Activity on bile acids of a <i>Clostridium bifermentans</i> cell‐free extract

Ferrari, Annamaria; Beretta, L.

doi:10.1016/0014-5793(77)80076-8

Cited by 28 publications

(13 citation statements)

References 10 publications

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“…In spite of the prevalence of this reaction in vivo, the demonstration of this enzyme activity in pure bacterial cultures has been successful only on rare occasions. A few strains of anaerobes comprising four strains of Clostrium (5,9,24,25), three of Bacteroides (1, 4) and several strains of anaerobic Lactobacillus (7,16,18) have so far been reported to be capable of performing this reaction. The present isolate, a gram-positive nonsporeforming anaerobic bacterium, has no counterpart among these published organisms.…”

Section: Discussionmentioning

confidence: 99%

Transformation of Bile Acids by Mixed Microbial Cultures from Human Feces and Bile Acid Transforming Activities of Isolated Bacterial Strains

Hirano

Masuda

Oda

et al. 1981

Microbiology and Immunology

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Microbial transformation of cholic acid and chenodeoxycholic acid by anaerobic mixed cultures of human fecal microorganisms was investigated, and the results were examined in relation to the bile acid transforming activities of 75 bacterial strains isolated from the same fecal cultures. The reactions involved in the mixed cultures were dehydrogenation and dehydroxylation of the 7a-hydroxy group in both primary bile acids and epimerization of the 3a-hydroxy group in all metabolic bile acids. Extensive epimerization of the 7a-hydroxy group of chenodeoxycholic acid yielding ursodeoxycholic acid was also demonstrated by certain fecal samples. 7a-Dehydrogenase activity was widespread among the fecal isolates (88% of 16 facultative anaerobes and 51% of 59 obligate anaerobes), and 7a-dehydroxylase activity was revealed in one of the isolates, an unidentified gram-positive nonsporeforming anaerobic bacterium. 3a-Epimerization was effected by seven strains assigned to Eubacterium lentum, which were also active for 3a-and 7a-dehydrogenations. No microorganism accounting for 7a-epimerization was recovered among the isolates. Splitting of conjugated bile acid was demonstrated by the majority of obligate anaerobes but the activity was rare among facultative anaerobes.Most of the microbial transformations of bile acids in the intestinal tract are reproducible in in vitro cultures offecal microorganisms. The major reactions involved are splitting of conjugated bile acids (deconjugation), removal of the hydroxy group, mainly at C-7 (7a-dehydroxylation), oxidation of hydroxy groups at C-7, C-3, and C-12 (the respective dehydrogenations) and conversion of the hydroxy group at C-3 from a-to ,B-configuration (3a-epimerization) (19,20). With regard to the kinds of microorganisms responsible for the respective reactions, however, only a few systematic studies have been attempted. Midtvedt and Norman (17) investigated the bile acid transforming capacities of 61 laboratory strains of intestinal origin, and Dickinson et al (3) evaluated the activities of 112 isolates from the digestive tract of the rat. They found the deconjugating and dehydrogenating 271

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Section: Discussionmentioning

confidence: 99%

Transformation of Bile Acids by Mixed Microbial Cultures from Human Feces and Bile Acid Transforming Activities of Isolated Bacterial Strains

Hirano

Masuda

Oda

et al. 1981

Microbiology and Immunology

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“…Therefore, 7a-dehydroxylation is the most quantitatively important bacterial bile salt biotransformation in the human colon. The rapid rate of conversion of primary to secondary bile acids is surprising given current estimates that this metabolic pathway is found in z0.0001% of total colonic flora (102)(103)(104). Human intestinal bacteria capable of bile acid 7a-dehydroxylation have been isolated (104,105), and 16S rDNA phylogenetic analysis has led to their classification to the genus Clostridium (106)(107)(108).…”

