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Recent findings indicate that the microbiome may have significant impact on the development of lung cancer by its effects on inflammation, dysbiosis or genome damage. The aim of this study was to compare the sputum microbiome of lung cancer (LC) patients with the chromosomal aberration (CA) and micronuclei (MN) frequency in peripheral blood lymphoc...
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Cervical cancer ranks among the most prevalent cancers globally with high-risk human papillomaviruses implicated in nearly 99% of cases. However, hidden players such as changes in the microbiota are now being examined as potential markers in the progression of this disease. Researchers suggest that changes in the vaginal microbiota might correlate...
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... DNA extraction, amplification, and sequencing of 16S rRNA on a MiSeq instrument (Illumina, USA) were performed according to the manufacturer's recommendations. A detailed description of the procedures is given in a previous publication (Druzhinin et al., 2021). ...
Recent studies have shown that the bacterial microbiome of the respiratory tract influences the development of lung cancer. Changes in the composition of the microbiome are observed in patients with chronic inflammatory processes. Such microbiome changes may include the occurrence of bacteria that cause oxidative stress and that are capable of causing genome damage in the cells of the host organism directly and indirectly. To date, the composition of the respiratory microbiome in patients with various histological variants of lung cancer has not been studied. In the present study, we determined the taxonomic composition of the sputum microbiome of 52 patients with squamous cell carcinoma of the lung, 52 patients with lung adenocarcinoma and 52 healthy control donors, using next-generation sequencing (NGS) on the V3-V4 region of the bacterial gene encoding 16S rRNA. The sputum microbiomes of patients with different histological types of lung cancer and controls did not show significant differences in terms of the species richness index (Shannon); however, the patients differed from the controls in terms of evenness index (Pielou). The structures of bacterial communities (beta diversity) in the adenocarcinoma and squamous cell carcinoma groups were also similar; however, when analyzed according to the matrix constructed by the Bray–Curtis method, there were differences between patients with squamous cell carcinoma and healthy subjects, but not between those with adenocarcinoma and controls. Using the LEFse method it was possible to identify an increase in the content of Bacillota ( Streptococcus and Bacillus ) and Actinomycetota ( Rothia ) in the sputum of patients with squamous cell carcinoma when compared with samples from patients with adenocarcinoma. There were no differences in the content of bacteria between the samples of patients with adenocarcinoma and the control ones. The content of representatives of the genera Streptococcus , Bacillus , Peptostreptococcus (phylum Bacillota ), Prevotella , Macellibacteroides (phylum Bacteroidota ), Rothia (phylum Actinomycetota ) and Actinobacillus (phylum Pseudomonadota ) was increased in the microbiome of sputum samples from patients with squamous cell carcinoma, compared with the control. Thus, the sputum bacterial microbiome of patients with different histological types of non-small-cell lung cancer has significant differences. Further research should be devoted to the search for microbiome biomarkers of lung cancer at the level of bacterial species using whole-genome sequencing.
... There they are well placed to cause chromosome damage, including single strand and double-strand breaks, through secreting nucleases and impairing DNA repair, similar to the mechanisms observed for H. pylori [50][51][52]. In lung cancer the presence of Porphyromonas, Fusobacterium and Bacteroides genera were significantly associated with chromosomal aberrations [53]. Fusobacterium spp. ...
There is growing evidence that altered microbiota abundance of a range of specific anaerobic bacteria are associated with cancer, including Peptoniphilus spp., Porphyromonas spp., Fusobacterium spp., Fenollaria spp., Prevotella spp., Sneathia spp ., Veillonella spp . and Anaerococcus spp. linked to multiple cancer types. In this review we explore these pathogenic associations. The mechanisms by which bacteria are known or predicted to interact with human cells are reviewed and we present an overview of the interlinked mechanisms and hypotheses of how multiple intracellular anaerobic bacterial pathogens may act together to cause host cell and tissue microenvironment changes associated with carcinogenesis and cancer cell invasion. These include combined effects on changes in cell signalling, DNA damage, cellular metabolism and immune evasion. Strategies for early detection and eradication of anaerobic cancer-associated bacterial pathogens that may prevent cancer progression are proposed.
