Comparing the effects of acute alcohol consumption in germ-free and conventional mice: the role of the gut microbiota

BMC Microbiology

Vieira AT¹  Godard ALB⁵  Teixeira MM¹  Nicoli JR⁴  Martins FS⁴  Moreira C⁴  Pedroso SH⁴  Cassali G²  Gamba C²  Almeida D⁵  Gonçalves JL⁵  Ferreira CM³  Lacerda NL⁵  Canesso MCC¹ 

[1] Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;Department of General Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;Department of Pharmacology, Institute of Biomedical Sciences - ICB-1, São Paulo University, São Paulo, Brazil;Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;Department of General Biology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

关键词: Inflammation;    Gut;    Liver;    Fiber;    Dysbiosis;    Microbiota;    Germ-free;    Alcohol;   

Others  :  1170533
DOI  :  10.1186/s12866-014-0240-4

 received in 2014-05-17, accepted in 2014-09-02,  发布年份 2014

【 摘 要 】

Background

Increasing evidence suggest that the gut microbiota plays an important role in liver pathology after acute alcohol intake. The aim of our study was to investigate the roles played by commensal bacteria in alcohol-induced liver injury and in the dysbiosis caused by alcohol intake in germ-free mice, as well as the possibility of protection against alcohol-induced injuries in animals fed a high-fiber diet. For these purposes, germ-free and conventional mice were submitted to acute alcohol intake, consisting of administration of ethanol in their drinking water for 7 days, with a higher dose of alcohol administered on day 7.

Results

There was no liver injury after alcohol consumption, and there was less neutrophil infiltration and lower pro-inflammatory cytokine levels (CXCL-1/KC and interleukin (IL)-6) in the liver in germ-free mice compared with alcohol-fed conventional mice. Additionally, conventionalization of germ-free mice with intestinal contents from alcohol-fed conventional mice induced injury and inflammation in both the liver and the intestine, suggesting that alcohol intake successively caused a perturbation of the intestinal microbiota (dysbiosis) and liver injury. Finally, previous treatment with a high-fiber diet decreased liver injury and gut permeability in alcohol-fed conventional mice.

Conclusions

In conclusion, the results of the present study provide evidence that the gut microbiota plays an important role in alcohol-induced liver injury, apparently through dysbiosis of the intestinal microbial ecosystem caused by alcohol intake. Furthermore, treatment with a high-fiber diet can counteract hepatocyte pathology and gut leakage and thus could be a promising therapeutic option.

