Interactive Relationships between Intestinal Flora and Bile Acids
Abstract
:1. Introduction
2. Architecture and Composition of the Intestinal Flora
3. Bile Acids
4. Interaction between Intestinal Flora and Bile Acids
4.1. Effects of the Intestinal Flora on Bile Acids
4.1.1. The Intestinal Flora Is Involved in Bile Acid Metabolism
- Deconjugation
- Dehydroxylation
- Oxidation and isomerization
4.1.2. The Intestinal Flora Affects Compositions of the Bile Acid Pool
4.2. Effects of Bile Acids on the Intestinal Flora
4.2.1. Bile Acids Inhibit the Growth and Proliferation of Bacteria
4.2.2. Bile Acids Affect the Composition of the Intestinal Flora
4.3. Role of the Intestinal Flora and Bile Acids in Related Diseases
4.3.1. Inflammatory Bowel Disease
4.3.2. Colorectal Cancer
4.3.3. Hepatocellular Carcinoma
4.3.4. Type 2 Diabetes
4.3.5. Polycystic Ovary Syndrome
5. Concluding Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Anwar, H.; Iftikhar, A.; Muzaffar, H.; Almatroudi, A.; Allemailem, K.S.; Navaid, S.; Saleem, S.; Khurshid, M. Biodiversity of Gut Microbiota: Impact of Various Host and Environmental Factors. BioMed Res. Int. 2021, 2021, 5575245. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.J.; Li, S.; Gan, R.Y.; Zhou, T.; Xu, D.P.; Li, H.B. Impacts of gut bacteria on human health and diseases. Int. J. Mol. Sci. 2015, 16, 7493–7519. [Google Scholar] [CrossRef]
- Albhaisi, S.A.M.; Bajaj, J.S.; Sanyal, A.J. Role of gut microbiota in liver disease. Am. J. Physiol. Gastrointest. Liver Physiol. 2020, 318, G84–G98. [Google Scholar] [CrossRef] [PubMed]
- Shi, N.; Li, N.; Duan, X.; Niu, H. Interaction between the gut microbiome and mucosal immune system. Mil. Med. Res. 2017, 4, 14. [Google Scholar] [CrossRef]
- Lavelle, A.; Sokol, H. Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 223–237. [Google Scholar] [CrossRef] [PubMed]
- Singh, J.; Metrani, R.; Shivanagoudra, S.R.; Jayaprakasha, G.K.; Patil, B.S. Review on Bile Acids: Effects of the Gut Microbiome, Interactions with Dietary Fiber, and Alterations in the Bioaccessibility of Bioactive Compounds. J. Agric. Food Chem. 2019, 67, 9124–9138. [Google Scholar] [CrossRef] [PubMed]
- Di Gregorio, M.C.; Cautela, J.; Galantini, L. Physiology and Physical Chemistry of Bile Acids. Int. J. Mol. Sci. 2021, 22, 1780. [Google Scholar] [CrossRef]
- Rodriguez-Morato, J.; Matthan, N.R. Nutrition and Gastrointestinal Microbiota, Microbial-Derived Secondary Bile Acids, and Cardiovascular Disease. Curr. Atheroscler. Rep. 2020, 22, 47. [Google Scholar] [CrossRef] [PubMed]
- Ticho, A.L.; Malhotra, P.; Dudeja, P.K.; Gill, R.K.; Alrefai, W.A. Intestinal Absorption of Bile Acids in Health and Disease. Compr. Physiol. 2019, 10, 21–56. [Google Scholar] [PubMed]
- Jia, B.; Park, D.; Hahn, Y.; Jeon, C.O. Metagenomic analysis of the human microbiome reveals the association between the abundance of gut bile salt hydrolases and host health. Gut Microbes 2020, 11, 1300–1313. [Google Scholar] [CrossRef]
- Milani, C.; Ferrario, C.; Turroni, F.; Duranti, S.; Mangifesta, M.; van Sinderen, D.; Ventura, M. The human gut microbiota and its interactive connections to diet. J. Hum. Nutr. Diet. 2016, 29, 539–546. [Google Scholar] [CrossRef]
- Tanaka, M.; Sanefuji, M.; Morokuma, S.; Yoden, M.; Momoda, R.; Sonomoto, K.; Ogawa, M.; Kato, K.; Nakayama, J. The association between gut microbiota development and maturation of intestinal bile acid metabolism in the first 3 y of healthy Japanese infants. Gut Microbes 2020, 11, 205–216. [Google Scholar] [CrossRef]
- Adlerberth, I.; Wold, A.E. Establishment of the gut microbiota in Western infants. Acta Paediatr. 2009, 98, 229–238. [Google Scholar] [CrossRef] [PubMed]
- Durack, J.; Lynch, S.V. The gut microbiome: Relationships with disease and opportunities for therapy. J. Exp. Med. 2019, 216, 20–40. [Google Scholar] [CrossRef] [PubMed]
- Hollister, E.B.; Riehle, K.; Luna, R.A.; Weidler, E.M.; Rubio-Gonzales, M.; Mistretta, T.A.; Raza, S.; Doddapaneni, H.V.; Metcalf, G.A.; Muzny, D.M.; et al. Structure and function of the healthy pre-adolescent pediatric gut microbiome. Microbiome 2015, 3, 36. [Google Scholar] [CrossRef] [PubMed]
- Adak, A.; Khan, M.R. An insight into gut microbiota and its functionalities. Cell Mol. Life Sci. 2019, 76, 473–493. [Google Scholar] [CrossRef] [PubMed]
- Gomaa, E.Z. Human gut microbiota/microbiome in health and diseases: A review. Antonie Van Leeuwenhoek 2020, 113, 2019–2040. [Google Scholar] [CrossRef]
