Microbiome In Lung Cancer Research Articles

Metagenomic characterization of the tracheobronchial microbiome in lung cancer

Metagenomic characterization of the tracheobronchial microbiome in lung cancer

Lung Microbiome in Lung Cancer: A New Horizon in Cancer Study.

Lung cancer is the second most prevalent cancer worldwide and a leading cause of cancer-related deaths. Recent technological advancements have revealed that the lung microbiome, previously thought to be sterile, is host to various microorganisms. The association between the lung microbiome and lung cancer initiation, progression, and metastasis is complex and contradictory. However, disruption in the homeostasis of microbiome compositions correlated with the increased risk of lung cancer. This review summarizes current knowledge about the most recent developments and trends in lung cancer-related microbiota or microbial components. This article aims to provide information on this rapidly evolving field while giving context to the general role of the lung microbiome in lung cancer. In addition, this review briefly discussed the causative association of lung microbiome with lung cancer. We will review the mechanisms by which lung microbiota influence carcinogenesis, focusing on microbiota dysbiosis. Moreover, we will also discuss the host-microbiome interaction as it plays a crucial role in stimulating and regulating the immune response. Finally, we will provide information on the diagnostic role of the microbiome in lung cancer. This article aims to offer an overview of the lung microbiome as a predictive and diagnostic biomarker in lung cancer.

Country-specific differences in the lung tumour microbiome.

e20044 Background: Sputum examination for the early detection of lung cancer continues to be explored ( Thunnissen 2003 ), however has so far resulted in a low diagnostic yield. An increasing number of studies have evidenced a mechanistic role of the lung microbiome in the induction of lung cancer ( Liu et al., 2020 ), and the presence of bacterial biomarkers in bronchoalveolar lavage and sputum have been proposed ( Cheng et al., 2020 ). It is currently unknown whether the sputum microbiome can appropriately capture the lung tumour microbiome. Given that the lung microbiome may vary by geography, this analysis was considered over two populations: China and Italy. Methods: Microbiome analysis was performed using BioCorteX’s industry-leading knowledge graph and integrated proprietary engines v20240126_153156. Data from 9 studies was used. In total, 461 samples from lung cancer patients in China (250 sputum, 211 tumour) and 60 from Italy (34 sputum, 26 tumour) were considered. Shannon’s diversity was used to consider within-sample diversity, and dimensional scaling based (MDS) on Bray-Curtis diversity was used to consider between-sample diversity. Results: All sample were checked to have a library size greater than 100, and more than 10 unique species. Only those species present in over 1% of samples were considered to reduce noise. In both China and Italy, tumour samples had a lower diversity than sputum samples (p = 0.00016 and p < 2.2e-16, respectively). Samples from Italy had a lower diversity than samples from China (p < 2.22e-16). In the MDS analysis, the tumour samples from China and Italy formed two distinct, non-overlapping clusters. A third cluster was formed from the union of sputum samples from both countries. These results were independent of any study-specific effects. Conclusions: These results indicate that the sputum microbiome is not representative of the tumour microbiome, and that the divergence of the tumour microbiome away from the sputum microbiome is country specific. The results of this analysis highlight that further work into differences in the lung tumour microbiome by country is warranted, especially in light of the growing body of evidence suggesting a causative role of the microbiome in lung cancer. It is also possible that lung cancer treatments may be impacted by the country-specific nature of the lung tumour microbiome.

