期刊论文详细信息
BMC Gastroenterology
Changes in gut bacterial populations and their translocation into liver and ascites in alcoholic liver cirrhotics
Pekka J Karhunen1  Janne Aittoniemi1  Risto Vuento1  Pekka Collin2  Tanja Pessi1  Sari Tuomisto1 
[1] Fimlab Laboratories, Pirkanmaa Hospital District, Biokatu 4, 33520 Tampere, Finland;Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
关键词: CD14;    Microbiology;    Bacterial translocation;    RT-qPCR;    Gut microbiota;    Alcoholic liver cirrhosis;   
Others  :  855688
DOI  :  10.1186/1471-230X-14-40
 received in 2013-10-09, accepted in 2014-02-19,  发布年份 2014
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【 摘 要 】

Background

The liver is the first line of defence against continuously occurring influx of microbial-derived products and bacteria from the gut. Intestinal bacteria have been implicated in the pathogenesis of alcoholic liver cirrhosis. Escape of intestinal bacteria into the ascites is involved in the pathogenesis of spontaneous bacterial peritonitis, which is a common complication of liver cirrhosis. The association between faecal bacterial populations and alcoholic liver cirrhosis has not been resolved.

Methods

Relative ratios of major commensal bacterial communities (Bacteroides spp., Bifidobacterium spp., Clostridium leptum group, Enterobactericaea and Lactobacillus spp.) were determined in faecal samples from post mortem examinations performed on 42 males, including cirrhotic alcoholics (n = 13), non-cirrhotic alcoholics (n = 15), non-alcoholic controls (n = 14) and in 7 healthy male volunteers using real-time quantitative PCR (RT-qPCR). Translocation of bacteria into liver in the autopsy cases and into the ascites of 12 volunteers with liver cirrhosis was also studied with RT-qPCR. CD14 immunostaining was performed for the autopsy liver samples.

Results

Relative ratios of faecal bacteria in autopsy controls were comparable to those of healthy volunteers. Cirrhotics had in median 27 times more bacterial DNA of Enterobactericaea in faeces compared to the healthy volunteers (p = 0.011). Enterobactericaea were also the most common bacteria translocated into cirrhotic liver, although there were no statistically significant differences between the study groups. Of the ascites samples from the volunteers with liver cirrhosis, 50% contained bacterial DNA from Enterobactericaea, Clostridium leptum group or Lactobacillus spp.. The total bacterial DNA in autopsy liver was associated with the percentage of CD14 expression (p = 0.045). CD14 expression percentage in cirrhotics was significantly higher than in the autopsy controls (p = 0.004).

Conclusions

Our results suggest that translocation of intestinal bacteria into liver may be involved as a one factor in the pathogenesis of alcoholic liver cirrhosis.