- Gonzalez Olmo, B.M.; Butler, M.J.; Barrientos, R.M. Evolution of the Human Diet and Its Impact on Gut Microbiota, Immune Responses, and Brain Health. Nutrients 2021, 13, 196. [Google Scholar] [CrossRef] [PubMed]
- Dewhirst, F.E.; Chen, T.; Izard, J.; Paster, B.J.; Tanner, A.C.; Yu, W.H.; Lakshmanan, A.; Wade, W.G. The human oral microbiome. J. Bacteriol. 2010, 192, 5002–5017. [Google Scholar] [CrossRef]
- Wade, W.G. The oral microbiome in health and disease. Pharmacol. Res. 2013, 69, 137–143. [Google Scholar] [CrossRef] [PubMed]
- Martinez-Guryn, K.; Leone, V.; Chang, E.B. Regional Diversity of the Gastrointestinal Microbiome. Cell Host Microbe 2019, 26, 314–324. [Google Scholar] [CrossRef] [PubMed]
- Pei, Z.; Bini, E.J.; Yang, L.; Zhou, M.; Francois, F.; Blaser, M.J. Bacterial biota in the human distal esophagus. Proc. Natl. Acad. Sci. USA 2004, 101, 4250–4255. [Google Scholar] [CrossRef] [PubMed]
- Jandhyala, S.M.; Talukdar, R.; Subramanyam, C.; Vuyyuru, H.; Sasikala, M.; Nageshwar Reddy, D. Role of the normal gut microbiota. World J. Gastroenterol. 2015, 21, 8787–8803. [Google Scholar] [CrossRef] [PubMed]
- Nardone, G.; Compare, D. The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases? United Eur. Gastroenterol. J. 2015, 3, 255–260. [Google Scholar] [CrossRef] [PubMed]
- O’Hara, A.M.; Shanahan, F. The gut flora as a forgotten organ. EMBO Rep. 2006, 7, 688–693. [Google Scholar] [CrossRef]
- Weaver, K.E. Enterococcal Genetics. Microbiol. Spectr. 2019, 7, 7.2.11. [Google Scholar] [CrossRef]
- Ma, Q.; Li, Y.; Li, P.; Wang, M.; Wang, J.; Tang, Z.; Wang, T.; Luo, L.; Wang, C.; Wang, T.; et al. Research progress in the relationship between type 2 diabetes mellitus and intestinal flora. Biomed. Pharmacother. 2019, 117, 109138. [Google Scholar] [CrossRef]
- Krawczyk, B.; Wityk, P.; Galecka, M.; Michalik, M. The Many Faces of Enterococcus spp.-Commensal, Probiotic and Opportunistic Pathogen. Microorganisms 2021, 9, 1900. [Google Scholar] [CrossRef]
- Murphy, E.C.; Frick, I.M. Gram-positive anaerobic cocci—Commensals and opportunistic pathogens. FEMS Microbiol. Rev. 2013, 37, 520–553. [Google Scholar] [CrossRef]
- Martin, R.M.; Bachman, M.A. Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Front. Cell Infect. Microbiol. 2018, 8, 4. [Google Scholar] [CrossRef]
- Chiang, J.Y. Bile acid metabolism and signaling. Compr. Physiol. 2013, 3, 1191–1212. [Google Scholar]
- Thomas, C.; Pellicciari, R.; Pruzanski, M.; Auwerx, J.; Schoonjans, K. Targeting bile-acid signalling for metabolic diseases. Nat. Rev. Drug Discov. 2008, 7, 678–693. [Google Scholar] [CrossRef] [PubMed]
- De Aguiar Vallim, T.Q.; Tarling, E.J.; Edwards, P.A. Pleiotropic roles of bile acids in metabolism. Cell Metab. 2013, 17, 657–669. [Google Scholar] [CrossRef]
- Styles, N.A.; Shonsey, E.M.; Falany, J.L.; Guidry, A.L.; Barnes, S.; Falany, C.N. Carboxy-terminal mutations of bile acid CoA:N-acyltransferase alter activity and substrate specificity. J. Lipid Res. 2016, 57, 1133–1143. [Google Scholar] [CrossRef]
- Jia, W.; Xie, G.; Jia, W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat. Rev. Gastroenterol. Hepatol. 2018, 15, 111–128. [Google Scholar] [CrossRef] [PubMed]
- Chen, M.L.; Takeda, K.; Sundrud, M.S. Emerging roles of bile acids in mucosal immunity and inflammation. Mucosal Immunol. 2019, 12, 851–861. [Google Scholar] [CrossRef] [PubMed]
- Joyce, S.A.; Gahan, C.G. Bile Acid Modifications at the Microbe-Host Interface: Potential for Nutraceutical and Pharmaceutical Interventions in Host Health. Annu. Rev. Food Sci. Technol. 2016, 7, 313–333. [Google Scholar] [CrossRef]
- Shiffka, S.J.; Kane, M.A.; Swaan, P.W. Planar bile acids in health and disease. Biochim. Biophys. Acta Biomembr. 2017, 1859, 2269–2276. [Google Scholar] [CrossRef]
- Thompson, R.S.; Gaffney, M.; Hopkins, S.; Kelley, T.; Gonzalez, A.; Bowers, S.J.; Vitaterna, M.H.; Turek, F.W.; Foxx, C.L.; Lowry, C.A.; et al. Ruminiclostridium 5, Parabacteroides distasonis, and bile acid profile are modulated by prebiotic diet and associate with facilitated sleep/clock realignment after chronic disruption of rhythms. Brain Behav. Immun. 2021, 97, 150–166. [Google Scholar] [CrossRef] [PubMed]
- Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 2003, 72, 137–174. [Google Scholar] [CrossRef] [PubMed]
- Doden, H.L.; Wolf, P.G.; Gaskins, H.R.; Anantharaman, K.; Alves, J.M.P.; Ridlon, J.M. Completion of the gut microbial epi-bile acid pathway. Gut Microbes 2021, 13, 1–20. [Google Scholar] [CrossRef] [PubMed]
- Busnelli, M.; Manzini, S.; Chiesa, G. The Gut Microbiota Affects Host Pathophysiology as an Endocrine Organ: A Focus on Cardiovascular Disease. Nutrients 2019, 12, 79. [Google Scholar] [CrossRef]
