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Impact of Primary and Secondary Bile Acids on Clostridioides difficile Infection

Agata Łukawska

Agata Łukawska

Department of Gastroenterology and Hepatology, Wroclaw Medical UniversityWroclaw, Poland
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Łukawska, Agata
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Agata Mulak

Agata Mulak

Department of Gastroenterology and Hepatology, Wroclaw Medical UniversityWroclaw, Poland
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14 mars 2022
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Catégorie d'article: Minireview
Publié en ligne: 14 mars 2022
Pages: 11 - 18
Reçu: 10 nov. 2021
Accepté: 31 janv. 2022
DOI: https://doi.org/10.33073/pjm-2022-007
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© 2022 Agata Łukawska et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Fig. 1

Main functions of bile acids. Bile acids (BAs), as the main bile component, are responsible for lipid emulsification, micelle formation, and participation in the absorption of lipids and liposoluble vitamins. BAs also have an important impact on gut microbiota composition. BAs are farnesoid X receptor (FXR) ligands leading to fibroblast growth factor 19 (FGF19) synthesis. Moreover, FXR stimulation influences gut microbiota composition and intestinal innate immune response. BAs also activate Takeda G-protein receptor 5 (TGR5), stimulating intestinal motility, inducing gallbladder relaxation, reducing intrahepatic biliary pressure, modulating the composition of the BA pool, and affecting glucose metabolism. Additionally, the TGR5 activation regulates inflammatory processes and energy expenditure. Based on Dawson and Karpen (2015).
Main functions of bile acids. Bile acids (BAs), as the main bile component, are responsible for lipid emulsification, micelle formation, and participation in the absorption of lipids and liposoluble vitamins. BAs also have an important impact on gut microbiota composition. BAs are farnesoid X receptor (FXR) ligands leading to fibroblast growth factor 19 (FGF19) synthesis. Moreover, FXR stimulation influences gut microbiota composition and intestinal innate immune response. BAs also activate Takeda G-protein receptor 5 (TGR5), stimulating intestinal motility, inducing gallbladder relaxation, reducing intrahepatic biliary pressure, modulating the composition of the BA pool, and affecting glucose metabolism. Additionally, the TGR5 activation regulates inflammatory processes and energy expenditure. Based on Dawson and Karpen (2015).

Fig. 2

Enterohepatic circulation and bile acid biotransformation. Primary bile acids (BAs) are produced in the liver and after conjugation with taurine or glycine are secreted into bile ducts. As a component of bile, they are accumulated in the gallbladder. After every meal, they are secreted into the intestinal lumen. In the small intestine, microbiota biotransformation starts. The deconjugation is performed by bile salt hydrolases (BSH), which constitute the key reaction enabling further transformations. Most BAs are absorbed in the distal ileum by the apical sodium-dependent bile acid transporter (ASBAT) to the portal vein from where they reach the liver and return into bile. The unabsorbed BAs pass to the large intestine, undergoing further microbial transformation. 7α-dehydroxylation is the crucial reaction in secondary BA origination. Some BAs are passively absorbed in the colon, and some are also eliminated in the feces. CA – cholic acid, CDCA – chenodeoxycholic acid, TCA – taurocholic acid, GCA – glycocholic acid, TCDCA – taurochenodeoxycholic acid, GCDCA – glycochenodeoxycholic acid, UDCA – ursodeoxycholic acid. Based on Fiorucci and Distrutti (2019).
Enterohepatic circulation and bile acid biotransformation. Primary bile acids (BAs) are produced in the liver and after conjugation with taurine or glycine are secreted into bile ducts. As a component of bile, they are accumulated in the gallbladder. After every meal, they are secreted into the intestinal lumen. In the small intestine, microbiota biotransformation starts. The deconjugation is performed by bile salt hydrolases (BSH), which constitute the key reaction enabling further transformations. Most BAs are absorbed in the distal ileum by the apical sodium-dependent bile acid transporter (ASBAT) to the portal vein from where they reach the liver and return into bile. The unabsorbed BAs pass to the large intestine, undergoing further microbial transformation. 7α-dehydroxylation is the crucial reaction in secondary BA origination. Some BAs are passively absorbed in the colon, and some are also eliminated in the feces. CA – cholic acid, CDCA – chenodeoxycholic acid, TCA – taurocholic acid, GCA – glycocholic acid, TCDCA – taurochenodeoxycholic acid, GCDCA – glycochenodeoxycholic acid, UDCA – ursodeoxycholic acid. Based on Fiorucci and Distrutti (2019).

Fig. 3

Impact of bile acids on the life cycle of Clostridioides difficile. C. difficile is a Gram-positive bacillus, with an ability to produce endospores. Spores may germinate and outgrow in the gastrointestinal tract to produce pathogenic vegetative forms secreting toxins. Primary BAs such as cholic acid (CA) and taurocholic acid (TCA) are endogenous triggers to C. difficile spore germination. However, other primary BAs, including chenodeoxycholic acid (CDCA), α and β stereoisomers of muricholic acid (MCA), arrest C. difficile spore germination. Secondary BAs such as DCA, LCA, ursodeoxycholic acid (UDCA), hyodeoxycholic acid (HDCA), and ω-MCA inhibit C. difficile spore germination and the growth of C. difficile vegetative forms. Based on Studer et al. (2016).
Impact of bile acids on the life cycle of Clostridioides difficile. C. difficile is a Gram-positive bacillus, with an ability to produce endospores. Spores may germinate and outgrow in the gastrointestinal tract to produce pathogenic vegetative forms secreting toxins. Primary BAs such as cholic acid (CA) and taurocholic acid (TCA) are endogenous triggers to C. difficile spore germination. However, other primary BAs, including chenodeoxycholic acid (CDCA), α and β stereoisomers of muricholic acid (MCA), arrest C. difficile spore germination. Secondary BAs such as DCA, LCA, ursodeoxycholic acid (UDCA), hyodeoxycholic acid (HDCA), and ω-MCA inhibit C. difficile spore germination and the growth of C. difficile vegetative forms. Based on Studer et al. (2016).
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Sujets de la revue:
Sciences de la vie, Microbiologie et virologie
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