Translocation of bacterial DNA from Gram-positive microorganisms is associated with a species-specific inflammatory response in serum and ascitic fluid of patients with cirrhosis

CIBERehd, Instituto de Salud Carlos III, Madrid, Spain, and Liver Unit, Hospital General Universitario, Alicante, Spain.
Clinical & Experimental Immunology (Impact Factor: 3.04). 12/2007; 150(2):230-7. DOI: 10.1111/j.1365-2249.2007.03494.x
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Translocation of bacterial-DNA in patients with cirrhosis and ascites triggers an innate immune response. Identification of characteristics to which this response is sensitive is relevant from a clinical standpoint. The aim of this study has been to determine if the proinflammatory immune response established in vivo in cirrhotic patients with ascites as a consequence of bacterial-DNA translocation is related to the identified bacterial species and their frequency of cytosine-guanosine content in serum and ascitic fluid. Patients with advanced cirrhosis and ascites were included in the study and distributed into groups I and II according to the absence or presence of bacterial-DNA translocation, respectively. Serum and ascitic fluid levels of proinflammatory cytokines after normalization of bacterial-DNA concentration and the activated form of nuclear factor-kappa B in ascitic fluid pellets were measured by enzyme-linked immunosorbent assay techniques. Translocation of bacterial-DNA with higher cytosine-guanosine content induced the highest cytokine response, which was higher than that in patients without bacterial-DNA translocation. The activated form of nuclear factor-kappa B in ascitic fluid pellets of patients with bacterial-DNA translocation was greater in patients with higher bacterial-DNA cytosine-guanosine content, whereas the amount of total nuclear factor-kappa B remained unaltered. Bacterial-DNA translocation induces a marked immune reaction in vivo in patients with advanced cirrhosis and ascites which is related, among other factors, to the bacterial-DNA cytosine-guanosine content. Therefore, the host's immune response to bacterial-DNA translocation constitutes a species-specific phenomenon.

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Available from: José Such, Dec 27, 2013
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    • "In conjunction with this, more recently, studies on the translocation of viral DNA has gained much interest [20], [21]. Many biomarkers, including LPS and CD4+ counts have been used to quantify microbial/bacterial translocation in various conditions like cirrhosis, ascites, non-alcoholic steatohepatitis (NASH) and HIV/AIDS [22], [23]. Alternatively, 16S rRNA genes can be utilized to quantify bacterial DNA in the circulation. "
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    ABSTRACT: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. An expanding body of evidence supports the role of human microbiome in the establishment of CVDs and, this has gained much attention recently. This work was aimed to study the circulating human microbiome in CVD patients and healthy subjects. The levels of circulating cell free DNA (circDNA) was higher in CVD patients (n=80) than in healthy controls (n=40). More specifically, the relative levels of circulating bacterial DNA and the ratio of 16S rRNA/β-globin gene copy numbers were higher in the circulation of CVD patients than healthy individuals. In addition, we found a higher circulating microbial diversity in CVD patients (n=3) in comparison to healthy individuals (n=3) by deep shotgun sequencing. At the phylum level, we observed a dominance of Actinobacteria in CVD patients, followed by Proteobacteria, in contrast to that in healthy controls, where Proteobacteria was predominantly enriched, followed by Actinobacteria. The circulating virome in CVD patients was enriched with bacteriophages with a preponderance of Propionibacterium phages, followed by Pseudomonas phages and Rhizobium phages in contrast to that in healthy individuals, where a relatively greater abundance of eukaryotic viruses dominated by Lymphocystis virus (LCV) and Torque Teno viruses (TTV) was observed. Thus, the release of bacterial and viral DNA elements in the circulation could play a major role leading to elevated circDNA levels in CVD patients. The increased circDNA levels could be either the cause or consequence of CVD incidence, which needs to be explored further.