... However, V.G. Druzhinin et al. reported no significant change in the diversity of sputum microorganisms between lung cancer patients and healthy individuals (Druzhinin et al., 2020;Druzhinin et al., 2021). These studies highlight notable disparities in b diversity. ...
... Additionally, they found that Bacteroides, Lachnoanaerobaculum, Porphyromonas, Mycoplasma, and Fusobacterium were associated with the frequency of chromosomal aberrations. Interestingly, the genera Megasphaera and Selenomonas bovis negatively correlated with micronuclei (MN) (Druzhinin et al., 2021). ...
Lung cancer has the highest mortality rate among all cancers worldwide. The 5-year overall survival rate for non-small cell lung cancer (NSCLC) is estimated at around 26%, whereas for small cell lung cancer (SCLC), the survival rate is only approximately 7%. This disease places a significant financial and psychological burden on individuals worldwide. The symbiotic microbiota in the human body has been significantly associated with the occurrence, progression, and prognosis of various diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Studies have demonstrated that respiratory symbiotic microorganisms and their metabolites play a crucial role in modulating immune function and contributing to the pathophysiology of lung cancer through their interactions with the host. In this review, we provide a comprehensive overview of the microbial characteristics associated with lung cancer, with a focus on the respiratory tract microbiota from different locations, including saliva, sputum, bronchoalveolar lavage fluid (BALF), bronchial brush samples, and tissue. We describe the respiratory tract microbiota’s biodiversity characteristics by anatomical region, elucidating distinct pathological features, staging, metastasis, host chromosomal mutations, immune therapies, and the differentiated symbiotic microbiota under the influence of environmental factors. Our exploration investigates the intrinsic mechanisms linking the microbiota and its host. Furthermore, we have also provided a comprehensive review of the immune mechanisms by which microbiota are implicated in the development of lung cancer. Dysbiosis of the respiratory microbiota can promote or inhibit tumor progression through various mechanisms, including DNA damage and genomic instability, activation and regulation of the innate and adaptive immune systems, and stimulation of epithelial cells leading to the upregulation of carcinogenesis-related pathways.
... Экстракцию ДНК, амплификацию и секвенирование 16S рРНК на приборе MiSeq (Illumina, США) выполняли в соответствии с рекомендациями производителя. Подробное описание процедур приведено ранее (Druzhinin et al., 2021). ...
52 пациентов с плоскоклеточным раком легкого, 52 пациентов с аденокарциномой легкого и 52 здоровых доноров контрольной группы использовали технологию массового параллельного секвенирования региона V3-V4 16S рРНК. Микробиомы мокроты больных с разными гистологическими типами рака легкого и контроля не имели значимых различий по индексу видового богатства (Шеннона), однако у пациентов они отличались от контроля по индексу выравненности (Пиелу). Структуры бактериальных сообществ (бета-разнообразие) между аденокарциномой и плоскоклеточным раком также были близкими. Тем не менее матрица, построенная по Брэю-Кёртису, позволила выявить различия между пациентами с плоскоклеточным раком и здоровыми субъектами, но не между аденокарциномой и контролем. Метод LEFse позволил идентифицировать в мокроте больных плоско-клеточным раком увеличение содержания Bacillota (Streptococcus и Bacillus) и Actinomycetota (Rothia) при сопоставлении с образцами пациентов с аденокарциномой. Не найдено различий в содержании бактерий между образцами больных аденокарциномой и контроля. В микробиоме образцов мокроты пациентов с плоскоклеточным раком по сравнению с контролем было повышено содержание представителей родов Streptococcus, Bacillus, Peptostreptococcus (филум Bacillota), Prevotella, Macellibacteroides (филум Bacteroidota), Rothia (филум Actinomycetota) и Actinobacillus (филум Pseudomonadota). Таким образом, бактериальный микробиом мокроты пациентов с разными гистологическими типами немелкоклеточного рака легкого имеет существенные различия. Дальнейшие исследования должны быть посвящены поиску микробиомных биомаркеров рака легкого на уровне бактериальных видов с использованием полногеномного секвенирования. Ключевые слова: немелкоклеточный рак легкого; плоскоклеточный рак легкого; аденокарцинома легкого; бактериальный микробиом; мокрота; таксономический состав; 16S рРНК; NGS секвенирование. Для цитирования: Дружинин В.Г., Баранова Е.Д., Деменков П.С., Мацкова Л.В., Ларионов А.В. Состав бактериального микробиома мокроты пациентов с разными патоморфологическими формами немелкоклеточного рака легкого. Вавиловский журнал генетики и селекции. 2024;28(2):204-214.
