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Microbiology Spectrum Aug 2023Many studies have suggested that gut microbiota dysbiosis may be one of the pathogenesis factors of diabetes mellitus (DM), while it is not clear whether it is involved...
Many studies have suggested that gut microbiota dysbiosis may be one of the pathogenesis factors of diabetes mellitus (DM), while it is not clear whether it is involved in the development of diabetic kidney diseases (DKD). The objective of this study was to determine bacterial taxa biomarkers during the progression of DKD by investigating bacterial compositional changes in early and late DKD. 16S rRNA gene sequencing was performed on fecal samples, including the diabetes mellitus (DM), DNa (early DKD), and DNb (late DKD) groups. Taxonomic annotation of microbial composition was performed. Samples were sequenced on the Illumina NovaSeq platform. At the genus level, we found counts of , , and were significantly elevated both in the DNa group (0.0001, 0.0007, and 0.0174, respectively) and the DNb group (0.0001, 0.0012, and 0.0003, respectively) compared with those in the DM group. Only the level of was significantly decreased in the DNa group than the DM group and in the DNb group than the DNa group. Counts of , were significantly decreased in the DNa group compared with those in the DM group (0.001 and 0.006, respectively) and in the DNb group compared with those in the DM group (0.0001 and 0.003, respectively). Levels of , and were positively correlated with an estimated glomerular filtration rate (eGFR), but negatively correlated with microalbuminuria (MAU), 24 h urinary protein quantity (24hUP), and serum creatinine (Scr). Moreover, the areas under the curve (AUCs) of and were 83.33% and 80.77%, respectively, for the DM and DNa cohorts, respectively. Notably, the largest AUC for DNa and DNb cohorts was also that of at 83.60%. Gut microbiota dysbiosis was found in the early and late stages of DKD, especially in the early stage. may be the most promising intestinal bacteria biomarker that can help distinguish different stages of DKD. It is not clear as to whether gut microbiota dysbiosis is involved in the progression of DKD. This study may be the first to explore gut microbiota compositional changes in diabetes, early-DKD, and late DKD. We identify different gut microbial characteristics during different stages of DKD. Gut microbiota dysbiosis is found in the early and late stages of DKD. may be the most promising intestinal bacteria biomarker that can help distinguish different stages of DKD, although further studies are warranted to illustrate these mechanisms.
Topics: Diabetic Nephropathies; Humans; Male; Female; Middle Aged; Gastrointestinal Microbiome; Clostridiales; Biomarkers; Diabetes Mellitus; Bacteria; Feces; Kidney Failure, Chronic
PubMed: 37341590
DOI: 10.1128/spectrum.00382-23 -
Pathogens (Basel, Switzerland) Jan 2024Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. and , which are known periodontal pathogens,... (Review)
Review
Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. and , which are known periodontal pathogens, have emerged as extensively studied participants with potential pathogenic abilities in carcinogenesis. However, the complex dynamics arising from interactions between these two pathogens were less addressed. This narrative review aims to summarize the current knowledge on the prevalence and mechanism implications of and in the carcinogenesis of oral squamous cell carcinoma (OSCC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). In particular, it explores the clinical and experimental evidence on the interplay between and in affecting oral and gastrointestinal carcinogenesis. and , which are recognized as keystone or bridging bacteria, were identified in multiple clinical studies simultaneously. The prevalence of both bacteria species correlated with cancer development progression, emphasizing the potential impact of the collaboration. Regrettably, there was insufficient experimental evidence to demonstrate the synergistic function. We further propose a hypothesis to elucidate the underlying mechanisms, offering a promising avenue for future research in this dynamic and evolving field.
PubMed: 38276166
DOI: 10.3390/pathogens13010093 -
Frontiers in Cellular and Infection... 2023When it comes to the onset of moyamoya disease (MMD), environmental variables are crucial. Furthermore, there is confusion about the relationship between the gut...
