentiation of regulatory T cells. In particular, circulating butyrate prompts the generation of extrathymic regulatory T cells. The low-levels of butyrate in human subjects could favor reduced regulatory T cell-mediated control, thus promoting a powerful immuno-pathological T-cell response.{{cite journal |display-authors=3|last1=Consolandi |first1=Clarissa |last2=Turroni |first2=Silvia |last3=Emmi |first3=Giacomo |last4=Severgnini |first4=Marco |last5=Fiori |first5=Jessica |last6=Peano |first6=Clelia |last7=Biagi |first7=Elena |last8=Grassi |first8=Alessia |last9=Rampelli |first9=Simone |last10=Silvestri |first10=Elena |last11=Centanni |first11=Manuela |last12=Cianchi |first12=Fabio |last13=Gotti |first13=Roberto |last14=Emmi |first14=Lorenzo |last15=Brigidi |first15=Patrizia |last16=Bizzaro |first16=Nicola |last17=De Bellis |first17=Gianluca |last18=Prisco |first18=Domenico |last19=Candela |first19=Marco |last20=D'Elios |first20=Mario M. |title=Behçet's syndrome patients exhibit specific microbiome signature |journal=Autoimmunity Reviews |date=April 2015 |volume=14 |issue=4 |pages=269–276 |doi=10.1016/j.autrev.2014.11.009 |pmid=25435420 |doi-access=free |hdl=2158/962790 |hdl-access=free }} On the other hand, gut butyrate has been reported to inhibit local pro-inflammatory cytokines. The absence or depletion of these BPB in the gut could therefore be a possible aide in the overly-active inflammatory response. Butyrate in the gut also protects the integrity of the intestinal epithelial barrier. Decreased butyrate levels therefore lead to a damaged or dysfunctional intestinal epithelial barrier.{{cite journal |display-authors=3|last1=Ye |first1=Zi |last2=Zhang |first2=Ni |last3=Wu |first3=Chunyan |last4=Zhang |first4=Xinyuan |last5=Wang |first5=Qingfeng |last6=Huang |first6=Xinyue |last7=Du |first7=Liping |last8=Cao |first8=Qingfeng |last9=Tang |first9=Jihong |last10=Zhou |first10=Chunjiang |last11=Hou |first11=Shengping |last12=He |first12=Yue |last13=Xu |first13=Qian |last14=Xiong |first14=Xiao |last15=Kijlstra |first15=Aize |last16=Qin |first16=Nan |last17=Yang |first17=Peizeng |title=A metagenomic study of the gut microbiome in Behcet's disease |journal=Microbiome |date=4 August 2018 |volume=6 |issue=1 |pages=135 |doi=10.1186/s40168-018-0520-6 |pmid=30077182 |pmc=6091101 |doi-access=free }} Butyrate reduction has also been associated with Clostridioides difficile proliferation. Conversely, a high-fiber diet results in higher butyric acid concentration and inhibition of C. difficile growth.{{Cite journal |last1=Di Bella |first1=Stefano |last2=Sanson |first2=Gianfranco |last3=Monticelli |first3=Jacopo |last4=Zerbato |first4=Verena |last5=Principe |first5=Luigi |last6=Giuffrè |first6=Mauro |last7=Pipitone |first7=Giuseppe |last8=Luzzati |first8=Roberto |date=2024-02-29 |editor-last=Staley |editor-first=Christopher |others=Mayuresh Abhyankar |title=Clostridioides difficile infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options |journal=Clinical Microbiology Reviews |volume=37 |issue=2 |pages=e0013523 |language=en |doi=10.1128/cmr.00135-23 |pmid=38421181 |pmc=11324037 |issn=0893-8512}}

