Butyric acid

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Butyric acid

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Space filling model of butyric acid colspan=2 style="background:#f8eaba; border-top:2px solid transparent; border-bottom:2px solid transparent; text-align:center;" #REDIRECTmw:Help:Magic words#Other
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IUPAC name
Butanoic acid
Other names
Butyric acid, 1-Propanecarboxylic acid, Propanecarboxylic acid, C4:0 (Lipid numbers)
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107-92-6 7pxY ChEBI CHEBI:30772 7pxY ChEMBL ChEMBL14227 7pxY ChemSpider 259 7pxY DrugBank DB03568 7pxY EC number 203-532-3 IUPHAR ligand 1059 Jmol-3D images Image
Image KEGG C00246 7pxY MeSH Butyric+acid PubChem Template:Chembox PubChem/format RTECS number ES5425000 Template:Chembox UNII UN number 2820 colspan=2 style="background:#f8eaba; border-top:2px solid transparent; border-bottom:2px solid transparent; text-align:center;" #REDIRECTmw:Help:Magic words#Other
This page is a soft redirect. Properties

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C4H8O2 Molar mass Lua error in Module:Math at line 495: attempt to index field 'ParserFunctions' (a nil value). g·mol−1 Appearance Colorless liquid Odor Unpleasant and obnoxious Density 1.135 g/cm3 (−43 °C)[1]
0.9528 g/cm3 (25 °C)[2] Melting point Script error: No such module "convert".[2] Boiling point Script error: No such module "convert".[2] Sublimes at −35 °C
ΔsublHo = 76 kJ/mol[3] Miscible Solubility Slightly soluble in CCl4[4]
Miscible with ethanol, ether log P 0.79[4] Vapor pressure 0.112 kPa (20 °C)[5]
0.74 kPa (50 °C)
9.62 kPa (100 °C)[3] 5.35·10−4 L·atm/mol[4] Acidity (pKa) 4.82[4] Thermal conductivity 1.46·105 W/m·K 1.398 (20 °C)[2] Viscosity 1.814 cP (15 °C)[6]
1.426 cP (25 °C)[4] colspan=2 style="background:#f8eaba; border-top:2px solid transparent; border-bottom:2px solid transparent; text-align:center;" #REDIRECTmw:Help:Magic words#Other
This page is a soft redirect. Structure

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Crystal structure Monoclinic (−43 °C)[1] Space group C2/m[1] Lattice constant a = 8.01 Å, b = 6.82 Å, c = 10.14 Å[1] Lattice constant α = 90°, β = 111.45°, γ = 90° Dipole moment 0.93 D (20 °C)[6] colspan=2 style="background:#f8eaba; border-top:2px solid transparent; border-bottom:2px solid transparent; text-align:center;" #REDIRECTmw:Help:Magic words#Other
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178.6 J/mol·K[3][4] 222.2 J/mol·K[6] −533.9 kJ/mol[3] 2183.5 kJ/mol[3] colspan=2 style="background:#f8eaba; border-top:2px solid transparent; border-bottom:2px solid transparent; text-align:center;" #REDIRECTmw:Help:Magic words#Other
This page is a soft redirect. Hazards

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SDS External MSDS GHS pictograms The corrosion pictogram in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)[7] GHS signal word Danger H314[7] P280, P305+351+338, P310[7] EU classification Harmful Xn Corrosive C R-phrases R20/21/22, R34, R36/37/38 S-phrases S26, S36, S45 NFPA 704

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Flash point Script error: No such module "convert".[5][7] Script error: No such module "convert".[7] Explosive limits 2.2–13.4%[5] 2000 mg/kg (oral, rat) colspan=2 style="background:#f8eaba; border-top:2px solid transparent; border-bottom:2px solid transparent; text-align:center;" #REDIRECTmw:Help:Magic words#Other
This page is a soft redirect. Related compounds

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Other anions
Butyrate Propionic acid
Acrylic acid
Succinic acid
Malic acid
Tartaric acid
Crotonic acid
Fumaric acid
Pentanoic acid
Related compounds
Methyl butyrate
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
 14pxY verify (what is10pxY/10pxN?) Infobox references

Butyric acid (from Greek βούτῡρον, meaning "butter"), also known under the systematic name butanoic acid, abbreviated BTA,[5] is a carboxylic acid with the structural formula CH3CH2CH2-COOH. Salts and esters of butyric acid are known as butyrates or butanoates. Butyric acid is found in milk, especially goat, sheep and buffalo milk, butter, Parmesan cheese, and as a product of anaerobic fermentation (including in the colon and as body odor). It has an unpleasant smell and acrid taste, with a sweetish aftertaste (similar to ether). It can be detected by mammals with good scent detection abilities (such as dogs) at 10 ppb, whereas humans can detect it in concentrations above 10 ppm.