- Ridlon, J.M.; Kang, D.J.; Hylemon, P.B. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res. 2006, 47, 241–259. [Google Scholar] [CrossRef] [PubMed]
- Ridlon, J.M.; Devendran, S.; Alves, J.M.; Doden, H.; Wolf, P.G.; Pereira, G.V.; Ly, L.; Volland, A.; Takei, H.; Nittono, H.; et al. The ‘in vivo lifestyle’ of bile acid 7alpha-dehydroxylating bacteria: Comparative genomics, metatranscriptomic, and bile acid metabolomics analysis of a defined microbial community in gnotobiotic mice. Gut Microbes 2020, 11, 381–404. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Dawson, P.A. Animal models to study bile acid metabolism. Biochim. Biophys. Acta Mol. Basis Dis. 2019, 1865, 895–911. [Google Scholar] [CrossRef] [PubMed]
- Wahlstrom, A.; Sayin, S.I.; Marschall, H.U.; Backhed, F. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism. Cell Metab. 2016, 24, 41–50. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Zhang, J. Bile acid metabolism and circadian rhythms. Am. J. Physiol. Gastrointest. Liver Physiol. 2020, 319, G549–G563. [Google Scholar] [CrossRef]
- Chiang, J.Y. Bile acid regulation of hepatic physiology: III. Bile acids and nuclear receptors. Am. J. Physiol. Gastrointest. Liver Physiol. 2003, 284, G349–G356. [Google Scholar] [CrossRef] [PubMed]
- Xie, G.; Jiang, R.; Wang, X.; Liu, P.; Zhao, A.; Wu, Y.; Huang, F.; Liu, Z.; Rajani, C.; Zheng, X.; et al. Conjugated secondary 12alpha-hydroxylated bile acids promote liver fibrogenesis. eBioMedicine 2021, 66, 103290. [Google Scholar] [CrossRef]
- Jia, W.; Wei, M.; Rajani, C.; Zheng, X. Targeting the alternative bile acid synthetic pathway for metabolic diseases. Protein Cell 2021, 12, 411–425. [Google Scholar] [CrossRef]
- Winston, J.A.; Theriot, C.M. Diversification of host bile acids by members of the gut microbiota. Gut Microbes 2020, 11, 158–171. [Google Scholar] [CrossRef] [PubMed]
- Sayin, S.I.; Wahlstrom, A.; Felin, J.; Jantti, S.; Marschall, H.U.; Bamberg, K.; Angelin, B.; Hyotylainen, T.; Oresic, M.; Backhed, F. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 2013, 17, 225–235. [Google Scholar] [CrossRef]
- Long, S.L.; Gahan, C.G.M.; Joyce, S.A. Interactions between gut bacteria and bile in health and disease. Mol. Aspects Med. 2017, 56, 54–65. [Google Scholar] [CrossRef]
- Staley, C.; Weingarden, A.R.; Khoruts, A.; Sadowsky, M.J. Interaction of gut microbiota with bile acid metabolism and its influence on disease states. Appl. Microbiol. Biotechnol. 2017, 101, 47–64. [Google Scholar] [CrossRef] [PubMed]
- Xiao, Y.; Zhao, J.; Zhang, H.; Zhai, Q.; Chen, W. Mining genome traits that determine the different gut colonization potential of Lactobacillus and Bifidobacterium species. Microb. Genom. 2021, 7, 000581. [Google Scholar] [CrossRef] [PubMed]
- Foley, M.H.; O’Flaherty, S.; Allen, G.; Rivera, A.J.; Stewart, A.K.; Barrangou, R.; Theriot, C.M. Lactobacillus bile salt hydrolase substrate specificity governs bacterial fitness and host colonization. Proc. Natl. Acad. Sci. USA 2021, 118, e2017709118. [Google Scholar] [CrossRef] [PubMed]
- Enright, E.F.; Griffin, B.T.; Gahan, C.G.M.; Joyce, S.A. Microbiome-mediated bile acid modification: Role in intestinal drug absorption and metabolism. Pharmacol. Res. 2018, 133, 170–186. [Google Scholar] [CrossRef] [PubMed]
- Begley, M.; Gahan, C.G.; Hill, C. The interaction between bacteria and bile. FEMS Microbiol. Rev. 2005, 29, 625–651. [Google Scholar] [CrossRef] [PubMed]
- Daly, J.W.; Keely, S.J.; Gahan, C.G.M. Functional and Phylogenetic Diversity of BSH and PVA Enzymes. Microorganisms 2021, 9, 732. [Google Scholar] [CrossRef]
- Chand, D.; Avinash, V.S.; Yadav, Y.; Pundle, A.V.; Suresh, C.G.; Ramasamy, S. Molecular features of bile salt hydrolases and relevance in human health. Biochim. Biophys. Acta Gen. Subj. 2017, 1861 Pt A, 2981–2991. [Google Scholar] [CrossRef]
- Bustos, A.Y.; Font de Valdez, G.; Fadda, S.; Taranto, M.P. New insights into bacterial bile resistance mechanisms: The role of bile salt hydrolase and its impact on human health. Food Res. Int. 2018, 112, 250–262. [Google Scholar] [CrossRef] [PubMed]
- Guzior, D.V.; Quinn, R.A. Review: Microbial transformations of human bile acids. Microbiome 2021, 9, 140. [Google Scholar] [CrossRef] [PubMed]
- Funabashi, M.; Grove, T.L.; Wang, M.; Varma, Y.; McFadden, M.E.; Brown, L.C.; Guo, C.; Higginbottom, S.; Almo, S.C.; Fischbach, M.A. A metabolic pathway for bile acid dehydroxylation by the gut microbiome. Nature 2020, 582, 566–570. [Google Scholar] [CrossRef] [PubMed]
