View source for Bile acid

{{Short description|Steroid acid in the bile of animals}}
{{Use American English|date=March 2025}}
{{Use dmy dates|date=March 2025}}
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'''Bile acids''' are [[steroid]] [[acid]]s found predominantly in the [[bile]] of [[mammal]]s and other [[vertebrate]]s.<ref name="chen">{{cite web |vauthors=Chen I, Cassaro S|title=Physiology, Bile Acids |url=https://www.ncbi.nlm.nih.gov/books/NBK549765/ |publisher=StatPearls, US National Library of Medicine |access-date=3 March 2025 |date=1 May 2023}}</ref> Diverse bile acids are synthesized in the [[liver]] in [[peroxisome]]s.<ref name=chen/><ref name="gastro">{{cite journal |vauthors=Fogelson KA, Dorrestein PC, Zarrinpar A, Knight R |title=The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases |journal=Gastroenterology |volume=164 |issue=7 |pages=1069–1085 |date=June 2023 |pmid=36841488 |pmc=10205675 |doi=10.1053/j.gastro.2023.02.022}}</ref> Bile acids are conjugated with [[taurine]] or [[glycine]] residues to give anions called '''bile salts'''.<ref name=chen/><ref name=gastro/>

'''Primary bile acids''' are those synthesized by the liver.<ref name=chen/><ref name=gastro/> '''Secondary bile acids''' result from bacterial actions in the [[colon (anatomy)|colon]].<ref name=chen/> In humans, [[taurocholic acid]] and [[glycocholic acid]] (derivatives of [[cholic acid]]) and [[taurochenodeoxycholic acid]] and [[glycochenodeoxycholic acid]] (derivatives of [[chenodeoxycholic acid]]) are the major bile salts.<ref name=chen/><ref name=gastro/> The salts of their 7-alpha-dehydroxylated derivatives, [[deoxycholic acid]] and [[lithocholic acid]], are also found, with derivatives of cholic, chenodeoxycholic and deoxycholic acids accounting for over 90% of human biliary bile acids.<ref name=chen/>

==Description==
Bile acids comprise about 80% of the organic compounds in bile (others are [[phospholipids]] and [[cholesterol]]).<ref name=chen/> An increased secretion of bile acids produces an increase in bile flow. Bile acids facilitate [[Digestion#Fat digestion|digestion of dietary fats and oils]].<ref name=chen/> They serve as [[micelle]]-forming [[surfactant]]s, which encapsulate nutrients, facilitating their absorption.<ref name=chen/> These micelles are suspended in the [[chyme]] before [[fatty acid metabolism#Dietary sources of fatty acids, their digestion, absorption, transport in the blood and storage|further processing]].<ref name=chen/> Bile acids also have hormonal actions throughout the body, particularly through the [[farnesoid X receptor]] and [[GPBAR1]] (also known as TGR5).<ref name=chen/><ref name=pmid19758712>{{cite journal |vauthors=Fiorucci S, Mencarelli A, Palladino G, Cipriani S |title=Bile-acid-activated receptors: targeting TGR5 and farnesoid-X-receptor in lipid and glucose disorders |journal=Trends Pharmacol. Sci. |volume=30 |issue=11 |pages=570–80 |date=November 2009  |pmid=19758712 |doi=10.1016/j.tips.2009.08.001 }}</ref>

Bile acid synthesis is the only manner in which humans or other mammals may excrete excess cholesterol, as the parent compound of all bile acids is cholesterol.<ref name=chen/>
[[File:Cholic Acid vs Other Bile Acids.svg|thumb|350px|Structure of [[cholic acid]] showing relationship to other bile acids]]

==Production==

=== Primary bile acids ===
Bile acid synthesis occurs in [[hepatocyte|liver cells]], which synthesize ''primary bile acids'' ([[cholic acid]] and [[chenodeoxycholic acid]] in humans) via [[cytochrome P450]]-mediated oxidation of cholesterol in a multi-step process. Approximately 600&nbsp;mg of bile salts are synthesized daily to replace bile acids lost in the feces, although, as described below, much larger amounts are secreted, reabsorbed in the gut and recycled.

