7 alpha-dehydroxylating bacteria enhance deoxycholic acid input and cholesterol saturation of bile in patients with gallstones

Berr, Frieder; Kullak-Ublick, G.A.; Paumgartner, Gustav; Münzing, Wolfgang; Hylemon, Philip B.

doi:10.1016/s0016-5085(96)70024-0

Cited by 139 publications

(101 citation statements)

References 6 publications

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“…In contrast, modified BAs have been implicated as carcinogens and cocarcinogens and considerable evidence exists for a role of modified BA in colorectal cancer (CRC) (19,20). However, because CRC is predominantly diagnosed in individuals Ͼ50 years of age (31), the effect of CRC on reproductive fitness in the ancestors of modern humans would have been negligible, and as such would not pose a significant counter selection to the shorter-term beneficial effects of BSH activity and subsequent BA modification (18).…”

Section: Discussionmentioning

confidence: 99%

“…Free primary BAs are subsequently open to a wider pathway of BA modification encoded by the gut microbiota, which generates secondary and tertiary forms through dehydroxylation, dehydrogenation, and sulfation (9,10,16,17). Deconjugated and modified BAs have been associated with acquisition of gallstones and colorectal cancer (18)(19)(20), and recent studies indicate that the mammalian gut microbiota can modulate host bile acid synthesis and metabolism, which may influence host lipid metabolism (21). BSH activity and subsequent BA modification in this community could significantly impact host physiology through perturbations of BA-controlled endocrine functions and influence risk of metabolic diseases such as obesity, diabetes, and atherosclerosis (11,12,21).…”

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confidence: 99%

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Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome

Jones¹,

Begley

Hill³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

857

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Bile salt hydrolases (BSHs) catalyze the ''gateway'' reaction in a wider pathway of bile acid modification by the gut microbiota. Because bile acids function as signaling molecules regulating their own biosynthesis, lipid absorption, cholesterol homeostasis, and local mucosal defenses in the intestine, microbial BSH activity has the potential to greatly influence host physiology. However, the function, distribution, and abundance of BSH enzymes in the gut community are unknown. Here, we show that BSH activity is a conserved microbial adaptation to the human gut environment with a high level of redundancy in this ecosystem. Through metagenomic analyses we identified functional BSH in all major bacterial divisions and archaeal species in the gut and demonstrate that BSH is enriched in the human gut microbiome. Phylogenetic analysis illustrates that selective pressure in the form of conjugated bile acid has driven the evolution of members of the NtnCGH-like family of proteins toward BSH activity in gut-associated species. Furthermore, we demonstrate that BSH mediates bile tolerance in vitro and enhances survival in the murine gut in vivo. Overall, we demonstrate the use of function-driven metagenomics to identify functional anchors in complex microbial communities, and dissect the gut microbiome according to activities relevant to survival in the mammalian gastrointestinal tract.bile modification ͉ microbiota ͉ functional anchor ͉ GI survival

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome

Jones¹,

Begley

Hill³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

857

728

View full text Add to dashboard Cite

show abstract

“…In support of these results, gallstone patients with gallbladders in situ compared to healthy controls have also been found to have elevated amounts of fecal secondary bile acids and an elevated amount and activity of the colonic bacteria producing them. 48,[55][56][57] The stronger association for right-side colon cancer and gallstone disease identified in this study calls for more research on the mechanisms involved. Because colon cancer and the formation of gallstones have both been associated with fecal secondary bile acids, the mechanisms involved may include the microbiota of the colon.…”

Section: Discussionmentioning

confidence: 99%

Association Between Screen-Detected Gallstone Disease and Cancer in a Cohort Study

2017

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“…[1][2][3] The antibacterial drug treatment elevates the total bile acid pool size and bile acid synthesis rate compared with that before treatment in the patients with gallstones. 4,5) Ampicillin (ABPC) treatment increases the bile acid pool size and hepatic bile acid concentration in experimental animals. 6) This disruption of bile acid homeostasis is in part due to the elevation of bile acid synthesis.…”

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confidence: 99%

Antibacterial Drug Treatment Increases Intestinal Bile Acid Absorption <i>via</i> Elevated Levels of Ileal Apical Sodium-Dependent Bile Acid Transporter but Not Organic Solute Transporter α Protein

Miyata

Hayashi

Yamakawa

et al. 2015

Biological & Pharmaceutical Bulletin

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Antibacterial drug treatment increases the bile acid pool size and hepatic bile acid concentration through the elevation of hepatic bile acid synthesis. However, the involvement of intestinal bile acid absorption in the increased bile acid pool size remains unclear. To determine whether intestinal bile acid absorption contributes to the increased bile acid pool in mice treated with antibacterial drugs, we evaluated the levels of bile acid transporter proteins and the capacity of intestinal bile acid absorption. Ileal apical sodiumdependent bile acid transporter (ASBT) mRNA and protein levels were significantly increased in ampicillin (ABPC)-treated mice, whereas organic solute transporter α (OSTα) mRNA levels, but not protein levels, significantly decreased in mice. Similar alterations in the expression levels of bile acid transporters were observed in mice treated with bacitracin/neomycin/streptomycin. The capacity for intestinal bile acid absorption was evaluated by an in situ loop method. Increased ileal absorption of taurochenodeoxycholic acid was observed in mice treated with ABPC. These results suggest that intestinal bile acid absorption is elevated in an ASBT-dependent manner in mice treated with antibacterial drugs.

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7 alpha-dehydroxylating bacteria enhance deoxycholic acid input and cholesterol saturation of bile in patients with gallstones

Cited by 139 publications

References 6 publications

Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome

Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome

Association Between Screen-Detected Gallstone Disease and Cancer in a Cohort Study

Antibacterial Drug Treatment Increases Intestinal Bile Acid Absorption <i>via</i> Elevated Levels of Ileal Apical Sodium-Dependent Bile Acid Transporter but Not Organic Solute Transporter α Protein

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