Gut microbiota and carcinogenesis in various human organs

Scientific research in recent years has revealed a significant role of the human microbiome in carcinogenesis. These data served as a rationale for the inclusion of polymorphic microbiomes in the key characteristics of carcinogenesis as an important mechanistic determinant of cancer, in addition to other fundamental biological processes manifested during multi-stage carcinogenesis. The microbiome of the gastrointestinal tract is most actively involved in the pathogenesis of malignant neoplasms of the digestive system due to changes in the quantitative and qualitative composition of the microbiota, and increase in the production of genotoxic bacterial metabolites as factors of carcinogenesis. This review also addresses the changes in the microbiome in lung cancer, associated mainly with the production of short-chain fatty aicids, and in breast and endometrial cancers with specific changes in the composition of the bacterial community towar)ds species involved in the metabolism of estrogen precursors. The probable mechanisms of microorganisms participation in the development of prostate cancer (the effect of lipopolysaccharides, antibiotics and deconjugated estrogen) are considered.
 Data on the relationship between the composition and metabolic characteristics of the microbiome in various cancer sites open up perspectives for its use in the diagnosis, treatment and prevention of malignant neoplasms and justify the need for further research in this area.

Gut microbial signature in lung cancer patients highlights specific taxa as predictors for durable clinical benefit

We aimed to determine microbial signature linked with lung cancer (LC) diagnosis and to define taxa linked with durable clinical benefit (DCB) of advanced LC patients. Stool samples for microbial 16S amplicon sequencing and clinical data were collected from 75 LC patients (50 of which were treated with checkpoint inhibitors) and 31 matched healthy volunteers. We compared LC to healthy controls and patients with DCB to those without. LC patients had lower α-diversity and higher between-subject diversity. Random Forests model to differentiate LC cases from controls ROC-AUC was 0.74. Clostridiales, Lachnospiraceae, and Faecalibacterium prausnitzii taxa abundance was decreased in LC compared to controls. High Akkermansia muciniphila correlated with DCB (HR 4.26, 95% CI 1.98–9.16), not only for the immunotherapy-treated patients. In addition, high Alistipes onderdonkii (HR 3.08, 95% CI 1.34–7.06) and high Ruminococcus (HR 7.76, 95% CI 3.23–18.65) correlated with DCB.Our results support the importance of gut microbiome in LC. We have validated the apparent predictive value of Akkermansia muciniphila, and highlighted Alistipes onderdonkii and Ruminococcus taxa correlation with DCB. Upon additional validations those can be used as biomarkers or as targets for future therapeutic interventions.

Special tissue microbiota such as Cyanobacteria are associated with the immune microenvironment of lung adenocarcinoma.

Lung cancer is the leading prevalent form of human cancer and has the highest mortality rate among all cancer types. The role and potential mechanism of the lung microbiome in lung cancer is still unknown. This study aims to investigate the microbiomes of lung cancer patients possessing different levels of infiltrated CD8+ T cells and programmed cell death-1 (PD-1) receptors, and further assess the correlation between specific microbes and the immune environment of lung tumor. We analyzed the microbiomes of lung cancer tissues from patients with different levels of infiltrated CD8+ T cells and PD-1 expression using 16S rRNA gene sequencing. The relative abundance of dominant phyla and genera was compared, and the correlation between microbial composition and immune markers was explored. Our results showed that lung cancer tissues displayed similar microbiome profiles, including Proteobacteria, Bacteroidetes, and Actinobacteria as the dominant phyla; and Chryseobacterium, Triticum aestivum (bread wheat), and Acinetobacter as the dominant genera. We found that the relative abundance of Chryseobacterium was positively correlated with CD8+ T cell infiltration and the level of PD-1 expression, while the relative abundance of Acinetobacter was negatively associated with the PD-1 level. In addition, higher beta diversity was identified in samples with low CD8+ T cell infiltration, but no significant correlation between beta diversity and PD-1 expression was observed. Furthermore, the relative abundance of Cyanobacteria was significantly higher in both the CD8 high and PD-1 high groups. Our study indicated that the lung microbiota played an indispensable role in the CD8+ T cell-mediated tumor immune response. These findings shed light on valuable insights into the intricate interplay between the lung microbiome and the immune system in the progression of lung cancer, offing potential therapeutic strategies targeting the lung microbiome.

Spatial meta-transcriptomics reveal associations of intratumor bacteria burden with lung cancer cells showing a distinct oncogenic signature

BackgroundThe lung intratumor microbiome influences lung cancer tumorigenesis and treatment responses, but detailed data on the extent, location, and effects of microbes within lung tumors are missing, information needed for...