The [[rate-limiting step]] in synthesis is the addition of a hydroxyl group of the 7th position of the steroid nucleus by the enzyme [[CYP7A1|cholesterol 7 alpha-hydroxylase]]. This enzyme is [[Downregulation and upregulation|down-regulated]] by cholic acid, up-regulated by cholesterol and is inhibited by the actions of the [[ileal]] [[hormone]] [[FGF15/19]].<ref name=chen/><ref name=gastro/>

Prior to secreting any of the bile acids (primary or secondary, see below), liver cells conjugate them with either [[glycine]] or [[taurine]], to form a total of 8 possible ''conjugated bile acids''. These conjugated bile acids are often referred to as ''bile salts''.<ref name=chen/><ref name=gastro/> The [[Acid dissociation constant|pKa]] of the unconjugated bile acids are between 5 and 6.5, and the pH of the duodenum ranges between 3 and 5, so when unconjugated bile acids are in the duodenum, they are almost always protonated (HA form), which makes them relatively insoluble in water. Conjugating bile acids with amino acids lowers the pKa of the bile-acid/amino-acid conjugate to between 1 and 4. Thus conjugated bile acids are almost always in their deprotonated (A-) form in the duodenum, which makes them much more water-soluble and much more able to fulfil their physiological function of emulsifying fats.<ref>'Essentials of Medical Biochemistry, Lieberman, Marks and Smith, eds, p432, 2007'</ref><ref name="pmid14097367">{{cite journal |author=Hofmann AF |title=The function of bile salts in fat absorption. The solvent properties of dilute micellar solutions of conjugated bile salts|journal=Biochem. J. |volume=89 |pages=57–68 |date=October 1963  |issue=1 |pmid=14097367 |pmc=1202272 |doi= 10.1042/bj0890057}}</ref>

=== Secondary bile acids ===
Once secreted into the lumen of the intestine, bile salts are modified by gut bacteria.<ref name=chen/> They are partially dehydroxylated. Their glycine and taurine groups are removed to give the ''secondary bile acids'', [[deoxycholic acid]] and [[lithocholic acid]].<ref name=chen/> Cholic acid is converted into deoxycholic acid and chenodeoxycholic acid into lithocholic acid. All four of these bile acids are recycled, in a process known as [[enterohepatic circulation]].<ref name=chen/>

==Functions==

=== Lipid digestion ===
As molecules with [[hydrophobic]] and [[hydrophilic]] regions, conjugated bile salts sit at the lipid/water interface and, above the right concentration, form [[micelles]].<ref name=chen/> The added solubility of conjugated bile salts aids in their function by preventing passive re-absorption in the small intestine. As a result, the concentration of bile acids/salts in the small intestine is high enough to form micelles and solubilize lipids.<ref name=chen/> "Critical micellar concentration" refers to both an intrinsic property of the bile acid itself and amount of bile acid necessary to function in the spontaneous and dynamic formation of micelles.<ref name=chen/><ref name=gastro/> Bile acid-containing micelles aid [[lipases]] to digest lipids and bring them near the intestinal [[brush border]] membrane, which results in fat absorption.<ref name=chen/>

Synthesis of bile acids is a major route of cholesterol metabolism in most species other than humans. The body produces about 800&nbsp;mg of cholesterol per day and about half of that is used for bile acid synthesis producing 400–600&nbsp;mg daily. Human adults secrete between 12 and 18&nbsp;g of bile acids into the intestine each day, mostly after meals. The bile acid pool size is between 4–6&nbsp;g, which means that bile acids are recycled several times each day. About 95% of bile acids are reabsorbed by [[active transport]] in the [[ileum]] and recycled back to the liver for further secretion into the biliary system and [[gallbladder]]. This [[enterohepatic circulation]] of bile acids allows a low rate of synthesis, only about 0.3&nbsp;g/day, but with large amounts being secreted into the intestine.<ref name=gastro/>

Bile acids have other functions, including eliminating cholesterol from the body, driving the flow of bile to eliminate certain catabolites (including [[bilirubin]]), emulsifying fat-soluble vitamins to enable their absorption, and aiding in motility and the reduction of the bacteria flora found in the small intestine and biliary tract.<ref name=chen/><ref name=gastro/>

