Onoue M, Kado S, Sakaitani Y, Uchida K, Morotomi M
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Cancer Lett. 1997 Feb 26;113(1-2):179-86. doi: 10.1016/s0304-3835(97)04698-3.
To shed light on the association of intestinal microflora with the development of colon cancer, we studied the modifying effects of intestinal microflora on the occurrence of 1,2-dimethylhydrazine (DMH)-induced colonic aberrant crypt foci (ACF) in germfree (GF), gnotobiotic (GB) and conventionalized (Cvd) rats. In the first part of this study, 10 week old germfree Fischer-344 rats were randomly assigned to three groups and two groups of rats were orally inoculated with mixtures of pure culture of Escherichia coli, Enterococcus faecium, and several strains of Bacteroides and Clostridium species (GB), or feces from conventional rats (Cvd). Inoculated rats were given two weekly i.p. injections of DMH (20 mg/kg body wt) at 13 and 14 weeks of age. Rats were sacrificed 11 or 34 weeks after the last DMH injection for ACF scoring. The total number of ACF, ACF with four or more crypts/focus, and mean number of aberrant crypts per focus (crypt multiplicity) in GB rats sacrificed at week 34 were 168% (P < 0.001), 442% (P < 0.001) and 138% (P < 0.001) of those in GF rats, respectively. On the other hand, the same values in Cvd rats were 42% (P < 0.001), 147% (P = 0.246) and 159% (P < 0.001) of those in GF rats, respectively. Similar results were observed in rats that were sacrificed at week 11. In the second part of this study, the effect of colonization of Bifidobacterium breve on the ACF profiles was examined in GB rats. The number of ACF with four or more crypts/focus and crypt multiplicity in GB plus B. breve rats at week 11 were significantly lower than those of GB rats (P < 0.01, and P < 0.05, respectively), although the former was not statistically significant at week 34. These findings suggest that some intestinal bacteria might behave as promoters and some as anti-promoters in colon carcinogenesis.
为了阐明肠道微生物群与结肠癌发生发展之间的关联，我们研究了肠道微生物群对无菌（GF）、悉生（GB）和常规化（Cvd）大鼠中1,2 - 二甲基肼（DMH）诱导的结肠异常隐窝病灶（ACF）发生的调节作用。在本研究的第一部分，将10周龄的无菌Fischer - 344大鼠随机分为三组，两组大鼠分别经口接种大肠杆菌、粪肠球菌以及几种拟杆菌属和梭菌属菌株的纯培养物混合物（GB），或常规大鼠的粪便（Cvd）。在13周和14周龄时，给接种的大鼠每周两次腹腔注射DMH（20 mg/kg体重）。在最后一次DMH注射后11周或34周处死大鼠以进行ACF评分。在第34周处死的GB大鼠中，ACF总数、每个病灶有四个或更多隐窝的ACF以及每个病灶异常隐窝的平均数量（隐窝多样性）分别是GF大鼠相应指标的168%（P < 0.001）、442%（P < 0.001）和138%（P < 0.001）。另一方面，Cvd大鼠的相同值分别是GF大鼠相应指标的42%（P < 0.001）、147%（P = 0.246）和159%（P < 0.001）。在第11周处死的大鼠中也观察到了类似结果。在本研究的第二部分，在GB大鼠中研究了短双歧杆菌定殖对ACF谱的影响。在第11周时，GB加短双歧杆菌大鼠中每个病灶有四个或更多隐窝的ACF数量和隐窝多样性显著低于GB大鼠（分别为P < 0.01和P < 0.05），尽管在第34周时前者无统计学意义。这些发现表明，在结肠癌发生过程中，一些肠道细菌可能起促进作用，而一些则起抗促进作用。
