Author:
Xi Yu,Liu FangJie,Qiu Bo,Li Ying,Xie XinQiang,Guo JinYu,Wu Lei,Liang TingTing,Wang DaQuan,Wang Juan,Chen Moutong,Xue Liang,Ding Yu,Zhang Jumei,Wu QingPing,Liu Hui
Abstract
PurposeTo evaluate the association of gut microbiome signature and disease progression in locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) by fecal metagenome analysis.MethodsMetagenome-wide association studies on baseline fecal samples from 18 LA-NSCLC patients before CCRT and 13 controls from healthy first-degree relatives were performed. Among the 18 LA-NSCLC patients, six patients were defined as the long progression-free survival (long-PFS) group (PFS≥11 months) while another 12 were in the short-PFS group (PFS<11 months). Alpha diversity, taxonomic composition, and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways were compared between groups.ResultsThe Firmicutes/Bacteroidetes value of long-PFS group was higher than those of short-PFS (p=0.073) and healthy individual groups (p=0.009). Meanwhile, long-PFS group had significantly higher diversities in Fungi, Archaea, and Viruses than short-PFS group. The KEGG pathways overrepresented in short-PFS group included fructose and mannose metabolism (p=0.028), streptomycin biosynthesis (p=0.028), acarbose and validamycin biosynthesis (p=0.013), ribosome biogenesis in eukaryotes (p=0.035), biosynthesis of vancomycin group antibiotics (p=0.004), apoptosis-fly (p=0.044), and tetracycline biosynthesis (p=0.044), while those overrepresented in long-PFS group included fatty acid biosynthesis (p=0.035), fatty acid metabolism (p=0.008), vancomycin resistance (p=0.008), longevity regulating pathway-worm (p=0.028), type II diabetes mellitus (p=0.004), and viral carcinogenesis (p=0.003). Further analysis of antibiotic resistome demonstrated that the short-PFS group had a trend with more antibiotic resistance genes than healthy control (p=0.070) and long-PFS groups (p=0.218). The vancomycin resistance sequences were significantly enriched in the long-PFS group compared to the short-PFS group (p=0.006).ConclusionsThe baseline gut microbiome composition and functionality might be associated with PFS in LA-NSCLC treated with CCRT. The outcome of CCRT might be modulated through bacterial metabolic pathways. The antibiotic resistance genes might play a role in disease progression and provide potential information on the relationship between the use of antibiotics and treatment efficacy of CCRT in LA-NSCLC.
Funder
National Natural Science Foundation of China
National Key Research and Development Program of China
Subject
Infectious Diseases,Microbiology (medical),Immunology,Microbiology
Cited by
5 articles.
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