Butyric acid is present in, and is the main distinctive smell of, human vomit.[8][9][10]

Butyric acid was first observed (in impure form) in 1814 by the French chemist Michel Eugène Chevreul. By 1818, he had purified it sufficiently to characterize it.[11] The name of butyric acid comes from the Latin word for butter, butyrum (or buturum), the substance in which butyric acid was first found.


Butyric acid is a fatty acid occurring in the form of esters in animal fats. The triglyceride of butyric acid makes up 3% to 4% of butter. When butter goes rancid, butyric acid is liberated from the glyceride by hydrolysis, leading to the unpleasant odor. It is an important member of the fatty acid subgroup called short-chain fatty acids. Butyric acid is a medium-strong acid that reacts with bases and strong oxidants, and attacks many metals.[12]

The acid is an oily, colorless liquid that is easily soluble in water, ethanol, and ether, and can be separated from an aqueous phase by saturation with salts such as calcium chloride. It is oxidized to carbon dioxide and acetic acid using potassium dichromate and sulfuric acid, while alkaline potassium permanganate oxidizes it to carbon dioxide. The calcium salt, Ca(C4H7O2)2·H2O, is less soluble in hot water than in cold.

Butyric acid has a structural isomer called isobutyric acid (2-methylpropanoic acid).


Personal protective equipment such as rubber or PVC gloves, protective eye goggles, and chemical-resistant clothing and shoes are used to minimize risks when handling butyric acid.

Inhalation of butyric acid may result in soreness of throat, coughing, a burning sensation and laboured breathing. Ingestion of the acid may result in abdominal pain, shock, and collapse. Physical exposure to the acid may result in pain, blistering and skin burns, while exposure to the eyes may result in pain, severe deep burns and loss of vision.[12]


It is industrially prepared by the fermentation of sugar or starch, brought about by the addition of putrefying cheese, with calcium carbonate added to neutralize the acids formed in the process. The butyric fermentation of starch is aided by the direct addition of Bacillus subtilis. Salts and esters of the acid are called butyrates or butanoates.

Butyric acid or fermentation butyric acid is also found as a hexyl ester hexyl butyrate in the oil of Heracleum giganteum (a type of hogweed) and as the octyl ester octyl butyrate in parsnip (Pastinaca sativa); it has also been noticed in skin flora and perspiration.


Butyric acid is used in the preparation of various butyrate esters. Low-molecular-weight esters of butyric acid, such as methyl butyrate, have mostly pleasant aromas or tastes. As a consequence, they find use as food and perfume additives. It is also used as an animal feed supplement, due to the ability to reduce pathogenic bacterial colonization.[13] 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.[14] Many of the commercially available flavors used in carp (Cyprinus carpio) baits use butyric acid as their ester base; however, it is not clear whether fish are attracted by the butyric acid itself or the substances added to it. Butyric acid was, however, one of the few organic acids shown to be palatable for both tench and bitterling.[15]

The substance has also been used as a stink bomb by Sea Shepherd Conservation Society to disrupt Japanese whaling crews,[16] as well as by anti-abortion protesters to disrupt abortion clinics.[17]



Butyrate is produced as end-product of a fermentation process solely performed by obligate anaerobic bacteria. Fermented Kombucha "tea" includes butyric acid as a result of the fermentation. This fermentation pathway was discovered by Louis Pasteur in 1861. Examples of butyrate-producing species of bacteria:

The pathway starts with the glycolytic cleavage of glucose to two molecules of pyruvate, as happens in most organisms. Pyruvate is then oxidized into acetyl coenzyme A using a unique mechanism that involves an enzyme system called pyruvate-ferredoxin oxidoreductase. Two molecules of carbon dioxide (CO2) and two molecules of elemental hydrogen (H2) are formed as waste products from the cell. Then,

Action Responsible enzyme
Acetyl coenzyme A converts into acetoacetyl coenzyme A acetyl-CoA-acetyl transferase
Acetoacetyl coenzyme A converts into β-hydroxybutyryl CoA β-hydroxybutyryl-CoA dehydrogenase
β-hydroxybutyryl CoA converts into crotonyl CoA crotonase
Crotonyl CoA converts into butyryl CoA (CH3CH2CH2C=O-CoA) butyryl CoA dehydrogenase
A phosphate group replaces CoA to form butyryl phosphate phosphobutyrylase
The phosphate group joins ADP to form ATP and butyrate butyrate kinase

ATP is produced, as can be seen, 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

C6H12O6 → C4H8O2 + 2 CO2 + 2 H2.