=== Cell signalling ===
Bile acids have metabolic actions in the body resembling those of hormones, acting through two specific receptors, the [[farnesoid X receptor]] and [[G protein-coupled bile acid receptor]] TGR5. <ref name=gastro/> They bind less specifically to some other receptors and have been reported to regulate the activity of certain enzymes and ion channels, <ref name= "pmid38664391">{{cite journal | vauthors =  Fleishman JS, Kumar S | title = Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets | journal = Signal Transduct Target Ther | volume = 9 | issue = 1 | date = 2024 | doi = 10.1038/s41392-024-01811-6 | pmc = 11045871 }}</ref> and the biosynthesis of diverse substances including endogenous fatty acid [[ethanolamides]], which have key roles in several physiological pathways including stress and pain responses, appetite, and lifespan. <ref name= "pmid25684574">{{cite journal | vauthors =  Magotti P, Bauer I, Garau G | title = Structure of Human N-Acylphosphatidylethanolamine-Hydrolyzing Phospholipase D: Regulation of Fatty Acid Ethanolamide Biosynthesis by Bile Acids | journal = Structure | volume = 23 | issue = 3 | date = 2015 | doi = 10.1016/j.str.2014.12.018 | pages=598–604 | pmc = 4351732 }}</ref>

==Structure and synthesis==
<gallery widths="180" class="skin-invert-image" caption="The structures of the principal human bile acids">
File:Cholic acid.svg|[[Cholic acid]]
File:Glycocholsäure.svg|[[Glycocholic acid]]
File:Taurocholic acid.svg|[[Taurocholic acid]]
File:Deoxycholic acid.svg|[[Deoxycholic acid]]
File:Chenodeoxycholic acid.svg|[[Chenodeoxycholic acid]]
File:Glycochenodeoxycholic acid.svg|[[Glycochenodeoxycholic acid]]
File:Taurochenodeoxycholic acid.svg|[[Taurochenodeoxycholic acid]]
File:Lithocholic acid acsv.svg|[[Lithocholic acid]]
</gallery>

Bile salts constitute a large family of molecules, composed of a steroid structure with four rings, a five- or eight-carbon side-chain terminating in a carboxylic acid, and several hydroxyl groups, the number and orientation of which is different among the specific bile salts.<ref name=chen/><ref name=gastro/> The four rings are labeled A, B, C, and D, from the farthest to the closest to the side chain with the carboxyl group. The D-ring is smaller by one carbon than the other three. The structure is commonly drawn with A at the left and D at the right.  The hydroxyl groups can be in either of two configurations: either up (or out), termed beta (β; often drawn by convention as a solid line), or down, termed alpha (α; displayed as a dashed line). All bile acids have a 3-hydroxyl group, derived from the parent molecule, cholesterol, in which the 3-hydroxyl is beta.<ref name=gastro/>
[[Image:Steroid lettering numbering.svg|class=skin-invert-image|thumb|320px|[[IUPAC nomenclature|IUPAC]] recommended ring lettering (left) and atom numbering (right) of the steroid skeleton. The four rings A-D form a [[sterane]] core.]]

The initial step in the classical pathway of hepatic synthesis of bile acids is the enzymatic addition of a 7α hydroxyl group by [[Cholesterol 7 alpha-hydroxylase|cholesterol 7α-hydroxylase]] (CYP7A1) forming [[7α-Hydroxycholesterol|7α-hydroxycholesterol]]. This is then metabolised to [[7α-hydroxy-4-cholesten-3-one]]. There are multiple steps in bile acid synthesis requiring 14 enzymes in all.<ref name=gastro/> These result in the junction between the first two steroid rings (A and B) being altered, making the molecule bent; in this process, the 3-hydroxyl is converted to the α orientation. The simplest 24-carbon bile acid has two hydroxyl groups at positions 3α and 7α.  This is 3α,7α-dihydroxy-5β-cholan-24-oic acid, or, as more usually known, [[chenodeoxycholic acid]]. This bile acid was first isolated from the [[domestic goose]], from which the "cheno" portion of the name was derived (Greek: χήν = goose). The 5β in the name denotes the orientation of the junction between rings A and B of the steroid nucleus (in this case, they are bent). The term "cholan" denotes a particular steroid structure of 24 carbons, and the "24-oic acid" indicates that the carboxylic acid is found at position 24, at the end of the side-chain. Chenodeoxycholic acid is made by many species, and is the prototypic functional bile acid.<ref name=chen/><ref name=gastro/>

