The association between inflammation, the microbiome and urethane-induced pulmonary adenocarcinoma

Abstract

Lung cancer is amongst the most common types of cancer throughout the world. The overall 5-year survival rate is ~17%. A number of studies have demonstrated that the microbiome existing within the host may affect the level of inflammation, and consequently contribute to the carcinogenesis of certain types of cancer. To investigate the role of inflammation and the microbiome in the carcinogenesis of lung cancer, an intervention study involving mice, including a control group (C; n=5), a urethane-induced pulmonary adenocarcinoma group (U; n=5) and a prebiotics intervention group (P; n=5) was carried out. This pulmonary adenocarcinoma model was reviewed, and incidences of the disease were identified using histopathology. The levels of the inflammatory cytokines nuclear factor κB (NF-κB), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and IL-6 in the sera samples were measured using an ELISA technique. In addition, high-throughput sequencing of the 16S ribosomal RNA gene segment was used to analyze the species present in the microbiome of the lower airways and intestinal tracts of mice. The results demonstrated that groups P and U exhibited altered histopathology and the development of lung adenocarcinoma tumors, but no differences were observed between the groups. The level of inflammation, determined by measuring the levels of NF-κB, TNF-α, IL-1β and IL-6 inflammatory cytokines, was significantly lower in group P compared with group U (P<0.05), and was significantly higher in group P compared with group C (P<0.05). Overall, the microbiomes of the lower respiratory and intestinal tracts did not change markedly among the 3 groups, in terms of the size of colonies and Shannon diversity indices. However, at a family and operational taxonomic unit (OTU) level, certain microbiota were altered. For example, the abundance of the Clostridiales and Lachnospiraceae families was lower in the lung and intestinal tracts subsequent to urethane-induced treatment compared with in the control group (P<0.05), and the level of abundance of the Clostridiales family increased to similar levels within the control group (P<0.05), when prebiotics were administered. The levels of abundance of the S24-7, Bacteroidales and Firmicutes families were higher in the intestinal tract compared with the control group (P<0.05), and following treatment with prebiotics, the levels of abundance of these families decreased to similar levels observed in the control group (P<0.05). In conclusion, inflammation and the microbiome serve important roles in the carcinogenesis of lung cancer. Additionally, prebiotics may increase the efficacy of lung cancer treatment by modulating levels of inflammation and the composition of the microbiome. The associations between inflammation, the microbiome and lung cancer require attention.