Gut microbiota influenced the xenograft MC38 tumor growth potentially through interfering host lipid and amino acid metabolisms, basing on the integrated analysis of microbiome and metabolomics

Abstract

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.

Keywords: Gut microbiota; Host metabolism; MC38 tumor; Metabolomics; Microbiome; UPLC-QTOF-MS/MS.