【 授权许可】

   
2014 Tuomisto et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Jarvelainen HA, Orpana A, Perola M, Savolainen VT, Karhunen PJ, Lindros KO: Promoter polymorphism of the CD14 endotoxin receptor gene as a risk factor for alcoholic liver disease. Hepatology 2001, 33:1148-1153.
  • [2]Yan AW, Schnabl B: Bacterial translocation and changes in the intestinal microbiome associated with alcoholic liver disease. World J Hepatol 2012, 4:110-118.
  • [3]Campos J, Gonzalez-Quintela A, Quinteiro C, Gude F, Perez LF, Torre JA, Vidal C: The -159C/T polymorphism in the promoter region of the CD14 gene is associated with advanced liver disease and higher serum levels of acute-phase proteins in heavy drinkers. Alcohol Clin Exp Res 2005, 29:1206-1213.
  • [4]LeVan TD, Bloom JW, Bailey TJ, Karp CL, Halonen M, Martinez FD, Vercelli D: A common single nucleotide polymorphism in the CD14 promoter decreases the affinity of Sp protein binding and enhances transcriptional activity. J Immunol 2001, 167:5838-5844.
  • [5]Lay C, Sutren M, Rochet V, Saunier K, Dore J, Rigottier-Gois L: Design and validation of 16S rRNA probes to enumerate members of the Clostridium leptum subgroup in human faecal microbiota. Environ Microbiol 2005, 7:933-946.
  • [6]Orrhage K, Nord CE: Bifidobacteria and lactobacilli in human health. Drugs Exp Clin Res 2000, 26:95-111.
  • [7]Williams KP, Gillespie JJ, Sobral BW, Nordberg EK, Snyder EE, Shallom JM, Dickerman AW: Phylogeny of gammaproteobacteria. J Bacteriol 2010, 192:2305-2314.
  • [8]Son G, Kremer M, Hines IN: Contribution of gut bacteria to liver pathobiology. Gastroenterol Res Pract 2010., 2010doi:10.1155/2010/453563. Epub 2010 Jul 28
  • [9]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.
  • [10]Basuroy S, Sheth P, Mansbach CM, Rao RK: Acetaldehyde disrupts tight junctions and adherens junctions in human colonic mucosa: protection by EGF and L-glutamine. Am J Physiol Gastrointest Liver Physiol 2005, 289:G367-G375.
  • [11]Steffen EK, Berg RD, Deitch EA: Comparison of translocation rates of various indigenous bacteria from the gastrointestinal tract to the mesenteric lymph node. J Infect Dis 1988, 157:1032-1038.
  • [12]Schaffert CS, Duryee MJ, Hunter CD, Hamilton BC 3rd, DeVeney AL, Huerter MM, Klassen LW, Thiele GM: Alcohol metabolites and lipopolysaccharide: roles in the development and/or progression of alcoholic liver disease. World J Gastroenterol 2009, 15:1209-1218.
  • [13]Zhao HY, Wang HJ, Lu Z, Xu SZ: Intestinal microflora in patients with liver cirrhosis. Chin J Dig Dis 2004, 5:64-67.
  • [14]Chen Y, Yang F, Lu H, Wang B, Chen Y, Lei D, Wang Y, Zhu B, Li L: Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 2011, 54:562-572.
  • [15]Khan J, Pikkarainen P, Karvonen AL, Mäkelä T, Peräaho M, Pehkonen E, Collin P: Ascites: aetiology, mortality and the prevalence of spontaneous bacterial peritonitis. Scand J Gastroenterol 2009, 44:970-974.
  • [16]Tuomisto S, Karhunen PJ, Vuento R, Aittoniemi J, Pessi T: Evaluation of postmortem bacterial migration using culturing and real-time quantitative PCR. J Forensic Sci 2013, 58:910-916.
  • [17]Tuomisto S, Karhunen PJ, Pessi T: Time-dependent post mortem changes in the composition of intestinal bacteria using real-time quantitative PCR. Gut Pathogens 2013, 5:35. BioMed Central Full Text
  • [18]Brunk CF, Li J, Avaniss-Aghajani E: Analysis of specific bacteria from environmental samples using a quantitative polymerase chain reaction. Curr Issues Mol Biol 2002, 4:13-18.
  • [19]Furet JP, Firmesse O, Gourmelon M, Bridonneau C, Tap J, Mondot S, Doré J, Corthier G: Comparative assessment of human and farm animal faecal microbiota using real-time quantitative PCR. FEMS Microbiol Ecol 2009, 68:351-362.
  • [20]Sen K, Asher DM: Multiplex PCR for detection of Enterobacteriaceae in blood. Transfusion 2001, 41:1356-1364.
  • [21]Pessi T, Karhunen V, Karjalainen PP, Ylitalo A, Airaksinen JK, Niemi M, Pietila M, Lounatmaa K, Haapaniemi T, Lehtimäki T, Laaksonen R, Karhunen PJ, Mikkelsson J: Bacterial signatures in thrombus aspirates of patients with myocardial infarction. Circulation 2013, 127:1219-1228.
  • [22]Yang S, Lin S, Kelen GD, Quinn TC, Dick JD, Gaydos CA, Rothman RE: Quantitative multiprobe PCR assay for simultaneous detection and identification to species level of bacterial pathogens. J Clin Microbiol 2002, 40:3449-3454.