- Mallonee, D.H.; Hylemon, P.B. Sequencing and expression of a gene encoding a bile acid transporter from Eubacterium sp. strain VPI 12708. J. Bacteriol. 1996, 178, 7053–7058. [Google Scholar] [CrossRef] [PubMed]
- Heinken, A.; Ravcheev, D.A.; Baldini, F.; Heirendt, L.; Fleming, R.M.T.; Thiele, I. Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease. Microbiome 2019, 7, 75. [Google Scholar] [CrossRef] [PubMed]
- Ridlon, J.M.; Harris, S.C.; Bhowmik, S.; Kang, D.J.; Hylemon, P.B. Consequences of bile salt biotransformations by intestinal bacteria. Gut Microbes 2016, 7, 22–39. [Google Scholar] [CrossRef] [PubMed]
- Mallonee, D.H.; Adams, J.L.; Hylemon, P.B. The bile acid-inducible baiB gene from Eubacterium sp. strain VPI 12708 encodes a bile acid-coenzyme A ligase. J. Bacteriol. 1992, 174, 2065–2071. [Google Scholar] [CrossRef] [PubMed]
- Devlin, A.S.; Fischbach, M.A. A biosynthetic pathway for a prominent class of microbiota-derived bile acids. Nat. Chem. Biol. 2015, 11, 685–690. [Google Scholar] [CrossRef] [PubMed]
- Fiorucci, S.; Distrutti, E. Bile Acid-Activated Receptors, Intestinal Microbiota, and the Treatment of Metabolic Disorders. Trends Mol. Med. 2015, 21, 702–714. [Google Scholar] [CrossRef]
- Liu, H.X.; Keane, R.; Sheng, L.; Wan, Y.J. Implications of microbiota and bile acid in liver injury and regeneration. J. Hepatol. 2015, 63, 1502–1510. [Google Scholar] [CrossRef] [PubMed]
- Ferrandi, E.E.; Bertolesi, G.M.; Polentini, F.; Negri, A.; Riva, S.; Monti, D. In search of sustainable chemical processes: Cloning, recombinant expression, and functional characterization of the 7α- and 7β-hydroxysteroid dehydrogenases from Clostridium absonum. Appl. Microbiol. Biotechnol. 2012, 95, 1221–1233. [Google Scholar] [CrossRef]
- Lepercq, P.; Gerard, P.; Beguet, F.; Raibaud, P.; Grill, J.P.; Relano, P.; Cayuela, C.; Juste, C. Epimerization of chenodeoxycholic acid to ursodeoxycholic acid by Clostridium baratii isolated from human feces. FEMS Microbiol. Lett. 2004, 235, 65–72. [Google Scholar] [CrossRef]
- Goossens, J.F.; Bailly, C. Ursodeoxycholic acid and cancer: From chemoprevention to chemotherapy. Pharmacol. Ther. 2019, 203, 107396. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Fan, D.; Hua, X.; Zhang, T. Large-scale production of ursodeoxycholic acid from chenodeoxycholic acid by engineering 7alpha- and 7beta-hydroxysteroid dehydrogenase. Bioprocess. Biosyst. Eng. 2019, 42, 1537–1545. [Google Scholar] [CrossRef]
- Doden, H.; Sallam, L.A.; Devendran, S.; Ly, L.; Doden, G.; Daniel, S.L.; Alves, J.M.P.; Ridlon, J.M. Metabolism of Oxo-Bile Acids and Characterization of Recombinant 12alpha-Hydroxysteroid Dehydrogenases from Bile Acid 7alpha-Dehydroxylating Human Gut Bacteria. Appl. Environ. Microbiol. 2018, 84, e00235-18. [Google Scholar] [CrossRef] [PubMed]
- Sun, L.; Cai, J.; Gonzalez, F.J. The role of farnesoid X receptor in metabolic diseases, and gastrointestinal and liver cancer. Nat. Rev. Gastroenterol. Hepatol. 2021, 18, 335–347. [Google Scholar] [CrossRef] [PubMed]
- Chiang, J.Y.L.; Ferrell, J.M. Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy. Am. J. Physiol. Gastrointest. Liver Physiol. 2020, 318, G554–G573. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Tang, R.; Leung, P.S.C.; Gershwin, M.E.; Ma, X. Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases. Autoimmun. Rev. 2017, 16, 885–896. [Google Scholar] [CrossRef] [PubMed]
- Han, S.; Zhang, R.; Jain, R.; Shi, H.; Zhang, L.; Zhou, G.; Sangwung, P.; Tugal, D.; Atkins, G.B.; Prosdocimo, D.A.; et al. Circadian control of bile acid synthesis by a KLF15-Fgf15 axis. Nat. Commun. 2015, 6, 7231. [Google Scholar] [CrossRef] [PubMed]
- Denson, L.A.; Sturm, E.; Echevarria, W.; Zimmerman, T.L.; Makishima, M.; Mangelsdorf, D.J.; Karpen, S.J. The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp. Gastroenterology 2001, 121, 140–147. [Google Scholar] [CrossRef] [PubMed]
- Out, C.; Patankar, J.V.; Doktorova, M.; Boesjes, M.; Bos, T.; de Boer, S.; Havinga, R.; Wolters, H.; Boverhof, R.; van Dijk, T.H.; et al. Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4. J. Hepatol. 2015, 63, 697–704. [Google Scholar] [CrossRef] [PubMed]
- Beuling, E.; Kerkhof, I.M.; Nicksa, G.A.; Giuffrida, M.J.; Haywood, J.; aan de Kerk, D.J.; Piaseckyj, C.M.; Pu, W.T.; Buchmiller, T.L.; Dawson, P.A.; et al. Conditional Gata4 deletion in mice induces bile acid absorption in the proximal small intestine. Gut 2010, 59, 888–895. [Google Scholar] [CrossRef]
