J Cancer 2019; 10(7):1651-1662. doi:10.7150/jca.28077

Research Paper

Salivary Microbial Dysbiosis is Associated with Systemic Inflammatory Markers and Predicted Oral Metabolites in Non-Small Cell Lung Cancer Patients

Weiquan Zhang1,2, Junwen Luo1,2, Xiaopeng Dong1, Shukang Zhao1,2, Yingtao Hao1, Chuanliang Peng1, Hubo Shi3, Yong Zhou4, Lei Shan1, Qifeng Sun1, Yuyang Li5, Xiaogang Zhao1✉

1. Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, China
2. School of Medicine, Shandong University, Jinan, Shandong 250012, China
3. Department of Thoracic Surgery, Shandong Provincial Chest Hospital, Jinan, Shandong 250013, China
4. Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong 250033, China
5. Department of Breast Thyroid Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, China.

Abstract

An increasing number of studies have suggested the dysbiosis of salivary microbiome has been linked to the advancement of multiple diseases and proved to be helpful for the diagnosis of them. Although epidemiological studies of salivary microbiota in carcinogenesis are mounting, no systemic study exists regarding the oral microbiota of non-small cell lung cancer (NSCLC) patients. In this study, we presented the characteristics of the salivary microbiota in patients from NSCLC and healthy controls by sequencing of the 16S rRNA microbial genes. Our result revealed distinct salivary microbiota composition in patients from NSCLC compared to the healthy controls. As principal co-ordinates analysis (PCoA) showed, saliva samples clearly differed between the two groups, considering the weighted (p = 0.001, R2 = 0.17), and unweighted (p = 0.001, R2 = 0.25) UniFrac distance. Phylum Firmicutes (31.69% vs 24.25%, p < 0.05) and its two genera Veillonella (15.51%% vs 9.35%, p < 0.05) and Streptococcus (9.96% vs 6.83%, p < 0.05) were strongly increased in NSCLC group compared to the controls. Additionally, the relative abundances of Fusobacterium (3.06% vs 4.92%, p = 0.08), Prevotella (1.45% vs 3.52%, p < 0.001), Bacteroides (0.56% vs 2.24%, p < 0.001), and Faecalibacterium (0.21% vs 1.00%, p < 0.001) in NSCLC group were generally decreased. Furthermore, we investigated the correlations between systemic inflammation markers and salivary microbiota. Neutrophil-lymphocyte ratio (NLR) positively correlated with the Veillonella (r =0.350, p = 0.007) and lymphocyte-monocyte ratio (LMR) negatively correlated with Streptococcus (r =-0.340, p = 0.008). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways inferred by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) showed that pathways related to xenobiotics biodegradation and metabolism (p < 0.05) and amino acid metabolism (p < 0.05) were enriched in the NSCLC group. Folate biosynthesis (p < 0.05) significantly decreased in NSCLC group. The specific correlations of clinical systemic inflammation markers and predicted KEGG pathways also could pronounce a broad understanding of salivary microbiota in patients with NSCLC. Moreover, our study extended the new sight into salivary microbiota-targeted interventions to clinically improve the therapeutic strategies for salivary dysbiosis in NSCLC patients. Further investigations of the potential mechanism of salivary microbiota in the progression of NSCLC are still in demand.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Zhang W, Luo J, Dong X, Zhao S, Hao Y, Peng C, Shi H, Zhou Y, Shan L, Sun Q, Li Y, Zhao X. Salivary Microbial Dysbiosis is Associated with Systemic Inflammatory Markers and Predicted Oral Metabolites in Non-Small Cell Lung Cancer Patients. J Cancer 2019; 10(7):1651-1662. doi:10.7150/jca.28077. Available from http://www.jcancer.org/v10p1651.htm