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

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

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.[18] One study found that resistant starch consistently produces more butyrate than other types of dietary fiber.[19] The production of SCFA from fibers in ruminant animals such as cattle is responsible for the butyrate content of milk and butter.[20]



Human enzyme and GPCR binding[21][22]
Inhibited enzyme IC50 (nM) Entry note
HDAC1 16,000
HDAC2 12,000
HDAC3 9,000
HDAC4 2,000,000 Lower bound
HDAC5 2,000,000 Lower bound
HDAC6 2,000,000 Lower bound
HDAC7 2,000,000 Lower bound
HDAC8 15000
HDAC9 2,000,000 Lower bound
CA1 511,000
CA2 1,032,000
GPCR target pEC50 Entry note
FFAR2 2.9–4.6 Full agonist
FFAR3 3.8–4.9 Full agonist
NIACR1 missing data Full agonist

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 which help regulate energy balance; unlike the other SCFAs, butyrate is also an agonist of niacin receptor 1. Butyric acid 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. Acetylated histones have a lower affinity for DNA than nonacetylated histones, due to the neutralization of electrostatic charge interactions. In general, it is thought that transcription factors will be unable to access regions where histones are tightly associated with DNA (i.e., nonacetylated, e.g., heterochromatin). Therefore, butyric acid is thought to enhance the transcriptional activity at promoters, which are typically silenced or downregulated due to histone deacetylase activity.

Two HDAC inhibitors, sodium butyrate (NaB) and trichostatin A (TSA), increase lifespan in experimental animals.[23]


Butyric acid is metabolized by various human XM-ligases (ACSM1, ACSM2B, ASCM3, ACSM4, ACSM5, and ACSM6), also known as butyrate–CoA ligase.[24] The metabolite produced by this reaction is butyryl–CoA, and occurs as follows:[24]

Adenosine triphosphate + Butyric acid + Coenzyme A → Adenosine monophosphate + Pyrophosphate + Butyryl-CoA

In humans, the butyrate prodrug tributyrin is metabolized by triacylglycerol lipase into dibutyrin and butyrate through the reaction:[25]

Tributyrin + H20 = Dibutyrin + Butyrate


Peripheral therapeutic effects

Butyrate is known to have numerous beneficial effects in humans on energy homeostasis and related diseases (e.g., diabetes and obesity), immune function, and inflammation, which mediate its antimicrobial and anticarcinogenic properties.[26][27] These effects are all known to occur through one more of its histone-modifying enzyme targets (i.e., the HDACs) or G-protein coupled receptor targets (i.e., FFAR2, FFAR3, and NIACR1).[26]

Immunomodulation, microbes, and inflammation

Butyrate has established antimicrobial properties in humans which are mediated through the antimicrobial peptide, LL-37, which it induces via HDAC inhibition on histone H3, where it subsequently increases FOXP3, a regulatory T cell (Treg) expression.[28][29][30] Among all the short-chain fatty acids that are produced in the microbiome, butyrate is the most potent promoter of intestinal Treg expression (e.g., FOXP3) and the only one among the group which is an NIACR1 ligand;[31] these Tregs in turn increase interleukin 10 (an anti-inflammatory cytokine) synthesis in the cell.[31]

Part of butyrate's effects on the immune system are mediated via its G-protein coupled receptor targets: NIACR1 (GPR109A), FFAR2 (GPR43), and FFAR3 (GPR41). Butyrate binding at FFAR3 induces neuropeptide Y release and promotes the functional homeostasis of colonic mucosa and the enteric immune system.[32]