- Quinn, R.A.; Melnik, A.V.; Vrbanac, A.; Fu, T.; Patras, K.A.; Christy, M.P.; Bodai, Z.; Belda-Ferre, P.; Tripathi, A.; Chung, L.K.; et al. Global chemical effects of the microbiome include new bile-acid conjugations. Nature 2020, 579, 123–129. [Google Scholar] [CrossRef]
- Sannasiddappa, T.H.; Lund, P.A.; Clarke, S.R. In Vitro Antibacterial Activity of Unconjugated and Conjugated Bile Salts on Staphylococcus aureus. Front. Microbiol. 2017, 8, 1581. [Google Scholar] [CrossRef] [PubMed]
- Sung, J.Y.; Shaffer, E.A.; Costerton, J.W. Antibacterial activity of bile salts against common biliary pathogens. Effects of hydrophobicity of the molecule and in the presence of phospholipids. Dig. Dis. Sci. 1993, 38, 2104–2112. [Google Scholar] [CrossRef]
- Coleman, R.; Lowe, P.J.; Billington, D. Membrane lipid composition and susceptibility to bile salt damage. Biochim. Biophys. Acta 1980, 599, 294–300. [Google Scholar] [CrossRef]
- Inagaki, T.; Moschetta, A.; Lee, Y.K.; Peng, L.; Zhao, G.; Downes, M.; Yu, R.T.; Shelton, J.M.; Richardson, J.A.; Repa, J.J.; et al. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc. Natl. Acad. Sci. USA 2006, 103, 3920–3925. [Google Scholar] [CrossRef] [PubMed]
- Yang, M.; Gu, Y.; Li, L.; Liu, T.; Song, X.; Sun, Y.; Cao, X.; Wang, B.; Jiang, K.; Cao, H. Bile Acid-Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside. Nutrients 2021, 13, 3143. [Google Scholar] [CrossRef] [PubMed]
- Li, T.; Chiang, J.Y. Bile acid signaling in metabolic disease and drug therapy. Pharmacol. Rev. 2014, 66, 948–983. [Google Scholar] [CrossRef]
- Kurdi, P.; Kawanishi, K.; Mizutani, K.; Yokota, A. Mechanism of growth inhibition by free bile acids in lactobacilli and bifidobacteria. J. Bacteriol. 2006, 188, 1979–1986. [Google Scholar] [CrossRef] [PubMed]
- Yokota, A.; Fukiya, S.; Islam, K.B.; Ooka, T.; Ogura, Y.; Hayashi, T.; Hagio, M.; Ishizuka, S. Is bile acid a determinant of the gut microbiota on a high-fat diet? Gut Microbes 2012, 3, 455–459. [Google Scholar] [CrossRef]
- Xu, M.; Cen, M.; Shen, Y.; Zhu, Y.; Cheng, F.; Tang, L.; Hu, W.; Dai, N. Deoxycholic Acid-Induced Gut Dysbiosis Disrupts Bile Acid Enterohepatic Circulation and Promotes Intestinal Inflammation. Dig. Dis. Sci. 2021, 66, 568–576. [Google Scholar] [CrossRef]
- Barrasa, J.I.; Olmo, N.; Lizarbe, M.A.; Turnay, J. Bile acids in the colon, from healthy to cytotoxic molecules. Toxicol. Vitro 2013, 27, 964–977. [Google Scholar] [CrossRef] [PubMed]
- Ovadia, C.; Perdones-Montero, A.; Fan, H.M.; Mullish, B.H.; McDonald, J.A.K.; Papacleovoulou, G.; Wahlstrom, A.; Stahlman, M.; Tsakmaki, A.; Clarke, L.C.D.; et al. Ursodeoxycholic acid enriches intestinal bile salt hydrolase-expressing Bacteroidetes in cholestatic pregnancy. Sci. Rep. 2020, 10, 3895. [Google Scholar] [CrossRef] [PubMed]
- Aguirre, A.M.; Yalcinkaya, N.; Wu, Q.; Swennes, A.; Tessier, M.E.; Roberts, P.; Miyajima, F.; Savidge, T.; Sorg, J.A. Bile acid-independent protection against Clostridioides difficile infection. PLoS Pathog. 2021, 17, e1010015. [Google Scholar] [CrossRef]
- Gruner, N.; Mattner, J. Bile Acids and Microbiota: Multifaceted and Versatile Regulators of the Liver-Gut Axis. Int. J. Mol. Sci. 2021, 22, 1397. [Google Scholar] [CrossRef] [PubMed]
- Islam, K.B.; Fukiya, S.; Hagio, M.; Fujii, N.; Ishizuka, S.; Ooka, T.; Ogura, Y.; Hayashi, T.; Yokota, A. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 2011, 141, 1773–1781. [Google Scholar] [CrossRef]
- Ward, J.B.J.; Lajczak, N.K.; Kelly, O.B.; O’Dwyer, A.M.; Giddam, A.K.; Ni Gabhann, J.; Franco, P.; Tambuwala, M.M.; Jefferies, C.A.; Keely, S.; et al. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am. J. Physiol. Gastrointest. Liver Physiol. 2017, 312, G550–G558. [Google Scholar] [CrossRef]
- Ghouri, Y.A.; Tahan, V.; Shen, B. Secondary causes of inflammatory bowel diseases. World J. Gastroenterol. 2020, 26, 3998–4017. [Google Scholar] [CrossRef]
- Matsuoka, K.; Kanai, T. The gut microbiota and inflammatory bowel disease. Semin. Immunopathol. 2015, 37, 47–55. [Google Scholar] [CrossRef]
- Imhann, F.; Vich Vila, A.; Bonder, M.J.; Fu, J.; Gevers, D.; Visschedijk, M.C.; Spekhorst, L.M.; Alberts, R.; Franke, L.; van Dullemen, H.M.; et al. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut 2018, 67, 108–119. [Google Scholar] [CrossRef]
- Lee, T.; Clavel, T.; Smirnov, K.; Schmidt, A.; Lagkouvardos, I.; Walker, A.; Lucio, M.; Michalke, B.; Schmitt-Kopplin, P.; Fedorak, R.; et al. Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut 2017, 66, 863–871. [Google Scholar] [CrossRef] [PubMed]
