Identification and characterization of two bile acid coenzyme A transferases from Clostridium scindens, a bile acid 7α-dehydroxylating intestinal bacterium

Ridlon, Jason M.; Hylemon, Phillip B.

doi:10.1194/jlr.m020313

Cited by 115 publications

(122 citation statements)

References 27 publications

(26 reference statements)

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“…4). 63,72 The function of the baiJ gene is unknown, though it is predicted to encode a flavoprotein possibly involved in C-C double bond oxidation/reduction. However, it is doubtful it is involved in the "reductive" The genes encoding enzymes carrying out bile acid metabolism in gut bacteria capable of producing secondary bile acids.…”

Section: Bile Acid 7a/7b-dehydroxylation By Intestinal Bacteriamentioning

confidence: 99%

“…Rodent, 61 but not human bile acid 7a-dehydroxylating bacteria are capable of 7a-dehydroxylating muricholic acids (6a, 7b-hydroxy; 6b, 7b-hydroxy). 62 Characterization of the genetics and molecular biology of bile acid 7a/b-dehydroxylation has been performed mainly in strains of Clostridium scindens, 8,63 particularly C. scindens VPI 12708 (formerly Eubacterium sp. strain VPI 12708).…”

Section: Bile Acid 7a/7b-dehydroxylation By Intestinal Bacteriamentioning

confidence: 99%

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Consequences of bile salt biotransformations by intestinal bacteria

et al. 2016

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Section: Bile Acid 7a/7b-dehydroxylation By Intestinal Bacteriamentioning

confidence: 99%

Section: Bile Acid 7a/7b-dehydroxylation By Intestinal Bacteriamentioning

confidence: 99%

Consequences of bile salt biotransformations by intestinal bacteria

et al. 2016

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“…Interestingly, a phylogenetic analysis of the bacterial OTUs revealed that Clostridium cluster XI is composed of a single bacterial taxon (OUT-1105) close to the DCA-producing strain Clostridium sordellii (35). Thus, although other bacteria may also participate, the simplest explanation for our data is that OUT-1105 contributes to an increase in the DCA level, at least to some extent, in obese mice.…”

Section: An Obesity-induced Gut Microbial Metabolite Promotes Hepatocmentioning

confidence: 60%

Obesity and Cancer: A Gut Microbial Connection

2014

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Multiple epidemiological studies have revealed that excess bodyweight, such as in people who are overweight or obese (defined by a body mass index higher than 25 kg/m 2 ), is a major risk factor for not only diabetes and cardiovascular diseases but also cancer. Effective strategies for obesity prevention are therefore needed for cancer prevention. However, because the prevalence of excess bodyweight in most developed countries has been increasing markedly over the past several decades, with no signs of abating, alternative approaches are also required to conquer obesity-associated cancer. Therefore, we sought to understand the molecular mechanisms underlying obesity-associated cancer. Although several phenomena have been proposed to explain how obesity increases cancer risk, the exact molecular mechanisms that integrate these phenomena have remained largely obscure. Recently, we have traced the association between obesity and increased cancer risk to gut microbiota communities that produce a DNA-damaging bile acid. The analyses also revealed the role of cellular senescence in cancer, which we have been studying for the past few decades. In this review, we provide an overview of our work and discuss the next steps, focusing on the potential clinical implications of these findings. Cancer Res; 74(7);

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“…At the same time, microbial inhabitants of the ileum and colon initiate another molecular modification: 7-dehydroxylation. The removal of the C-7 hydroxyl group, a highly efficient process performed by resident genera, including Clostridium, converts cholate to deoxycholate, a secondary bile acid (24,25). These secondary bile acids are also recovered via enterohepatic circulation and returned to the gallbladder to be released in the duodenum upon gallbladder contraction.…”

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Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

et al. 2016

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bSalmonella spp. are carried by and can acutely infect agricultural animals and humans. After ingestion, salmonellae traverse the upper digestive tract and initiate tissue invasion of the distal ileum, a virulence process carried out by the type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). Salmonellae coordinate SPI-1 expression with anatomical location via environmental cues, one of which is bile, a complex digestive fluid that causes potent repression of SPI-1 genes. The individual components of bile responsible for SPI-1 repression have not been previously characterized, nor have the bacterial signaling processes that modulate their effects been determined. Here, we characterize the mechanism by which bile represses SPI-1 expression. Individual bile acids exhibit repressive activity on SPI-1-regulated genes that requires neither passive diffusion nor OmpF-mediated entry. By using genetic methods, the effects of bile and bile acids were shown to require the invasion gene transcriptional activator hilD and to function independently of known upstream signaling pathways. Protein analysis techniques showed that SPI-1 repression by bile acids is mediated by posttranslational destabilization of HilD. Finally, we found that bile acids function synergistically to achieve the overall repressive activity of bile. These studies demonstrate a common mechanism by which diverse environmental cues (e.g., certain short-chain fatty acids and bile acids) inhibit SPI-1 expression. These data provide information relevant to Salmonella pathogenesis during acute infection in the intestine and during chronic infection of the gallbladder and inform the basis for development of therapeutics to inhibit invasion as a means of repressing Salmonella pathogenicity.

show abstract

Identification and characterization of two bile acid coenzyme A transferases from Clostridium scindens, a bile acid 7α-dehydroxylating intestinal bacterium

Cited by 115 publications

References 27 publications

Consequences of bile salt biotransformations by intestinal bacteria

Consequences of bile salt biotransformations by intestinal bacteria

Obesity and Cancer: A Gut Microbial Connection

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

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