DataSheet1_Alterations of the Gut Microbiome and Fecal Metabolome in Colorectal Cancer: Implication of Intestinal Metabolism for Tumorigenesis.docx

Objective: The gut microbiota and its metabolites are important for host physiological homeostasis, while dysbiosis is related to diseases including the development of cancers such as colorectal cancer (CRC). In this study, we characterized the relationship of an altered gut microbiome with the fecal metabolome in CRC patients in comparison with volunteers having a normal colorectal mucous membrane (NC).
Methods: The richness and composition of the microbiota in fecal samples of 30 CRC patients and 36 NC controls were analyzed through 16S rRNA gene sequencing, and the metabolome was determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry. Spearman correlation analysis was to determine the correlation between the gut microbiome and fecal metabolome in CRC patients.
Results: There were significant alterations in the gut microbiome and fecal metabolome in CRC patients compared with NC controls. Bacteroidetes, Firmicutes, Actinobacteriota, and Proteobacteria dominated the gut microbial communities at the phylum level in both groups. Compared with NC controls, CRC patients had a lower frequency of Blautia and Lachnospiracaea but a higher abundance of Bacteroides fragilis and Prevotella. Regarding the fecal metabolome, twenty-nine metabolites were identified as having significantly changed, showing increased levels of adrenic acid, decanoic acid, arachidonic acid, and tryptophan but a reduction in various monosaccharides in the fecal samples of CRC patients. Moreover, increased abundance of Bacteroides fragilis was strongly associated with decreased levels of monosaccharides, while Blautia was positively associated with the production of monosaccharides in the fecal samples.
Conclusion: These results highlight alterations of gut microbiota in association with certain metabolites in CRC progression, implying potential diagnostic and intervention potential for CRC.

研究目的：肠道菌群（gut microbiota）及其代谢产物对宿主生理稳态至关重要，而菌群失调（dysbiosis）与包括结直肠癌（colorectal cancer, CRC）在内的多种癌症发生密切相关。本研究旨在对比CRC患者与结直肠黏膜正常者（normal colorectal mucous membrane, NC），解析失调的肠道菌群与粪便代谢组（fecal metabolome）之间的关联。
研究方法：本研究通过16S rRNA基因测序（16S rRNA gene sequencing）分析30例CRC患者及36例结直肠黏膜正常对照者的粪便样本中菌群的丰度与组成，并采用超高效液相色谱串联质谱（ultra-performance liquid chromatography coupled to tandem mass spectrometry）检测粪便代谢组；同时通过斯皮尔曼相关分析（Spearman correlation analysis）探究CRC患者肠道菌群与粪便代谢组之间的关联。
研究结果：与结直肠黏膜正常对照者相比，CRC患者的肠道菌群与粪便代谢组均发生显著改变。两组肠道菌群在门水平均以拟杆菌门（Bacteroidetes）、厚壁菌门（Firmicutes）、放线菌门（Actinobacteriota）及变形菌门（Proteobacteria）为主。与对照组相比，CRC患者粪便中布劳特氏菌属（Blautia）与毛螺菌科（Lachnospiracaea）的检出频率降低，而脆弱拟杆菌（Bacteroides fragilis）与普雷沃菌属（Prevotella）的丰度升高。在粪便代谢组层面，共鉴定出29种存在显著差异的代谢物：CRC患者粪便中肾上腺酸（adrenic acid）、癸酸（decanoic acid）、花生四烯酸（arachidonic acid）及色氨酸（tryptophan）水平升高，而各类单糖（monosaccharides）水平降低。进一步分析显示，脆弱拟杆菌丰度升高与单糖水平降低显著相关，而布劳特氏菌属则与粪便中单糖的产生呈正相关。
研究结论：本研究结果揭示了结直肠癌进展过程中肠道菌群的改变与特定代谢物的关联，提示其在CRC诊断及干预中具有潜在应用价值。