Abstract 3055: Field cancerization and microbiome in lung cancer

Abstract Lung Cancer carcinogenesis is the outcome of a field of premalignant changes that occur in the bronchial tree leading to the overt emergence of the malignant lung cancer. We sought to study the proteome of the microbiome associated with the premalignant bronchial mucosa epithelia. The overall goal is the identify functional relationships between the bronchial mucosa microbiome and the risk of developing lung cancer. We evaluated the proteome of the microbiome using mass spectrometry and specialized microbiome authentication software. This method was applied to a case-control study of plasma samples donors of physician health study who donated plasma at different times prior to the onset of Non-Small Cell Lung Cancer. We also examined bronchial mucosa tissue samples near to, and distant from, the tumor harvested from surgical lobectomy specimens. Highly significant protein biomarker differences were found in the plasma and in the tissue samples that were blindly associated with cancer. These included specific proteins from the mucosal microbiome that may have functional role in the carcinogenic process. These key diagnostic risk markers were shared between the premalignant bronchial mucosa tissue and the plasma, supporting the concept that risk markers of bronchial mucosa lung cancer carcinogenesis can be detected in the peripheral circulation. Citation Format: Rayan I. Alhammad, Ngoc B. Vuong, Weidong Zhou, Claudius Mueller, Donald J Johann Jr, Amith R. Katta, Monique V. Hoek, Fahad M. Alsaab, Alessandra Luchini, Lance Liotta. Field cancerization and microbiome in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3055.

Spatial meta-transcriptomics reveal intratumor bacterial association with lung cancer cells showing a distinct oncogenic signature.

8531 Background: The lung intratumor microbiome influences lung cancer tumorigenesis and treatment responses, but detailed data on the extent, location, and effects of microbes within lung tumors is missing, information needed to improve treatment outcomes and prognosis. Methods: To address this gap, we developed a novel spatial meta-transcriptomic method simultaneously detecting the expression level of 1,811 host genes and three microbe targets (16S rRNA, 28S rRNA and CMV). After rigorous validation, we analyzed the spatial meta-transcriptomic profiles of tumor cells, T cells, macrophages, other immune cells, and stroma in tumor samples from 12 patients with early-stage lung cancer. Results: Bacterial burden was significantly higher in tumor cells compared to T cells, macrophages, other immune cells, and stroma. This burden increased from tumor-adjacent normal lung and tertiary lymphoid structures to tumor cells to the airways, suggesting that lung intratumor bacteria derive from the latter route of entry. Expression of oncogenic β-catenin and epithelial-mesenchymal transition pathway genes was strongly correlated with bacterial burden, as were tumor subtypes, mutation profile, histology and smoking history. Conclusions: Intratumor bacteria were enriched with tumor cells and associated with multiple oncogenic pathways, supporting a rationale for reducing the local intratumor microbiome in lung cancer to optimize clinical outcomes. This research was supported in part by the Intramural Research Programs of the NCI and NIAID. Other funding sources included ASCO Young Investigator Award, SITC-AstraZeneca Immunotherapy in Lung Cancer (Early Stage NSCLC) Clinical Fellowship Award, NIH Bench-to-Bedside and Back Program (BtB), NCI R00 award (CA226400), Emerson Collective Cancer Research fund, Lung Cancer Research Foundation (LCRF) pilot grant and W.W. Smith Trust Foundation award. This study was approved by NCI institutional review board (NCT00242723 and NCT02146170) and Animal Use and Care Committee at the University of Pennsylvania (#806875).