  • [23]Suzuki N, Yoshida A, Nakano Y: Quantitative analysis of multi-species oral biofilms by TaqMan real-time PCR. Clin Med Res 2005, 3:176-185.
  • [24]Tuominen VJ, Ruotoistenmaki S, Viitanen A, Jumppanen M, Isola J: ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67. Breast Cancer Res 2010, 12:R56. BioMed Central Full Text
  • [25]Kakiyama G, Pandak WM, Gillevet PM, Hylemon PB, Heuman DM, Daita K, Takei H, Muto A, Nittono H, Ridlon JM, White MB, Noble NA, Monteith P, Fuchs M, Thacker LR, Sikaroodi M, Bajaj JS: Modulation of the fecal bile acid profile by gut microbiota in cirrhosis. J Hepatol 2013, 58:949-955.
  • [26]Hume DA, Ross IL, Himes SR, Sasmono RT, Wells CA, Ravasi T: The mononuclear phagocyte system revisited. J Leukoc Biol 2002, 72:621-627.
  • [27]Laskin DL, Weinberger B, Laskin JD: Functional heterogeneity in liver and lung macrophages. J Leukoc Biol 2001, 70:163-170.
  • [28]Levy E, Xanthou G, Petrakou E, Zacharioudaki V, Tsatsanis C, Fotopoulos S, Xanthou M: Distinct roles of TLR4 and CD14 in LPS-induced inflammatory responses of neonates. Pediatr Res 2009, 66:179-184.
  • [29]Adachi Y, Moore LE, Bradford BU, Gao W, Thurman RG: Antibiotics prevent liver injury in rats following long-term exposure to ethanol. Gastroenterology 1995, 108:218-224.
  • [30]Nanji AA, Khettry U, Sadrzadeh SM, Yamanaka T: Severity of liver injury in experimental alcoholic liver disease. Correlation with plasma endotoxin, prostaglandin E2, leukotriene B4, and thromboxane B2. Am J Pathol 1993, 142:367-373.
  • [31]Tamai H, Kato S, Horie Y, Ohki E, Yokoyama H, Ishii H: Effect of acute ethanol administration on the intestinal absorption of endotoxin in rats. Alcohol Clin Exp Res 2000, 24:390-394.
  • [32]Tabata T, Tani T, Endo Y, Hanasawa K: Bacterial translocation and peptidoglycan translocation by acute ethanol administration. J Gastroenterol 2002, 37:726-731.
  • [33]Garcia-Tsao G: Spontaneous bacterial peritonitis. Gastroenterol Clin North Am 1992, 21:257-275.
  • [34]Vilstrup H: Cirrhosis and bacterial infections. Rom J Gastroenterol 2003, 12:297-302.
  • [35]Terg R, Fassio E, Guevara M, Cartier M, Longo C, Lucero R, Landeira C, Romero G, Dominguez N, Muñoz A, Levi D, Miguez C, Abecasis R: Ciprofloxacin in primary prophylaxis of spontaneous bacterial peritonitis: a randomized, placebo-controlled study. J Hepatol 2008, 48:774-779.
  • [36]Madrid AM, Hurtado C, Venegas M, Cumsille F, Defilippi C: Long-Term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function. Am J Gastroenterol 2001, 96:1251-1255.
  • [37]Brandl K, Plitas G, Mihu CN, Ubeda C, Jia T, Fleisher M, Schnabl B, DeMatteo RP, Pamer EG: Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature 2008, 455:804-807.
  • [38]Novella M, Solà R, Soriano G, Andreu M, Gana J, Ortiz J, Coll S, Sàbat M, Vila MC, Guarner C, Vilardell F: Continuous versus inpatient prophylaxis of the first episode of spontaneous bacterial peritonitis with norfloxacin. Hepatology 1997, 25:532-536.
  • [39]Campillo B, Dupeyron C, Richardet JP, Mangeney N, Leluan G: Epidemiology of severe hospital-acquired infections in patients with liver cirrhosis: effect of long-term administration of norfloxacin. Clin Infect Dis 1998, 26:1066-1070.
  • [40]Kirpich IA, Solovieva NV, Leikhter SN, Shidakova NA, Lebedeva OV, Sidorov PI, Bazhukova TA, Soloviev AG, Barve SS, McClain CJ, Cave M: Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: a pilot study. Alcohol 2008, 42:675-682.
  • [41]Leber B, Spindelboeck W, Stadlbauer V: Infectious complications of acute and chronic liver disease. Semin Respir Crit Care Med 2012, 33:80-95.
  • [42]Hartmann P, Chen WC, Schnabl B: The intestinal microbiome and the leaky gut as therapeutic targets in alcoholic liver disease. Front Physiol 2012, 3:402.
  • [43]Hayashi H, Sakamoto M, Benno Y: Phylogenetic analysis of the human gut microbiota using 16S rDNA clone libraries and strictly anaerobic culture-based methods. Microbiol Immunol 2002, 46:535-548.
  • [44]Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA: Diversity of the human intestinal microbial flora. Science 2005, 308:1635-1638.
  • [45]Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI: A core gut microbiome in obese and lean twins. Nature 2009, 457:480-484.
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