Mater Medical Research Institute and Department of Medicine, University of Queensland, Mater Health Services, South Brisbane, Queensland, Australia.
Am J Gastroenterol. 2010 Nov;105(11):2420-8. doi: 10.1038/ajg.2010.281. Epub 2010 Jul 20.
Mucosa-associated bacteria are increased in inflammatory bowel disease (IBD), which suggests the possibility of an increased source of digestible endogenous mucus substrate. We hypothesized that mucolytic bacteria are increased in IBD, providing increased substrate to sustain nonmucolytic mucosa-associated bacteria.
Mucolytic bacteria were characterized by the ability to degrade human secretory mucin (MUC2) in pure and mixed anaerobic cultures. Real-time PCR was used to enumerate mucosa-associated mucolytic bacteria in 46 IBD and 20 control patients. Bacterial mucolytic activity was tested in vitro using purified human MUC2.
We confirm increased total mucosa-associated bacteria 16S rRNA gene in macroscopically and histologically normal intestinal epithelium of both Crohn's disease (CD) (mean 1.9-fold) and ulcerative colitis (UC) (mean 1.3-fold). We found a disproportionate increase in some mucolytic bacteria. Mean Ruminococcus gnavus were increased >4-fold and Ruminococcus torques ∼100-fold in macroscopically and histologically normal intestinal epithelium of both CD and UC. The most abundantly detected mucolytic bacterium in controls, Akkermansia muciniphila, was reduced many fold in CD and in UC. Coculture of A. muciniphila with MUC2 as the sole carbon source led to reduction in its abundance while it augmented growth of other bacteria.
Mucolytic bacteria are present in healthy humans, where they are an integral part of the mucosa-associated bacterial consortium. The disproportionate increase in R. gnavus and R. torques could explain increased total mucosa-associated bacteria in IBD.
黏膜相关细菌在炎症性肠病(IBD)中增加,这表明可消化的内源性黏蛋白底物的来源增加。我们假设黏蛋白溶解菌在 IBD 中增加,为非黏蛋白溶解的黏膜相关细菌提供了更多的底物。
黏蛋白溶解菌的特征是在纯和混合厌氧培养物中降解人分泌黏蛋白(MUC2)的能力。实时 PCR 用于计数 46 例 IBD 和 20 例对照患者的黏膜相关黏蛋白溶解菌。使用纯化的人 MUC2 在体外测试细菌黏蛋白溶解活性。
我们确认在克罗恩病(CD)(平均 1.9 倍)和溃疡性结肠炎(UC)(平均 1.3 倍)的肉眼和组织学正常的肠上皮中,总黏膜相关细菌 16S rRNA 基因增加。我们发现一些黏蛋白溶解菌的不成比例增加。在 CD 和 UC 的肉眼和组织学正常的肠上皮中,瘤胃球菌(Ruminococcus gnavus)的平均值增加了>4 倍,旋转瘤胃球菌(Ruminococcus torques)增加了约 100 倍。在对照组中最丰富的黏蛋白溶解菌阿克曼氏菌(Akkermansia muciniphila)在 CD 和 UC 中减少了许多倍。当 A. muciniphila 与 MUC2 作为唯一碳源共培养时,其丰度降低,而其他细菌的生长增加。
黏蛋白溶解菌存在于健康的人体中,是黏膜相关细菌群落的组成部分。瘤胃球菌和旋转瘤胃球菌的不成比例增加可以解释 IBD 中总黏膜相关细菌的增加。