BACKGROUND AND PURPOSE
When it comes to the onset of moyamoya disease (MMD), environmental variables are crucial. Furthermore, there is confusion about the relationship between the gut microbiome, an environmental variable, and MMD. Consequently, to identify the particular bacteria that cause MMD, we examined the gut microbiome of MMD individuals and healthy controls (HC).
METHODS
A prospective case-control investigation was performed from June 2021 to May 2022. The fecal samples of patients with MMD and HC were obtained. Typically, 16S rRNA sequencing was employed to examine their gut microbiota. The QIIME and R softwares were used to examine the data. The linear discriminant analysis effect size analysis was used to determine biomarkers. Multivariate analysis by linear models (MaAsLin)2 were used to find associations between microbiome data and clinical variables. Model performance was assessed using the receiver operating characteristic curve and the decision curve analysis.
RESULTS
This investigation involved a total of 60 MMD patients and 60 HC. The MMD group's Shannon and Chao 1 indices were substantially lower than those of the HC cohort. β-diversity was significantly different in the weighted UniFrac distances. At the phylum level, the relative abundance of / was significantly higher/lower in the MMD group than that in the HC group. By MaAsLin2 analysis, the relative abundance of the 2 genera, and , increased in the MMD group, while the relative abundance of the 2 genera, and decreased in the MMD group. A predictive model was constructed by using these 4 genera. The area under the receiver operating characteristic curve was 0.921. The decision curve analysis indicated that the model had usefulness in clinical practice.
CONCLUSIONS
The gut microbiota was altered in individuals with MMD, and was characterized by increased abundance of and and decreased abundance of and . These 4 genera could be used as biomarkers and predictors in clinical practice.
Topics: Humans; Adult; Gastrointestinal Microbiome; Moyamoya Disease; RNA, Ribosomal, 16S; Feces; Bacteria; Fusobacterium; Biomarkers; Bifidobacterium
PubMed: 37915847
DOI: 10.3389/fcimb.2023.1252681 -
Journal of Endodontics May 2024In this study, we used metatranscriptomics for the first time to investigate microbial composition, functional signatures, and antimicrobial resistance gene expression...
INTRODUCTION
In this study, we used metatranscriptomics for the first time to investigate microbial composition, functional signatures, and antimicrobial resistance gene expression in endodontic infections.
METHODS
Root canal samples were collected from ten teeth, including five primary and five persistent/secondary endodontic infections. RNA from endodontic samples was extracted, and RNA sequencing was performed on a NovaSeq6000 system (Illumina). Taxonomic analysis was performed using the Kraken2 bacterial database. Then, sequences with a taxonomic classification were annotated against the Universal Protein Knowledgebase for functional annotation and the Comprehensive Antibiotic Resistance Database for AR-like gene identification.
RESULTS
Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria represented the dominant phyla, whereas Fusobacteria, Spirochetes, and Synergistetes were among the nondominant phyla. The top ten species were mainly represented by obligate (or quasiobligate) anaerobes, including Gram-negative (eg, Capnocytophaga sp. oral taxon 323, Fusobacterium nucleatum, Prevotella intermedia, Prevotella oris, Tannerella forsythia, and Tannerella sp. oral taxon HOT-286) and Gram-positive species (eg, Olsenella uli and Parvimonas micra). Transcripts encoding moonlighting proteins (eg, glycolytic proteins, translational elongation factors, chaperonin, and heat shock proteins) were highly expressed, potentially affecting bacterial adhesion, biofilm formation, host defense evasion, and inflammation induction. Endodontic bacteria expressed genes conferring resistance to antibiotic classes commonly used in dentistry, with a high prevalence and expression of tetracycline and lincosamide resistance genes. Antibiotic efflux and antibiotic target alteration/protection were the main resistance mechanisms.
CONCLUSIONS
Metatranscriptomics revealed the activity of potential endodontic pathogens, which expressed putative virulence factors and a wide diversity of genes potentially involved in AR.
PubMed: 38719087
DOI: 10.1016/j.joen.2024.03.015 -
Microbiology Spectrum Aug 2023Fusobacterium nucleatum is a Gram-negative bacterium that has been identified as an important pathogenic gut bacterium associated with colorectal cancer. Compared with...