An alternative (acidic) pathway of bile acid synthesis is initiated by [[mitochondrial]] sterol 27-hydroxylase ([[CYP27A1]]), expressed in liver, and also in macrophages and other tissues. CYP27A1 contributes significantly to total bile acid synthesis by catalyzing sterol side chain oxidation, after which cleavage of a three-carbon unit in the [[peroxisomes]] leads to formation of a C24 bile acid. Minor pathways initiated by 25-hydroxylase in the liver and 24-hydroxylase in the brain also may contribute to bile acid synthesis. 7α-hydroxylase ([[CYP7B1]]) generates [[oxysterols]], which may be further converted in the liver to CDCA.<ref name=chen/><ref name=gastro/>

[[Cholic acid]], 3α,7α,12α-trihydroxy-5β-cholan-24-oic acid, the most abundant bile acid in humans and many other species, was discovered before chenodeoxycholic acid. It is a tri-hydroxy-bile acid with 3 hydroxyl groups (3α, 7α and 12α). In its synthesis in the liver, 12α hydroxylation is performed by the additional action of [[CYP8B1]]. As this had already been described, the discovery of chenodeoxycholic acid (with 2 hydroxyl groups) made this new bile acid a "deoxycholic acid" in that it had one fewer hydroxyl group than cholic acid.<ref name=chen/><ref name=gastro/>

[[Deoxycholic acid]] is formed from cholic acid by 7-dehydroxylation, resulting in 2 hydroxyl groups (3α and 12α). This process with chenodeoxycholic acid results in a bile acid with only a 3α hydroxyl group, termed [[lithocholic acid]] (litho = stone) having been identified first in a gallstone from a calf. It is poorly water-soluble and rather toxic to cells.<ref name=chen/><ref name=gastro/>

Different vertebrate families have evolved to use modifications of most positions on the steroid nucleus and side-chain of the bile acid structure. To avoid the problems associated with the production of lithocholic acid, most species add a third hydroxyl group to chenodeoxycholic acid. The subsequent removal of the 7α hydroxyl group by intestinal bacteria will then result in a less toxic but still-functional dihydroxy bile acid. Over the course of vertebrate evolution, a number of positions have been chosen for placement of the third hydroxyl group. Initially, the 16α position was favored, in particular in birds. Later, this position was superseded in a large number of species selecting the 12α position. Primates (including humans) utilize 12α for their third hydroxyl group position, producing cholic acid. In mice and other rodents, 6β hydroxylation forms [[muricholic acid]]s (α or β depending on the 7 hydroxyl position). Pigs have 6α hydroxylation in [[hyocholic acid]] (3α,6α,7α-trihydroxy-5β-cholanoic acid), and other species have a hydroxyl group on position 23 of the side-chain.

Many other bile acids have been described, often in small amounts, resulting from bacterial enzymatic or other modifications. The "iso-" epimers have the 3-hydroxyl group in the β position. The "allo-" epimers have the 5α configuration, which changes the relative position of the A and B rings.<ref name=chen/><ref name=gastro/>

[[Ursodeoxycholic acid]] was first isolated from [[bear bile]], which has been used medicinally for centuries. Its structure resembles chenodeoxycholic acid but with the 7-hydroxyl group in the β position.<ref name=chen/><ref name=gastro/>

