Cheung Man Kit, Yue Grace Gar Lee, Tsui Kei Yin, Gomes Adele Joyce, Kwan Hoi Shan, Chiu Philip Wai Yan, Lau Clara Bik San
Department of Surgery, The Chinese University of Hong Kong Shatin, New Territories, Hong Kong.
Institute of Chinese Medicine, The Chinese University of Hong Kong Shatin, New Territories, Hong Kong.
Am J Cancer Res. 2020 Aug 1;10(8):2409-2427. eCollection 2020.
Esophageal squamous cell carcinoma (ESCC) is the main type of esophageal cancer (EC) worldwide, causing half a million deaths each year. Recent evidence has demonstrated the role of the gut microbiota in health and disease. However, our current understanding of the gut microbiome in EC remains scarce. Here, we characterized the gut and esophageal microbiome in a metastatic mouse model of ESCC and examined the functional roles of the gut microbiota in EC development in fecal microbiota transplantation (FMT) experiments. Nude mice intraperitoneally xenografted with human EC-109 cells showed significant alterations in the overall structure, but not alpha diversity, of the gut and esophageal microbiome as compared to naïve control mice. Xenograft of EC cells depleted the order in the gut microbiome, and enriched multiple predicted metabolic pathways, including those involved in carbohydrate and lipid metabolism, in the esophageal microbiome. FMT of stool from healthy mice to antibiotic-treated xenograft-bearing mice significantly attenuated liver metastasis, suggesting a protective role of the commensal gut microbiota in EC. Moreover, we showed that combination chemotherapy with cisplatin and 5-fluorouracil, and the anti-EC medicinal herb (AP) differentially affected the gut and esophageal microbiome in EC. FMT experiment revealed a reduced anti-metastatic efficacy of AP on liver metastasis in antibiotic-treated xenograft-bearing mice, suggesting a role of the commensal gut microbiota in the anti-metastatic efficacy of the herb. In conclusion, our findings reveal for the first time an interplay between the gut microbiota and EC and provide insights into the treatment strategies for EC.
食管鳞状细胞癌（ESCC）是全球食管癌（EC）的主要类型，每年导致50万人死亡。最近的证据表明肠道微生物群在健康和疾病中的作用。然而，我们目前对EC中肠道微生物组的了解仍然很少。在这里，我们在ESCC转移小鼠模型中对肠道和食管微生物组进行了表征，并在粪便微生物群移植（FMT）实验中研究了肠道微生物群在EC发展中的功能作用。与未处理的对照小鼠相比，腹腔内接种人EC-109细胞的裸鼠在肠道和食管微生物组的整体结构上有显著改变，但α多样性没有改变。EC细胞的异种移植使肠道微生物组中的菌目减少，并使食管微生物组中的多种预测代谢途径富集，包括那些参与碳水化合物和脂质代谢的途径。将健康小鼠的粪便移植到经抗生素处理的荷瘤异种移植小鼠中，可显著减轻肝转移，表明共生肠道微生物群在EC中具有保护作用。此外，我们表明顺铂和5-氟尿嘧啶联合化疗以及抗EC草药（AP）对EC中的肠道和食管微生物组有不同影响。FMT实验显示，在经抗生素处理的荷瘤异种移植小鼠中，AP对肝转移的抗转移疗效降低，表明共生肠道微生物群在该草药的抗转移疗效中起作用。总之，我们的研究结果首次揭示了肠道微生物群与EC之间的相互作用，并为EC的治疗策略提供了见解。