... One of the studies showing a potential connection between the airway microbiome and the development of lung cancer was the study Druzhinin et al. [53], which analyzed the frequencies of chromosomal aberration and micronuclei in relation to the bacterial composition. The study aimed to explore the relationship between the sputum microbiome and genetic abnormalities associated with LC, and revealed significant differences in the sputum beta diversity of the microbiome between LC patients and control subjects. ...
Simple Summary
Research has clearly shown a connection between the respiratory tract microbiome and lung cancer. The composition and metabolism of the bacterial community in lung cancer patients differ from those in healthy individuals. Further large-scale studies are needed to understand the microbiome’s role in lung cancer, including identifying bacterial species, deciphering mechanisms and relationships with the macro-organisms, and addressing analysis-related issues. Large-scale research is also needed on the lung mycobiome and virome. Identifying microorganisms involved in oncogenic processes could improve lung cancer patient screening, diagnosis, and therapeutic options. This review presents the current state of knowledge on the role of the respiratory tract microbiome in lung carcinogenesis. We highlight what we know and what we don’ yet know about the human lung oncobiome.
Abstract
The importance of microbiota in developing and treating diseases, including lung cancer (LC), is becoming increasingly recognized. Studies have shown differences in microorganism populations in the upper and lower respiratory tracts of patients with lung cancer compared to healthy individuals, indicating a link between dysbiosis and lung cancer. However, it is not only important to identify “which bacteria are present” but also to understand “how” they affect lung carcinogenesis. The interactions between the host and lung microbiota are complex, and our knowledge of this relationship is limited. This review presents research findings on the bacterial lung microbiota and discusses the mechanisms by which lung-dwelling microorganisms may directly or indirectly contribute to the development of lung cancer. These mechanisms include influences on the host immune system regulation and the local immune microenvironment, the regulation of oncogenic signaling pathways in epithelial cells (causing cell cycle disorders, mutagenesis, and DNA damage), and lastly, the MAMPs-mediated path involving the effects of bacteriocins, TLRs signaling induction, and TNF release. A better understanding of lung microbiota’s role in lung tumor pathology could lead to identifying new diagnostic and therapeutic biomarkers and developing personalized therapeutic management for lung cancer patients.
... Additionally, we did not find a marked difference between the two groups in the taxonomic composition (beta diversity). Different studies reported different alpha and beta diversity results in lung cancer, including increased alpha diversity [15,16], decreased alpha diversity [17,18], increased beta diversity [19,20], decreased beta diversity [17,21,22], and no diversity changes [21,23]. Overall, these results indicate that there is still no definite consensus about the diversity of the lung microbiome composition in lung cancer. ...
Abstract Background It has been demonstrated in the literature that a dysbiotic microbiome could have a negative impact on the host immune system and promote disease onset or exacerbation. Co-occurrence networks have been widely adopted to identify biomarkers and keystone taxa in the pathogenesis of microbiome-related diseases. Despite the promising results that network-driven approaches have led to in various human diseases, there is a dearth of research pertaining to key taxa that contribute to the pathogenesis of lung cancer. Therefore, our primary goal in this study is to explore co-existing relationships among members of the lung microbial community and any potential gained or lost interactions in lung cancer. Results Using integrative and network-based approaches, we integrated four studies assessing the microbiome of lung biopsies of cancer patients. Differential abundance analyses showed that several bacterial taxa are different between tumor and tumor-adjacent normal tissues (FDR adjusted p-value
... Chromosome aberrations (CAs), micronucleus (MN), sister chromatid exchange (SCE), and comet tests are the most frequently used cytogenetic tests in genotoxicity identification analyses [10][11][12]. CA assay is effective in detecting both the clastogenic and aneugenic effects of the tested substance [13][14][15]. Chromosome instability revealed by SCE is closely related to the negative effect of a substance influencing the replication mechanism and repair of DNA damage [16][17][18][19]. The cytokinesis block micronucleus cytome (CBMN-Cyt) assay allows for the observation of micronucleus (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs). ...