- Sinha, S.R.; Haileselassie, Y.; Nguyen, L.P.; Tropini, C.; Wang, M.; Becker, L.S.; Sim, D.; Jarr, K.; Spear, E.T.; Singh, G.; et al. Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation. Cell Host Microbe 2020, 27, 659–670. [Google Scholar] [CrossRef] [PubMed]
- Duboc, H.; Rajca, S.; Rainteau, D.; Benarous, D.; Maubert, M.A.; Quervain, E.; Thomas, G.; Barbu, V.; Humbert, L.; Despras, G.; et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 2013, 62, 531–539. [Google Scholar] [CrossRef]
- Nishida, A.; Nishino, K.; Sakai, K.; Owaki, Y.; Noda, Y.; Imaeda, H. Can control of gut microbiota be a future therapeutic option for inflammatory bowel disease? World J. Gastroenterol. 2021, 27, 3317–3326. [Google Scholar] [CrossRef]
- Zuo, T.; Ng, S.C. The Gut Microbiota in the Pathogenesis and Therapeutics of Inflammatory Bowel Disease. Front. Microbiol. 2018, 9, 2247. [Google Scholar] [CrossRef] [PubMed]
- Xu, M.; Shen, Y.; Cen, M.; Zhu, Y.; Cheng, F.; Tang, L.; Zheng, X.; Kim, J.J.; Dai, N.; Hu, W. Modulation of the Gut Microbiota-farnesoid X Receptor Axis Improves Deoxycholic Acid-induced Intestinal Inflammation in Mice. J. Crohns Colitis 2021, 15, 1197–1210. [Google Scholar] [CrossRef] [PubMed]
- Van den Bossche, L.; Hindryckx, P.; Devisscher, L.; Devriese, S.; Van Welden, S.; Holvoet, T.; Vilchez-Vargas, R.; Vital, M.; Pieper, D.H.; Vanden Bussche, J.; et al. Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice. Appl. Environ. Microbiol. 2017, 83, 02766-16. [Google Scholar] [CrossRef]
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef]
- Arnold, C.N.; Goel, A.; Blum, H.E.; Boland, C.R. Molecular pathogenesis of colorectal cancer: Implications for molecular diagnosis. Cancer 2005, 104, 2035–2047. [Google Scholar] [CrossRef] [PubMed]
- Wang, T.; Cai, G.; Qiu, Y.; Fei, N.; Zhang, M.; Pang, X.; Jia, W.; Cai, S.; Zhao, L. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 2012, 6, 320–329. [Google Scholar] [CrossRef] [PubMed]
- Cao, H.; Xu, M.; Dong, W.; Deng, B.; Wang, S.; Zhang, Y.; Wang, S.; Luo, S.; Wang, W.; Qi, Y.; et al. Secondary bile acid-induced dysbiosis promotes intestinal carcinogenesis. Int. J. Cancer 2017, 140, 2545–2556. [Google Scholar] [CrossRef] [PubMed]
- Pai, R.; Tarnawski, A.S.; Tran, T. Deoxycholic acid activates beta-catenin signaling pathway and increases colon cell cancer growth and invasiveness. Mol. Biol. Cell 2004, 15, 2156–2163. [Google Scholar] [CrossRef] [PubMed]
- Cheng, K.; Raufman, J.P. Bile acid-induced proliferation of a human colon cancer cell line is mediated by transactivation of epidermal growth factor receptors. Biochem. Pharmacol. 2005, 70, 1035–1047. [Google Scholar] [CrossRef]
- Chen, D.; Jin, D.; Huang, S.; Wu, J.; Xu, M.; Liu, T.; Dong, W.; Liu, X.; Wang, S.; Zhong, W.; et al. Clostridium butyricum, a butyrate-producing probiotic, inhibits intestinal tumor development through modulating Wnt signaling and gut microbiota. Cancer Lett. 2020, 469, 456–467. [Google Scholar] [CrossRef]
- Chang, C.W.; Lee, H.C.; Li, L.H.; Chiang Chiau, J.S.; Wang, T.E.; Chuang, W.H.; Chen, M.J.; Wang, H.Y.; Shih, S.C.; Liu, C.Y.; et al. Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer. Int. J. Mol. Sci. 2020, 21, 386. [Google Scholar] [CrossRef]
- Wang, Y.; Li, H. Gut microbiota modulation: A tool for the management of colorectal cancer. J. Transl. Med. 2022, 20, 178. [Google Scholar] [CrossRef]
- Garrido, A.; Djouder, N. Cirrhosis: A Questioned Risk Factor for Hepatocellular Carcinoma. Trends Cancer 2021, 7, 29–36. [Google Scholar] [CrossRef]
- Yu, L.X.; Schwabe, R.F. The gut microbiome and liver cancer: Mechanisms and clinical translation. Nat. Rev. Gastroenterol. Hepatol. 2017, 14, 527–539. [Google Scholar] [CrossRef]
- Dapito, D.H.; Mencin, A.; Gwak, G.Y.; Pradere, J.P.; Jang, M.K.; Mederacke, I.; Caviglia, J.M.; Khiabanian, H.; Adeyemi, A.; Bataller, R.; et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 2012, 21, 504–516. [Google Scholar] [CrossRef]
- Lapidot, Y.; Amir, A.; Nosenko, R.; Uzan-Yulzari, A.; Veitsman, E.; Cohen-Ezra, O.; Davidov, Y.; Weiss, P.; Bradichevski, T.; Segev, S.; et al. Alterations in the Gut Microbiome in the Progression of Cirrhosis to Hepatocellular Carcinoma. mSystems 2020, 5, e00153-20. [Google Scholar] [CrossRef]
- Xie, G.; Wang, X.; Huang, F.; Zhao, A.; Chen, W.; Yan, J.; Zhang, Y.; Lei, S.; Ge, K.; Zheng, X.; et al. Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis. Int. J. Cancer 2016, 139, 1764–1775. [Google Scholar] [CrossRef] [PubMed]
- Schwabe, R.F.; Greten, T.F. Gut microbiome in HCC—Mechanisms, diagnosis and therapy. J. Hepatol. 2020, 72, 230–238. [Google Scholar] [CrossRef]
