Gut Microbial Signature of Hepatocellular Cancer in Men With Cirrhosis.


Journal

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
ISSN: 1527-6473
Titre abrégé: Liver Transpl
Pays: United States
ID NLM: 100909185

Informations de publication

Date de publication:
05 2021
Historique:
revised: 12 12 2020
received: 27 10 2020
accepted: 14 01 2021
pubmed: 26 1 2021
medline: 20 5 2021
entrez: 25 1 2021
Statut: ppublish

Résumé

The gut microbiome is altered in cirrhosis. Recent evidence has suggested a key role for the gut microbiota in the progression of cirrhosis and the development of hepatocellular carcinoma (HCC). We studied the differences in the microbial composition in patients with cirrhosis with prior and future HCC in the context of other complications (eg, infections, hepatic encephalopathy). The following 2 cohorts were recruited prospectively: the prior HCC cohort, in which outpatients with HCC within 2 years were age-matched, sex-matched, and Model for End-Stage Liver Disease (MELD) score-matched with those without HCC; and the future HCC cohort, in which patients were followed for 2 years and divided into future HCC versus no HCC after age, sex, and MELD-score matching and other complications were also recorded. Microbiota composition and predicted function were analyzed with ribosomal RNA sequencing and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PiCRUST)and compared between (1) prior HCC versus none and (2) future HCC versus none, and in the future cohort, comparisons were also made between those patients who developed (1) HCC only versus without complications, (2) HCC only versus non-HCC complications only, and (3) HCC + other complications versus non-HCC complications only. A total of 142 men (76 total in the prior cohort [38 with/38 without HCC] and 66 total in the future cohort [33 with/33 without future HCC]) were included. The groups had similar etiology, lactulose/rifaximin/proton pump inhibitor use, diabetes mellitus, and non-HCC complications. Microbial diversity was similar between prior HCC/not or future HCC/not. On DESeq2 higher Clostridium sensu stricto and Anaerotruncus were significantly associated with protection from HCC, whereas the reverse was seen with Raoultella and Haemophilus regardless of prior/future HCC comparisons. Functions focused on urea cycle, bioenergetics, tryptophan, and toluene metabolism were different between the groups. Rothia was specific for other complications. Despite age, sex, and MELD-score matching and accounting for other complications, gut microbiota composition and the predicted function are different in men with cirrhosis with and without prior HCC and can be extended toward future HCC development.

Identifiants

pubmed: 33492761
doi: 10.1002/lt.25994
pii: 01445473-202105000-00008
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

629-640

Subventions

Organisme : NCATS NIH HHS
ID : R21 TR002024
Pays : United States
Organisme : NCATS NIH HHS
ID : R21 TR003095
Pays : United States

Informations de copyright

Copyright Copyright © 2021 American Association for the Study of Liver Diseases.

Références

Schwabe RF, Greten TF. Gut microbiome in HCC—mechanisms, diagnosis and therapy. J Hepatol 2020;72:230–238.
Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 2019;16:589–604.
Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 2018;68:723–750.
Bajaj JS, Heuman DM, Hylemon PB, Sanyal AJ, White MB, Monteith P, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol 2014;60:940–947.
Ponziani FR, Bhoori S, Castelli C, Putignani L, Rivoltini L, Del Chierico F, et al. Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease. Hepatology 2019;69:107–120.
Ren Z, Li A, Jiang J, Zhou L, Yu Z, Lu H, et al. Gut microbiome analysis as a tool towards targeted non‐invasive biomarkers for early hepatocellular carcinoma. Gut 2019;68:1014–1023.
Lapidot Y, Amir A, Nosenko R, Uzan‐Yulzari A, Veitsman E, Cohen‐Ezra O, et al. Alterations in the gut microbiome in the progression of cirrhosis to hepatocellular carcinoma. mSystems 2020;5:e00153‐20. doi: 10.1128/mSystems.00153‐20.
Sydor S, Best J, Messerschmidt I, Manka P, Vilchez‐Vargas R, Brodesser S, et al. Altered microbiota diversity and bile acid signaling in cirrhotic and noncirrhotic NASH‐HCC. Clin Transl Gastroenterol 2020;11:e00131.
Xie G, Wang X, Huang F, Zhao A, Chen W, Yan J, et al. Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis. Int J Cancer 2016;139:1764–1775.
Hatton G, Shawcross DL. Is treating the gut microbiome the key to achieving better outcomes in cirrhosis? Expert Rev Gastroenterol Hepatol 2019;13:1–2.
Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334:693–699.
Liu TC, Gurram B, Baldridge MT, Head R, Lam V, Luo C, et al. Paneth cell defects in Crohn’s disease patients promote dysbiosis. JCI Insight 2016;1:e86907.
Bajaj JS, Fagan A, White MB, Wade JB, Hylemon PB, Heuman DM, et al. Specific gut and salivary microbiota patterns are linked with different cognitive testing strategies in minimal hepatic encephalopathy. Am J Gastroenterol 2019;114:1080–1090.
Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol 2010;11:R106.
Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 2013;31:814–821.
Caspi R, Altman T, Billington R, Dreher K, Foerster H, Fulcher CA, et al. The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res 2014;42:D459–D471.
Shamsaddini A, Dadkhah K, Gillevet PM. BiomMiner: an advanced exploratory microbiome analysis and visualization pipeline. PLoS One 2020;15:e0234860.
Liu Q, Li F, Zhuang Y, Xu J, Wang J, Mao X, et al. Alteration in gut microbiota associated with hepatitis B and non‐hepatitis virus related hepatocellular carcinoma. Gut Pathog 2019;11:1.
Nava GM, Stappenbeck TS. Diversity of the autochthonous colonic microbiota. Gut Microbes 2011;2:99–104.
Vital M, Gao J, Rizzo M, Harrison T, Tiedje JM. Diet is a major factor governing the fecal butyrate‐producing community structure across Mammalia, Aves and Reptilia. ISME J 2015;9:832–843.
Lopetuso LR, Scaldaferri F, Petito V, Gasbarrini A. Commensal Clostridia: leading players in the maintenance of gut homeostasis. Gut Pathog 2013;5:23.
Porru S, Placidi D, Carta A, Gelatti U, Ribero ML, Tagger A, et al. Primary liver cancer and occupation in men: a case‐control study in a high‐incidence area in Northern Italy. Int J Cancer 2001;94:878–883.
Qin N, Yang F, Li A, Prifti E, Chen Y, Shao L, et al. Alterations of the human gut microbiome in liver cirrhosis. Nature 2014;513:59–64.
Horvath A, Rainer F, Bashir M, Leber B, Schmerboeck B, Klymiuk I, et al. Biomarkers for oralization during long‐term proton pump inhibitor therapy predict survival in cirrhosis. Sci Rep 2019;9:12000.
Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 2013;500:232–236.
Grazul H, Kanda LL, Gondek D. Impact of probiotic supplements on microbiome diversity following antibiotic treatment of mice. Gut Microbes 2016;7:101–114.
Li YH, Liu Y, Li YD, Liu YH, Li F, Ju Q, et al. GABA stimulates human hepatocellular carcinoma growth through overexpressed GABAA receptor theta subunit. World J Gastroenterol 2012;18:2704–2711.
Wang X, Zhang A, Sun H. Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma. Hepatology 2013;57:2072–2077.

Auteurs

Somaya Albhaisi (S)

Department of Internal Medicine Virginia Commonwealth University Richmond VA Microbiome Analysis Center George Mason University Manassas VA Division of Gastroenterology, Hepatology and Nutrition Virginia Commonwealth University and Central Virginia Healthcare System Richmond VA.

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