In a 2013 research study conducted by Furusawa et al., microbe-derived butyrate was found to be essential in inducing the differentiation of colonic regulatory T cells in mice. This is of great importance and possibly relevant to the pathogenesis and vasculitis associated with many inflammatory diseases because regulatory T cells have a central role in the suppression of inflammatory and allergic responses.{{cite journal| last1= Cait| first1 = Alissa| last2= Hughes| first2 = Michael R|date= May 2018| title= Microbiome-driven allergic lung inflammation is ameliorated by short chain fatty acids| journal= Mucosal Immunology| volume= 11| issue= 3| pages= 785–796| doi= 10.1038/mi.2017.75| pmid = 29067994| doi-access= free}} In several research studies, it has been demonstrated that butyrate induced the differentiation of regulatory T cells in vitro and in vivo.{{cite journal |display-authors=3|last1=Furusawa |first1=Yukihiro |last2=Obata |first2=Yuuki |last3=Fukuda |first3=Shinji |last4=Endo |first4=Takaho A. |last5=Nakato |first5=Gaku |last6=Takahashi |first6=Daisuke |last7=Nakanishi |first7=Yumiko |last8=Uetake |first8=Chikako |last9=Kato |first9=Keiko |last10=Kato |first10=Tamotsu |last11=Takahashi |first11=Masumi |last12=Fukuda |first12=Noriko N. |last13=Murakami |first13=Shinnosuke |last14=Miyauchi |first14=Eiji |last15=Hino |first15=Shingo |last16=Atarashi |first16=Koji |last17=Onawa |first17=Satoshi |last18=Fujimura |first18=Yumiko |last19=Lockett |first19=Trevor |last20=Clarke |first20=Julie M. |last21=Topping |first21=David L. |last22=Tomita |first22=Masaru |last23=Hori |first23=Shohei |last24=Ohara |first24=Osamu |last25=Morita |first25=Tatsuya |last26=Koseki |first26=Haruhiko |last27=Kikuchi |first27=Jun |last28=Honda |first28=Kenya |last29=Hase |first29=Koji |last30=Ohno |first30=Hiroshi |title=Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells |journal=Nature |date=13 November 2013 |volume=504 |issue=7480 |pages=446–450 |doi=10.1038/nature12721 |pmid=24226770 |bibcode=2013Natur.504..446F |s2cid=4408815}} The anti-inflammatory capacity of butyrate has been extensively analyzed and supported by many studies. It has been found that microorganism-produced butyrate expedites the production of regulatory T cells, although the specific mechanism by which it does so is unclear.{{cite journal |display-authors=3|last1=Arpaia |first1=Nicholas |last2=Campbell |first2=Clarissa |last3=Fan |first3=Xiying |last4=Dikiy |first4=Stanislav |last5=van der Veeken |first5=Joris |last6=deRoos |first6=Paul |last7=Liu |first7=Hui |last8=Cross |first8=Justin R. |last9=Pfeffer |first9=Klaus |last10=Coffer |first10=Paul J. |last11=Rudensky |first11=Alexander Y. |title=Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation |journal=Nature |date=13 November 2013 |volume=504 |issue=7480 |pages=451–455 |doi=10.1038/nature12726 |pmid=24226773 |pmc=3869884 |bibcode=2013Natur.504..451A }} More recently, it has been shown that butyrate plays an essential and direct role in modulating gene expression of cytotoxic T-cells.{{cite journal |display-authors=3|last1=Luu |first1=Maik |last2=Weigand |first2=Katharina |last3=Wedi |first3=Fatana |last4=Breidenbend |first4=Carina |last5=Leister |first5=Hanna |last6=Pautz |first6=Sabine |last7=Adhikary |first7=Till |last8=Visekruna |first8=Alexander |title=Regulation of the effector function of CD8+ T cells by gut microbiota-derived metabolite butyrate |journal=Scientific Reports |date=26 September 2018 |volume=8 |issue=1 |pages=14430 |doi=10.1038/s41598-018-32860-x |pmid=30258117 |pmc=6158259 |bibcode=2018NatSR...814430L }} Butyrate also has an anti-inflammatory effect on neutrophils, reducing their migration to wounds. This effect is mediated via the receptor Hydroxycarboxylic acid receptor 1.{{Cite journal|last1=Cholan|first1=Pradeep Manuneedhi|last2=Han|first2=Alvin|last3=Woodie|first3=Brad R.|last4=Watchon|first4=Maxinne|last5=Kurz|first5=Angela RM|last6=Laird|first6=Angela S.|last7=Britton|first7=Warwick J.|last8=Ye|first8=Lihua|last9=Holmes|first9=Zachary C.|last10=McCann|first10=Jessica R.|last11=David|first11=Lawrence A.|date=2020-11-09|title=Conserved anti-inflammatory effects and sensing of butyrate in zebrafish|url= |journal=Gut Microbes|volume=12|issue=1|pages=1–11|doi=10.1080/19490976.2020.1824563|issn=1949-0976|pmid=33064972|pmc=7575005}}