Fusobacterium nucleatum is a Gram-negative bacterium that has been identified as an important pathogenic gut bacterium associated with colorectal cancer. Compared with the normal intestine, the pH value of the tumor microenvironment is weakly acidic. The metabolic changes of F. nucleatum in the tumor microenvironment, especially the protein composition of its outer membrane vesicles, remain unclear. Here, we systematically analyzed the effect of environmental pH on the proteome of outer membrane vesicles (OMVs) from F. nucleatum by tandem mass tag (TMT) labeling-high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. A total of 991 proteins were identified in acidic OMVs (aOMVs) and neutral OMVs (nOMVs), including known virulence proteins and putative virulence proteins. Finally, 306 upregulated proteins and 360 downregulated proteins were detected in aOMVs, and approximately 70% of the expression of OMV proteins was altered under acidic conditions. A total of 29 autotransporters were identified in F. nucleatum OMVs, and 13 autotransporters were upregulated in aOMVs. Interestingly, three upregulated autotransporters (D5REI9, D5RD69, and D5RBW2) show homology to the known virulence factor Fap2, suggesting that they may be involved in various pathogenic pathways such as the pathway for binding with colorectal cancer cells. Moreover, we found that more than 70% of MORN2 domain-containing proteins may have toxic effects on host cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that a number of proteins were significantly enriched in multiple pathways involving fatty acid synthesis and butyrate synthesis. Seven metabolic enzymes involved in fatty acid metabolism pathways were identified in the proteomic data, of which 5 were upregulated and 2 were downregulated in aOMVs, while 14 metabolic enzymes involved in the butyric acid metabolic pathway were downregulated in aOMVs. In conclusion, we found a key difference in virulence proteins and pathways in the outer membrane vesicles of F. nucleatum between the tumor microenvironment pH and normal intestinal pH, which provides new clues for the prevention and treatment of colorectal cancer. F. nucleatum is an opportunistic pathogenic bacterium that can be enriched in colorectal cancer tissues, affecting multiple stages of colorectal cancer development. OMVs have been demonstrated to play key roles in pathogenesis by delivering toxins and other virulence factors to host cells. By employing quantitative proteomic analysis, we found that the pH conditions could affect the protein expression of the outer membrane vesicles of F. nucleatum. Under acidic conditions, approximately 70% of the expression of proteins in OMVs was altered. Several virulence factors, such as type 5a secreted autotransporter (T5aSSs) and membrane occupation and recognition nexus (MORN) domain-containing proteins, were upregulated under acidic conditions. A large number of proteins showed significant enrichments in multiple pathways involving fatty acid synthesis and butyrate synthesis. Proteomics analysis of the outer membrane vesicles secreted by pathogenic bacteria in the acidic tumor microenvironment is of great significance for elucidating the pathogenicity mechanism and its application in vaccine and drug delivery vehicles.
Topics: Humans; Fusobacterium nucleatum; Proteomics; Type V Secretion Systems; Chromatography, Liquid; Tandem Mass Spectrometry; Virulence Factors; Membrane Proteins; Colorectal Neoplasms; Fatty Acids; Bacterial Outer Membrane Proteins; Tumor Microenvironment
PubMed: 37341631
DOI: 10.1128/spectrum.00394-23 -
European Journal of Immunology Nov 2023Caspase activation results in pyroptosis, an inflammatory cell death that contributes to several inflammatory diseases by releasing inflammatory cytokines and cellular...
