Sydor, Svenja, Best, Jan ORCID: 0000-0003-2074-0930, Messerschmidt, Insa, Manka, Paul, Vilchez-Vargas, Ramiro, Brodesser, Susanne, Lucas, Christina, Wegehaupt, Annemarie, Wenning, Chiara, Assmuth, Sophia, Hohenester, Simon, Link, Alexander, Faber, Klaas Nico, Moshage, Han ORCID: 0000-0002-4764-0246, Javier Cubero, Francisco, Friedman, Scott L., Gerken, Guido, Trauner, Michael ORCID: 0000-0002-1275-6425, Canbay, Ali and Bechmann, Lars P. (2020). Altered Microbiota Diversity and Bile Acid Signaling in Cirrhotic and Noncirrhotic NASH-HCC. Clin. Transl. Gastroenterol., 11. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 2155-384X

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Abstract

OBJECTIVES: The precipitous increase in nonalcoholic steatohepatitis (NASH) is accompanied by a dramatic increase in the incidence of NASH-related hepatocellular carcinoma (HCC). HCC in NASH has a higher propensity to arise without pre-existing cirrhosis compared with other chronic liver diseases. METHODS: To identify the potential links between liver and gut in NASH-related hepatocarcinogenesis, we compared the gut microbiota and mediators of bile acid (BA) signaling in the absence or presence of cirrhosis through the analysis of stool and serum samples from patients with NASH non-HCC and NASH-HCC and healthy volunteers. RESULTS: Serum levels of total and individual BA were higher in NASH compared with healthy controls. Furthermore, serum levels of the primary conjugated BAs glycine-conjugated cholic acid, taurine-conjugated cholic acid, glycine-conjugated chenodeoxycholic acid, and taurine-conjugated chenodeoxycholic acid were significantly increased in cirrhotic vs noncirrhotic patients, independent of the occurrence of HCC. By contrast, serum FGF19 levels were higher in patients with NASH-HCC and associated with tumor markers as well as an attenuation of BA synthesis. Specific alterations in the gut microbiome were found for several bacteria involved in the BA metabolism including Bacteroides and Lactobacilli. Specifically, the abundance of Lactobacilli was associated with progressive disease, serum BA levels, and liver injury in NASH and NASH-HCC. DISCUSSION: Here, we demonstrate a clear association of the altered gut microbiota and primary conjugated BA composition in cirrhotic and noncirrhotic patients with NASH-HCC. Microbiota-associated alterations in BA homeostasis and farnesoid X receptor signaling, via FGF19, might thus contribute to fibrogenesis, liver injury, and tumorigenesis in NASH-HCC.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Sydor, SvenjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Best, JanUNSPECIFIEDorcid.org/0000-0003-2074-0930UNSPECIFIED
Messerschmidt, InsaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manka, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vilchez-Vargas, RamiroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brodesser, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lucas, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wegehaupt, AnnemarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wenning, ChiaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assmuth, SophiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hohenester, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Link, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Faber, Klaas NicoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moshage, HanUNSPECIFIEDorcid.org/0000-0002-4764-0246UNSPECIFIED
Javier Cubero, FranciscoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedman, Scott L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerken, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trauner, MichaelUNSPECIFIEDorcid.org/0000-0002-1275-6425UNSPECIFIED
Canbay, AliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bechmann, Lars P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-341888
DOI: 10.14309/ctg.0000000000000131
Journal or Publication Title: Clin. Transl. Gastroenterol.
Volume: 11
Date: 2020
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Place of Publication: PHILADELPHIA
ISSN: 2155-384X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FATTY LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; METABOLISM; ACTIVATION; SEVERITY; CANCER; INJURY; AXISMultiple languages
Gastroenterology & HepatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/34188

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