-
Nature Microbiology Jun 2024Bacteria such as the oral microbiome member Peptostreptococcus anaerobius can exacerbate colorectal cancer (CRC) development. Little is known regarding whether these...
Bacteria such as the oral microbiome member Peptostreptococcus anaerobius can exacerbate colorectal cancer (CRC) development. Little is known regarding whether these immunomodulatory bacteria also affect antitumour immune checkpoint blockade therapy. Here we show that administration of P. anaerobius abolished the efficacy of anti-PD1 therapy in mouse models of CRC. P. anaerobius both induced intratumoral myeloid-derived suppressor cells (MDSCs) and stimulated their immunosuppressive activities to impair effective T cell responses. Mechanistically, P. anaerobius administration activated integrin αβ-NF-κB signalling in CRC cells to induce secretion of CXCL1 and recruit CXCR2 MDSCs into tumours. The bacterium also directly activated immunosuppressive activity of intratumoral MDSCs by secreting lytC_22, a protein that bound to the Slamf4 receptor on MDSCs and promoted ARG1 and iNOS expression. Finally, therapeutic targeting of either integrin αβ or the Slamf4 receptor were revealed as promising strategies to overcome P. anaerobius-mediated resistance to anti-PD1 therapy in CRC.
Topics: Animals; Myeloid-Derived Suppressor Cells; Mice; Colorectal Neoplasms; Programmed Cell Death 1 Receptor; Humans; Cell Line, Tumor; Integrin alpha2beta1; Immune Checkpoint Inhibitors; Signaling Lymphocytic Activation Molecule Family; Mice, Inbred C57BL; Signal Transduction; Drug Resistance, Neoplasm; Disease Models, Animal; Female; NF-kappa B
PubMed: 38750176
DOI: 10.1038/s41564-024-01695-w -
Microbiology Spectrum Jun 2024Malignant central airway stenosis is treated with airway stent placement, but post-placement microbial characteristics remain unclear. We studied microbial features in...
UNLABELLED
Malignant central airway stenosis is treated with airway stent placement, but post-placement microbial characteristics remain unclear. We studied microbial features in 60 patients post-stent placement, focusing on changes during granulation tissue proliferation. Samples were collected before stent ( = 29), after stent on day 3 ( = 20), and after granulation tissue formation (AS-GTF, = 43). Metagenomic sequencing showed significant respiratory tract microbiota changes with granulation tissue. The microbiota composition, dominated by , , and , was similar among the groups. At the species level, the AS-GTF group exhibited significant differences, with and enriched. Analysis based on tracheoesophageal fistula presence identified and as the main differential species, enriched in the fistula subgroup. Viral and fungal detection showed and as the main species, respectively. These findings highlight microbiota changes after stent placement, potentially associated with granulation tissue proliferation, informing stent placement therapy and anti-infective treatment optimization.
IMPORTANCE
Malignant central airway stenosis is a life-threatening condition that can be effectively treated with airway stent placement. However, despite its clinical importance, the microbial characteristics of the respiratory tract following stent insertion remain poorly understood. This study addresses this gap by investigating the microbial features in patients with malignant central airway stenosis after stent placement, with a specific focus on microbial changes during granulation tissue proliferation. The findings reveal significant alterations in the diversity and structure of the respiratory tract microbiota following the placement of malignant central airway stents. Notably, certain bacterial species, including and , exhibit distinct patterns in the after-stent granulation tissue formation group. Additionally, the presence of tracheoesophageal fistula further influences the microbial composition. These insights provide valuable references for optimizing stent placement therapy and enhancing clinical anti-infective strategies.
Topics: Humans; Stents; Female; Male; Microbiota; Middle Aged; Aged; Bacteria; Airway Obstruction; Respiratory System; Granulation Tissue; Adult; Aged, 80 and over; Tracheoesophageal Fistula
PubMed: 38747599
DOI: 10.1128/spectrum.03472-23 -
Nature Medicine May 2024Despite substantial progress in cancer microbiome research, recognized confounders and advances in absolute microbiome quantification remain underused; this raises...