- Zhang, H.L.; Yu, L.X.; Yang, W.; Tang, L.; Lin, Y.; Wu, H.; Zhai, B.; Tan, Y.X.; Shan, L.; Liu, Q.; et al. Profound impact of gut homeostasis on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats. J. Hepatol. 2012, 57, 803–812. [Google Scholar] [CrossRef]
- Li, J.; Sung, C.Y.; Lee, N.; Ni, Y.; Pihlajamaki, J.; Panagiotou, G.; El-Nezami, H. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. Proc. Natl. Acad. Sci. USA 2016, 113, E1306–E1315. [Google Scholar] [CrossRef]
- Dai, H.; Otsuka, A.; Tanabe, K.; Yanagita, T.; Nakayama, J.; Kitagaki, H. Glucosylceramide Changes Bacterial Metabolism and Increases Gram-Positive Bacteria through Tolerance to Secondary Bile Acids In Vitro. Int. J. Mol. Sci. 2022, 23, 5300. [Google Scholar] [CrossRef]
- D’Haens, G.R.; Jobin, C. Fecal Microbial Transplantation for Diseases Beyond Recurrent Clostridium Difficile Infection. Gastroenterology 2019, 157, 624–636. [Google Scholar] [CrossRef] [PubMed]
- Zhang, L.; Chu, J.; Hao, W.; Zhang, J.; Li, H.; Yang, C.; Yang, J.; Chen, X.; Wang, H. Gut Microbiota and Type 2 Diabetes Mellitus: Association, Mechanism, and Translational Applications. Mediat. Inflamm. 2021, 2021, 5110276. [Google Scholar] [CrossRef]
- Larsen, N.; Vogensen, F.K.; van den Berg, F.W.; Nielsen, D.S.; Andreasen, A.S.; Pedersen, B.K.; Al-Soud, W.A.; Sorensen, S.J.; Hansen, L.H.; Jakobsen, M. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE 2010, 5, e9085. [Google Scholar] [CrossRef]
- Mantovani, A.; Dalbeni, A.; Peserico, D.; Cattazzo, F.; Bevilacqua, M.; Salvagno, G.L.; Lippi, G.; Targher, G.; Danese, E.; Fava, C. Plasma Bile Acid Profile in Patients with and without Type 2 Diabetes. Metabolites 2021, 11, 453. [Google Scholar] [CrossRef]
- Huang, H.H.; Lee, W.J.; Chen, S.C.; Chen, T.F.; Lee, S.D.; Chen, C.Y. Bile Acid and Fibroblast Growth Factor 19 Regulation in Obese Diabetics, and Non-Alcoholic Fatty Liver Disease after Sleeve Gastrectomy. J. Clin. Med. 2019, 8, 815. [Google Scholar] [CrossRef]
- Han, J.L.; Lin, H.L. Intestinal microbiota and type 2 diabetes: From mechanism insights to therapeutic perspective. World J. Gastroenterol. 2014, 20, 17737–17745. [Google Scholar] [CrossRef]
- Sansome, D.J.; Xie, C.; Veedfald, S.; Horowitz, M.; Rayner, C.K.; Wu, T. Mechanism of glucose-lowering by metformin in type 2 diabetes: Role of bile acids. Diabetes Obes. Metab. 2020, 22, 141–148. [Google Scholar] [CrossRef]
- Forslund, K.; Hildebrand, F.; Nielsen, T.; Falony, G.; Le Chatelier, E.; Sunagawa, S.; Prifti, E.; Vieira-Silva, S.; Gudmundsdottir, V.; Pedersen, H.K.; et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 2015, 528, 262–266. [Google Scholar] [CrossRef] [PubMed]
- Huda, M.N.; Kim, M.; Bennett, B.J. Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes. Front. Endocrinol. 2021, 12, 632335. [Google Scholar] [CrossRef]
- McCartney, C.R.; Marshall, J.C. Clinical Practice. Polycystic Ovary Syndrome. N. Engl. J. Med. 2016, 375, 54–64. [Google Scholar] [CrossRef] [PubMed]
- Macut, D.; Bjekic-Macut, J.; Rahelic, D.; Doknic, M. Insulin and the polycystic ovary syndrome. Diabetes Res. Clin. Pract. 2017, 130, 163–170. [Google Scholar] [CrossRef] [PubMed]
- Liu, R.; Zhang, C.; Shi, Y.; Zhang, F.; Li, L.; Wang, X.; Ling, Y.; Fu, H.; Dong, W.; Shen, J.; et al. Dysbiosis of Gut Microbiota Associated with Clinical Parameters in Polycystic Ovary Syndrome. Front. Microbiol. 2017, 8, 324. [Google Scholar] [CrossRef] [PubMed]
- Guo, J.; Shao, J.; Yang, Y.; Niu, X.; Liao, J.; Zhao, Q.; Wang, D.; Li, S.; Hu, J. Gut Microbiota in Patients with Polycystic Ovary Syndrome: A Systematic Review. Reprod. Sci. 2022, 29, 69–83. [Google Scholar] [CrossRef]
- Zhou, L.; Ni, Z.; Yu, J.; Cheng, W.; Cai, Z.; Yu, C. Correlation Between Fecal Metabolomics and Gut Microbiota in Obesity and Polycystic Ovary Syndrome. Front. Endocrinol. 2020, 11, 628. [Google Scholar] [CrossRef]
- Yang, X.; Wu, R.; Qi, D.; Fu, L.; Song, T.; Wang, Y.; Bian, Y.; Shi, Y. Profile of Bile Acid Metabolomics in the Follicular Fluid of PCOS Patients. Metabolites 2021, 11, 845. [Google Scholar] [CrossRef] [PubMed]
- Zhang, B.; Shen, S.; Gu, T.; Hong, T.; Liu, J.; Sun, J.; Wang, H.; Bi, Y.; Zhu, D. Increased circulating conjugated primary bile acids are associated with hyperandrogenism in women with polycystic ovary syndrome. J. Steroid Biochem. Mol. Biol. 2019, 189, 171–175. [Google Scholar] [CrossRef] [PubMed]
- Qi, X.; Yun, C.; Sun, L.; Xia, J.; Wu, Q.; Wang, Y.; Wang, L.; Zhang, Y.; Liang, X.; Wang, L.; et al. Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome. Nat. Med. 2019, 25, 1225–1233. [Google Scholar] [CrossRef] [PubMed]
