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Colonic inflammation and secondary bile acids in alcoholic cirrhosis.
Kakiyama, Genta; Hylemon, Phillip B; Zhou, Huiping; Pandak, William M; Heuman, Douglas M; Kang, Dae Joong; Takei, Hajime; Nittono, Hiroshi; Ridlon, Jason M; Fuchs, Michael; Gurley, Emily C; Wang, Yun; Liu, Runping; Sanyal, Arun J; Gillevet, Patrick M; Bajaj, Jasmohan S.
Afiliação
  • Kakiyama G; Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia;
  • Hylemon PB; Department of Microbiology, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia;
  • Zhou H; Department of Immunology, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia;
  • Pandak WM; Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia;
  • Heuman DM; Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia;
  • Kang DJ; Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia;
  • Takei H; Junshin Clinic Bile Acid Institute, Tokyo, Japan; and.
  • Nittono H; Junshin Clinic Bile Acid Institute, Tokyo, Japan; and.
  • Ridlon JM; Department of Microbiology, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia;
  • Fuchs M; Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia;
  • Gurley EC; Department of Microbiology, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia;
  • Wang Y; Department of Immunology, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia;
  • Liu R; Department of Immunology, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia;
  • Sanyal AJ; Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia;
  • Gillevet PM; Microbiome Analysis Center, George Mason University, Manassas, Virginia.
  • Bajaj JS; Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia; jsbajaj@vcu.edu.
Am J Physiol Gastrointest Liver Physiol ; 306(11): G929-37, 2014 Jun 01.
Article em En | MEDLINE | ID: mdl-24699327
Alcohol abuse with/without cirrhosis is associated with an impaired gut barrier and inflammation. Gut microbiota can transform primary bile acids (BA) to secondary BAs, which can adversely impact the gut barrier. The purpose of this study was to define the effect of active alcohol intake on fecal BA levels and ileal and colonic inflammation in cirrhosis. Five age-matched groups {two noncirrhotic (control and drinkers) and three cirrhotic [nondrinkers/nonalcoholics (NAlc), abstinent alcoholic for >3 mo (AbsAlc), currently drinking (CurrAlc)]} were included. Fecal and serum BA analysis, serum endotoxin, and stool microbiota using pyrosequencing were performed. A subgroup of controls, NAlc, and CurrAlc underwent ileal and sigmoid colonic biopsies on which mRNA expression of TNF-α, IL-1ß, IL-6, and cyclooxygenase-2 (Cox-2) were performed. One hundred three patients (19 healthy, 6 noncirrhotic drinkers, 10 CurrAlc, 38 AbsAlc, and 30 NAlc, age 56 yr, median MELD: 10.5) were included. Five each of healthy, CurrAlc, and NAlc underwent ileal/colonic biopsies. Endotoxin, serum-conjugated DCA and stool total BAs, and secondary-to-primary BA ratios were highest in current drinkers. On biopsies, a significantly higher mRNA expression of TNF-α, IL-1ß, IL-6, and Cox-2 in colon but not ileum was seen in CurrAlc compared with NAlc and controls. Active alcohol use in cirrhosis is associated with a significant increase in the secondary BA formation compared with abstinent alcoholic cirrhotics and nonalcoholic cirrhotics. This increase in secondary BAs is associated with a significant increase in expression of inflammatory cytokines in colonic mucosa but not ileal mucosa, which may contribute to alcohol-induced gut barrier injury.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos e Sais Biliares / Doenças do Colo / Alcoolismo / Inflamação / Cirrose Hepática Limite: Humans / Middle aged Idioma: En Revista: Am J Physiol Gastrointest Liver Physiol Assunto da revista: FISIOLOGIA / GASTROENTEROLOGIA Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos e Sais Biliares / Doenças do Colo / Alcoolismo / Inflamação / Cirrose Hepática Limite: Humans / Middle aged Idioma: En Revista: Am J Physiol Gastrointest Liver Physiol Assunto da revista: FISIOLOGIA / GASTROENTEROLOGIA Ano de publicação: 2014 Tipo de documento: Article