... The mitotic index is considered as a sensitive marker for assessing mitotic changes caused by damage of cell structure or function. The decrease in the mitotic index can be interpreted that the cell stops growing at any time in the interphase, or the cell loses its capacity to reproduce, or the activation of some mechanisms that cause the death of the cell [13,15]. High concentrations of octyl gallate cause a decrease in the mitotic index, indicating that it may be cytotoxic. ...
Several antioxidant food additives are added to oils, soups, sauces, chewing gum, potato chips etc. One of them is octyl gallate. The purpose of this study was to evaluate the potential genotoxicity of octyl gallate in human lymphocytes, using in vitro chromosomal abnormalities (CA), sister chromatid exchange (SCE), cytokinesis block micronucleus cytome (CBMN-Cyt), micronucleus-FISH (MN-FISH), and comet tests. Different concentrations (0.50, 0.25, 0.125, 0.063, and 0.031 μg/mL) of octyl gallate were used. A negative (distilled water), a positive (0.20 μg/mL Mitomycin-C), and a solvent control (8.77 μL/mL ethanol) were also applied for each treatment. Octyl gallate did not cause changes in chromosomal abnormalities, micronucleus, nuclear bud (NBUD) and nucleoplasmic bridge (NPB) frequency. Similarly, there was no significant difference in DNA damage (comet assay), percentage of centromere positive and negative cells (MN-FISH test) compared to the solvent control. Moreover, octyl gallate did not affect replication and nuclear division index. On the other hand, it significantly increased the SCE/cell ratio in three highest concentrations compared to solvent control at 24 h treatment. Similarly, at 48 h treatment, the frequency of SCE raised significantly compared to solvent controls at all the concentrations (except 0.031 μg/mL). An important reduce was detected in mitotic index values in highest concentration at 24 h treatment and almost all concentrations (except 0.031 and 0.063 µg / mL) at 48 h treatment. The results obtained suggest that octyl gallate has no an important genotoxicological action on human peripheral lymphocytes at the concentrations applied in this study.
... Oral samples can be obtained via oral wash [28,51,73] or saliva [38,57,60,61,67,68,71,78,85]. Other than oral samples, another easily accessible sampling site/biospecimen is sputum [25,27,37,42,46,49,50,58,60,63,69,76,87] or posterior oropharynx [21,62]; the sputum is the second most-used sample for lung cancer-associated microbiome studies. In an analysis of potential biomarkers for NSCLC metastasis using sputum and gut microbiomes, Lu et al. [42] suggested that several microbial biomarkers are shared between the sputum and gut, and the prediction power of sputum microbial biomarkers is similar to that of the combination of the sputum and gut. ...
... There are 11 independent lung cancer-associated microbiome sequencing studies [21,25,32,36,38,42,50,52,58,64,81] and one traditional culture-dependent study [97] demonstrating the association between Haemophilus enrichment (at various sites) and lung cancer (although such an association was not as significant as those between lung cancer and Veillonella). The commonly identified species of Haemophilus include Haemophilus parainfluenzae and Haemophilus influenzae, but Haemophilus haemolyticus is reported as well. ...
As our “hidden organ”, microbes widely co-exist at various sites on the human body. These microbes are collectively referred to as the microbiome. A considerable number of studies have already proven that the microbiome has significant impacts on human health and disease progression, including cancers. The recent discovery of cancer-specific microbiomes renders these cancer-associated microbes as potential biomarkers and therapeutic targets. While at low biomass levels, the lung microbiome still dramatically influences the initiation, progression and treatment of lung cancers. However, research on lung cancer-associated microbiomes is emerging, and most profiling studies are performed within three years. Unfortunately, there are substantial inconsistencies across these studies. Variations in microbial diversity were observed, and different microbial biomarkers for lung cancer have been proposed. In this review, we summarized the current findings of lung cancer microbiome studies and attempt to explain the potential reasons for the dissimilarities. Other than lung microbiomes, oral and airway microbiomes are highly related to lung microbiomes and are therefore included as well. In addition, several lung cancer-associated bacterial genera have been detected by different independent studies. These bacterial genera may not be perfect biomarkers, but they still serve as promising risk factors for lung cancers and show great prognostic value.
