Liu Yongqiang, Mei Wangli, Huang Xinyan, Yao Xudong, Kong Cheng, Chen Yifan
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Urology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Oncol. 2025 Jul 14;15:1604876. doi: 10.3389/fonc.2025.1604876. eCollection 2025.
Tumor metabolomics of colorectal cancer (CRC) is significantly different from normal tissues, due to nutrient deprivation, metabolite accumulation, acidity and hypoxia. Besides, gut microbiota has been confirmed to affect the progression of CRC. Microbiota metabolites might participate in the metabolic reprogramming of CRC cells and further regulate tumor microenvironment.
10 CRC-related strains are cultured in vitro (10 replicates per bacterium), including Enterotoxic Escherichia coli (ETEC), Peptostreptococcus anaerobius (Pa), Fusobacterium necroporum (Fne), Fusobacterium nucleatum (Fn), Lactobacillus plantarum (Lp), Lactobacillus acidophilus (La), Lactobacillus casei (Lc), Lactobacillus rhamnosus gg (LGG), Bifidobacterium bifidum (Bbi), Bifidobacterium Breve (Bbr). Bacterial culture supernatant is subjected to gas chromatography-mass spectrometry.
The 10 CRC-related strains have characteristic metabolite profiles, mainly referring to specific saccharides, amino acids, bile acids, polyamines and bioactive compounds. Saccharides and organic acids increase significantly in (Lp, LA, Lc and LGG) compared with culture medium and other strains, such as galactinol, 1-ketose, beta-gentiobiose, glutaric acid, 3-phenyllactic acid, indlol-3-lactate. Chlorogenic acid, a beneficial polyphenol, increases significantly in Bbr. The abundance of amino acids and their derivatives changes significantly in (Bbi and Bbr), such as 2-hydroxy-2-methylbutanoic acid, N-acetyl-5-hydroxytryptamine and glutamate. Bile acids (lithocholic acid and cholic acid), polyamine (spermine), amino acids and derivatives (N-acetylaspartate, glutamate) increased significantly in the CRC-related pathogens (ETEC, Pa, Fn and Fne). Correspondingly, metabolic pathways are significantly affected, mainly including amino acid metabolism and nucleotide metabolism.
The 10 CRC-related strains possess significantly different metabolites and metabolic pathways. Specific metabolites and corresponding metabolic pathways might explain microbial CRC-promoting or -suppressing mechanisms.
由于营养缺乏、代谢物积累、酸性环境和缺氧,结直肠癌(CRC)的肿瘤代谢组学与正常组织显著不同。此外,肠道微生物群已被证实会影响CRC的进展。微生物群代谢物可能参与CRC细胞的代谢重编程,并进一步调节肿瘤微环境。
体外培养10种与CRC相关的菌株(每种细菌10个重复样本),包括产肠毒素大肠杆菌(ETEC)、厌氧消化链球菌(Pa)、坏死梭杆菌(Fne)、具核梭杆菌(Fn)、植物乳杆菌(Lp)、嗜酸乳杆菌(La)、干酪乳杆菌(Lc)、鼠李糖乳杆菌gg(LGG)、两歧双歧杆菌(Bbi)、短双歧杆菌(Bbr)。对细菌培养上清液进行气相色谱-质谱分析。
这10种与CRC相关的菌株具有特征性的代谢物谱,主要涉及特定的糖类、氨基酸、胆汁酸、多胺和生物活性化合物。与培养基和其他菌株相比,(Lp、La、Lc和LGG)中的糖类和有机酸显著增加,如棉子糖、1-酮糖、β-龙胆二糖、戊二酸、3-苯乳酸、吲哚-3-乳酸。有益的多酚类物质绿原酸在Bbr中显著增加。(Bbi和Bbr)中的氨基酸及其衍生物丰度变化显著,如2-羟基-2-甲基丁酸、N-乙酰-5-羟色胺和谷氨酸。与CRC相关的病原体(ETEC、Pa、Fn和Fne)中的胆汁酸(石胆酸和胆酸)、多胺(精胺)、氨基酸及其衍生物(N-乙酰天冬氨酸、谷氨酸)显著增加。相应地,代谢途径受到显著影响,主要包括氨基酸代谢和核苷酸代谢。
这10种与CRC相关的菌株具有显著不同的代谢物和代谢途径。特定的代谢物和相应的代谢途径可能解释微生物促进或抑制CRC的机制。