The composition of lung microbiome in lung cancer: a systematic review and meta-analysis

BackgroundAlthough recent studies have indicated that imbalance in the respiratory microbiome composition is linked to several chronic respiratory diseases, the association between the lung microbiome and lung cancer has not been extensively studied. Conflicting reports of individual studies on respiratory microbiome alterations in lung cancer complicate the matter for specifying how the lung microbiome is linked to lung cancer. Consequently, as the first meta-analysis on this topic, we integrate publicly available 16S rRNA gene sequence data on lung tissue samples of lung cancer patients to identify bacterial taxa which differ consistently between case and control groups.ResultsThe findings of the current study suggest that the relative abundance of several bacterial taxa including Actinobacteria phylum, Corynebacteriaceae and Halomonadaceae families, and Corynebacterium, Lachnoanaerobaculum, and Halomonas genera is significantly decreased (p < 0.05) in lung tumor tissues of lung cancer patients in comparison with tumor-adjacent normal tissues.ConclusionsDespite the underlying need for scrutinizing the findings further, the present study lays the groundwork for future research and adds to our limited understanding of the key role of the lung microbiome and its complex interaction with lung cancer. More data on demographic factors and tumor tissue types would help establish a greater degree of accuracy in characterizing the lung microbial community which accords with subtypes and stages of the disease and fully capturing the changes of the lung microbiome in lung cancer.

Exploring the role of respiratory microbiome in lung cancer: A systematic review.

Giving the potential contribute in cancer initiation and progression, lung microbiota represents a promising topic in cancer research, although still unexplored. We performed a systematic literature search to identify clinical studies evaluating lung microbiota composition, its correlation with lung cancer patients' clinico-pathological features and prognosis. Of the identified 370 studies, 21 were eligible and included. Although studies were heterogeneous, lung cancer resulted to be enriched in peculiar microbial communities, with differences in composition and diversity according to clinico-pathological parameters. Few studies explored how lung microbiota influences cancer outcome. In light of these findings and borrowing the suggestions coming from gut microbiota, we speculate that respiratory microbiome may influence pathogenesis, progression and outcome of lung cancer. Taking advantage of the experience of chronical lung diseases, prospective studies should be designed to evaluate lung microbiota changes throughout any phase of lung cancer course, particularly with the advent of immunotherapy as pivotal treatment.

Abstract 1782: Acidovorax temperans modulates the host immune microenvironment to promote lung cancer development

Abstract Lung cancer is the most common cause of cancer-related death worldwide in both men and women. The overall survival of lung cancer remains poor due to limitations in diagnostic and therapeutic strategies. Therefore, the development of novel biomarkers is urgently needed to improve patient prognosis. Growing evidence has demonstrated alterations of the normal microbiome in lung cancer. Dysbiosis may alter normal microbiota-host interactions and induce immune dysregulation, and therefore contribute to the promotion of tumorigenesis. Although multiple studies show an association between dysbiosis, host immune response and tumorigenesis, the underlying mechanisms are still unclear. We previously characterized a distinct group of taxa that are enriched in lung adenocarcinoma and squamous cell carcinoma. Among these taxa, Acidovorax spp. were associated with cigarette smoking and TP53 mutations, with Acidovorax temperans identified by full-length 16S sequencing. We hypothesized that enrichment of A. temperans in the lung microbial community may modulate the immune microenvironment and therefore contribute to tumor development. We used an autochthonous mouse model of lung adenocarcinoma, in which tumorigenesis is driven by oncogenic K-Ras and a gain-of function mutant p53 under the control of the Cre-lox system. We administered biweekly intranasal instillations of A. temperans to mimic the effects of chronic tobacco smoking. Following bacterial instillation, the lung tumor development was determined by magnetic resonance imaging (MRI) at 13 weeks post Ad-Cre instillation. Mice challenged with A. temperans exhibited significantly larger tumor burden and a deleterious effect on survival compared to the sham group. Given the importance of the immune system in modulating tumor development, we then investigated whether A. temperans exposure induced changes in the immune microenvironment through high parametric flow cytometry post 5th instillation and post MRI. Lungs from mice instilled with A. temperans showed an increased number of total leukocytes. The vast majority of leukocytes were pro-inflammatory cells and predominantly neutrophils. Moreover, we also found an increase in CD4+ T cells and double negative T cells, and an increase in RORγt+/IL17+ subpopulations in both of these T cell groups. Consistent with these results, the IL-17 expression level was upregulated in response to A. temperans instillation. Taken together, these results indicate that A. temperans exposure induces a robust pro-inflammatory response, thereby increasing immune infiltration in the tumor microenvironment and promoting development of lung adenocarcinoma. Citation Format: Chenran Zhang, Natalia von Muhlinen, Araya Romina, Joshua Stone, Romina Goldszmid, Curtis Harris. Acidovorax temperans modulates the host immune microenvironment to promote lung cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1782.

