Fadden K, Owen R W
Merck, Sharp and Dohme, Hoddesdon, Hertfordshire, UK.
Eur J Cancer Prev. 1992 Feb;1(2):113-27.
The effect of lactulose on intestinal bacterial metabolism in two identical single-stage chemostats has been studied. The study was designed as a single stage crossover. Both cultures were inoculated and treated in an identical manner except that whilst one fermenter was subject to pH control the other was not and vice versa. Complex bacterial populations were maintained for 23 days and many of the metabolic functions carried out by the micro-organisms in vivo were demonstrated in vitro. The predominant organisms belonged to the genera Bacteroides, Bifidobacterium and Clostridium with abundant levels of anaerobic Gram-positive rods. The redox potential in each fermenter showed considerable variation with maximum values of below -300 eV being attained. An indication of the stability of the bacterial communities was the production of short-chain volatile fatty acids; during steady-state conditions the mean ratio of the major acids acetic, propionic and butyric being 3.90:0.69:1.00 and 3.65:0.76:1.00 in each fermenter, respectively. During steady-state conditions, 7 alpha-dehydroxylation of the primary bile acid chenodeoxycholic acid was maintained at a constant rate with lithocholic acid representing over 85% of total steroid. Addition of the soluble fibre lactulose to the cultures had a profound effect on many of the parameters tested. Without pH control the culture pH dropped to below 5.0 and this coincided with a substantial decrease in total anaerobes, especially Bacteroides spp., an increase in Lactobacillus spp. (concomitant with an increase in lactic acid), a decrease in the concentration of short-chain volatile fatty acids and a substantial decrease in 7 alpha-dehydroxylation of chenodeoxycholic acid. These results show that it is possible to maintain viable intestinal bacteria in vitro using a continuous culture chemostat and that the cultures respond to changing conditions as evinced by the inhibition of 7 alpha-dehydroxylation of chenodeoxycholic acid on addition of lactulose. This indicates that the model may be of further use in studying the modulation of secondary bile acid formation, a possible risk factor in colorectal carcinogenesis.
研究了乳果糖对两个相同的单级恒化器中肠道细菌代谢的影响。该研究设计为单阶段交叉实验。两种培养物的接种和处理方式相同，只是一个发酵罐进行pH控制，另一个不进行pH控制，反之亦然。复杂的细菌群体维持了23天，并且微生物在体内执行的许多代谢功能在体外得到了证实。主要的微生物属于拟杆菌属、双歧杆菌属和梭菌属，厌氧革兰氏阳性杆菌含量丰富。每个发酵罐中的氧化还原电位显示出相当大的变化，达到了低于-300 eV的最大值。细菌群落稳定性的一个指标是短链挥发性脂肪酸的产生；在稳态条件下，每个发酵罐中主要酸乙酸、丙酸和丁酸的平均比例分别为3.90:0.69:1.00和3.65:0.76:1.00。在稳态条件下，初级胆汁酸鹅去氧胆酸的7α-脱羟基作用以恒定速率维持，石胆酸占总类固醇的85%以上。向培养物中添加可溶性纤维乳果糖对许多测试参数有深远影响。在没有pH控制的情况下，培养物的pH降至5.0以下，这与总厌氧菌数量大幅减少同时发生，尤其是拟杆菌属，乳酸杆菌属增加（伴随着乳酸增加），短链挥发性脂肪酸浓度降低，鹅去氧胆酸的7α-脱羟基作用大幅降低。这些结果表明，使用连续培养恒化器可以在体外维持有活力的肠道细菌，并且培养物对变化的条件有反应，如添加乳果糖后鹅去氧胆酸的7α-脱羟基作用受到抑制所证明的。这表明该模型可能在研究次级胆汁酸形成的调节方面有进一步用途，次级胆汁酸形成是结直肠癌发生的一个可能风险因素。
