Väkeväinen S, Tillonen J, Blom M, Jousimies-Somer H, Salaspuro M
Research Unit of Alcohol Diseases, Helsinki University Central Hospital, Finland.
Alcohol Clin Exp Res. 2001 Mar;25(3):421-6.
Acetaldehyde is a known local carcinogen in the digestive tract in humans. Bacterial overgrowth in the hypochlorhydric stomach enhances production of acetaldehyde from ethanol in vivo after alcohol ingestion. Therefore, microbially produced acetaldehyde may be a potential risk factor for alcohol-related gastric and cardiac cancers. This study was aimed to investigate which bacterial species and/or groups are responsible for acetaldehyde formation in the hypochlorhydric human stomach and to characterize their alcohol dehydrogenase (ADH) enzymes.
After 7 days of treatment with 30 mg of lansoprazole twice a day, a gastroscopy was performed on eight volunteers to obtain hypochlorhydric gastric juice. Samples were cultured and bacteria were isolated and identified; thereafter, their acetaldehyde production capacity was measured gas chromatographically by incubating intact bacterial suspensions with ethanol at 37 degrees C. Cytosolic ADH activities, Km values, and protein concentration were determined spectrophotometrically.
Acetaldehyde production of the isolated bacterial strains (n = 51) varied from less than 1 to 13,690 nmol of acetaldehyde/10(9) colony-forming units/hr. ADH activity of the strains that produced more than 100 nmol of acetaldehyde/10(9) colony-forming units/hr (n = 23) varied from 3.9 to 1253 nmol of nicotinamide adenine dinucleotide per minute per milligram of protein, and Km values for ethanol ranged from 0.65 to 116 mM and from 0.5 to 3.1 M (high Km). There was a statistically significant correlation (r = 0.64, p < 0.001) between ADH activity and acetaldehyde production from ethanol in the tested strains. The most potent acetaldehyde producers were Neisseria and Rothia species and Streptococcus salivarius, whereas nearly all Stomatococcus, Staphylococcus, and other Streptococcus species had a very low capacity to produce acetaldehyde.
This study demonstrated that certain bacterial species or groups that originate from the oral cavity are responsible for the bulk of acetaldehyde production in the hypochlorhydric stomach. These findings provide new information with the respect to the local production of carcinogenic acetaldehyde in the upper digestive tract of achlorhydric human subjects.
乙醛是已知的人类消化道局部致癌物。胃酸分泌不足的胃中细菌过度生长会增强酒精摄入后体内乙醇生成乙醛的过程。因此,微生物产生的乙醛可能是酒精相关胃癌和贲门癌的潜在危险因素。本研究旨在调查胃酸分泌不足的人类胃中哪些细菌种类和/或菌群负责乙醛的形成,并对其乙醇脱氢酶(ADH)进行表征。
8名志愿者每天两次服用30毫克兰索拉唑,治疗7天后进行胃镜检查以获取胃酸分泌不足的胃液。对样本进行培养,分离并鉴定细菌;此后,通过在37℃下将完整细菌悬液与乙醇孵育,用气相色谱法测量其乙醛生成能力。用分光光度法测定胞质ADH活性、Km值和蛋白质浓度。
分离出的细菌菌株(n = 51)的乙醛生成量从每10⁹ 菌落形成单位/小时小于1纳摩尔到13,690纳摩尔不等。每10⁹ 菌落形成单位/小时产生超过100纳摩尔乙醛的菌株(n = 23)的ADH活性从每分钟每毫克蛋白质3.9纳摩尔烟酰胺腺嘌呤二核苷酸到1253纳摩尔不等,乙醇的Km值范围为0.65至116毫摩尔以及0.5至3.1摩尔(高Km)。在测试菌株中,ADH活性与乙醇生成乙醛之间存在统计学显著相关性(r = 0.64,p < 0.001)。最强的乙醛生产者是奈瑟菌属和罗氏菌属以及唾液链球菌,而几乎所有口腔球菌属、葡萄球菌属和其他链球菌属产生乙醛的能力都非常低。
本研究表明,来自口腔的某些细菌种类或菌群是胃酸分泌不足的胃中大部分乙醛产生的原因。这些发现为胃酸缺乏的人类受试者上消化道中致癌乙醛的局部产生提供了新信息。