In the gut microbiomes found in the class Mammalia, omnivores and herbivores have butyrate-producing bacterial communities dominated by the butyryl-CoA:acetate CoA-transferase pathway, whereas carnivores have butyrate-producing bacterial communities dominated by the butyrate kinase pathway.{{cite journal|doi=10.1038/ismej.2014.179|title=Diet is a major factor governing the fecal butyrate-producing community structure across Mammalia, Aves and Reptilia |year=2015 |last1=Vital |first1=Marius |last2=Gao |first2=Jiarong |last3=Rizzo |first3=Mike |last4=Harrison |first4=Tara |last5=Tiedje |first5=James M. |journal=The ISME Journal |volume=9 |issue=4 |pages=832–843 |pmid=25343515 |pmc=4817703 |bibcode=2015ISMEJ...9..832V }}

The odor of butyric acid, which emanates from the sebaceous follicles of all mammals, works on ticks as a signal.

Butyrate's effects on the immune system are mediated through the inhibition of class I histone deacetylases and activation of its G-protein coupled receptor targets: Hydroxycarboxylic acid receptor 2 (GPR109A), FFAR2 (GPR43), and FFAR3 (GPR41). Among the short-chain fatty acids, butyrate is the most potent promoter of intestinal regulatory T cells in vitro and the only one among the group that is an {{chem2|HCA2}} ligand. It has been shown to be a critical mediator of the colonic inflammatory response. It possesses both preventive and therapeutic potential to counteract inflammation-mediated ulcerative colitis and colorectal cancer.

