Tuomisto Sari, Pessi Tanja, Collin Pekka, Vuento Risto, Aittoniemi Janne, Karhunen Pekka J
Department of Forensic Medicine, University of Tampere, School of Medicine, Medisiinarinkatu 3, 33014 Tampere, Finland.
BMC Gastroenterol. 2014 Feb 24;14:40. doi: 10.1186/1471-230X-14-40.
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.
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.
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).
Our results suggest that translocation of intestinal bacteria into liver may be involved as a one factor in the pathogenesis of alcoholic liver cirrhosis.
肝脏是抵御肠道中不断涌入的微生物衍生产物和细菌的第一道防线。肠道细菌与酒精性肝硬化的发病机制有关。肠道细菌进入腹水参与了自发性细菌性腹膜炎的发病过程，而自发性细菌性腹膜炎是肝硬化的常见并发症。粪便细菌群落与酒精性肝硬化之间的关联尚未明确。
使用实时定量聚合酶链反应（RT-qPCR），在42名男性尸检的粪便样本中测定主要共生细菌群落（拟杆菌属、双歧杆菌属、纤细梭菌群、肠杆菌科和乳酸杆菌属）的相对比例，这些男性包括肝硬化酗酒者（n = 13）、非肝硬化酗酒者（n = 15）、非酒精性对照者（n = 14）以及7名健康男性志愿者。还通过RT-qPCR研究了尸检病例中细菌向肝脏的移位以及12名肝硬化志愿者腹水中细菌的移位情况。对尸检肝脏样本进行CD14免疫染色。
尸检对照者粪便中的细菌相对比例与健康志愿者相当。与健康志愿者相比，肝硬化患者粪便中肠杆菌科细菌DNA的中位数多27倍（p = 0.011）。肠杆菌科也是最常见的移位至肝硬化肝脏的细菌，尽管各研究组之间无统计学显著差异。在肝硬化志愿者的腹水样本中，50%含有来自肠杆菌科、纤细梭菌群或乳酸杆菌属的细菌DNA。尸检肝脏中的总细菌DNA与CD14表达百分比相关（p = 0.045）。肝硬化患者的CD14表达百分比显著高于尸检对照者（p = 0.004）。
我们的结果表明，肠道细菌向肝脏的移位可能是酒精性肝硬化发病机制中的一个因素。
