Moen Birgitte, Henjum Kristi, Måge Ingrid, Knutsen Svein Halvor, Rud Ida, Hetland Ragna Bogen, Paulsen Jan Erik
Nofima - Norwegian Institute of Food, Fisheries and Aquaculture Research, Ås, Norway.
Department of Pharmacology, Oslo University and Oslo University Hospital, Oslo, Norway.
PLoS One. 2016 May 19;11(5):e0155402. doi: 10.1371/journal.pone.0155402. eCollection 2016.
Foods naturally high in dietary fiber are generally considered to protect against development of colorectal cancer (CRC). However, the intrinsic effect of dietary fiber on intestinal carcinogenesis is unclear. We used azoxymethane (AOM) treated A/J Min/+ mice, which developed a significantly higher tumor load in the colon than in the small intestine, to compare the effects of dietary inulin (IN), cellulose (CE) or brewers spent grain (BSG) on intestinal tumorigenesis and cecal microbiota. Each fiber was tested at two dose levels, 5% and 15% (w/w) content of the AIN-93M diet. The microbiota was investigated by next-generation sequencing of the 16S rRNA gene (V4). We found that mice fed IN had approximately 50% lower colonic tumor load than mice fed CE or BSG (p<0.001). Surprisingly, all three types of fiber caused a dose dependent increase of colonic tumor load (p<0.001). The small intestinal tumor load was not affected by the dietary fiber interventions. Mice fed IN had a lower bacterial diversity than mice fed CE or BSG. The Bacteroidetes/Firmicutes ratio was significantly (p = 0.003) different between the three fiber diets with a higher mean value in IN fed mice compared with BSG and CE. We also found a relation between microbiota and the colonic tumor load, where many of the operational taxonomic units (OTUs) related to low tumor load were significantly enriched in mice fed IN. Among the OTUs related to low tumor load were bacteria affiliated with the Bacteroides genus. These results suggest that type of dietary fiber may play a role in the development of CRC, and that the suppressive effect of IN on colonic tumorigenesis is associated with profound changes in the cecal microbiota profile.
天然富含膳食纤维的食物通常被认为可预防结直肠癌（CRC）的发生。然而，膳食纤维对肠道致癌作用的内在影响尚不清楚。我们使用经氧化偶氮甲烷（AOM）处理的A/J Min/+小鼠（其结肠中的肿瘤负荷显著高于小肠）来比较膳食菊粉（IN）、纤维素（CE）或啤酒糟（BSG）对肠道肿瘤发生和盲肠微生物群的影响。每种纤维均在两个剂量水平进行测试，即AIN-93M饮食中含量为5%和15%（w/w）。通过对16S rRNA基因（V4）进行新一代测序来研究微生物群。我们发现，喂食IN的小鼠结肠肿瘤负荷比喂食CE或BSG的小鼠低约50%（p<0.001）。令人惊讶的是，所有三种类型的纤维均导致结肠肿瘤负荷呈剂量依赖性增加（p<0.001）。膳食纤维干预对小肠肿瘤负荷没有影响。喂食IN的小鼠细菌多样性低于喂食CE或BSG的小鼠。三种纤维饮食之间的拟杆菌门/厚壁菌门比率存在显著差异（p = 0.003），与BSG和CE相比，喂食IN的小鼠该比率平均值更高。我们还发现微生物群与结肠肿瘤负荷之间存在关联，在喂食IN的小鼠中，许多与低肿瘤负荷相关的可操作分类单元（OTU）显著富集。在与低肿瘤负荷相关的OTU中，有属于拟杆菌属的细菌。这些结果表明，膳食纤维类型可能在CRC的发生中起作用，并且IN对结肠肿瘤发生的抑制作用与盲肠微生物群谱的深刻变化有关。