Butyrate is a major metabolite in colonic lumen arising from bacterial fermentation of dietary fiber and has been shown to be a critical mediator of the colonic inflammatory response. Butyrate possesses both preventive and therapeutic potential to counteract inflammation-mediated ulcerative colitis and colorectal cancer. One mechanism underlying butyrate function in suppression of colonic inflammation is inhibition of the IFN-γSTAT1 signaling pathways, which at least 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.[33] 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).[33]


The role of butyrate differs between normal and cancerous cells. This is known as the "butyrate paradox". Butyrate inhibits colonic tumor cells, and promotes healthy colonic epithelial cells;[34] but the signaling mechanism is not well understood.[35] A review suggested the chemopreventive benefits of butyrate depend in part on amount, time of exposure with respect to the tumorigenic process, and the type of fat in the diet.[18] The production of volatile fatty acids such as butyrate from fermentable fibers may contribute to the role of dietary fiber in colon cancer.[18]


A review on the relationship between the microbiome and diabetes asserted that butyrate can induce "profound immunometabolic effects" in animal models of and humans with type 2 diabetes;[27] it also noted a relationship between the presence of obesity or diabetes and a state of marked dysbiosis in a host, which is not yet completely understood.[27] While acknowledging that there is strong evidence for the use of butyrate in such disorders, the review called for more research into the pathophysiology (i.e., biomolecular mechanisms) of these diseases, so as to improve therapeutic approaches to these diseases.[27]

Modifying the neuroepigenome


Cognitive deficits and memory

See also


12px This article incorporates text from a publication now in the public domainChisholm, Hugh, ed. (1911). Encyclopædia Britannica (11th ed.). Cambridge University Press. 