    PLoS ONE 08/2014; 9(8). DOI:10.1371/journal.pone.0105221 · 3.23 Impact Factor
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    • "Enterococci were involved in nearly a quarter of the cases in our study, and these infections appear to be significantly associated with the use of quinolone prophylaxis, in particular in patients with confirmed SBP. Thus, quinolone prophylaxis, which is widely accepted and used by physicians in primary or secondary prevention of SBP [15], reduces the risk of infection, but favors the emergence of bacteria with natural or acquired resistance, such as enterococci, that are able to translocate [6,16]. This has to be kept in mind when considering fluoroquinolone prophylaxis, in particular for primary prophylaxis of SBP, which should be restricted to cirrhotic patients with low-protein ascites (<15 g/L), poor liver function and a fragile hemodynamic status, and to patients who are recovering from an episode of SBP who have a high risk of developing SBP [5,6]. "
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    ABSTRACT: Background Current recommendations for empirical antimicrobial therapy in spontaneous bacterial peritonitis (SBP) are based on quite old trials. Since microbial epidemiology and the management of patients have changed, whether these recommendations are still appropriate must be confirmed. Methods An observational study that exhaustively collected the clinical and biological data associated with positive ascitic fluid cultures was conducted in four French university hospitals in 2010–2011. Results Two hundred and sixty-eight documented positive cultures were observed in 190 cirrhotic patients (median age 61.5 years, 58.5% Child score C). Of these, 57 were classified as confirmed SBP and 140 as confirmed bacterascites. The predominant flora was Gram-positive cocci, whatever the situation (SBP, bacterascites, nosocomial/health-care related or not). Enteroccocci (27.7% E. faecium) were isolated in 24% of the episodes, and in 48% from patients receiving quinolone prophylaxis. E. coli were susceptible to amoxicillin-clavulanate and to third-generation cephalosporins in 62.5% and 89.5% of cases, respectively. No single antibiotic allowed antimicrobial coverage of more than 60%. Only combinations such as amoxicillin + third-generation cephalosporin or cotrimoxazole allowed coverage close to 75-80% in non-nosocomial episodes. Combinations based on broader spectrum antibiotics should be considered for empirical therapy of nosocomial infections. Conclusions Our study confirmed the changing spectrum of pathogens in SBP and bacterascites, and the need for more complex antibiotic strategies than those previously recommended. Our findings also underline the need for new clinical trials conducted in the current epidemiological context.
    BMC Infectious Diseases 05/2014; 14(1):287. DOI:10.1186/1471-2334-14-287 · 2.61 Impact Factor
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    ABSTRACT: BackgroundSmall intestinal bacterial overgrowth (SIBO) is regarded as the major risk factor of bacterial translocation. Few studies have investigated the direct relation between SIBO and translocation in cirrhotic patients. The purpose of this study is to examine the correlation between SIBO and bacterial DNA in the peripheral blood of patients with cirrhosis. AimsThe purpose of this study is to examine the correlation between SIBO and bacterial DNA in the peripheral blood of patients with cirrhosis. MethodsFifty-three cirrhosis cases and 42 controls underwent a lactulose breath test (LBT) every 15min for 180min. To detect and identify the presence of bacterial DNA fragments in peripheral blood, multiplex polymerase chain reaction (PCR) was performed. ResultsThe positive rate of LBT was significantly different between the two groups: 60.4% in the patient group and 28.6% in the controls. The SIBO positive rate was 81.3% in the cirrhosis patients with ascites, which was significantly higher than 51.4% in the cirrhosis patients with no ascites (P=0.03). Eight of the nine patients (88.9%) who had a history of one or more hepatic encephalopathy was SIBO-positive, which was higher than the patients who had had no hepatic encephalopathy. In the cirrhosis group, 32 patients (60.4%) were SIBO-positive, and ten of them (31.3%) were bacterial DNA-positive. Only one case (4.8%) was bacterial DNA-positive in the absence of SIBO-positive. In a multivariate analysis, only the existence of SIBO was the independent risk factor for bacterial DNA (P=0.026). Conclusions SIBO in cirrhosis patients was observed at a very high frequency, and SIBO showed a high correlation with bacterial translocation, suggesting that SIBO could be a major risk factor of bacterial translocation, especially in ascitic patients. KeywordsCirrhosis-Small Intestinal bacterial overgrowth-Bacterial translocation-Bacterial DNA-Hydrogen breath test
    Digestive Diseases and Sciences 05/2010; 55(5):1465-1471. DOI:10.1007/s10620-009-0870-9 · 2.61 Impact Factor
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