Butyrate has established antimicrobial properties in humans that are mediated through the antimicrobial peptide LL-37, which it induces via HDAC inhibition on histone H3.{{cite journal |vauthors=Wang G |title=Human antimicrobial peptides and proteins |journal=Pharmaceuticals |volume=7 |issue=5 |pages=545–594 |year=2014 |pmid=24828484 |pmc=4035769 |doi=10.3390/ph7050545 |doi-access=free}}
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035769/table/pharmaceuticals-07-00545-t003/ Table 3: Select human antimicrobial peptides and their proposed targets]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035769/table/pharmaceuticals-07-00545-t004/ Table 4: Some known factors that induce antimicrobial peptide expression]{{cite journal | vauthors = Yonezawa H, Osaki T, Hanawa T, Kurata S, Zaman C, Woo TD, Takahashi M, Matsubara S, Kawakami H, Ochiai K, Kamiya S | title = Destructive effects of butyrate on the cell envelope of Helicobacter pylori | journal = J. Med. Microbiol. | volume = 61 | issue = Pt 4 | pages = 582–589 | year = 2012 | pmid = 22194341 | doi = 10.1099/jmm.0.039040-0 }}{{cite journal | vauthors = McGee DJ, George AE, Trainor EA, Horton KE, Hildebrandt E, Testerman TL | title = Cholesterol enhances Helicobacter pylori resistance to antibiotics and LL-37 | journal = Antimicrob. Agents Chemother. | volume = 55 | issue = 6 | pages = 2897–904 | year = 2011 | pmid = 21464244 | pmc = 3101455 | doi = 10.1128/AAC.00016-11 }} In vitro, butyrate increases gene expression of FOXP3 (the transcription regulator for {{abbr|Tregs|regulatory T cells}}) and promotes colonic regulatory T cells (Tregs) through the inhibition of class I histone deacetylases; through these actions, it increases the expression of interleukin 10, an anti-inflammatory cytokine.{{cite journal | vauthors = Hoeppli RE, Wu D, Cook L, Levings MK | title = The environment of regulatory T cell biology: cytokines, metabolites, and the microbiome | journal = Front Immunol | volume = 6 | page = 61 | date=February 2015 | pmid = 25741338 | pmc = 4332351 | doi = 10.3389/fimmu.2015.00061| doi-access = free}}
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332351/figure/F1/ Figure 1: Microbial-derived molecules promote colonic Treg differentiation.] Butyrate also suppresses colonic inflammation by inhibiting the IFN-γ–STAT1 signaling pathways, which is mediated partially through histone deacetylase inhibition. While transient IFN-γ signaling is generally associated with normal host immune response, chronic IFN-γ signaling is often associated with chronic inflammation. It has been shown that butyrate inhibits activity of HDAC1 that is bound to the Fas gene promoter in T cells, resulting in hyperacetylation of the Fas promoter and up-regulation of Fas receptor on the T-cell surface.{{cite journal | vauthors = Zimmerman MA, Singh N, Martin PM, Thangaraju M, Ganapathy V, Waller JL, Shi H, Robertson KD, Munn DH, Liu K | title = Butyrate suppresses colonic inflammation through HDAC1-dependent Fas upregulation and Fas-mediated apoptosis of T cells | journal = Am. J. Physiol. Gastrointest. Liver Physiol. | volume = 302 | issue = 12 | pages = G1405–1415 | year = 2012 | pmid = 22517765 | pmc = 3378095 | doi = 10.1152/ajpgi.00543.2011}}

Similar to other {{chem2|HCA2}} agonists studied, butyrate also produces marked anti-inflammatory effects in a variety of tissues, including the brain, gastrointestinal tract, skin, and vascular tissue.{{cite journal | vauthors = Offermanns S, Schwaninger M | title = Nutritional or pharmacological activation of HCA(2) ameliorates neuroinflammation | journal = Trends Mol Med | volume = 21 | issue = 4 | pages = 245–255 | year = 2015 | pmid = 25766751 | doi = 10.1016/j.molmed.2015.02.002}}{{cite journal | vauthors = Chai JT, Digby JE, Choudhury RP | title = GPR109A and vascular inflammation | journal = Curr Atheroscler Rep | volume = 15 | issue = 5 | page = 325 | date = May 2013 | pmid = 23526298 | pmc = 3631117 | doi = 10.1007/s11883-013-0325-9}}{{cite journal | vauthors = Graff EC, Fang H, Wanders D, Judd RL | title = Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2 | journal = Metab. Clin. Exp. | volume = 65 | issue = 2 | pages = 102–113 | date= February 2016 | pmid = 26773933 | doi = 10.1016/j.metabol.2015.10.001}} Butyrate binding at FFAR3 induces neuropeptide Y release and promotes the functional homeostasis of colonic mucosa and the enteric immune system.{{cite journal | vauthors = Farzi A, Reichmann F, Holzer P | title = The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour | journal = Acta Physiol (Oxf) | volume = 213 | issue = 3 | pages = 603–627 | year = 2015 | pmid = 25545642 | pmc = 4353849 | doi = 10.1111/apha.12445}}