Abstract B24: The microbiome in lung cancer under immunotherapy: Significant compositional differences associated with treatment response and AEs

Abstract Background: In recent years, attention has shifted to modification of tumor response to immunotherapy via the host microbiome. The mechanisms of these associations, causative or consequential, remain incompletely understood. We seek to explore this further with a longitudinal study of lung cancer patient microbiomes and immunotherapy-related adverse effects (AEs) preceding and during immunotherapy. Methods: Patients with lung cancer (LC) treated with immunotherapy (anti-PD-1/L1 agents including pembrolizumab, nivolumab, atezolizumab, and durvalumab) with or without chemotherapy at the University of Iowa from November 2018–April 2019 were consented for this ongoing study. Fecal samples and nasal and buccal swabs were obtained prior to therapy. Patients were treated and monitored per respective disease protocol; responses were recorded per RECIST 1.1 and AEs per CTCAE 5.0. Samples underwent DNA extraction followed by 16S rRNA metagenomic analysis and taxonomic profiling using Divisive Amplicon Denoising Algorithm (DADA)-2 pipeline. Microbiomes from all body sites were compared and correlated to treatment response and AEs. In addition, baseline LC gut microbiomes were compared to fecal samples provided by healthy controls (HC) in the same geographic location. This project is registered on clinicaltrials.gov (NCT03688347). Results: Gut microbiota significantly differed compared to oral and buccal microbiota in all patients. Gut microbiota from LC patients was compared to HC samples from the same geographic area. LC patients exhibited drastically different baseline composition, including dramatic increases in Firmicutes, Actinobacteria, and Verrucomicrobia, and significant decreases in Bacteroidetes, Proteobacteria, and Cyanobacteria. We noticed a clear inversion of Firmicutes/Bacteroidetes ratio between HC and LC patients, differences also reflected at the genus level. NSCLC patients experiencing immunotherapy-related adverse events were found to have at baseline markedly fewer Bifidobacterium and Desulfovibrio (p &amp;lt; 0.05 and FDR &amp;lt;0.05) when compared to those who did not experience AEs, regardless of grouping parameters (e.g., grade 0 vs. 1-4; 0-1 vs. 2-4; and 0 vs. 1-2 vs. 3-4). In addition, patients who responded to combined immunotherapy and chemotherapy (best response &amp;gt;= PR) exhibited enriched baseline Clostridiales (phylum Firmicutes, p=0.018) but reduced Rikenellaceae (phylum Bacteroidetes, p=0.016). Conclusion: Our study found promising trends in microbiome constitution. Compared to HC, we found significant differences in baseline LC gut microbiome at phylum and genus levels. More importantly, there are notable differences comparing LC patients who suffered AEs to those with none and between immunotherapy responders vs. nonresponders. Our project marks an important first step in a long-term study that could shed new light on the microbiome’s influence on immunotherapy treatment outcomes. Citation Format: Justin J. Chau, Meeta Yadav, Muhammad Furqan, Keri Mercer, Evan Eastman, Shailesh Shahi, Qun Dai, Carlos Chan, George Weiner, Taher Abu Hejleh, Ashutosh Mangalam, Jun Zhang. The microbiome in lung cancer under immunotherapy: Significant compositional differences associated with treatment response and AEs [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B24.