... DNA extraction, 16S rRNA gene amplification and sequencing were performed as described early [16]. ...
... This may be because the relatively small sample size used for the comparisons in this study (n = 23 for NSCLC patients and n = 20 for controls) affected the statistical power. Therefore, to assess the significance of increased Streptococcus in the sputum of NSCLC patients, we believe it is necessary to use a larger set of samples, as in our previous study [16]. ...
Recent findings indicate that the microbiota is involved in the development of lung cancer by inducing inflammatory responses and generating genome damage. This study aimed to compare sputum microbiomes from the mouth and oropharynx in non-small cell lung carcinoma (NSCLC) patients. A second goal was to search for bacterial taxonomic units that behave differently in the microbiome of NSCLC patients and healthy subjects. In the study, the taxonomic composition of the sputum and oropharyngeal microbiomes of 23 male patients with untreated NSCLC and 20 healthy subjects were compared. Next-generation sequencing of bacterial 16S rRNA genes was used to determine the taxonomic composition of the respiratory microbiome. Using the Kruskal-Wallis test, increased alpha diversity was observed in the sputum microbiome compared to that of the oropharynx, but this was evident only in NSCLC patients and not in healthy subjects. Using the Robust Aitchison PCA test, differences in beta diversity were found between sputum and oropharynx samples, and these differences were significant both for NSCLC patients (p = 0.045) and healthy controls (p = 0.009). However, no significant statistical differences were detected using the Robust Aitchison PCA when only comparing oropharyngeal samples from NSCLC patients and controls, nor when comparing sputum samples alone. Analysis of differences in the relative percentage of individual bacterial taxa using the Mann-Whitney U-test, and taking into account the FDR correction, showed an increase in the genus Rothia in oropharyngeal samples of NSCLC patients, as compared to control subjects (4.98 ± 6.33 vs 2.21 ± 6.28; p = 0.0008). However, linear discriminant analysis using LefSe did not show Rothia as a differentially regulated feature between NSCLC and controls in the oropharynx. Thus, more research is needed to identify possible bacterial NSCLC biomarkers in the oropharynx.
... We then conducted the linear discriminant effect size (LEfSe) analysis to explore marked differences of bacteria between the two groups ( Figure 5(b)). Genus Fusobacterium and Neisseria, family Neisseriaceae and Actinomycetaceae, and order Burkholderiales were characteristic bacteria in lung cancer, while decreased genus Actinomyces and class Spirochaetia was found in lung cancer, which corroborates the findings in previous sequencing-based studies [9,[61][62][63][64][65][66]. ...
... With our established metaproteomics platform, we identified several lung cancer-associated bacteria from the genus to the class level that is consistent with previous sequencingbased studies [9,[61][62][63][64][65][66] and revealed novel lung cancerrelated bacteria that were underestimated by conventional methods. Through an independent cohort validation, 7 species were confirmed to be lung cancer associated. ...
The human oral microbiome correlates with numerous diseases, including lung cancer. Identifying the functional changes by metaproteomics helps understand the disease-related dysbiosis, yet characterizing low-abundant bacteria is challenging. Here, we developed a free-flow isoelectric focusing electrophoresis-mass spectrometry- (FFIEF-MS-) based metaproteomics strategy to reduce host interferences and enrich low-abundant bacteria for in-depth interpretation of the oral microbiome. With our method, the number of interfering peptides decreased by 52.87%, whereas the bacterial peptides and species increased by 94.97% and 44.90%, respectively, compared to the conventional metaproteomics approach. We identified 3647 bacterial proteins, which is the most comprehensive oral metaproteomics study to date. Lung cancer-associated bacteria were validated among an independent cohort. The imbalanced Fusobacterium nucleatum and Prevotella histicola and their dysregulated functions in inhibiting immune response and maintaining cell redox homeostasis were revealed. The FFIEF-MS may serve as a valuable strategy to study the mechanisms between human diseases and microbiomes with broader applications.