[[Obeticholic acid]], 6α-ethyl-chenodeoxycholic acid, is a semi-synthetic bile acid with greater activity as an FXR agonist, which has been developed as a pharmaceutical agent in certain liver diseases.<ref name="pmid33722778">{{cite journal | vauthors = Kulkarni AV, Tevethia HV, Arab JP, Candia R, Premkumar M, Kumar P, Sharma M, Reddy DN, Padaki NR | title = Efficacy and safety of obeticholic acid in liver disease-A systematic review and meta-analysis | journal = Clinics and Research in Hepatology and Gastroenterology | volume = 45 | issue = 3 | pages = 101675 | date = May 2021 | pmid = 33722778 | doi = 10.1016/j.clinre.2021.101675 | s2cid = 232242410 | url = }}</ref>

==Hormonal actions==
Bile acids also act as steroid hormones, secreted from the liver, absorbed from the intestine and having various direct metabolic actions in the body through the nuclear receptor [[Farnesoid X receptor]] (FXR), also known by its gene name {{Gene|NR1H4}}.<ref name="pmid10334992">{{cite journal |vauthors=Makishima M, Okamoto AY, Repa JJ |title=Identification of a nuclear receptor for bile acids |journal=Science |volume=284 |issue=5418 |pages=1362–5 |date=May 1999  |pmid=10334992 |doi= 10.1126/science.284.5418.1362|bibcode=1999Sci...284.1362M |display-authors=etal}}</ref><ref name="pmid10334993">{{cite journal |vauthors=Parks DJ, Blanchard SG, Bledsoe RK |title=Bile acids: natural ligands for an orphan nuclear receptor |journal=Science |volume=284 |issue=5418 |pages=1365–8 |date=May 1999  |pmid=10334993 |doi= 10.1126/science.284.5418.1365|bibcode=1999Sci...284.1365P |display-authors=etal}}</ref><ref name="pmid10360171">{{cite journal |vauthors=Wang H, Chen J, Hollister K, Sowers LC, Forman BM |title=Endogenous bile acids are ligands for the nuclear receptor FXR/BAR |journal=Mol. Cell |volume=3 |issue=5 |pages=543–53 |date=May 1999  |pmid=10360171 |doi= 10.1016/s1097-2765(00)80348-2|doi-access=free }}</ref> Another bile acid receptor is the cell membrane receptor known as [[G protein-coupled bile acid receptor]] 1 or [[G protein-coupled bile acid receptor|TGR5]]. Many of their functions as signaling molecules in the liver and the intestines are by activating FXR, whereas TGR5 may be involved in metabolic, endocrine and neurological functions.<ref name="pmid19758712"/><ref name="pmid31984784">{{cite journal | vauthors = Chiang JY, Ferrell JM | title = Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 318 | issue = 3 | pages = G554–G573 | date = March 2020 | pmid = 31984784 | pmc = 7099488 | doi = 10.1152/ajpgi.00223.2019 | url = }}</ref>

===Regulation of synthesis===
As [[surfactant]]s or [[detergent]]s, bile acids are potentially toxic to cells, and so their [[concentration]]s are tightly regulated. Activation of FXR in the liver inhibits synthesis of bile acids, and is one mechanism of feedback control when bile acid levels are too high. Secondly, FXR activation by bile acids during absorption in the intestine increases transcription and synthesis of [[FGF19]], which then inhibits bile acid synthesis in the liver.<ref>{{cite journal |last=Kim|first=I |author2=Ahn, SH |author3=Inagaki, T |author4=Choi, M |author5=Ito, S |author6=Guo, GL |author7=Kliewer, SA |author8=Gonzalez, FJ|title=Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine|journal=Journal of Lipid Research|year=2007|volume=48|issue=12|pages=2664–72|pmid=17720959|doi=10.1194/jlr.M700330-JLR200|doi-access=free}}</ref>

===Metabolic functions===
Emerging evidence associates FXR activation with alterations in [[triglyceride]] [[metabolism]], [[glucose metabolism]], and liver growth.<ref name=chen/><ref name=gastro/><ref>{{Cite journal|last1=Shapiro|first1=Hagit|last2=Kolodziejczyk|first2=Aleksandra A.|last3=Halstuch|first3=Daniel|author4-link=Eran Elinav|last4=Elinav|first4=Eran|date=2018-01-16|title=Bile acids in glucose metabolism in health and disease|journal=Journal of Experimental Medicine|volume=215|issue=2|language=en|pages=383–396|doi=10.1084/jem.20171965|pmid=29339445|pmc=5789421|issn=0022-1007}}</ref>

