The Microbiome Of Tumor Patients And Its Relationship With Antitumor Therapy

Background and objective:As the largest microbiome of host,gut microbiome associates with immune and metabolism.Gut microbiome also relates with tumor genesis,progression and antitumor therapy.This study aims to investigate the characteristics of gut microbiome of tumor hosts and the correlations between gut microbiome and antitumor therapy.Methods:34 tumor patients were collected prospectively,including their gender,age,tumor types,smoking,drinking,underlying diseases,TNM stages and antitumor therapies.Fecal samples were gathered at baseline and at efficacy evaluation.Lymphocyte subsets at baseline and results of therapeutic efficacy were recorded.Gut microbiome were sequenced by 16 S r DNA V4 region on Ion S5 TMXL plat.Operational taxonomic units(OTUs)were clustered by 97% consistency.After species annotations,the α diversity and β diversity of the samples were calculated.Significance analysis of differences in species and community structures between groups,network analysis and model prediction,and gene function prediction were committed.Groups were classified by(1)tumor types including 9 individuals of digestive tract tumors,19 individuals of lung cancers and 6 individuals of primary hepatocellular carcinomas;(2)therapeutic reponses including 17 cases of stable diseases(SD),11 cases of partial regression(PR)and 6 cases of progressive diseases(PD).Kaplan-Meier survival analysis and log-rank test were committed.Results:1.No statistical difference was detected on the α diversity(P>0.05,Tukey)and βdiversity(P>0.05,NMDS)among groups of tumor types.2.Unidentified_Lachnospiraceae was identified as a biomarker of gut microbiome between SD vs PR groups and SD vs PD groups by LEf Se(LDA score >4).3.6,21 and 33 gene functions were significantly different between PR vs SD groups,SD vs PD groups and PR vs PD groups by t-test(P<0.05).Gene functions associating with protein folding,chlorophyll metabolism,and glyoxylate and dicarboxylate anabolism accumulated in groups obtaining better therapeutic responses.Gene functions associating with transcription,translation,repair and nucleotide metabolism were abundant in groups with worse therapeutic responses.4.No significant changes of the α diversity and β diversity of gut microbiome were observed before and after antitumor therapy(P>0.05).5.Pearson correlation analysis showed that the relative abundance of proteobacteria was negatively associated with T lymphocytes(CD3+)(r=-0.776,P=0.002)and inducing/assiting T lymphocytes(CD3+CD4+)(r=-0.568,P=0.043);the relative abundance of Proteobacteria was positively associated with NK cells(CD16+CD56+)(r=0.820,P=0.001);the relative abundance of faecalibacterium was positively associated with B lymphocytes(CD19+)(r=0.632,P=0.043).6.Kaplan-Meier survival analysis showed that the α diversity of gut microbiome related with progression-free survival(PFS).Compared with lower Shannon index subgroups,individuals with higher Shannon index obtained longer PFS(7.9m vs 2.8m,P<0.001).Likewise,individuals with higher Simpson index also obtained longer PFS compared to those with lower Simpson index(7.4m vs 2.8m,P=0.011).Conclusions:1.The gut microbiomes of hosts with different tumor types are not significantly different.2.Unidentified_Lachnospiraceae is a biomarker of therapeutic response.3.For hosts with well therapeutic responses,gene functions associating with protein folding,chlorophyll metabolism,and glyoxylate and dicarboxylate anabolism accumulate in gut microbiome.Whereas hosts with bad therapeutic responses,gene functions associating with transcription,translation,repair,nucleotide metabolism and amino acid metabolism are abundant.4.No significant changes of gut microbiome diversity during antitumor therapy.5.In phylum,the relative abundance of proteobacteria negatively associates with T lymphocytes and inducing/assiting T lymphocytes,but positively associates with NK cells;In genus,the relative abundance of faecalibacterium positively associates with B lymphocytes.6.The higher α diversity of gut microbiome,the better progression-free survival of hosts.