  1. 1.0 1.1 1.2 1.3 Strieter FJ, Templeton DH (1962). "Crystal structure of butyric acid". Acta Crystallographica 15 (12): 1240. doi:10.1107/S0365110X6200328X.  edit
  2. 2.0 2.1 2.2 2.3 Lide, David R., ed. (2009). CRC Handbook of Chemistry and Physics (90th ed.). Boca Raton, Florida: CRC Press. ISBN 978-1-4200-9084-0. 
  3. 3.0 3.1 3.2 3.3 3.4 Butanoic acid in Linstrom, P.J.; Mallard, W.G. (eds.) NIST Chemistry WebBook, NIST Standard Reference Database Number 69. National Institute of Standards and Technology, Gaithersburg MD. (retrieved 2014-06-13)
  4. 4.0 4.1 4.2 4.3 4.4 4.5 CID 264 from PubChem
  5. 5.0 5.1 5.2 5.3 "Butanoic Acid". ALS Environmental. Retrieved 2014-06-13. 
  6. 6.0 6.1 6.2
  7. 7.0 7.1 7.2 7.3 7.4 Sigma-Aldrich Co., Butyric acid. Retrieved on 2014-06-13.
  8. What Is Butyric Acid? (with pictures). (2014-03-19). Retrieved on 2014-03-31.
  9. HMDB: Showing metabocard for Butyric acid (HMDB00039). Retrieved on 2014-03-31.
  10. Butyric acid. New World Encyclopedia. Retrieved on 2014-03-31.
  11. Unfortunately, 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. This led to problems because Henri Braconnot, a 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 susbstance that's responsible for the smell of butter: Chevreul (1815) "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, vol. 94, pages 73–79; in a footnote spanning pages 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: Chevreul (1817) "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, vol. 3, pages 79–81. 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), pages 115–133.
  12. 12.0 12.1 ICSC 1334 – BUTYRIC ACID. (1998-11-23). Retrieved on 2014-03-31.
  13. Supplementation of Coated Butyric Acid in the Feed Reduces Colonization and Shedding of Salmonella in Poultry. Retrieved on 2014-03-31.
  14. Freezer Baits,
  15. Kasumyan AO, Døving KB (2003). "Taste preferences in fishes". Fish and Fisheries 4 (4): 289–347. doi:10.1046/j.1467-2979.2003.00121.x. 
  16. Japanese Whalers Injured by Acid-Firing Activists,, February 10, 2010
  17. National Abortion Federation, HISTORY OF VIOLENCE Butyric Acid Attacks. Retrieved on 2014-03-31.
  18. 18.0 18.1 18.2 Lupton JR (Feb 2004). "Microbial degradation products influence colon cancer risk: the butyrate controversy". The Journal of Nutrition 134 (2): 479–82. PMID 14747692. 
  19. Cummings JH, Macfarlane GT, Englyst HN (Feb 2001). "Prebiotic digestion and fermentation". The American Journal of Clinical Nutrition 73 (2 Suppl): 415S–420S. PMID 11157351. 
  20. Grummer RR (Sep 1991). "Effect of feed on the composition of milk fat" (PDF). Journal of Dairy Science 74 (9): 3244–57. PMID 1779073. doi:10.3168/jds.S0022-0302(91)78510-X. 
  21. "Butyric acid". IUPHAR. IUPHAR/BPS Guide to PHARMACOLOGY. Retrieved 23 May 2015. 
  22. "butanoic acid, 4 and Sodium; butyrate". BindingDB. The Binding Database. Retrieved 23 May 2015. 
  23. Zhang M, Poplawski M, Yen K, Cheng H, Bloss E, Zhu X et al. (Nov 2009). Dillin A, ed. "Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling". PLoS Biology 7 (11): e1000245. PMC 2774267. PMID 19924292. doi:10.1371/journal.pbio.1000245. 
  24. 24.0 24.1 "Butyric Acid". HMDB. Human Metabolome Database. Retrieved 25 May 2015. 
  25. "triacylglycerol lipase - Homo sapiens". BRENDA. Technische Universität Braunschweig. Retrieved 25 May 2015. 
  26. 26.0 26.1 Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I (2015). "Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation". Nutrients 7 (4): 2839–49. PMC 4425176. PMID 25875123. doi:10.3390/nu7042839. 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. 
  27. 27.0 27.1 27.2 27.3 Tilg H, Moschen AR (September 2014). "Microbiota and diabetes: an evolving relationship". Gut 63 (9): 1513–1521. PMID 24833634. doi:10.1136/gutjnl-2014-306928. Recent studies have suggested that gut bacteria play a fundamental role in diseases such as obesity, diabetes and cardiovascular disease. Data are accumulating in animal models and humans suggesting that obesity and type 2 diabetes (T2D) are associated with a profound dysbiosis. First human metagenome-wide association studies demonstrated highly significant correlations of specific intestinal bacteria, certain bacterial genes and respective metabolic pathways with T2D. Importantly, especially butyrate-producing bacteria such as Roseburia intestinalis and Faecalibacterium prausnitzii concentrations were lower in T2D subjects. This supports the increasing evidence, that butyrate and other short-chain fatty acids are able to exert profound immunometabolic effects. 