Butyrate has been shown to be a critical mediator of the colonic inflammatory response. It is responsible for about 70% of energy from the colonocytes, being a critical SCFA in colon homeostasis.{{cite journal |last1=Zeng |first1=Huawei |last2=Lazarova |first2=DL |last3=Bordonaro |first3=M |title=Mechanisms linking dietary fiber, gut microbiota and colon cancer prevention |journal=World Journal of Gastrointestinal Oncology |date=2014 |volume=6 |issue=2 |pages=41–51 |doi=10.4251/wjgo.v6.i2.41 |pmid=24567795 |pmc=3926973 |doi-access=free }} Butyrate possesses both preventive and therapeutic potential to counteract inflammation-mediated ulcerative colitis (UC) and colorectal cancer.{{cite journal |doi=10.3390/nu11051026|doi-access=free |title=Effects of Intestinal Microbial–Elaborated Butyrate on Oncogenic Signaling Pathways |url=https://www.mdpi.com/2072-6643/11/5/1026/pdf |format=pdf|year=2019 |last1=Chen |first1=Jiezhong |last2=Zhao |first2=Kong-Nan |last3=Vitetta |first3=Luis |journal=Nutrients |volume=11 |issue=5 |page=1026 |pmid=31067776 |pmc=6566851 |s2cid=148568580 }} It produces different effects in healthy and cancerous cells: this is known as the "butyrate paradox". In particular, butyrate inhibits colonic tumor cells and stimulates proliferation of healthy colonic epithelial cells.{{cite journal | vauthors = Klampfer L, Huang J, Sasazuki T, Shirasawa S, Augenlicht L | title = Oncogenic Ras promotes butyrate-induced apoptosis through inhibition of gelsolin expression | journal = The Journal of Biological Chemistry | volume = 279 | issue = 35 | pages = 36680–36688 | date = August 2004 | pmid = 15213223 | doi = 10.1074/jbc.M405197200 | doi-access = free }}{{cite journal|vauthors=Vanhoutvin SA, Troost FJ, Hamer HM, Lindsey PJ, Koek GH, Jonkers DM, Kodde A, Venema K, Brummer RJ |title=Butyrate-induced transcriptional changes in human colonic mucosa |journal=PLOS ONE |volume=4 |issue=8 |pages=e6759 |year=2009 |pmid=19707587 |pmc=2727000 |doi=10.1371/journal.pone.0006759 |bibcode=2009PLoSO...4.6759V |editor1-last=Bereswill |editor1-first=Stefan |doi-access=free }} The explanation why butyrate is an energy source for normal colonocytes and induces apoptosis in colon cancer cells, is the Warburg effect in cancer cells, which leads to butyrate not being properly metabolized. This phenomenon leads to the accumulation of butyrate in the nucleus, acting as a histone deacetylase (HDAC) inhibitor.{{cite journal |display-authors=3|last1=Encarnação |first1=J. C. |last2=Abrantes |first2=A. M. |last3=Pires |first3=A. S. |last4=Botelho |first4=M. F. |title=Revisit dietary fiber on colorectal cancer: butyrate and its role on prevention and treatment |journal=Cancer and Metastasis Reviews |date=30 July 2015 |volume=34 |issue=3 |pages=465–478 |doi=10.1007/s10555-015-9578-9 |pmid=26224132 |s2cid=18573671 }} One mechanism underlying butyrate function in suppression of colonic inflammation is inhibition of the IFN-γ/STAT1 signalling pathways. It has been shown that butyrate inhibits activity of HDAC1 that is bound to the Fas gene promoter in T cells, resulting in hyperacetylation of the Fas promoter and upregulation of Fas receptor on the T cell surface. It is thus suggested that butyrate enhances apoptosis of T cells in the colonic tissue and thereby eliminates the source of inflammation (IFN-γ production).{{cite journal |display-authors=3|last1=Zimmerman |first1=Mary A. |last2=Singh |first2=Nagendra |last3=Martin |first3=Pamela M. |last4=Thangaraju |first4=Muthusamy |last5=Ganapathy |first5=Vadivel |last6=Waller |first6=Jennifer L. |last7=Shi |first7=Huidong |last8=Robertson |first8=Keith D. |last9=Munn |first9=David H. |last10=Liu |first10=Kebin |title=Butyrate suppresses colonic inflammation through HDAC1-dependent Fas upregulation and Fas-mediated apoptosis of T cells |journal=American Journal of Physiology. Gastrointestinal and Liver Physiology |date=15 June 2012 |volume=302 |issue=12 |pages=G1405–G1415 |doi=10.1152/ajpgi.00543.2011 |pmid=22517765 |pmc=3378095 }} Butyrate inhibits angiogenesis by inactivating Sp1 transcription factor activity and downregulating vascular endothelial growth factor gene expression.{{cite journal |display-authors=3|last1=Prasanna Kumar |first1=S. |last2=Thippeswamy |first2=G. |last3=Sheela |first3=M.L. |last4=Prabhakar |first4=B.T. |last5=Salimath |first5=B.P. |title=Butyrate-induced phosphatase regulates VEGF and angiogenesis via Sp1 |journal=Archives of Biochemistry and Biophysics |date=October 2008 |volume=478 |issue=1 |pages=85–95 |doi=10.1016/j.abb.2008.07.004 |pmid=18655767 }}

