Gut microbial dysbiosis is associated with development and progression of radiation enteritis during pelvic radiotherapy
Gut microbial dysbiosis is associated with development and progression of radiation enteritis during pelvic radiotherapy
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肠道微生物失调与盆腔放疗期间放射性肠炎的发生和进展有关
DOI：
10.1111/jcmm.14289
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发表时间：
2019-05-01
影响因子：
5.3
通讯作者：
Yuan, Zhiyong
中科院分区：
文献类型：
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作者：
Wang, Zhongqiu;Wang, Qingxin;Yuan, Zhiyong
放射性肠炎（RE）是盆腔放疗最常见的并发症。在此，我们调查了肠道微生物谱的变化及其与盆腔放疗患者肠炎的关系。在放射治疗期间从18名宫颈癌患者中收集粪便样本。使用Illumina HiSeq平台基于16 S rRNA测序表征微生物群谱。使用细菌-上皮共培养物评价上皮炎症反应。RE患者体内存在菌群失调，其特征为α多样性显著降低，β多样性增加，变形菌和γ-变形菌丰度相对较高，拟杆菌丰度较低。粪球菌明显富集放射治疗前的患者谁后来发展RE。Metastat分析进一步揭示了独特的等级相关微生物特征，例如轻度肠炎患者中更丰富的Virgibacillus和Alcanivorax。此外，使用细菌-上皮共培养物，与对照微生物群相比，RE患者来源的微生物群诱导上皮炎症和屏障功能障碍，增强TNF-α和IL-1β表达。总之，我们定义了RE患者肠道微生物群的整体情况。我们的研究结果表明，肠道微生物群的生态失调可能有助于RE的发展和进展。肠道微生物群可以为RE的预测、疾病活动性评估和治疗选择提供一组生物标志物。
Radiation enteritis (RE) is the most common complication of radiotherapy for pelvic irradiation receivers. Herein we investigated the alterations in gut microbial profiles and their association with enteritis in patients undergoing pelvic radiotherapy. Faecal samples were collected from 18 cervical cancer patients during radiotherapy. Microbiota profiles were characterized based on 16S rRNA sequencing using the Illumina HiSeq platform. Epithelial inflammatory response was evaluated using bacterial‐epithelial co‐cultures. Dysbiosis was observed among patients with RE, which was characterized by significantly reduced α‐diversity but increased β‐diversity, relative higher abundance of Proteobacteria and Gammaproteobacteria and lower abundance of Bacteroides. Coprococcus was clearly enriched prior to radiotherapy in patients who later developed RE. Metastat analysis further revealed unique grade‐related microbial features, such as more abundant Virgibacillus and Alcanivorax in patients with mild enteritis. Additionally, using bacterial‐epithelial co‐cultures, RE patient‐derived microbiota induced epithelial inflammation and barrier dysfunction, enhanced TNF‐α and IL‐1β expression compared with control microbiota. Taken together, we define the overall picture of gut microbiota in patients with RE. Our results suggest that dysbiosis of gut microbiota may contribute to development and progression of RE. Gut microbiota can offer a set of biomarkers for prediction, disease activity evaluation and treatment selection in RE.