The ‘<i>in vivo</i> lifestyle’ of bile acid 7α-dehydroxylating bacteria: comparative genomics, metatranscriptomic, and bile acid metabolomics analysis of a defined microbial community in gnotobiotic mice

Ridlon, Jason M.; Devendran, Saravanan; Alves, João M. P.; Doden, Heidi L.; Wolf, Patricia G.; Pereira, Gabriel Vasconcelos; Ly, Lindsey K.; Volland, Alyssa; Takei, Hiroyuki; Nittono, Hiroshi; Murai, Tsuyoshi; Kurosawa, Takao; Chlipala, George E.; Green, Stefan J.; Hernandez, Alvaro G.; Fields, Christopher J.; Wright, Christy L.; Kakiyama, Genta; Cann, Isaac; Kashyap, Purna C.; McCracken, Vance J.; Gaskins, H. Rex

doi:10.1080/19490976.2019.1618173

Cited by 99 publications

(146 citation statements)

References 74 publications

(111 reference statements)

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“…Ninety‐five percent of them are transported back to the liver via a process known as enterohepatic circulation. The remaining 5% escape this process and are metabolized by gut bacteria (eg, Clostridium hylemonae and Clostridium hiranonis ), primarily in the colon, into secondary bile acids, including lithocholic acid and DCA . A number of animal studies in the past few decades have shown the carcinogenic effect of DCA in gastroenterological organs .…”

Section: Deoxyxcholic Acid Accelerates Colorectal Cancer Carcinogenesismentioning

confidence: 99%

“…Bacteria related to colitis-associated CRC Enterotoxigenic Bacteroides fragilis 8 Adherent-invasive Escherichia coli 9 Genotoxic compound producing bacteria Pks + Escherichia coli strains (colibactin) 13 Clostridium hylemonae (deoxycholic acid) 12 Clostridium hiranonis (deoxycholic acid) 12 Bacteria related to non-colitis-associated CRC Fusobacterium nucleatum 10,11,[14][15][16]19,20 Parvimonas micra 20,26 Peptostreptococcus stomatis 19,20 Peptostreptococcus anaerobius 20,25 Atopobium parvulum 28 Actinomyces odontolyticus 28,30 factors in carcinogenesis, or whether they are a result of microbial adaptation to the tumor environment. Nevertheless, CRC-associated microbiota are currently globally accepted as CRC screening biomarkers that can be used as an alternative for the fecal occult blood test.…”

Section: Ta B L E 1 Association Between Gut Bacteria and Colorectal Cmentioning

confidence: 99%

“…The remaining 5% escape this process and are metabolized by gut bacteria (eg, Clostridium hylemonae and Clostridium hiranonis), primarily in the colon, into secondary bile acids, including lithocholic acid and DCA. 12 A number of animal studies in the past few decades have shown the carcinogenic effect of DCA in gastroenterological organs. [37][38][39][40] Studies in mouse models and human cell lines have identified Wnt signaling pathway activation as the tumor-promoting mechanism.…”

Section: Deox Y Xcholi C Acid Acceler Ate S Colorec Tal C An Cer C mentioning

confidence: 99%

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Significance of the gut microbiome in multistep colorectal carcinogenesis

2020

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Colorectal cancer (CRC) is highly prevalent worldwide. In 2018, there were over 1.8 million new cases. Most sporadic CRC develop from polypoid adenomas and are preceded by intramucosal carcinoma (stage 0), which can progress into more malignant forms. This developmental process is known as the adenoma‐carcinoma sequence. Early detection and endoscopic removal are crucial for CRC management. Accumulating evidence suggests that the gut microbiota is associated with CRC development in humans. Comprehensive characterization of this microbiota is of great importance to assess its potential as a diagnostic marker in the very early stages of CRC. In this review, we summarized recent studies on CRC‐associated bacteria and their carcinogenic mechanisms in animal models, human cell lines and human cohorts. High‐throughput technologies have facilitated the identification of CRC‐associated bacteria in human samples. We have presented our metagenome and metabolome studies on fecal samples collected from a large Japanese cohort that revealed stage‐specific phenotypes of the microbiota in CRC. Furthermore, we have discussed the potential carcinogenic mechanisms of the gut microbiota, from which we can infer whether changes in the gut microbiota are a cause or effect in the multi‐step process of CRC carcinogenesis.

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Section: Deoxyxcholic Acid Accelerates Colorectal Cancer Carcinogenesismentioning

confidence: 99%

Section: Ta B L E 1 Association Between Gut Bacteria and Colorectal Cmentioning

confidence: 99%

Section: Deox Y Xcholi C Acid Acceler Ate S Colorec Tal C An Cer C mentioning

confidence: 99%

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Significance of the gut microbiome in multistep colorectal carcinogenesis

2020

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“…Several enzymes within the bai operon are capable of completing the steps in this transformation, including the bile acid transporter BaiG, the bile acid 7α-dehydratase BaiE, and the flavoprotein BaiN (13, 17–19). While regulation of the bai operon has yet to be completely elucidated, in vitro studies show that CA upregulates genes in the bai operon and DCA downregulates them in C. scindens ATCC 35704, C. hylemonae , and C. hiranonis (20, 21).…”

Section: Introductionmentioning

confidence: 99%

Strain-dependent inhibition ofClostridioides difficileby commensalClostridiaencoding the bile acid inducible(bai)operon

