Clin Nutrition:营养不良的结直肠癌患者的粪便会加速癌症进展

2023-03-13 MedSci原创 MedSci原创 发表于上海

结肠癌是常见的发生于结肠部位的消化道恶性肿瘤,结肠癌与人们食用红肉(如牛肉)有着很大的相关性。好发于直肠与乙状结肠交界处,以40~50岁年龄组发病率最高,男女之比为2~3:1。

      结直肠癌(CRC)是最常见的恶性肿瘤之一,然而,CRC的发病机制仍不清楚。在所有肠道环境因素中,肠道微生物群在 CRC 进展中起主要作用。此外,肠道微生物群与营养不良、肥胖、糖尿病、心脏病、癌症和自身免疫性疾病有关。新出现的数据表明,CRC 患者的营养状况会影响肠道微环境并影响肿瘤进展。营养不良会增加CRC 患者术后并发症、抗癌治疗副作用、预后不良和死亡率的风险,从而导致住院和医疗的持续时间和费用增加。此外,以前的研究主要关注营养不良的 CRC 患者预后不良的生物标志物,而本项研究工作强调了营养不良的 CRC 患者微生物群的动态变化,这为这些患者的诊断标准提供了新的见解。

 

      为此,在这项工作中,研究人员准备了主观全局评估(PG-SGA)工具和 16sRNA 测序来检测肠道微生物群的变化以及营养状况与肠道微生物群之间的关联。(冗余分析/典型对应分析)RDA/CCA 分析用于评估来自营养不良的 CRC 的粪便微生物群与临床营养指标之间的关系。为了研究 CRC 肠道微生物群的机制,将营养不良的 CRC 患者的粪便样本移植到 C57BL/6J 和 DSS/AOM 小鼠模型中。此外,制备了FACS和IHC来检测 B 细胞和巨噬细胞的浸润。

 

      研究结果显示不同营养状况患者的粪便微生物群存在显着差异,研究人员发现特定微生物群物种,即Atopobium v​​aginae、Selenomonas sputigena和Faecalibacterium prausnitzii,可能被认为是营养不良的诊断生物标志物,表明预后不良。与低表达水平相比, A. vaginae在 CRC 组织中的高表达水平显示出较差的总生存期(平均生存期:23.0 个月 VS  29.0 个月)。来自营养不良的结直肠癌的粪便被发现具有致癌性。更重要的是,研究证据表明,粪便微生物群移植后, B 细胞和巨噬细胞被招募来激活 CRC 中的特定肿瘤免疫。B细胞的消耗显着抑制了粪便微生物群诱导的M2b极化以及体内肿瘤相关巨噬细胞的致瘤活性。

图:营养不良的结直肠癌患者的粪便会恶化疾病预后

 

      本项研究证实营养不良条件下 CRC 中的粪便微生物群表现出加速 CRC 进展和调节 B 细胞和巨噬细胞的特定特征。使用特定的粪便微生物种类可能是识别患者营养不良状态和证明 CRC 预后不良的可行方法。

 

 

原始出处:

XuChao. Et al. Faeces from malnourished colorectal cancer patients accelerate cancer progression. Clinical Nutrition.2022.

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    2022-03-31 ms2000000335050471

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    2022-03-15 Homburg

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