Characterization of microbiome in bronchoalveolar lavage fluid of patients with lung cancer comparing with benign mass like lesions

Highlights

• Microbiota in lung cancer were investigated in BAL fluid.

• Microbiota in lung cancer were compared with benign lung mass.

• The genera Veillonella and Megasphaera have the potential to become a biomarker in lung cancer.

Abstract

Objectives

Disruption in the stability of respiratory microbiota is known to be associated with many chronic respiratory diseases. However, only few studies have examined microbiomes in lung cancer. Therefore, we characterized and compared the microbiomes of patients with lung cancer and those with benign mass-like lesions.

Materials and methods

Bronchoalveolar fluid was collected prospectively to evaluate lung masses in patients who had undergone bronchoscopies from May to September 2015. Twenty-eight patients (20 male, 8 female) were enrolled: 20 diagnosed with lung cancer and 8 diagnosed with benign diseases. Samples were analysed by 16S rRNA-based next-generation sequencing.

Results

The participants’ mean age was 64 ± 11 years. Bacterial operational taxonomic units were classified into 26 phyla, 44 classes, 81 orders, 153 families, 288 genera, and 797 species. The relative abundance of two phyla (Firmicutes and TM7) was significantly increased in patients with lung cancer (p = 0.037 and 0.035, respectively). Furthermore, two genera (Veillonella and Megasphaera) were relatively more abundant in lung cancer patients (p = 0.003 and 0.022, respectively). The area under the curve of a combination of these two genera used to predict lung cancer was 0.888 (sensitivity = 95.0%, specificity = 75.0% and sensitivity = 70.0%, specificity = 100.0%; p = 0.002).

Conclusion

The results indicate that differences exist in the bacterial communities of patients with lung cancer and those with benign mass-like lesions. The genera Veillonella and Megasphaera showed the potential to serve as biomarkers to predict lung cancer. Thus, the lung microbiota may change the environment in patients with lung cancer.

Introduction

Traditionally, lungs have been thought of as a sterile space. However, recent studies have demonstrated that there are rich and varied microbiomes in healthy lungs [1]. Furthermore, diseased lungs have dominant microbiota that differ from that of healthy lungs; patients with allergies and chronic obstructive pulmonary disease (COPD) have relatively more abundant Proteobacteria phylum and Hemophilus spp. than that in the control, whereas Prevotella spp. were more frequently detected in controls [2].

At present, lung cancer is the most common cancer worldwide, and it is the leading cause of cancer-related morbidity and mortality both men and women [3], [4]. Many previous studies have identified molecular markers (EGFR, PD-1, and ALK) related to lung cancer development. These studies have resulted in novel, tailored therapeutic drugs for patients with lung cancer [5], [6], [7].

Some microbiota are known to be associated with cancer. For example, Helicobacter pylori is associated with gastric cancer, and human papillomavirus and Chlamydia trachomatis are known to be associated with cervical cancer [8], [9], [10]. Although cancer-related microbiomes are not as well studied in lung cancer compared with other solid cancers, a recent meta-analysis showed pneumonia and Mycobacterium tuberculosis significant risk factors for lung cancer [11]. Furthermore, Meyer et al. showed that periodontitis could be associated with lung cancer [12]. These studies suggest that specific microbiota may be related to lung cancer. Additionally, a recent study found that sputum samples of patients with lung cancer who had never smoked showed more predominant Granulicatella, Abiotrophia, and Streptococcus spp. and fewer OTUs relative to that of the control [13]. Gui et al. reported that certain microbiota (Lactobacillus) had a therapeutic effect in a lung cancer mouse model [14].

Therefore, examining the microbiomes in patients with lung cancer is important and necessary to better understand the pathogenesis of this disease and to plan therapeutic interventions. However, until recently, there have only been a few studies on the microbiomes in patients with lung cancer. The purpose of this study was to characterize the microbiomes in patients with lung cancer compared to those with benign mass-like lung lesions using 16S rRNA-based next-generation sequencing (NGS).