Section: Introductionmentioning

confidence: 99%

Bile salt biotransformations by human intestinal bacteria

Ridlon

Kang

Hylemon

2006

Journal of Lipid Research

2,329

2,417

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Secondary bile acids, produced solely by intestinal bacteria, can accumulate to high levels in the enterohepatic circulation of some individuals and may contribute to the pathogenesis of colon cancer, gallstones, and other gastrointestinal (GI) diseases. Bile salt hydrolysis and hydroxy group dehydrogenation reactions are carried out by a broad spectrum of intestinal anaerobic bacteria, whereas bile acid 7-dehydroxylation appears restricted to a limited number of intestinal anaerobes representing a small fraction of the total colonic flora. Microbial enzymes modifying bile salts differ between species with respect to pH optima, enzyme kinetics, substrate specificity, cellular location, and possibly physiological function. Crystallization, site-directed mutagenesis, and comparisons of protein secondary structure have provided insight into the mechanisms of several bile acid-biotransforming enzymatic reactions. Molecular cloning of genes encoding bile salt-modifying enzymes has facilitated the understanding of the genetic organization of these pathways and is a means of developing probes for the detection of bile salt-modifying bacteria. The potential exists for altering the bile acid pool by targeting key enzymes in the 7a/b-dehydroxylation pathway through the development of pharmaceuticals or sequestering bile acids biologically in probiotic bacteria, which may result in their effective removal from the host after excretion.-Ridlon, J. M., D-J. Kang, and P. B. Hylemon. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res. 2006. 47: 241-259.

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“…By contrast, other groups showed the negative results for the activity in Bifidobacterium strains (17,18), Bacteroides strains (19,20), or Lactobacillus strains (18,21). Only certain strains belonging to Eubacterium and Clostridium have been examined specifically for their 7α-dehydroxylating activity (22)(23)(24)(25)(26). It is considered that the difficulty in isolating 7α-dehydroxylating bacteria from the intestine arises from the small populations of these bacteria in the intestine (27,28), although most of the primary bile acids in the intestine are deconjugated and further transformed into secondary bile acids.…”

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confidence: 93%

Deoxycholic acid formation in gnotobiotic mice associated with human intestinal bacteria

Narushima

Itoh

Miyamoto

et al. 2006

Lipids

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In humans and animals, intestinal flora is indispensable for bile acid transformation. The goal of our study was to establish gnotobiotic mice with intestinal bacteria of human origin in order to examine the role of intestinal bacteria in the transformation of bile acids in vivo using the technique of gnotobiology. Eight strains of bile acid-deconjugating bacteria were isolated from ex-germ-free mice inoculated with a human fecal dilution of 10(-6), and five strains of 7alpha-dehydroxylating bacteria were isolated from the intestine of limited human flora mice inoculated only with clostridia. The results of biochemical tests and 16S rDNA sequence analysis showed that seven out of eight bile acid-deconjugating strains belong to a bacteroides cluster (Bacteroides vulgatus, B. distasonis, and B. uniformis), and one strain had high similarity with Bilophila wadsworthia. All five strains that converted cholic acid to deoxycholic acid had greatest similarity with Clostridium hylemonae. A combination of 10 isolated strains converted taurocholic acid into deoxycholic acid both in vitro and in the mouse intestine. These results indicate that the predominant bacteria, mainly Bacteroides, in human feces comprise one of the main bacterial groups for the deconjugation of bile acids, and clostridia may play an important role in 7aplha-dehydroxylation of free-form primary bile acids in the intestine although these strains are not predominant. The gnotobiotic mouse with bacteria of human origin could be a useful model in studies of bile acid metabolism by human intestinal bacteria in vivo.

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Activity on bile acids of a Clostridium bifermentans cell‐free extract

Cited by 28 publications

References 10 publications

Transformation of Bile Acids by Mixed Microbial Cultures from Human Feces and Bile Acid Transforming Activities of Isolated Bacterial Strains

Transformation of Bile Acids by Mixed Microbial Cultures from Human Feces and Bile Acid Transforming Activities of Isolated Bacterial Strains

Bile salt biotransformations by human intestinal bacteria

Deoxycholic acid formation in gnotobiotic mice associated with human intestinal bacteria

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