Refined fiber inulin promotes inflammation-associated colon tumorigenesis by modulating microbial succinate production.
Refined fiber inulin promotes inflammation-associated colon tumorigenesis by modulating microbial succinate production.
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DOI：
10.1002/cnr2.1863
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发表时间：
2023-11
期刊：
影响因子：
--
通讯作者：
Singh V
中科院分区：
文献类型：
--
作者：
Tian S;Paudel D;Hao F;Neupane R;Castro R;Patterson AD;Tiwari AK;Prabhu KS;Singh V
炎症性肠病（IBD）与结肠癌的风险增加有关。天然存在于蔬菜和全谷物中的膳食纤维（DF）对肠道健康有许多有益的影响。然而，精制DF对肠道健康的影响仍不清楚。因此，我们阐明了精制DF菊粉对结肠炎症和肿瘤发生的影响。给4周龄野生型（WT）小鼠喂食含有不溶性DF纤维素（对照）或精制DF菊粉的饲料4周。然后将小鼠亚组转换为含有葡聚糖硫酸钠（DSS，1.4%wt/vol）的饮用水用于结肠炎诱导。在另一个小鼠亚组中，在初始剂量的致突变物质氧化偶氮甲烷（AOM; 7.5 mg/kg体重; i. p.）后，通过3个7天交替周期的DSS启动结肠炎相关结直肠癌（CRC）。AOM处理7周后，将小鼠安乐死并检查CRC发展。食用含菊粉饮食的小鼠在DSS给药后表现出严重的结肠炎，表现为体重减轻、直肠出血和结肠炎症增加多于DSS给药对照组。相应地，组织学分析显示菊糖喂养组中结肠结构的广泛破坏和免疫细胞的大量浸润。接下来我们检查了菊糖对CRC发展的影响。令人惊讶的是，在DSS周期期间，在菊粉喂养的组中观察到显著的死亡率（~50%），而在对照组中未观察到。因此，完成研究的剩余菊糖喂养小鼠表现出广泛的结肠肿瘤发生。免疫组织化学表征显示，在从菊粉喂养组获得的肿瘤切片中，细胞增殖标志物Ki 67的表达相对较高，并且Wnt信号传导活化。肠道微生物群和代谢物分析显示，在菊粉喂养的小鼠中，琥珀酸生产者的扩增和盲肠琥珀酸的升高。人结肠直肠癌细胞（HCT 116）增殖更迅速时，补充琥珀酸在发炎的环境中，这表明，管腔琥珀酸升高可能有助于肿瘤的发生。我们的研究揭示了在饮食中补充精制菊粉会诱导肠腔中琥珀酸的异常积累，这在一定程度上有助于促进结肠炎症和肿瘤发生。
There is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer numerous beneficial effects on intestinal health. However, the effects of refined DFs on intestinal health remain unclear. Therefore, we elucidated the impact of the refined DF inulin on colonic inflammation and tumorigenesis. Four‐week‐old wild‐type (WT) mice were fed diets containing insoluble DF cellulose (control) or refined DF inulin for 4 weeks. A subgroup of mice was then switched to drinking water containing dextran sulfate sodium (DSS, 1.4% wt/vol) for colitis induction. In another subgroup of mice, colitis‐associated colorectal cancer (CRC) was initiated with three 7‐day alternate cycles of DSS following an initial dose of mutagenic substance azoxymethane (AOM; 7.5 mg/kg body weight; i.p.). Post 7 weeks of AOM treatment, mice were euthanized and examined for CRC development. Mice consuming inulin‐containing diet exhibited severe colitis upon DSS administration, as evidenced by more body weight loss, rectal bleeding, and increased colonic inflammation than the DSS‐treated control group. Correspondingly, histological analysis revealed extensive disruption of colon architecture and massive infiltration of immune cells in the inulin‐fed group. We next examined the effect of inulin on CRC development. Surprisingly, significant mortality (~50%) was observed in the inulin‐fed but not in the control group during the DSS cycle. Consequently, the remaining inulin‐fed mice, which completed the study exhibited extensive colon tumorigenesis. Immunohistochemical characterization showed comparatively high expression of the cell proliferation marker Ki67 and activation of the Wnt signaling in tumor sections obtained from the inulin‐fed group. Gut microbiota and metabolite analysis revealed expansion of succinate producers and elevated cecal succinate in inulin‐fed mice. Human colorectal carcinoma cells (HCT116) proliferated more rapidly when supplemented with succinate in an inflamed environment, suggesting that elevated luminal succinate may contribute to tumorigenesis. Our study uncovers that supplementation of diet with refined inulin induces abnormal succinate accumulation in the intestinal lumen, which in part contributes to promoting colon inflammation and tumorigenesis.
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影响因子：
--
作者：
Baydi Z;Limami Y;Khalki L;Zaid N;Naya A;Mtairag EM;Oudghiri M;Zaid Y
通讯作者：
Zaid Y
影响因子：
64.8
作者：
Chassaing B;Koren O;Goodrich JK;Poole AC;Srinivasan S;Ley RE;Gewirtz AT
通讯作者：
Gewirtz AT
DOI：
10.1007/s10552-013-0201-5
发表时间：
2013-06
期刊：
Cancer causes & control : CCC
影响因子：
--
作者：
Johnson CM;Wei C;Ensor JE;Smolenski DJ;Amos CI;Levin B;Berry DA
通讯作者：
Berry DA
影响因子：
3.7
作者：
Chassaing B;Srinivasan G;Delgado MA;Young AN;Gewirtz AT;Vijay-Kumar M
通讯作者：
Vijay-Kumar M
影响因子：
12.2
作者：
Holscher HD
通讯作者：
Holscher HD