【 授权许可】

   
2014 MCC et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]O'Shea RS, Dasarathy S, McCullough AJ: Alcoholic liver disease. Hepatology 2010, 51:307-328.
• [2]Purohit V: International collaboration on alcoholic liver disease and pancreatitis: opportunities. J Gastroenterol Hepatol 2006, 21(Suppl 3):S107-S108.
• [3]Gao B, Bataller R: Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 2011, 141:1572-1585.
• [4]Nanji AA, Khettry U, Sadrzadeh SM: Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver (disease). Exp Biol Med 1994, 205:243-247.
• [5]Bode C, Kugler V, Bode JC: Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess. J Hepatol 1987, 4:8-14.
• [6]Yan AW, Fouts DE, Brandl J, Starkel P, Torralba M, Schott E, Tsukamoto H, Nelson KE, Brenner DA, Schnabl B: Enteric dysbiosis associated with a mouse model of alcoholic liver disease. Hepatology 2011, 53:96-105.
• [7]Bhagwandeen BS, Apte M, Manwarring L, Dickeson J: Endotoxin induced hepatic necrosis in rats on an alcohol diet. J Pathol 1987, 152:47-53.
• [8]Ramaiah SK, Jaeschke H: Hepatic neutrophil infiltration in the pathogenesis of alcohol-induced liver injury. Toxicol Mech Methods 2007, 17:431-440.
• [9]Mutlu E, Keshavarzian A, Engen P, Forsyth CB, Sikaroodi M, Gillevet P: Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. Alcohol Clin Exp Res 2009, 33:1836-1846.
• [10]Mutlu EA, Gillevet PM, Rangwala H, Sikaroodi M, Naqvi A, Engen PA, Kwasny M, Lau CK, Keshavarzian A: Colonic microbiome is altered in alcoholism. Am J Physiol Gastrointest Liver Physiol 2012, 302:G966-G978.
• [11]Barcelos LS, Talvani A, Teixeira AS, Cassali GD, Andrade SP, Teixeira MM: Production and in vivo effects of chemokines CXCL1-3/KC and CCL2/JE in a model of inflammatory angiogenesis in mice. Inflamm Res 2004, 53:576-584.
• [12]De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P: Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A 2010, 107:14691-14696.
• [13]Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI: An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006, 444:1027-1031.
• [14]Franchi L, Kamada N, Nakamura Y, Burberry A, Kuffa P, Suzuki S, Shaw MH, Kim YG, Nunez G: NLRC4-driven production of IL-1beta discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat Immunol 2012, 13:449-456.
• [15]DeSantis DA, Ko CW, Liu Y, Liu X, Hise AG, Nunez G, Croniger CM: Alcohol-induced liver injury is modulated by Nlrp3 and Nlrc4 inflammasomes in mice. Mediat Inflamm 2013, 2013:751374.
• [16]Szabo G, Bala S, Petrasek J, Gattu A: Gut-liver axis and sensing microbes. Dig Dis 2010, 28:737-744.
• [17]Szabo G, Bala S: Alcoholic liver disease and the gut-liver axis. World J Gastroenterol 2010, 16:1321-1329.
• [18]Fukui H, Brauner B, Bode JC, Bode C: Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay. J Hepatol 1991, 12:162-169.
• [19]Zhou Z, Wang L, Song Z, Lambert JC, McClain CJ, Kang YJ: A critical involvement of oxidative stress in acute alcohol-induced hepatic TNF-alpha production. Am J Pathol 2003, 163:1137-1146.
• [20]Wang Y, Hu Y, Chao C, Yuksel M, Colle I, Flavell RA, Ma Y, Yan H, Wen L: Role of IRAK-M in alcohol induced liver injury. PLoS One 2013, 8:e57085.
• [21]Bonnet M, Buc E, Sauvanet P, Darcha C, Dubois D, Pereira B, Dechelotte P, Bonnet R, Pezet D, Darfeuille-Michaud A: Colonization of the human gut by E. coli and colorectal cancer risk. Clin Cancer Res 2014, 20:859-867.
• [22]Chassaing B, Darfeuille-Michaud A: The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. Gastroenterology 2011, 140:1720-1728.
• [23]Darfeuille-Michaud A, Boudeau J, Bulois P, Neut C, Glasser AL, Barnich N, Bringer MA, Swidsinski A, Beaugerie L, Colombel JF: High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology 2004, 127:412-421.
• [24]Schnabl B, Brenner DA: Interactions Between the Intestinal Microbiome and Liver Diseases. Gastroenterology 2014, 146:1513-1524.
• [25]Yan AW, Schnabl B: Bacterial translocation and changes in the intestinal microbiome associated with alcoholic liver disease. World J Hepatol 2012, 4:110-118.
• [26]Wegener M, Schaffstein J, Dilger U, Coenen C, Wedmann B, Schmidt G: Gastrointestinal transit of solid¿liquid meal in chronic alcoholics. Dig Dis Sci 1991, 36:917-923.
• [27]Bode C, Bode JC: Alcohol's role in gastrointestinal tract disorders. Alcohol Health Res World 1997, 21:76-83.
• [28]Macia L, Thorburn AN, Binge LC, Marino E, Rogers KE, Maslowski KM, Vieira AT, Kranich J, Mackay CR: Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases. Immunol Rev 2012, 245:164-176.
• [29]Peng X, Li S, Luo J, Wu X, Liu L: Effects of dietary fibers and their mixtures on short chain fatty acids and microbiota in mice guts. Food Funct 2013, 4:932-938.
• [30]Vieira AT, Teixeira MM, Martins FS: The Role of Probiotics and Prebiotics in Inducing Gut Immunity. Front Immunol 2013, 4:445.
• [31]Schroder K, Tschopp J: The inflammasomes. Cell 2010, 140:821-832.
• [32]Barcelo A, Claustre J, Moro F, Chayvialle JA, Cuber JC, Plaisancie P: Mucin secretion is modulated by luminal factors in the isolated vascularly perfused rat colon. Gut 2000, 46:218-224.
• [33]Pleasants JE: Letter: Legislation¿the solution to a dilemma. J Oral Surg 1974, 32:166.
• [34]Fagundes CT, Amaral FA, Souza AL, Vieira AT, Xu D, Liew FY, Souza DG, Teixeira MM: ST2, an IL-1R family member, attenuates inflammation and lethality after intestinal ischemia and reperfusion. J Leukoc Biol 2007, 81:492-499.
• [35]Bertola A, Park O, Gao B: Chronic plus binge ethanol feeding synergistically induces neutrophil infiltration and liver injury in mice: A critical role for E-selectin. Hepatology 2013, 58:1814-1823.
• [36]Souza DG, Vieira AT, Soares AC, Pinho V, Nicoli JR, Vieira LQ, Teixeira MM: The essential role of the intestinal microbiota in facilitating acute inflammatory responses. J Immunol 2004, 173:4137-4146.
• [37]Reeves PG, Nielsen FH, Fahey GC Jr: AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 1993, 123:1939-1951.
• [38]Folch J, Lees M, Sloane Stanley GH: A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957, 226:497-509.
• [39]Wang Y, Seitz HK, Wang XD: Moderate alcohol consumption aggravates high-fat diet induced steatohepatitis in rats. Alcohol Clin Exp Res 2010, 34:567-573.