- He, F.F.; Li, Y.M. Role of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome: A review. J. Ovarian Res. 2020, 13, 73. [Google Scholar] [CrossRef] [PubMed]
- Zhang, F.; Ma, T.; Cui, P.; Tamadon, A.; He, S.; Huo, C.; Yierfulati, G.; Xu, X.; Hu, W.; Li, X.; et al. Diversity of the Gut Microbiota in Dihydrotestosterone-Induced PCOS Rats and the Pharmacologic Effects of Diane-35, Probiotics, and Berberine. Front. Microbiol. 2019, 10, 175. [Google Scholar] [CrossRef] [PubMed]
- Guo, Y.; Qi, Y.; Yang, X.; Zhao, L.; Wen, S.; Liu, Y.; Tang, L. Association between Polycystic Ovary Syndrome and Gut Microbiota. PLoS ONE 2016, 11, e0153196. [Google Scholar] [CrossRef] [PubMed]
Phylum | Class | Order | Family | Genus | Species |
---|---|---|---|---|---|
Firmicutes | Clostridia | Clostridiales | Clostridiaceae | Faecalibacterium | Faecalibacterium prausnitzii |
Clostridium | Clostridium spp. | ||||
Lachnospiraceae | Coprocococcus | Coprococcus eutactus | |||
Peptostreptococcaceae | Peptostreptococcus | Peptostreptococcus anaerobius | |||
Veillonellaceae | Veillonella | Veillonella parvula | |||
Bacilli | Lactobacillales | Lactobacillaceae | Lactobacillus | Lactobacillus acidophilus | |
Enterococcaceae | Enterococcus | Enterococcus faecalis | |||
Bacillales | Listeriaceae | Listeria | Listeria iuanuii | ||
Bacteroidetes | Flavobacteria | Flavobacteriales | Flavobacteriaceae | Flavobacterium | |
Bacteroidetes | Bacteroidales | Bacteroidaceae | Bacteroides | Bacteroides fragilis | |
Bacteroides caccae | |||||
Bacteroides pyogenes | |||||
Porphyromonadaceae | Porphyromonas | ||||
Parabacteroides | Parabacteroides distasonis | ||||
Rikenellaceae | Alistipes | Alistipes finegoldii | |||
Prevotellaceae | Prevotella | Prevotella spp. | |||
Proteobacteria | Gamma proteobacteria | Enterobacteriales | Enterobacteriaceae | Escherichia | Escherichia coli |
Enterobacter | Enterobacter areogenes | ||||
Delta proteobacteria | Desulfovibrionales Desulfobacterales | Desulfovibrionaceae Desulfobacteraceae | Desulfovibrio | Desulfovibrio intestinalis | |
Desulfobacter | |||||
Epsilon proteobacteria | Campylobacterales | Helicobacteraceae | Helicobacter | Helicobacter pylori | |
Actinobacteria | Actinobacteria | Actinomycetales | Actinomycetaceae | Actinobaculum | |
Corynebacteriaceae | Corynebacterium | Corynebacterium glutamicum | |||
Bifidobacteriales | Bifidobacteriaceae | Bifidobacterium | Bifidobacterium adolescentis | ||
Bifidobacterium longum | |||||
Fusobacteria | Fusobacteria | Fusobacteriales | Fusobacteriaceae | Fusobacterium | Fusobacterium nucleatum |
Verrucomicrobia | Verrucomicrobiae | Verrucomicrobiales | Verrucomicrobiaceae | Akkermansia | Akkermansia muciniphila |
Structural Formula | Abbreviation | C3 | C6 | C7 | C12 |
---|---|---|---|---|---|
| CA | 3α-OH | H | 7α-OH | 12α-OH |
| CDCA | 3α-OH | H | 7α-OH | H |
| DCA | 3α-OH | H | H | 12α-OH |
| LCA | 3α-OH | H | H | H |
| α-MCA | 3α-OH | 6β-OH | 7α-OH | H |
| β-MCA | 3α-OH | 6β-OH | 7β-OH | H |
| ω-MCA | 3α-OH | 6α-OH | 7β-OH | H |
| 3-oxoCA | oxo | H | 7α-OH | 12α-OH |
| IsoCA | 3β-OH | H | 7α-OH | 12α-OH |
| 7-oxoDCA | 3α-OH | H | oxo | 12α-OH |
| 7-epiCA | 3α-OH | H | 7β-OH | 12α-OH |
| 12-oxoCDCA | 3α-OH | H | 7α-OH | oxo |
| 12-epiCA | 3α-OH | H | 7α-OH | 12β-OH |
| 3-oxoCDCA | oxo | H | 7α-OH | H |
| IsoCDCA | 3β-OH | H | 7α-OH | H |
| 7-oxoLCA | 3α-OH | H | oxo | H |
| UDCA | 3α-OH | H | 7β-OH | H |
| 3-oxoDCA | oxo | H | H | 12α-OH |
| IsoDCA | 3β-OH | H | H | 12α-OH |
| 12-oxoLCA | 3α-OH | H | H | oxo |
| EpiDCA | 3α-OH | H | H | 12β-OH |
| HDCA | 3α-OH | 6α-OH | H | H |
| UCA | 3α-OH | H | 7β-OH | 12α-OH |
| HCA | 3α-OH | 6α-OH | 7α-OH | H |
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Guo, X.; Okpara, E.S.; Hu, W.; Yan, C.; Wang, Y.; Liang, Q.; Chiang, J.Y.L.; Han, S. Interactive Relationships between Intestinal Flora and Bile Acids. Int. J. Mol. Sci. 2022, 23, 8343. https://doi.org/10.3390/ijms23158343
Guo X, Okpara ES, Hu W, Yan C, Wang Y, Liang Q, Chiang JYL, Han S. Interactive Relationships between Intestinal Flora and Bile Acids. International Journal of Molecular Sciences. 2022; 23(15):8343. https://doi.org/10.3390/ijms23158343
Chicago/Turabian StyleGuo, Xiaohua, Edozie Samuel Okpara, Wanting Hu, Chuyun Yan, Yu Wang, Qionglin Liang, John Y. L. Chiang, and Shuxin Han. 2022. "Interactive Relationships between Intestinal Flora and Bile Acids" International Journal of Molecular Sciences 23, no. 15: 8343. https://doi.org/10.3390/ijms23158343