In summary, the production of volatile fatty acids such as butyrate from fermentable fibers may contribute to the role of dietary fiber in colon cancer. Short-chain fatty acids, which include butyric acid, are produced by beneficial colonic bacteria (probiotics) that feed on, or ferment prebiotics, which are plant products that contain dietary fiber. These short-chain fatty acids benefit the colonocytes by increasing energy production, and may protect against colon cancer by inhibiting cell proliferation.

Conversely, some researchers have sought to eliminate butyrate and consider it a potential cancer driver.{{cite web|url=https://media.utoronto.ca/media-releases/low-carb-diet-cuts-risk-of-colon-cancer-study-finds/|title=Low-carb diet cuts risk of colon cancer, study finds {{!}} University of Toronto Media Room|website=media.utoronto.ca|access-date=2016-05-04}} Studies in mice indicate it drives transformation of MSH2-deficient colon epithelial cells.{{Cite journal|last1=Belcheva|first1=Antoaneta|last2=Irrazabal|first2=Thergiory|last3=Robertson|first3=Susan J.|last4=Streutker|first4=Catherine|last5=Maughan|first5=Heather|last6=Rubino|first6=Stephen|last7=Moriyama|first7=Eduardo H.|last8=Copeland|first8=Julia K.|last9=Kumar|first9=Sachin|date=2014-07-17|title=Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells|journal=Cell|volume=158|issue=2|pages=288–299|doi=10.1016/j.cell.2014.04.051|issn=1097-4172|pmid=25036629|doi-access=free}}

Owing to the importance of butyrate as an inflammatory regulator and immune system contributor, butyrate depletions could be a key factor influencing the pathogenesis of many vasculitic conditions. It is thus essential to maintain healthy levels of butyrate in the gut. Fecal microbiota transplants (to restore BPB and symbiosis in the gut) could be effective by replenishing butyrate levels. In this treatment, a healthy individual donates their stool to be transplanted into an individual with dysbiosis. A less-invasive treatment option is the administration of butyrate—as oral supplements or enemas—which has been shown to be very effective in terminating symptoms of inflammation with minimal-to-no side-effects. In a study where patients with ulcerative colitis were treated with butyrate enemas, inflammation decreased significantly, and bleeding ceased completely after butyrate provision.{{cite journal|display-authors=3|last1=Scheppach|first1=W.|last2=Sommer|first2=H.|last3=Kirchner|first3=T.|last4=Paganelli|first4=G. M.|last5=Bartram|first5=P.|last6=Christl|first6=S.|last7=Richter|first7=F.|last8=Dusel|first8=G.|last9=Kasper|first9=H.|date=1992|title=Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis|journal=Gastroenterology|volume=103|issue=1|pages=51–56|doi=10.1016/0016-5085(92)91094-K|pmid=1612357|doi-access=free}}