=== Bile acids are cofactors of membrane NAPE-PLD ===
Bile acids bind to some other proteins in addition to their hormone receptors (FXR and TGR5) and their transporters. Among these protein targets, the membrane enzyme [[N-acyl phosphatidylethanolamine-specific phospholipase D]] (NAPE-PLD) of the endocannabinoid system. <ref name= "pmid25684574"/> Bile acids are essential confactors for the biogenesis of [[lipid signaling]] amides (e.g., [[Anandamide]], [[Palmitoylethanolamide]], [[Oleoylethanolamide]]) mediated by NAPE-PLD. These lipid molecules (e.g. the endogenous [[cannabinoid]] [[anandamide]]) have important roles in several physiological pathways including stress and pain responses, appetite, and lifespan.<ref name=gastro/> NAPE-PLD thus facilitates crosstalk between bile acids signals and lipid amide signals. <ref name= "pmid27571266">{{cite journal | vauthors =  Margheritis E, Castellani B, Garau G | title = Bile Acid Recognition by NAPE-PLD. | journal = ACS Chem Biol | volume = 11 | issue = 10 | date = 2016 | doi = 10.1021/acschembio.6b00624 | pmid=27571266 | pages=2908–2914 }}</ref> The interaction between enzyme and bile acids stabilizes the protein dimer, promoting its association to membrane phospholipids and the key role of NAPE-PLD in [[antihypertensive]] therapy and neurovascular protection. <ref name="pmid39999832">{{cite journal | vauthors = Chiarugi S, Margheriti F, Garau G | title = NAPE-PLD is target of thiazide diuretics | journal = Cell Chem Biol  | date = 2025 | volume = 32 | issue = 3 | pages = 449–462 | pmid = 39999832 | doi = 10.1016/j.chembiol.2025.01.008 }}</ref>

==Clinical significance==
{{see also|Bile acid synthesis disorders}}
===Hyperlipidemia===
As bile acids are made from endogenous cholesterol, disruption of the enterohepatic circulation of bile acids will lower cholesterol. [[Bile acid sequestrant]]s bind bile acids in the gut, preventing reabsorption. In so doing, more endogenous cholesterol is shunted into the production of bile acids, thereby lowering cholesterol levels. The sequestered bile acids are then excreted in the feces.<ref name="pmid21392720">{{cite journal |author=Davidson MH |title=A systematic review of bile acid sequestrant therapy in children with familial hypercholesterolemia |journal=J Clin Lipidol |volume=5 |issue=2 |pages=76–81 |year=2011 |pmid=21392720 |doi=10.1016/j.jacl.2011.01.005 }}</ref>

===Cholestasis===
Tests for bile acids are useful in both human and veterinary medicine, as they aid in the diagnosis of a number of conditions, including types of [[cholestasis]] such as [[intrahepatic cholestasis of pregnancy]], [[portosystemic shunt]], and [[hepatic microvascular dysplasia]] in dogs.<ref name="pmid9926012">{{cite journal |vauthors=Allen L, Stobie D, Mauldin GN, Baer KE |title=Clinicopathologic features of dogs with hepatic microvascular dysplasia with and without portosystemic shunts: 42 cases (1991-1996) |journal=J. Am. Vet. Med. Assoc. |volume=214 |issue=2 |pages=218–20 |date=January 1999  |doi=10.2460/javma.1999.214.02.218 |pmid=9926012 }}</ref> Structural or functional abnormalities of the biliary system result in an increase in bilirubin ([[jaundice]]) and in bile acids in the blood. Bile acids are related to the itching ([[pruritus]]) which is common in cholestatic conditions such as [[primary biliary cirrhosis]] (PBC), [[primary sclerosing cholangitis]] or [[intrahepatic cholestasis of pregnancy]].<ref name="pmid17535422">{{cite journal |vauthors=Pusl T, Beuers U |title=Intrahepatic cholestasis of pregnancy |journal=Orphanet J Rare Dis |volume=2 |pages=26 |year=2007 |pmid=17535422 |pmc=1891276 |doi=10.1186/1750-1172-2-26 |doi-access=free }}</ref> Treatment with [[ursodeoxycholic acid]] has been used for many years in these cholestatic disorders.<ref name="pmid1674105">{{cite journal |vauthors=Poupon RE, Balkau B, Eschwège E, Poupon R |title=A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group |journal=N. Engl. J. Med. |volume=324 |issue=22 |pages=1548–54 |date=May 1991  |pmid=1674105 |doi=10.1056/NEJM199105303242204 |doi-access=free }}</ref><ref name="pmid16317669">{{cite journal |vauthors=Glantz A, Marschall HU, Lammert F, Mattsson LA |title=Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexamethasone and ursodeoxycholic acid |journal=Hepatology |volume=42 |issue=6 |pages=1399–405 |date=December 2005  |pmid=16317669 |doi=10.1002/hep.20952 |s2cid=19147632 |doi-access=free }}</ref>

