Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, China.
J Appl Microbiol. 2022 Aug;133(2):1014-1026. doi: 10.1111/jam.15620. Epub 2022 May 25.
The altered faecal metabolites and microbiota might be involved in the development of breast cancer. We aimed to investigate the effect of differential metabolites on the proliferative activity of breast cancer cells.
We collected faecal samples from 14 breast cancer patients and 14 healthy subjects. Untargeted metabolomics analysis, short-chain fatty acid (SCFA) targeted analysis, and 16S rDNA sequencing was performed. The gut metabolite composition of patients changed significantly. Levels of norvaline, glucuronate and galacturonate were lower in the cancer group than in the Control (p < 0.05). 4-Methylcatechol and guaiacol increased (p < 0.05). Acetic acid and butyric acid were lower in the cancer group than in the control group (p < 0.05). Isobutyric acid and pentanoic acid were higher in the cancer group than in the control (p < 0.05). In the genus, the abundance of Rothia and Actinomyces increased in the cancer group, compared with the control group (p < 0.05). The differential microbiotas were clearly associated with differential metabolites but weakly with SCFAs. The abundance of Rothia and Actinomyces was markedly positively correlated with 4-methylcatechol and guaiacol (p < 0.05) and negatively correlated with norvaline (p < 0.05). L-norvaline inhibited the content of Arg-1 in a concentration-dependent manner. Compared with the L-norvaline or doxorubicin hydrochloride (DOX) group, the proliferation abilities of 4 T1 cells were the lowest in the L-norvaline combined with DOX (p < 0.05). The apoptosis rate increased (p < 0.05).
Faecal metabolites and microbiota were significantly altered in breast cancer. Levels of differential metabolites (i.e. Norvaline) were significantly correlated with the abundance of differential microbiota. L-norvaline combined with DOX could clearly inhibit the proliferation activity of breast cancer cells.
This might provide clues to uncover potential biomarkers for breast cancer diagnosis and treatment.
改变的粪便代谢物和微生物群可能参与乳腺癌的发展。我们旨在研究差异代谢物对乳腺癌细胞增殖活性的影响。
我们收集了 14 名乳腺癌患者和 14 名健康受试者的粪便样本。进行了非靶向代谢组学分析、短链脂肪酸 (SCFA) 靶向分析和 16S rDNA 测序。患者的肠道代谢物组成发生了显著变化。与对照组相比，癌症组中的正缬氨酸、葡糖醛酸和半乳糖醛酸水平较低（p<0.05）。4-甲基儿茶酚和愈创木酚增加（p<0.05）。癌症组中的乙酸和丁酸低于对照组（p<0.05）。癌症组中的异丁酸和戊酸高于对照组（p<0.05）。在属水平上，与对照组相比，癌症组中的罗特氏菌和放线菌丰度增加（p<0.05）。差异微生物群与差异代谢物明显相关，但与 SCFA 弱相关。罗特氏菌和放线菌的丰度与 4-甲基儿茶酚和愈创木酚呈显著正相关（p<0.05），与正缬氨酸呈负相关（p<0.05）。L-正缬氨酸呈浓度依赖性抑制 Arg-1 的含量。与 L-正缬氨酸或盐酸多柔比星（DOX）组相比，L-正缬氨酸联合 DOX 组的 4T1 细胞增殖能力最低（p<0.05）。凋亡率增加（p<0.05）。
乳腺癌患者粪便代谢物和微生物群发生明显改变。差异代谢物（即正缬氨酸）的水平与差异微生物群的丰度显著相关。L-正缬氨酸联合 DOX 可明显抑制乳腺癌细胞的增殖活性。
这可能为发现潜在的乳腺癌诊断和治疗生物标志物提供线索。