Respiratory Bacterial Microbiota and Individual Bacterial Variability in Lung Cancer and Bronchiectasis Patients.

Respiratory bacterial microbiota plays a key role in human health. Lung cancer microbiome is a significant yet an understudied area while bronchiectasis microbiome is often studied. We assessed the bacterial microbiota in the upper and lower respiratory tract of the patients with lung cancer and bronchiectasis against a healthy group and their variations in individuality. 16S rRNA gene based metagenomic sequencing was used to detect entire bacterial community along with conventional aerobic bacterial culturing. In comparison to healthy, increased bacterial diversity was observed in diseased population. Abundance of more than 1% was considered and bacteria were identified in 97% similarity. Only lung cancer patients exhibited bacteria specific to the disease: Corynebacterium tuberculostearicum and Keratinibaculum paraultunense. However, Enterococcus faecalis and Delftia tsuruhatensis were also observed limited to lung cancer and bronchiectasis respectively, in less than 1% but supported with bacterial culturing. In conclusion the disease condition and intra-group variability should be considered in future with larger cohorts to understand individual patient variability highlighting the social habits and gender of the individual.

Diminishing microbiome richness and distinction in the lower respiratory tract of lung cancer patients: A multiple comparative study design with independent validation

ObjectivesCurrent evidence suggests that microorganisms are associated with neoplastic diseases; however, the role of the airway microbiome in lung cancer remains unknown. To investigate the taxonomic profiles of the lower respiratory tract (LRT) microbiome in patients with lung cancer. Materials and methodsBALF samples were collected in a discovery set comprising 150 individuals, including 91 patients with lung cancer, 29 patients with nonmalignant pulmonary diseases and 30 healthy subjects, and an independent validation set including 85 participants. The samples were assessed by metagenomics analysis. Random forest regression analysis was performed to select a diagnostic panel. ResultsIn the discovery set, richness was reduced in lung cancer patients compared with that in healthy subjects, and the microbiome of patients with nonmalignant diseases resembled that of patients with lung cancer. Interestingly, Bradyrhizobium japonicum was only found in patients with lung cancer, whereas Acidovorax was found in patients with cancer and nonmalignant pulmonary diseases. A microbiota-related diagnostic model consisting of age, pack year of smoking and eleven types of bacteria was built, and the area under the curve (AUC) for discriminating the patients with cancer was 0.882 (95%CI: 0.807-0.957) in the training set and 0.796 (95%CI: 0.673-0.920) in the independent validation set. ConclusionOur study demonstrates that the LRT microbiome richness is diminished in lung cancer patients compared with that in healthy subjects and that microbiota-specific biomarkers may be useful for diagnosing patients for whom lung biopsy is not feasible.

Human Lung Microbiome on the Way to Cancer.

Recent research on cancer-associated microbial communities led to the accumulation of data on the interplay between bacteria, immune and tumor cells, the pathways of bacterial induction of carcinogenesis, and its meaningfulness for medicine. Microbial communities that have any kind of impact on tumor progression and microorganisms associated with tumors have been defined as oncobiome. Over the last decades, a number of studies were dedicated to Helicobacter pylori and its role in the progression of stomach tumors, so this correlation can be regarded as proven. Involvement of bacteria in the induction of lung cancer has been largely ignored for a long time, though some correlations between this type of cancer and lung microbiome were established. Despite the fact that in the present the microbial impact on lung cancer progression has many confirmations, the underlying mechanisms are poorly understood. Microorganisms can contribute to tumor initiation and progression through production of bacteriotoxins and other proinflammatory factors. The purpose of this review is to organize the available data on lung cancer microbiome and its role in malignant tumor progression.