===Gallstones===
{{Main|Gallstones}}
The relationship of bile acids to cholesterol saturation in bile and cholesterol precipitation to produce gallstones has been studied extensively. Gallstones may result from increased saturation of cholesterol or [[bilirubin]], or from bile stasis. Lower concentrations of bile acids or phospholipids in bile reduce cholesterol solubility and lead to microcrystal formation. Oral therapy with chenodeoxycholic acid and/or ursodeoxycholic acid has been used to dissolve cholesterol gallstones.<ref name="pmid5006919">{{cite journal |vauthors=Danzinger RG, Hofmann AF, Schoenfield LJ, Thistle JL |title=Dissolution of cholesterol gallstones by chenodeoxycholic acid |journal=N. Engl. J. Med. |volume=286 |issue=1 |pages=1–8 |date= January 1972 |pmid=5006919 |doi=10.1056/NEJM197201062860101 }}</ref><ref name="pmid4580472">{{cite journal |vauthors=Thistle JL, Hofmann AF |title=Efficacy and specificity of chenodeoxycholic acid therapy for dissolving gallstones |journal=N. Engl. J. Med. |volume=289 |issue=13 |pages=655–9 |date=September 1973  |pmid=4580472 |doi=10.1056/NEJM197309272891303 }}</ref><ref name="pmid11136285">{{cite journal |vauthors=Petroni ML, Jazrawi RP, Pazzi P |title=Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial. The British-Italian Gallstone Study group |journal=Aliment. Pharmacol. Ther. |volume=15 |issue=1 |pages=123–8 |date=January 2001  |pmid=11136285 |doi= 10.1046/j.1365-2036.2001.00853.x|display-authors=etal|doi-access=free }}</ref> Stones may recur when treatment is stopped. Bile acid therapy may be of value to prevent stones in certain circumstances such as following [[bariatric surgery]].<ref name="pmid18574646">{{cite journal |vauthors=Uy MC, Talingdan-Te MC, Espinosa WZ, Daez ML, Ong JP |title=Ursodeoxycholic acid in the prevention of gallstone formation after bariatric surgery: a meta-analysis |journal=Obes Surg |volume=18 |issue=12 |pages=1532–8 |date=December 2008  |pmid=18574646 |doi=10.1007/s11695-008-9587-7 |s2cid=207302960 }}</ref>

===Bile acid diarrhea===
Excess concentrations of bile acids in the colon are a cause of [[chronic diarrhea]]. It is commonly found when the ileum is abnormal or has been surgically removed, as in [[Crohn's disease]], or cause a condition that resembles diarrhea-predominant [[irritable bowel syndrome]] (IBS-D). This condition of bile acid diarrhea/[[bile acid malabsorption]] can be diagnosed by the [[SeHCAT]] test and treated with [[bile acid sequestrants]].<ref>{{cite journal|last=Pattni|first=S|author2=Walters, JR|title=Recent advances in the understanding of bile acid malabsorption|journal=British Medical Bulletin|year=2009|volume=92|pages=79–93|pmid=19900947|doi=10.1093/bmb/ldp032|doi-access=free}}</ref>