Butyric acid is an {{abbrlink|HDAC|histone deacetylase}} inhibitor that is selective for class I HDACs in humans. HDACs are histone-modifying enzymes that can cause histone deacetylation and repression of gene expression. HDACs are important regulators of synaptic formation, synaptic plasticity, and long-term memory formation. Class I HDACs are known to be involved in mediating the development of an addiction.{{cite journal |vauthors=Robison AJ, Nestler EJ | title = Transcriptional and epigenetic mechanisms of addiction | journal = Nat. Rev. Neurosci. | volume = 12 | issue = 11 | pages = 623–637 |date=November 2011 |pmid=21989194 |pmc=3272277 |doi=10.1038/nrn3111}}{{cite journal | vauthors = Nestler EJ | title = Epigenetic mechanisms of drug addiction | journal = Neuropharmacology | volume = 76 Pt B | pages = 259–268 | date = January 2014 | pmid = 23643695 | pmc = 3766384 | doi = 10.1016/j.neuropharm.2013.04.004 }}{{cite journal | vauthors = Walker DM, Cates HM, Heller EA, Nestler EJ | title = Regulation of chromatin states by drugs of abuse | journal = Curr. Opin. Neurobiol. | volume = 30 | pages = 112–121 | date = February 2015 | pmid = 25486626 | doi = 10.1016/j.conb.2014.11.002 | pmc=4293340}} Butyric acid and other HDAC inhibitors have been used in preclinical research to assess the transcriptional, neural, and behavioral effects of HDAC inhibition in animals addicted to drugs.{{cite journal | vauthors = Ajonijebu DC, Abboussi O, Russell VA, Mabandla MV, Daniels WM | title = Epigenetics: a link between addiction and social environment | journal = Cellular and Molecular Life Sciences | volume = 74 | issue = 15 | pages = 2735–2747 | date = August 2017 | pmid = 28255755 | doi = 10.1007/s00018-017-2493-1 | s2cid = 40791780 | pmc = 11107568 }}{{cite journal | vauthors = Legastelois R, Jeanblanc J, Vilpoux C, Bourguet E, Naassila M | title = Mécanismes épigénétiques et troubles de l'usage d'alcool : une cible thérapeutique intéressante? | trans-title = Epigenetic mechanisms and alcohol use disorders: a potential therapeutic target | language = fr | journal = Biologie Aujourd'hui | volume = 211 | issue = 1 | pages = 83–91 | date = 2017 | pmid = 28682229 | doi = 10.1051/jbio/2017014 | doi-access = free}}

The butyrate or butanoate ion, {{chem2|C3H7COO-|auto=yes}}, is the conjugate base of butyric acid. It is the form found in biological systems at physiological pH. A butyric (or butanoic) compound is a carboxylate salt or ester of butyric acid.

• Sodium butyrate

• Butyl butyrate
• Butyryl-CoA
• Cellulose acetate butyrate (aircraft dope)
• Estradiol benzoate butyrate
• Ethyl butyrate
• Methyl butyrate
• Pentyl butyrate
• Tributyrin

• List of saturated fatty acids
• Histone
• Histone-modifying enzyme
• Histone acetylase
• Histone deacetylase
• Hydroxybutyric acids
• α-Hydroxybutyric acid
• β-Hydroxybutyric acid
• γ-Hydroxybutyric acid
• Oxobutyric acids
• 2-Oxobutyric acid (α-ketobutyric acid)
• 3-Oxobutyric acid (acetoacetic acid)
• 4-Oxobutyric acid (succinic semialdehyde)
• β-Methylbutyric acid
• β-Hydroxy β-methylbutyric acid

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{{EB1911|wstitle=Butyric Acid}}

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{{reflist|group=Color legend}}

{{Commons category|Butyric acid}}

• [https://webbook.nist.gov/cgi/cbook.cgi?Name=butanoic+acid&Units=SI NIST Standard Reference Data for butanoic acid]

{{Fatty acids}}

{{HDAC inhibitors}}

{{GABA metabolism and transport modulators}}

{{Authority control}}

Category:GABA analogues

Category:Flavors

Category:Alkanoic acids

Category:Fatty acids

Category:Foul-smelling chemicals

Category:Biomolecules

Category:Histone deacetylase inhibitors