Despite substantial progress in cancer microbiome research, recognized confounders and advances in absolute microbiome quantification remain underused; this raises concerns regarding potential spurious associations. Here we study the fecal microbiota of 589 patients at different colorectal cancer (CRC) stages and compare observations with up to 15 published studies (4,439 patients and controls total). Using quantitative microbiome profiling based on 16S ribosomal RNA amplicon sequencing, combined with rigorous confounder control, we identified transit time, fecal calprotectin (intestinal inflammation) and body mass index as primary microbial covariates, superseding variance explained by CRC diagnostic groups. Well-established microbiome CRC targets, such as Fusobacterium nucleatum, did not significantly associate with CRC diagnostic groups (healthy, adenoma and carcinoma) when controlling for these covariates. In contrast, the associations of Anaerococcus vaginalis, Dialister pneumosintes, Parvimonas micra, Peptostreptococcus anaerobius, Porphyromonas asaccharolytica and Prevotella intermedia remained robust, highlighting their future target potential. Finally, control individuals (age 22-80 years, mean 57.7 years, standard deviation 11.3) meeting criteria for colonoscopy (for example, through a positive fecal immunochemical test) but without colonic lesions are enriched for the dysbiotic Bacteroides2 enterotype, emphasizing uncertainties in defining healthy controls in cancer microbiome research. Together, these results indicate the importance of quantitative microbiome profiling and covariate control for biomarker identification in CRC microbiome studies.
Topics: Humans; Colorectal Neoplasms; Middle Aged; Feces; Female; Aged; Male; RNA, Ribosomal, 16S; Adult; Gastrointestinal Microbiome; Aged, 80 and over; Young Adult; Microbiota; Leukocyte L1 Antigen Complex
PubMed: 38689063
DOI: 10.1038/s41591-024-02963-2 -
Vavilovskii Zhurnal Genetiki I Selektsii Apr 2024Recent studies have shown that the bacterial microbiome of the respiratory tract influences the development of lung cancer. Changes in the composition of the microbiome...
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.
PubMed: 38680177
DOI: 10.18699/vjgb-24-25 -
Pharmaceuticals (Basel, Switzerland) Mar 2024SARS-CoV-2 infections, commonly referred to as COVID-19, remain a critical risk to both human life and global economies. Particularly, COVID-19 patients with weak...
SARS-CoV-2 infections, commonly referred to as COVID-19, remain a critical risk to both human life and global economies. Particularly, COVID-19 patients with weak immunity may suffer from different complications due to the bacterial co-infections/super-infections/secondary infections. Therefore, different variants of alternative antibacterial therapeutic agents are required to inhibit those infection-causing drug-resistant pathogenic bacteria. This study attempted to explore these bacterial pathogens and their inhibitors by using integrated statistical and bioinformatics approaches. By analyzing bacterial 16S rRNA sequence profiles, at first, we detected five bacterial genera and taxa (, , , and based on differentially abundant bacteria between SARS-CoV-2 infection and control samples that are significantly enriched in 23 metabolic pathways. A total of 183 bacterial genes were found in the enriched pathways. Then, the top-ranked 10 bacterial genes (, , , , , , , , , and ) were selected as the pathogenic bacterial key genes (bKGs) by their protein-protein interaction (PPI) network analysis. Then, we detected bKG-guided top-ranked eight drug molecules (Bemcentinib, Ledipasvir, Velpatasvir, Tirilazad, Acetyldigitoxin, Entreatinib, Digitoxin, and Elbasvir) by molecular docking. Finally, the binding stability of the top-ranked three drug molecules (Bemcentinib, Ledipasvir, and Velpatasvir) against three receptors (, and ) was investigated by computing their binding free energies with molecular dynamic (MD) simulation-based MM-PBSA techniques, respectively, and was found to be stable. Therefore, the findings of this study could be useful resources for developing a proper treatment plan against bacterial co-/super-/secondary-infection in SARS-CoV-2 infections.
PubMed: 38675393
DOI: 10.3390/ph17040432 -
Scientific Reports Apr 2024Salivary stones, known as sialoliths, form within the salivary ducts due to abnormal salivary composition and cause painful symptoms, for which surgical removal is the...
