Differences in gut microbiota and metabolites between colorectal cancer patients with different metastatic statuses

Xia Yang; Zhang Xinlian; Duan Ling; Ling Xiaoling

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Differences in gut microbiota and metabolites between colorectal cancer patients with different metastatic statuses

更新时间：2025-08-25

- Differences in gut microbiota and metabolites between colorectal cancer patients with different metastatic statuses
- Journal of Chongqing Medical University Pages: 1-9(2025)
- 作者机构：
  
  1.兰州大学第一临床医学院，兰州 730000
  2.兰州市第一人民医院血液科，兰州 730000
- 作者简介：
- 基金信息：
- DOI：
  CLC： R735.3
- Received：07 May 2025，
  
  Published Online：25 August 2025，
- 稿件说明：
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夏阳,张新莲,段玲等.肠道菌群及代谢物在不同转移状态肠癌患者中的差异分析[J].重庆医科大学学报,

Xia Yang,Zhang Xinlian,Duan Ling,et al.Differences in gut microbiota and metabolites between colorectal cancer patients with different metastatic statuses[J].Journal of Chongqing Medical University,
夏阳,张新莲,段玲等.肠道菌群及代谢物在不同转移状态肠癌患者中的差异分析[J].重庆医科大学学报, DOI：10.13406/j.cnki.cyxb..

Xia Yang,Zhang Xinlian,Duan Ling,et al.Differences in gut microbiota and metabolites between colorectal cancer patients with different metastatic statuses[J].Journal of Chongqing Medical University, DOI：10.13406/j.cnki.cyxb..

摘要

目的

本研究通过对不同转移状态的结直肠癌（colorectal cancer，CRC）患者肠道菌群及粪便代谢物的联合分析，探讨二者对CRC发生、发展的影响。

方法

选取符合纳入标准的CRC患者及本地健康人群为研究对象，分为健康组（C组）、CRC无远处转移组（S组）、CRC单发转移组（DZ组）、CRC多发转移组（Z组），将患者的粪便样本进行16S rDNA 和非靶向代谢组学分析，分析不同组间肠道菌群及代谢物差异，并通过Spearman相关性分析揭示菌群-代谢物关联。

结果

①菌群多样性：四组间肠道菌群Alpha多样性差异无统计学意义（

0.05），Beta多样性具有统计学差异（

0.05）。②菌群组成：变形菌门、厚壁菌门、拟杆菌门、放线菌门为主要差异菌群。不同组别间肠道菌群组成形成差异，宏基因组序列分析及线性判别分析综合研究发现除了DZ组与Z组肠间道菌群无明显差异性外，其余组间肠道菌群均存在差异性。③代谢物差异：关键差异代谢物包括：哈帕吲哚D（S组高表达）、章鱼碱（DZ/Z组高表达）和次黄嘌呤（Z组高表达）。④菌群-代谢物关联：粪便代谢物与肠道差异菌属表现出明显的相关性，如毛螺菌属NK4A136组和韦荣氏球菌属与丙氨酸-亮氨酸呈正相关（

0.05）；毛螺菌属NK4A136组和F0058与亮肽素呈明显负相关。

结论

不同转移状态CRC患者肠道菌群及粪便代谢物存在差异，CRC的发生、发展可能与肠道菌群及粪便代谢物存在关联。

Abstract

Objective

To investigate the differences in gut microbiota and metabolites between colorectal cancer（CRC） patients with different metastatic statuses，as well as their influence on the development and progression of CRC.

Methods

The CRC patients who met the inclusion criteria and local healthy individuals were enrolled as subjects，and they were divided into healthy group（group C），CRC without distant metastasis group（group S），CRC with single metastasis group（group DZ），and CRC with multiple metastases group（group Z）. Fecal samples were collected，and 16S rDNA sequencing and untargeted metabolomics analysis were performed to investigate the differences in gut microbiota and metabolites between groups，while a Spearman correlation analysis was performed to reveal the correlation between gut microbiota and metabolites.

Results

As for the diversity of gut microbiota，there was no significant difference in alpha diversity between the four groups（

0.05），but there was a significant difference in beta diversity between the four groups（

0.05）. As for the composition of gut microbiota，Proteobacteria，Firmicutes，Bacteroidetes，and Actinobacteria were the main differentially expressed bacteria，and there was a difference in the composition of gut microbiota between groups； metagenome sequencing and linear discriminant analysis showed that there was a significant difference in gut microbiota between all groups except between group DZ and group Z. As for metabolites，key differentially expressed metabolites included Hapalindole D（highly expressed in group S），Octopine（highly expressed in groups DZ and Z），and Hypoxanthine（highly expressed in group Z）. As for the correlation between gut microbiota and metabolites，fecal metabolites were significantly correlated with differentially expressed bacteria in gut microbiota； for example，Lachnospiraceae NK4A136 and Veillonella were positively correlated with the alanine-leucine peptide fragment（

0.05），while Lachnospiraceae NK4A136 and F0058 were negatively correlated with leupeptin.

Conclusion

There are differences in gut microbiota and fecal metabolites between CRC patients with different metastatic statuses，and the development and progression of CRC may be associated with gut microbiota and fecal metabolites.

关键词

Keywords

references

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