  28. Wang G (2014). "Human antimicrobial peptides and proteins". Pharmaceuticals (Basel) 7 (5): 545–94. PMC 4035769. PMID 24828484. doi:10.3390/ph7050545. The establishment of a link between light therapy, vitamin D and human cathelicidin LL-37 expression provides a completely different way for infection treatment. Instead of treating patients with traditional antibiotics, doctors may be able to use light or vitamin D [291,292]. Indeed using narrow-band UV B light, the level of vitamin D was increased in psoriasis patients (psoriasis is a common autoimmune disease on skin) [293]. In addition, other small molecules such as butyrate can induce LL-37 expression [294]. Components from Traditional Chinese Medicine may regulate the AMP expression as well [295]. These factors may induce the expression of a single peptide or multiple AMPs [296]. It is also possible that certain factors can work together to induce AMP expression. While cyclic AMP and butyrate synergistically stimulate the expression of chicken β-defensin 9 [297], 4-phenylbutyrate (PBA) and 1,25-dihydroxyvitamin D3 (or lactose) can induce AMP gene expression synergistically [294,298]. It appears that stimulation of LL-37 expression by histone deacetylase (HDAC) inhibitors is cell dependent. Trichostatin and sodium butyrate increased the peptide expression in human NCI-H292 airway epithelial cells but not in the primary cultures of normal nasal epithelial cells [299]. However, the induction of the human LL-37 expression may not be a general approach for bacterial clearance. During Salmonella enterica infection of human monocyte-derived macrophages, LL-37 is neither induced nor required for bacterial clearance [300]. 
    Table 3: Select human antimicrobial peptides and their proposed targets
    Table 4: Some known factors that induce antimicrobial peptide expression
  29. Yonezawa H, Osaki T, Hanawa T, Kurata S, Zaman C, Woo TD et al. (2012). "Destructive effects of butyrate on the cell envelope of Helicobacter pylori". J. Med. Microbiol. 61 (Pt 4): 582–9. PMID 22194341. doi:10.1099/jmm.0.039040-0. 
  30. McGee DJ, George AE, Trainor EA, Horton KE, Hildebrandt E, Testerman TL (2011). "Cholesterol enhances Helicobacter pylori resistance to antibiotics and LL-37". Antimicrob. Agents Chemother. 55 (6): 2897–904. PMC 3101455. PMID 21464244. doi:10.1128/AAC.00016-11. 
  31. 31.0 31.1 Hoeppli RE, Wu D, Cook L, Levings MK (February 2015). "The environment of regulatory T cell biology: cytokines, metabolites, and the microbiome". Front Immunol 6: 61. PMC 4332351. PMID 25741338. doi:10.3389/fimmu.2015.00061. Specific species that have been recognized by their high levels of butyrate production include Faecalibacterium prausnitzii and the cluster IV and XIVa of genus Clostridium ... Administration of acetate, propionate, and butyrate in drinking water mimics the effect of Clostridium colonization in germ-free mice, resulting in an elevated Treg frequency in the colonic lamina propria and increased IL-10 production by these Tregs (180, 182). Of the three main SCFAs, butyrate has been found to be the most potent inducer of colonic Tregs. Mice fed a diet enriched in butyrylated starches have more colonic Tregs than those fed a diet containing propinylated or acetylated starches (181). Arpaia et al. tested an array of SCFAs purified from commensal bacteria and confirmed butyrate was the strongest SCFA-inducer of Tregs in vitro (180). Mechanistically, it has been proposed that butyrate, and possibly propionate, promote Tregs through inhibiting histone deacetylase (HDAC), causing increased acetylation of histone H3 in the Foxp3 CNS1 region, and thereby enhancing FOXP3 expression (180, 181). Short-chain fatty acids partially mediate their effects through G-protein coupled receptors (GPR), including GPR41, GPR43, and GPR109A. GPR41 and GPR43 are stimulated by all three major SCFAs (191), whereas GPR109A only interacts with butyrate (192). 
    Figure 1: Microbial-derived molecules promote colonic Treg differentiation.
  32. Farzi A, Reichmann F, Holzer P (2015). "The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour". Acta Physiol (Oxf) 213 (3): 603–27. PMC 4353849. PMID 25545642. doi:10.1111/apha.12445. In the context of this review it is particularly worth noting that short chain fatty acids such as butyrate, which the colonic microbiota generates by fermentation of otherwise indigestible dietary fibre (Cherbut et al. 1998), stimulate L cells to release PYY via the G-protein coupled receptor Gpr41 (Samuel et al. 2008). In this way, short chain fatty acids can indirectly attenuate gastrointestinal motility as well as electrolyte and water secretion (Cox 2007b). More importantly, short chain fatty acids exert homeostatic actions on the function of the colonic mucosa and immune system (Hamer et al. 2008, Tazoe et al. 2008, Guilloteau et al. 2010, Macia et al. 2012a, Smith et al. 2013). Whether PYY plays a role in these effects of short chain fatty acids awaits to be investigated, but may be envisaged from the finding that PYY promotes mucosal cell differentiation (Hallden & Aponte 1997). 
  33. 33.0 33.1 Zimmerman MA, Singh N, Martin PM, Thangaraju M, Ganapathy V, Waller JL et al. (2012). "Butyrate suppresses colonic inflammation through HDAC1-dependent Fas upregulation and Fas-mediated apoptosis of T cells". Am. J. Physiol. Gastrointest. Liver Physiol. 302 (12): G1405–15. PMC 3378095. PMID 22517765. doi:10.1152/ajpgi.00543.2011. 
  34. Vanhoutvin SA, Troost FJ, Hamer HM, Lindsey PJ, Koek GH, Jonkers DM et al. (2009). Bereswill S, ed. "Butyrate-induced transcriptional changes in human colonic mucosa". PloS One 4 (8): e6759. PMC 2727000. PMID 19707587. doi:10.1371/journal.pone.0006759. 
  35. Klampfer L, Huang J, Sasazuki T, Shirasawa S, Augenlicht L (Aug 2004). "Oncogenic Ras promotes butyrate-induced apoptosis through inhibition of gelsolin expression" (PDF). The Journal of Biological Chemistry 279 (35): 36680–8. PMID 15213223. doi:10.1074/jbc.M405197200. 

External links

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