Role of the Microbiota in Primary Lung Cancer Initiation and Progression

Abstract Lung cancer is the leading cause of cancer-related death in men in 87 countries and in women in 26 countries. The commensal microbiota lives on the epithelial barriers of the host and is vital for the health of the organism. Specific microbial species have been described to affect neoplastic pathology both at the gastrointestinal tract level and systematically in organs that are not normally associated with the gut microbiota. Studies have revealed the importance of the gut microbiota in the efficacy of anti-cancer therapies (chemo and immunotherapy) However, the role of lung microbiome in lung cancer remains largely unknown. We aimed to study the role of the lung microbiota during lung carcinogenesis progression in the context of p53/K-ras mutation and its impact on the tumor microenvironment. To further analyze the impact of the lung microbiota on lung cancer initiation, P53-Kras mutant germ-free mice will be colonized by intranasal instillation with bacteria identified in human lungs samples from lung cancer patients such as Variovorax paradoxus (V.paradoxus) and Acidovorax temperans (A.temperans) and the tumor burden will be calculated. Our data indicates Germ-free mice instilled with V. paradoxus trended towards an increase tumor burden compared to respective controls while A. temperans -associated germ-free mice seems to delay tumor growth. Germ-free mice, at 18 and 24 weeks post-Ad-Cre virus instillation, tends to have an increased tumor burden than their SPF counterparts. Also, changes in immune infiltrate were observed after flow cytometric analysis with preliminary data showing a decrease in CD45 positives cells the cells in mice instilled with V. paradoxus as well as an increase in Monocytes and Macrophages populations.

Dysbiosis of the Gut Microbiome in Lung Cancer.

Lung cancer (LC) is one of the most serious malignant tumors, which has the fastest growing morbidity and mortality worldwide. A role of the lung microbiota in LC pathogenesis has been analyzed, but a comparable role of the gut microbiota has not yet been investigated. In this study, the gut microbiota of 30 LC patients and 30 healthy controls were examined via next-generation sequencing of 16S rRNA and analyzed for diversity and biomarkers. We found that there was no decrease in significant microbial diversity (alpha diversity) in LC patients compared to controls (P observed = 0.1422), while the composition (beta diversity) differed significantly between patients and controls (phylum [stress = 0.153], class [stress = 0.16], order [stress = 0.146], family [stress = 0.153]). Controls had a higher abundance of the bacterial phylum Actinobacteria and genus Bifidobacterium, while patients with LC showed elevated levels of Enterococcus. These bacteria were found as possible biomarkers for LC. A decline of normal function of the gut microbiome in LC patients was also observed. These results provide the basic guidance for a systematic, multilayered assessment of the role of the gut microbiome in LC, which has a promising potential for early prevention and targeted intervention.

Dysbiosis of the Gut Microbiome is associated with Tumor Biomarkers in Lung Cancer.

Lung cancer is a malignancy with high morbidity and mortality worldwide. More evidences indicated that gut microbiome plays an important role in the carcinogenesis and progression of cancers by metabolism, inflammation and immune response. However, the study about the characterizations of gut microbiome in lung cancer is limited. In this study, the fecal samples were collected from 16 healthy individuals and 30 lung cancer patients who were divided into 3 groups based on different tumor biomarkers (cytokeratin 19 fragment, neuron specific enolase and carcinoembryonic antigen, respectively) and were analyzed using 16S rRNA gene amplicon sequencing. Each lung cancer group has characterized gut microbial community and presents an elimination, low-density, and loss of bacterial diversity microbial ecosystem compared to that of the healthy control. The microbiome structures in family and genera levels are more complex and significantly varied from each group presenting more different and special pathogen microbiome such as Enterobacteriaceae, Streptococcus, Prevotella, etc and fewer probiotic genera including Blautia, Coprococcus, Bifidobacterium and Lachnospiraceae. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and COG annotation demonstrated decreased abundance of some dominant metabolism-related pathways in the lung cancer. This study explores for the first time the features of gut microbiome in lung cancer patients and may provide new insight into the pathogenesis of lung cancer system, with the implication that gut microbiota may serve as a microbial marker and contribute to the derived metabolites, development and differentiation in lung cancer system.