Visapää J P, Jokelainen K, Nosova T, Salaspuro M
Research Unit of Alcohol Diseases, Helsinki University Central Hospital, Finland.
Alcohol Clin Exp Res. 1998 Aug;22(5):1161-4.
Heavy drinking is associated with many gastrointestinal symptoms and diseases, such as rapid intestinal transit time, diarrhea, colon polyps, and colorectal cancer. Acetaldehyde produced from ethanol by intestinal microbes has recently been suggested to be one of the pathogenetic factors related to alcohol-associated gastrointestinal morbidity. Furthermore, acetaldehyde is absorbed from the colon into portal blood and may thus contribute to the development of alcoholic liver injury. The present study was aimed to investigate the significance of gut aerobic flora in intracolonic acetaldehyde formation. For this study, 58 male Wistar rats (aged 9 to 11 weeks) were used. Half of the rats received ciprofloxacin for four consecutive days. Control rats (n = 29) received standard chow. On the fifth day of treatment, 1.5 g/kg body weight of ethanol was administered intraperitoneally to 19 rats receiving ciprofloxacin and 19 control rats. Ten ciprofloxacin-treated and 10 control rats received equal volumes of physiological saline intraperitoneally. Two hours after the injection of ethanol or saline, the samples of colonic contents and blood were obtained. Acetaldehyde and ethanol levels of the samples were determined by headspace gas chromatography. The intracolonic acetaldehyde level 2 hr after ethanol administration was 483+/-169 microM (maximum: 2.7 mM). High intracolonic acetaldehyde after ethanol injection was significantly reduced by ciprofloxacin treatment. After ciprofloxacin, intracolonic acetaldehyde levels before and after the injection of ethanol were 25+/-4.8 and 23+/-15 microM, respectively. Ciprofloxacin treatment resulted also in significantly higher blood (p < 0.005) and intracolonic (p < 0.0001) ethanol levels than in the control animals. Furthermore, ciprofloxacin treatment totally abolished the formation of endogenous ethanol in the large intestine. This study demonstrates that alcoholic fermentation and intracoIonic acetaldehyde production can be blocked by diminishing the amount of intracolonic aerobic bacteria with ciprofloxacin. Our findings indicate that the bacteriocolonic pathway for ethanol oxidation is mediated almost exclusively by gut aerobic microbes, and this knowledge may provide new insights into the studies on the pathogenesis of alcohol-related gastrointestinal symptoms and diseases.
大量饮酒与许多胃肠道症状和疾病相关，如肠道转运时间加快、腹泻、结肠息肉和结直肠癌。肠道微生物将乙醇转化产生的乙醛最近被认为是与酒精相关胃肠道疾病发病机制相关的致病因素之一。此外，乙醛从结肠吸收入门静脉血，因此可能促进酒精性肝损伤的发展。本研究旨在探讨肠道需氧菌在结肠内乙醛形成中的意义。在本研究中，使用了58只雄性Wistar大鼠（9至11周龄）。一半的大鼠连续四天接受环丙沙星治疗。对照大鼠（n = 29）给予标准饲料。在治疗的第五天，对19只接受环丙沙星治疗的大鼠和19只对照大鼠腹腔注射1.5 g/kg体重的乙醇。10只接受环丙沙星治疗的大鼠和10只对照大鼠腹腔注射等量的生理盐水。注射乙醇或生理盐水两小时后，获取结肠内容物和血液样本。通过顶空气相色谱法测定样本中的乙醛和乙醇水平。乙醇给药后2小时结肠内乙醛水平为483±169 μM（最大值：2.7 mM）。环丙沙星治疗显著降低了乙醇注射后结肠内的高乙醛水平。环丙沙星治疗后，注射乙醇前后结肠内乙醛水平分别为25±4.8 μM和23±15 μM。环丙沙星治疗还导致血液（p < 0.005）和结肠内（p < 0.0001）乙醇水平显著高于对照动物。此外，环丙沙星治疗完全消除了大肠内内源性乙醇的形成。本研究表明，用环丙沙星减少结肠内需氧菌数量可阻断酒精发酵和结肠内乙醛产生。我们的研究结果表明，乙醇氧化的细菌 - 结肠途径几乎完全由肠道需氧微生物介导，这一认识可能为酒精相关胃肠道症状和疾病发病机制的研究提供新的见解。
