scholarly journals Fenofibrate Improves Liver Function and Reduces the Toxicity of the Bile Acid Pool in Patients With Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Who Are Partial Responders to Ursodiol

2020 ◽  
Vol 108 (6) ◽  
pp. 1213-1223
Author(s):  
Nisanne S. Ghonem ◽  
Adam M. Auclair ◽  
Christopher L. Hemme ◽  
Gina M. Gallucci ◽  
Randolph Rosa Rodriguez ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Function ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Primary Biliary Cholangitis ◽  
Bile Acid Pool ◽  
Acid Pool

scholarly journals A metabolic pathway for bile acid dehydroxylation by the gut microbiome

2019 ◽  
Author(s):  
Masanori Funabashi ◽  
Tyler L. Grove ◽  
Victoria Pascal ◽  
Yug Varma ◽  
Molly E. McFadden ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Lithocholic Acid ◽  
Primary Biliary Cholangitis ◽  
Bile Acid Pool ◽  
Secondary Bile Acid ◽  
Acid Pool ◽  
Road Map ◽  
Host Physiology

ABSTRACTThe gut microbiota synthesize hundreds of molecules, many of which are known to impact host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at ~500 μM and are known to block C. difficile growth1, promote hepatocellular carcinoma2, and modulate host metabolism via the GPCR TGR53. More broadly, DCA, LCA and their derivatives are a major component of the recirculating bile acid pool4; the size and composition of this pool are a target of therapies for primary biliary cholangitis and nonalcoholic steatohepatitis. Despite the clear impact of DCA and LCA on host physiology, incomplete knowledge of their biosynthetic genes and a lack of genetic tools in their native producer limit our ability to modulate secondary bile acid levels in the host. Here, we complete the pathway to DCA/LCA by assigning and characterizing enzymes for each of the steps in its reductive arm, revealing a strategy in which the A-B rings of the steroid core are transiently converted into an electron acceptor for two reductive steps carried out by Fe-S flavoenzymes. Using anaerobic in vitro reconstitution, we establish that a set of six enzymes is necessary and sufficient for the 8-step conversion of cholic acid to DCA. We then engineer the pathway into Clostridium sporogenes, conferring production of DCA and LCA on a non-producing commensal and demonstrating that a microbiome-derived pathway can be expressed and controlled heterologously. These data establish a complete pathway to two central components of the bile acid pool, and provide a road map for deorphaning and engineering pathways from the microbiome as a critical step toward controlling the metabolic output of the gut microbiota.

scholarly journals The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease

2017 ◽  
Vol 6 (1) ◽  
pp. 112-122 ◽  
Author(s):  
J Torres ◽  
C Palmela ◽  
H Brito ◽  
X Bao ◽  
H Ruiqi ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Primary Sclerosing Cholangitis ◽  
Bowel Disease ◽  
Sclerosing Cholangitis ◽  
Colorectal Neoplasia ◽  
Bile Acid Pool ◽  
Inflammatory Bowel

Background Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. Aim The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. Methods Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. Results The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. Conclusions Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.

Altered microbiota and bile acid composition in patients with primary sclerosing cholangitis

2019 ◽  
Author(s):  
T Liwinski ◽  
R Zenouzi ◽  
C John ◽  
H Ehlken ◽  
MC Rühlemann ◽  
...  
Keyword(s):  
Bile Acid ◽  
Primary Sclerosing Cholangitis ◽  
Acid Composition ◽  
Sclerosing Cholangitis

Overexpression of sterol 12α-hydroxylase (CYP8b1): Effect on rates of cholic acid (CA) synthesis and alteration in bile acid pool composition

2001 ◽  
Vol 120 (5) ◽  
pp. A1
Author(s):  
William M. Pandak ◽  
Phillip B. Hylemon ◽  
Patricia Bohdan ◽  
Ingemar Bjorkhem ◽  
Gosta Eggertsen ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Bile Acid Pool ◽  
Acid Pool

Bile Acid Pool in the Rat: Bile Acids and Steroids. 78.

1960 ◽  
Vol 48 (3-4) ◽  
pp. 439-442 ◽  
Author(s):  
Sten Eriksson
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Rat Bile

Effect of Zanchol and Chenic Acid on Bile Acid Pool Size and Gallstones in Hamsters

1982 ◽  
Vol 283 (1) ◽  
pp. 23-31 ◽  
Author(s):  
H. Cohen ◽  
G.G. Bonorris ◽  
J.W. Marks ◽  
L.J. Schoenfield
Keyword(s):  
Bile Acid ◽  
Pool Size ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Bile Acid Pool Size

Cholestatic Liver Injury: Care of Patients With Primary Biliary Cholangitis or Primary Sclerosing Cholangitis

2016 ◽  
Vol 27 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Laurie Larson ◽  
Michelle James ◽  
Andrea Gossard
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Disease Recurrence ◽  
Outpatient Setting ◽  
Primary Biliary Cholangitis ◽  
Malignant Neoplasms ◽  
Cholestatic Liver Disease ◽  
Gallbladder Polyps ◽  
Increased Risk ◽  
Common Causes

The most common causes of chronic cholestatic liver disease are primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Both disease processes are characterized by a destruction of intrahepatic and/or extrahepatic biliary ducts. The etiology is not entirely clear; however, there is an underlying autoimmune component contributing to both disease processes. Although PBC and PSC are often diagnosed and managed in the outpatient setting, in some instances, a patient may have jaundice, fatigue, and pruritus requiring evaluation and determination of the cholestatic cause. Patients with PSC should be monitored for evidence of cholangiocarcinoma, colon cancer, and gallbladder polyps as they are at an increased risk of malignant neoplasms. Liver transplant has the potential for improving quality of life, although disease recurrence is a risk.

scholarly journals The control of bile acid pool size: Effect of jejunal resection and phenobarbitone on bile acid metabolism in the rat

Gut ◽  
1974 ◽  
Vol 15 (4) ◽  
pp. 247-253 ◽  
Author(s):  
H. Y. I. Mok ◽  
P. M. Perry ◽  
R. H. Dowling
Keyword(s):  
Bile Acid ◽  
Size Effect ◽  
Acid Metabolism ◽  
Pool Size ◽  
Bile Acid Metabolism ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Bile Acid Pool Size
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