Salivary stones, known as sialoliths, form within the salivary ducts due to abnormal salivary composition and cause painful symptoms, for which surgical removal is the primary treatment. This study explored the role of the salivary microbial communities in the formation of sialoliths. We conducted a comparative analysis of microbial communities present in the saliva and salivary stones, and sequenced the 16S rRNA gene in samples obtained from patients with sialoliths and from healthy individuals. Although the diversity in the saliva was high, the essential features of the microbial environment in sialoliths were low diversity and evenness. The association of microbial abundance between stones and saliva revealed a positive correlation between Peptostreptococcus and Porphyromonas, and a negative correlation for Pseudomonas in saliva. The functional potential differences between saliva and stones Bacterial chemotaxis and the citrate cycle were negatively correlated with most genera found in salivary stone samples. However, the functions required for organic compound degradation did not differ between the saliva samples. Although some microbes were shared between the sialoliths and saliva, their compositions differed significantly. Our study presents a novel comparison between salivary stones and salivary microbiomes, suggesting potential preventive strategies against sialolithiasis.
Topics: Humans; Saliva; Female; Male; Microbiota; RNA, Ribosomal, 16S; Middle Aged; Adult; Salivary Gland Calculi; Aged; Salivary Calculi; Peptostreptococcus; Porphyromonas
PubMed: 38649387
DOI: 10.1038/s41598-024-59546-x -
Nature Communications Apr 2024The incidence of young-onset colorectal cancer (yCRC) has been increasing in recent decades, but little is known about the gut microbiome of these patients. Most studies...
The incidence of young-onset colorectal cancer (yCRC) has been increasing in recent decades, but little is known about the gut microbiome of these patients. Most studies have focused on old-onset CRC (oCRC), and it remains unclear whether CRC signatures derived from old patients are valid in young patients. To address this, we assembled the largest yCRC gut metagenomes to date from two independent cohorts and found that the CRC microbiome had limited association with age across adulthood. Differential analysis revealed that well-known CRC-associated taxa, such as Clostridium symbiosum, Peptostreptococcus stomatis, Parvimonas micra and Hungatella hathewayi were significantly enriched (false discovery rate <0.05) in both old- and young-onset patients. Similar strain-level patterns of Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were observed for oCRC and yCRC. Almost all oCRC-associated metagenomic pathways had directionally concordant changes in young patients. Importantly, CRC-associated virulence factors (fadA, bft) were enriched in both oCRC and yCRC compared to their respective controls. Moreover, the microbiome-based classification model had similar predication accuracy for CRC status in old- and young-onset patients, underscoring the consistency of microbial signatures across different age groups.
Topics: Humans; Gastrointestinal Microbiome; Colorectal Neoplasms; Adult; Age of Onset; Male; Female; Middle Aged; Aged; Metagenome; Metagenomics; Bacteria; Young Adult; Feces; Cohort Studies
PubMed: 38649355
DOI: 10.1038/s41467-024-47523-x -
BMC Microbiology Apr 2024Oral microbiota imbalance is associated with the progression of various lung diseases, including lung cancer. Pulmonary nodules (PNs) are often considered a critical...
BACKGROUND
Oral microbiota imbalance is associated with the progression of various lung diseases, including lung cancer. Pulmonary nodules (PNs) are often considered a critical stage for the early detection of lung cancer; however, the relationship between oral microbiota and PNs remains unknown.
METHODS
We conducted a 'Microbiome with pulmonary nodule series study 1' (MCEPN-1) where we compared PN patients and healthy controls (HCs), aiming to identify differences in oral microbiota characteristics and discover potential microbiota biomarkers for non-invasive, radiation-free PNs diagnosis and warning in the future. We performed 16 S rRNA amplicon sequencing on saliva samples from 173 PN patients and 40 HCs to compare the characteristics and functional changes in oral microbiota between the two groups. The random forest algorithm was used to identify PN salivary microbial markers. Biological functions and potential mechanisms of differential genes in saliva samples were preliminarily explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of Orthologous Groups (COG) analyses.