===Bile acids and colon cancer===
Bile acids may have some importance in the development of [[colorectal cancer]].<ref name=gastro/> Deoxycholic acid is increased in the colonic contents of humans in response to a high fat diet.<ref name=gastro/> In populations with a high incidence of colorectal cancer, fecal concentrations of bile acids are higher, particularly deoxycholic acid.<ref name=gastro/>

The effects of ursodeoxycholic acid in modifying the risk of colorectal cancer is under study, particularly in [[primary sclerosing cholangitis]] and [[inflammatory bowel disease]], with varying results partly related to dosage.<ref name="fior">{{cite journal |vauthors=Fiorucci S, Carino A, Baldoni M, Santucci L, Costanzi E, Graziosi L, Distrutti E, Biagioli M |title=Bile Acid Signaling in Inflammatory Bowel Diseases |journal=Digestive Diseases and Sciences |volume=66 |issue=3 |pages=674–693 |date=March 2021 |pmid=33289902 |pmc=7935738 |doi=10.1007/s10620-020-06715-3}}</ref>

A 2025 [[meta-analysis]] on the relationship of fecal bile acid concentrations to the development and progression of colorectal cancer  found that higher fecal concentrations of cholic acid and chenodeoxycholic acid are associated with a higher risk and higher incidence of colorectal cancer.<ref name = Yang2025>{{cite journal |vauthors=Yang S, Wang Y, Sheng L, Cui W, Ma C |title=The effect of fecal bile acids on the incidence and risk-stratification of colorectal cancer: an updated systematic review and meta-analysis |journal=Scientific Reports |volume=15 |issue=1 |pages=740 |date=January 2025 |pmid=39753873 |doi=10.1038/s41598-024-84801-6|pmc=11698987 }}</ref> Accumulating evidence also indicates that the gut microbiota can influence the distribution of bile acids in the colon and thus are a significant factor in colorectal cancer development.<ref name=gastro/>

Bile acids have not only been implicated as carcinogens in the colon but also at other sites in the gastrointestinal tract.<ref>{{cite journal |vauthors=Bernstein H, Bernstein C |title=Bile acids  as carcinogens in the colon, and at other sites in the gastrointestinal system |journal=Exp Biol Med (Maywood) |volume=248 |issue=1 |pages=79–89 |date=January 2023 |pmid=36408538 |pmc=9989147 |doi=10.1177/15353702221131858 |url=}}</ref>

=== Dermatology ===
Bile acids may be used in subcutaneous injections to remove unwanted fat (see [[Mesotherapy]]).  Deoxycholic acid as an injectable has received FDA approval to dissolve submental fat.<ref>{{cite web|title=Deoxycholic acid injection|url=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a615026.html|publisher=Medline plus|access-date=26 August 2015}}</ref> Phase III trials showed significant responses although many subjects had mild adverse reactions of bruising, swelling, pain, numbness, erythema, and firmness around the treated area.<ref>{{cite journal|vauthors=Ascher B, Hoffmann K, Walker P, Lippert S, Wollina U, Havlickova B | title=Efficacy, patient-reported outcomes and safety profile of ATX-101 (deoxycholic acid), an injectable drug for the reduction of unwanted submental fat: results from a phase III, randomized, placebo-controlled study. | journal=J Eur Acad Dermatol Venereol | year= 2014 | volume= 28 | issue= 12 | pages= 1707–15 | pmid=24605812 | doi=10.1111/jdv.12377 | pmc=4263247 }}</ref><ref name="pmid25724831">{{cite journal|vauthors=Wollina U, Goldman A | title=ATX-101 for reduction of submental fat. | journal=Expert Opin Pharmacother | year= 2015 | volume= 16 | issue= 5 | pages= 755–62 | pmid=25724831 | doi=10.1517/14656566.2015.1019465 | s2cid=23094631 }}</ref>

==References==
{{Reflist}}

==External links==
* {{MeshName|Bile Acids and Salts}}
{{Steroid classification}}
{{Bile and liver therapy}}
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{{Xenobiotic-sensing receptor modulators}}
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[[Category:Bile acids| ]]
[[Category:Farnesoid X receptor agonists]]
[[Category:Hepatology]]