Reed

Nethery

Stewart

et al. 2020

Preprint

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Strain-dependent inhibition of Clostridioides difficile by commensal Clostridia encoding 1 the bile acid inducible (bai) operon 2 Abstract 24Clostridioides difficile is one of the leading causes of antibiotic-associated diarrhea. Gut 25 microbiota-derived secondary bile acids and commensal Clostridia that encode the bile 26 acid inducible (bai) operon are associated with protection from C. difficile infection 27 (CDI), although the mechanism is not known. In this study we hypothesized that 28 commensal Clostridia are important for providing colonization resistance against C. 29 difficile due to their ability to produce secondary bile acids, as well as potentially 30 competing against C. difficile for similar nutrients. To test this hypothesis, we examined 31 the ability of four commensal Clostridia encoding the bai operon (C. scindens VPI 32 12708, C. scindens ATCC 35704, C. hiranonis, and C. hylemonae) to convert CA to 33 DCA in vitro, and if the amount of DCA produced was sufficient to inhibit growth of a 34 clinically relevant C. difficile strain. We also investigated the competitive relationship 35 between these commensals and C. difficile using an in vitro co-culture system. We 36 found that inhibition of C. difficile growth by commensal Clostridia supplemented with 37 CA was strain-dependent, correlated with the production of ~2 mM DCA, and increased 38 expression of bai operon genes. We also found that C. difficile was able to outcompete 39 all four commensal Clostridia in an in vitro co-culture system. These studies are 40 instrumental in understanding the relationship between commensal Clostridia and C. 41 difficile in the gut, which is vital for designing targeted bacterial therapeutics. Future 42 studies dissecting the regulation of the bai operon in vitro and in vivo and how this 43 affects CDI will be important. 44Importance 45 3 Commensal Clostridia encoding the bai operon such as C. scindens have been 46 associated with protection against CDI, however the mechanism for this protection is 47 unknown. Herein, we show four commensal Clostridia that encode the bai operon effect 48 C. difficile growth in a strain-dependent manner, with and without the addition of 49 cholate. Inhibition of C. difficile by commensals correlated with the efficient conversion 50 of cholate to deoxycholate, a secondary bile acid that inhibits C. difficile germination, 51 growth, and toxin production. Competition studies also revealed that C. difficile was able 52 to outcompete the commensals in an in vitro co-culture system. These studies are 53 instrumental in understanding the relationship between commensal Clostridia and C. 54 difficile in the gut, which is vital for designing targeted bacterial therapeutics. 55 Introduction 56Clostridioides difficile is an anaerobic, spore forming, toxigenic bacterial pathogen (1). 57 C. difficile infection (CDI) is a major cause of antibiotic associated diarrhea and a 58 significant health issue, causing 453,000 infections and is associated with 29,000 59 deaths and 4.8 billion dollars ...

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“…Because bile [8] contains a large amount of water as well as bile pigments, bile salts, cholesterol, lecithin, fatty acids, inorganic salts, and other ingredients, our research team designed a superhydrophobic, oleophobic coating, which is intended to be used on the inner and outer walls of a bile duct stent. It was assumed that since the coating has a bile-repellent effect on polar groups (e.g., water, ions, and polar amino acids) and non-polar groups (e.g., lipids and non-polar amino acids), it would repel bile.…”

Section: Introductionmentioning

confidence: 99%

Investigation of a New Superhydrophobic, Oleophobic-Coated Biliary Duct Stent and its Preventive Effect on Biliary Mud in Vitro

Zhang

Qian

et al. 2019

Preprint

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Background and AimA new type of superhydrophobic, oleophobic-coated biliary stent was created, and its characteristics and preventive effect on biliary mud deposition in vitro are studied herein. MethodsThe observational experiment included a bare stent group and coated stent group, with 10 stents per group. The groups were used in a model of the extracorporeal biliary perfusion system with bacterial infection, and the experiment was terminated when the stent was completely blocked. Changes of bile characteristics before and after the experiment, patency time, and amount of bile sludge deposition were compared between the groups. The t-test and analysis of variance were used to analyze the data. ResultsIn the bare stent group, contact angles of bile were about 80.4 degrees and 79.8 degrees before and after the experiment, respectively. There was no change in the effect of bile aversion after the experiment between the groups (P < 0.05). In the coated stent group, contact angles of bile changed from 143.3 degrees before the experiment to 135.7 degrees after the experiment; the effect of the coating decreased significantly after the experiment (P > 0.05). The patency times were 8 weeks and 23 weeks in the bare and coated stent groups, respectively (P > 0.05). Depositions of biliary mud were 47 mg and 13 mg in the bare and coated stent groups, respectively (P > 0.05). ConclusionThe superhydrophobic, oleophobic-coated biliary stent can repel bile better and play a role in preventing bile sludge deposition in the extracorporeal biliary perfusion system.

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The ‘in vivo lifestyle’ of bile acid 7α-dehydroxylating bacteria: comparative genomics, metatranscriptomic, and bile acid metabolomics analysis of a defined microbial community in gnotobiotic mice

Abstract: Gaskins (2020) The 'invivo lifestyle' of bile acid 7αdehydroxylating bacteria: comparative genomics, metatranscriptomic, and bile acid metabolomics analysis of a defined microbial community in gnotobiotic mice,

Cited by 99 publications

References 74 publications

Significance of the gut microbiome in multistep colorectal carcinogenesis

Significance of the gut microbiome in multistep colorectal carcinogenesis

Strain-dependent inhibition ofClostridioides difficileby commensalClostridiaencoding the bile acid inducible(bai)operon

Investigation of a New Superhydrophobic, Oleophobic-Coated Biliary Duct Stent and its Preventive Effect on Biliary Mud in Vitro

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