目的: 分析高海拔地区结直肠良恶性肿瘤患者肠道菌群变化，并与低海拔地区人群进行比较。方法: 收集2020—2022年于西藏自治区人民医院接受结肠镜检查的61例患者的临床资料，根据结肠镜检查结果分为4组高海拔对照组(29例)、非腺瘤性息肉组(12例)、腺瘤组(10例)和结直肠癌组(10例)，收集同期在北京大学第三医院接受结肠镜检查且结果正常者17例为低海拔对照组。结肠镜检查肠道准备前收取受试者的粪便标本，进行细菌DNA提取，对16S rRNA基因V3~V4可变区进行PCR扩增及高通量测序，得到粪便样本的菌群组成，进行物种的多样性分析。结果: α多样性分析显示，高海拔结直肠癌组样本物种多样性与高海拔非腺瘤性息肉组及低海拔对照组间差异有统计学意义，且高海拔结直肠癌组样本的物种多样性较其他两组高；但5组间的β多样性差异无统计学意义。门水平的差异分析发现，低海拔对照组中放线菌门(Actinobacteria)丰度明显低于高海拔各组，而高海拔结直肠癌组放线菌门丰度明显低于其他3个高海拔组。属水平的差异分析发现，低海拔对照组中拟杆菌属(Bacteroides)、考拉杆菌属(Phascolarctobacterium)、梭状芽胞杆菌属(Lachnoclostridium)丰度明显较所有高海拔组高；布鲁菌属(Blautia)、科林斯菌属(Collinsella)在高海拔对照组中丰度最高；低海拔对照组中未检测到乳酸杆菌属(Lactobacillus)，而高海拔各组间乳酸杆菌属丰度差异有统计学意义(P≤0.001)，且高海拔对照组明显高于其他3组；高海拔结直肠癌组双歧杆菌属(Bifidobacterium)丰度明显下降，但克里斯滕森氏菌科R-7群(Christensenellaceae_R-7_group)丰度明显升高。结论: 与高海拔及低海拔对照组相比，高海拔结直肠良恶性肿瘤患者肠道菌群的多样性及丰富度存在差异，且在门及属水平上的物种丰度也存在差异，表明海拔因素可能对肠道菌群有一定的影响。

Objective: To analyze the changes of intestinal flora in patients with benign and malignant colorectal tumors in high altitude areas and to compare them with the normal population in low altitude areas. Methods: The clinical data of 61 patients who underwent colonoscopy in the People' s Hospital of Tibet Autonomous Region from 2020 to 2022 were collected as the high altitude group. According to the colonoscopy results, they were divided into control group (29 cases), non-adenomatous polyp group (12 cases), adenoma group (10 cases), colorectal cancer group (10 cases). 17 patients who had negative colonoscopy results in the Peking University Third Hospital during the same period were collected as the low altitude control group. Before bowel preparation for colonoscopy, the fecal samples were collected. Then the DNA of bacteria in the fecal samples was extracted. The V3-V4 variable region of the 16S rRNA gene was PCR amplified and high-throughput sequenced. The species diversity of fecal flora was analyzed. Results: Alpha diversity analysis showed that the species diversity of samples from the high altitude colorectal cancer group differed statistically from that of the high altitude non-adenomatous polyp group and the low altitude control group, and the species diversity of colorectal samples from the high altitude colorectal cancer group was higher than that of the other two groups. While beta diversity showed no significant difference among the five groups. Differences were found in phylum level analysis that the abundance of Actinobacteriota in the low altitude control group was significantly lower than those in each group of the high altitude area, while the abundance of Actinobacteriota in the colorectal cancer group was significantly lower than those in the other 3 groups of the high altitude area. Differences were found in genus level analysis that the abundance of Bacteroides, Phascclarctobacterium and Lachnoclostridium in the low altitude control group was significantly higher than those of all the groups in the high altitude area; the abundance of Blautia and Collinsella in the high altitude control group was the highest. Lactobacillus was not detected in the low altitude control group, while there was a highly significant difference (P < 0.05) in the level of Lactobacillus in the four groups of high altitude area, and the abundance of Lactobacillus was significantly higher in the control group than those of the other three groups. In the four groups of samples at high altitude, the abundance of Bifidobacterium decreased significantly, while the abundance of Christensenellaceae_R-7_group increased significantly. Conclusion: Compared with the high and low altitude controls, the diversity and abundance of intestinal flora in patients with colorectal benign and malignant tumors at high altitudes are different. And the abundance of species are also diffe-rent at the phylum and genus levels, suggesting that altitude factors may have some influence on intestinal flora.

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作者贡献声明  李军：提出研究思路，总体把关和审定论文；李秋红：数据收集；韩丹、次仁央金：数据整理，统计学处理，结果分析与解释，论文撰写。