RESULTS
The diversity of salivary microorganisms was higher in the PN group than in the HC group. Significant differences were noted in community composition and abundance of oral microorganisms between the two groups. Neisseria, Prevotella, Haemophilus and Actinomyces, Porphyromonas, Fusobacterium, 7M7x, Granulicatella and Selenomonas were the main differential genera between the PN and HC groups. Fusobacterium, Porphyromonas, Parvimonas, Peptostreptococcus and Haemophilus constituted the optimal marker sets (area under curve, AUC = 0.80), which can distinguish between patients with PNs and HCs. Further, the salivary microbiota composition was significantly correlated with age, sex, and smoking history (P < 0.001), but not with personal history of cancer (P > 0.05). Bioinformatics analysis of differential genes showed that patients with PN showed significant enrichment in protein/molecular functions related to immune deficiency and energy metabolisms, such as the cytoskeleton protein RodZ, nicotinamide adenine dinucleotide phosphate dehydrogenase (NADPH) dehydrogenase, major facilitator superfamily transporters and AraC family transcription regulators.
CONCLUSIONS
Our study provides the first evidence that the salivary microbiota can serve as potential biomarkers for identifying PN. We observed a significant association between changes in the oral microbiota and PNs, indicating the potential of salivary microbiota as a new non-invasive biomarker for PNs.
TRIAL REGISTRATION
Clinical trial registration number: ChiCTR2200062140; Date of registration: 07/25/2022.
Topics: Humans; Saliva; RNA, Ribosomal, 16S; Microbiota; Biomarkers; Lung Neoplasms; Oxidoreductases
PubMed: 38643115
DOI: 10.1186/s12866-024-03280-x -
NPJ Biofilms and Microbiomes Apr 2024Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with...
Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/β-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Epigenomics; Dysbiosis; Mouth Neoplasms; Carcinoma, Squamous Cell; Bacteria; Fusobacterium nucleatum; Head and Neck Neoplasms; Epigenesis, Genetic; Microbiota; Tumor Microenvironment
PubMed: 38589501
DOI: 10.1038/s41522-024-00511-x -
Microorganisms Feb 2024Calf intestines are colonized by rich and complex microbial communities, playing a crucial role in animal physiology, metabolism, nutrition, and immune function. In this...
Differential Microbial Composition and Interkingdom Interactions in the Intestinal Microbiota of Holstein and German Simmental × Holstein Cross F1 Calves: A Comprehensive Analysis of Bacterial and Fungal Diversity.
Calf intestines are colonized by rich and complex microbial communities, playing a crucial role in animal physiology, metabolism, nutrition, and immune function. In this study, we provide insight into the composition of fecal microbial bacteria and fungi, respectively, as well as the cross-kingdom interactions. We investigated the intestinal microbiota of different breeds of calves by characterizing the bacterial and fungal communities in the rectal feces of Holstein calves and German Simmental × Holstein cross F1 generation (GXH) using 16S rRNA and ITS amplicon sequencing techniques. PICRUSt2 (version 2.2.0) were used to determine microbial diversity and function and explore the reasons why Holstein calves are more susceptible to diarrhea. The results revealed no significant difference in the diversity of fecal microbiota among the groups ( > 0.05). We identified and as the dominant bacterial phyla in the fecal bacterial communities of the two breeds of calves. and play important roles in the fungal community but differ in relative abundance. was the dominant genus at the group level for calf fecal microbiota in both breeds. The relative abundance of , -, , and was higher in Holstein calves, and the relative abundance of , , , and was lower than GXH group. and were the dominating genera of fecal fungi in both groups of calves. LEfSe analysis revealed 33 different bacteria and 23 different fungi between the two groups, with more differential strains found in GXH. In addition, the feces fungi-bacteria interkingdom interactions varied among breeds. Thus, the composition and structure of bacterial and fungal communities in calf feces varied by breed, indicating a potential association between breed and microbial communities. We also found differences in the network between bacterial-fungal kingdoms. We explain the reasons for Holstein calves being more prone to diarrhea. This indicated that breed makes differences in calf diarrhea rates by influencing gut microbial composition and interactions.
PubMed: 38543537
DOI: 10.3390/microorganisms12030486