Gut Dysbiosis in Non-Small Cell Lung Cancer Risk

Background: The imbalance of gut microbiota, dysbiosis, has been linking to various malignant diseases. The aim of this study was to identify the characteristics of gut microbiota in age-matched treatment-naïve non-small cell lung cancer (NSCLC) patients and healthy individuals, and try to investigate gut microbes-related pathway in contributing to NSCLC risk.Methods: Age-matched 34 NSCLC patients and 268 healthy individuals were enrolled. The hypervariable V3-V4 amplicons of the 16S rRNA in freshly collected fecal samples were sequenced. The diversity, microbial composition, function pathway, smoking history, and gut microbe-related comorbidities were together analyzed to access the risk-associated factors.Results: As expected, microbial alpha diversity was decreased in NSCLC, and beta diversity was significantly different between patients and controls (p<0.001). After adjusted for gender, smoking history, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and 11 abundant microbes with significant difference between patients and controls, the enrichment of Anaerotruncus spp. and Bacteroides caccae were associated with NSCLC risk (p=0.003 and 0.007, respectively). The receiver operating characteristic (ROC) curves generated the area under the curves (AUCs) were 71.4%, and 66.9% for the Anaerotruncus spp. and Bacteroides caccae (both p<0.001). Furthermore, the abundance of Bacteroides caccae was positively correlated to those increased steroid hormone biosynthesis (p<0.001), N-glycan biosynthesis (p=0.023), glycosaminoglycan degradation (p<0.001), lipoic acid metabolism (p=0.039), peroxisome (p<0.001), and apoptosis (p<0.001), but inversely correlated to decreased glycerolipid metabolism (p<0.001) in NSCLC patients. Anaerotruncus spp. was positively associated with decreased biosynthesis of ansamycin only (p=0.001). There was no overlapping signaling pathway modulated by Bacteroides caccae and Anaerotrucus spp.Conclusion: Our study revealed that fecal Anaerotruncus spp. and Bacteroides caccae were abundant and might be involved in NSCLC risk regardless of gender, smoking history, and gut microbe-related comorbidities. Further investigations on the mechanism underlying gut dysbiosis in the development of NSCLC are warranted.