Department of Metabolomics, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Department of Pharmaceutical Analysis, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China.
Department of Pharmaceutical Analysis, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Mar 1;1192:123136. doi: 10.1016/j.jchromb.2022.123136. Epub 2022 Feb 5.
Gut microbiota is associated with tumor progress and host metabolic disorder, but whether gut microbiota regulation can affect cancer growth through interfering host metabolism maintains unknown yet. Here, we used combined antibiotics (ABX) to build an extremely altered gut microbiota ecosystem and study its influence on the xenograft MC38 tumor as well as the associations of the effects with host metabolisms. The MC38 tumor bearing mouse was treated with ABX (vancomycin, neomycin and imipenem-cilastatin) to build the extremely altered microbiota ecosystem, the gut microbiota diversity alteration was determined by 16S rRNA based gene sequencing. The effects of the altered microbiota on tumor were assessed by cell apoptosis and growth rate of the tumor. The potential metabolic biomarkers and involved metabolism pathways were screened out by UPLC-QTOF-MS/MS based untargeted metabolomics and KEGG analysis respectively. The correlations between key metabolites and microbiota were analyzed by Spearman correlation analysis. Compared with the un-treated mice, the tumor growth of ABX-treated mice was significantly suppressed, and the cell apoptosis was obviously promoted. The gut microbiota diversity was decreased significantly with the dominant bacteria phylum Bacteroidetes and Firmicutes replaced by Proteobacteria, which involved 14 significantly altered bacteria genera. Four potential targeted metabolism pathways, including sphingolipid, glycerophospholipid, arginine-proline and primary bile acid metabolism, were screened out, and the involved key metabolites such as ceramide, phosphatidylethanolamine, phosphatidylcholine, taurocholic acid and L-proline were correlated significantly with the altered bacteria genera. Through the integrated analysis of microbiome and metabolomics, it was revealed that gut microbiota regulation may inhibit the xenograft MC38 tumor growth potentially by interfering host lipid and amino acid metabolisms, such as sphingolipid, glycerophospholipid, primary bile acid and arginine-proline metabolisms in this case.
肠道微生物群与肿瘤进展和宿主代谢紊乱有关，但肠道微生物群调节是否通过干扰宿主代谢来影响癌症生长尚不清楚。在这里，我们使用联合抗生素（ABX）构建了一个极度改变的肠道微生物生态系统，并研究了其对异种移植 MC38 肿瘤的影响以及这些影响与宿主代谢之间的关联。使用 ABX（万古霉素、新霉素和亚胺培南-西司他丁）处理 MC38 荷瘤小鼠，以构建极度改变的微生物生态系统，通过 16S rRNA 基因测序确定肠道微生物多样性的改变。通过细胞凋亡和肿瘤生长速度评估改变的微生物对肿瘤的影响。通过 UPLC-QTOF-MS/MS 基于非靶向代谢组学和 KEGG 分析分别筛选潜在的代谢生物标志物和涉及的代谢途径。通过 Spearman 相关分析分析关键代谢物与微生物群之间的相关性。与未处理的小鼠相比，ABX 处理的小鼠的肿瘤生长明显受到抑制，细胞凋亡明显增强。肠道微生物多样性显著降低，优势菌门拟杆菌门和厚壁菌门被变形菌门取代，涉及 14 个明显改变的细菌属。筛选出四个潜在的靶向代谢途径，包括鞘脂、甘油磷脂、精氨酸-脯氨酸和初级胆汁酸代谢，涉及关键代谢物如神经酰胺、磷脂酰乙醇胺、磷脂酰胆碱、牛磺胆酸和 L-脯氨酸与改变的细菌属显著相关。通过微生物组和代谢组学的综合分析，揭示了肠道微生物群调节可能通过干扰宿主脂质和氨基酸代谢来抑制异种移植 MC38 肿瘤的生长，在这种情况下，如鞘脂、甘油磷脂、初级胆汁酸和精氨酸-脯氨酸代谢。
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