Caspase activation results in pyroptosis, an inflammatory cell death that contributes to several inflammatory diseases by releasing inflammatory cytokines and cellular contents. Fusobacterium nucleatum is a periodontal pathogen frequently detected in human cancer and inflammatory bowel diseases. Studies have reported that F. nucleatum infection leads to NLRP3 activation and pyroptosis, but the precise activation process and disease association remain poorly understood. This study demonstrated that F. nucleatum infection exacerbates acute colitis in mice and activates pyroptosis through caspase-11-mediated gasdermin D cleavage in macrophages. Furthermore, F. nucleatum infection in colitis mice induces the enhancement of IL-1⍺ secretion from the colon, affecting weight loss and severe disease activities. Neutralization of IL-1⍺ protects F. nucleatum infected mice from severe colitis. Therefore, F. nucleatum infection facilitates inflammation in acute colitis with IL-1⍺ from colon tissue by activating noncanonical inflammasome through gasdermin D cleavage.
Topics: Humans; Animals; Mice; Inflammasomes; Fusobacterium nucleatum; Gasdermins; Colitis; Caspases; NLR Family, Pyrin Domain-Containing 3 Protein
PubMed: 37471504
DOI: 10.1002/eji.202350455 -
Molecular Medicine Reports Mar 2024Periodontitis is a common chronic inflammatory and destructive disease in the mouth and is considered to be associated with systemic diseases. Accumulating evidence has... (Review)
Review
Periodontitis is a common chronic inflammatory and destructive disease in the mouth and is considered to be associated with systemic diseases. Accumulating evidence has suggested that periodontitis is a risk factor for pulmonary diseases such as pneumonia, chronic obstructive pulmonary disease (COPD), asthma, coronavirus disease 2019 (COVID‑19) and lung cancer. The presence of common periodontal pathogens has been detected in samples from a variety of pulmonary diseases. Periodontal pathogens can be involved in lung diseases by promoting the adhesion and invasion of respiratory pathogens, regulating the apoptosis of respiratory epithelium and inducing overexpression of mucin and disrupting the balance of immune systemin respiratory epithelium cells. Additionally, measures to control plaque and maintain the health of periodontal tissue can decrease the incidence of respiratory adverse events. This evidence suggests a close association between periodontitis and pulmonary diseases. The present study aimed to review the clinical association between periodontitis and pneumonia, COPD, asthma, COVID‑19 and lung cancer, and propose a possible mechanism and potential role of periodontal pathogens in linking periodontal disease and lung disease. This could provide a direction for further research on the association between periodontitis and lung disease and provide novel ideas for the clinical diagnosis and treatment management of these two diseases.
Topics: Humans; Asthma; COVID-19; Fusobacterium nucleatum; Lung Neoplasms; Periodontitis; Pneumonia; Porphyromonas gingivalis; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases
PubMed: 38240101
DOI: 10.3892/mmr.2024.13166 -
Science Advances Apr 2024Type VI CRISPR-Cas systems are among the few CRISPR varieties that target exclusively RNA. The CRISPR RNA-guided, sequence-specific binding of target RNAs, such as phage...
Type VI CRISPR-Cas systems are among the few CRISPR varieties that target exclusively RNA. The CRISPR RNA-guided, sequence-specific binding of target RNAs, such as phage transcripts, activates the type VI effector, Cas13. Once activated, Cas13 causes collateral RNA cleavage, which induces bacterial cell dormancy, thus protecting the host population from the phage spread. We show here that the principal form of collateral RNA degradation elicited by Cas13a expressed in cells is the cleavage of anticodons in a subset of transfer RNAs (tRNAs) with uridine-rich anticodons. This tRNA cleavage is accompanied by inhibition of protein synthesis, thus providing defense from the phages. In addition, Cas13a-mediated tRNA cleavage indirectly activates the RNases of bacterial toxin-antitoxin modules cleaving messenger RNA, which could provide a backup defense. The mechanism of Cas13a-induced antiphage defense resembles that of bacterial anticodon nucleases, which is compatible with the hypothesis that type VI effectors evolved from an abortive infection module encompassing an anticodon nuclease.
Topics: RNA, Transfer; CRISPR-Cas Systems; Anticodon; Escherichia coli; Leptotrichia; CRISPR-Associated Proteins; Bacteriophages; RNA Cleavage
PubMed: 38657076
DOI: 10.1126/sciadv.adl0164 -
Journal of Dental Research Mar 2024Colorectal cancer (CRC) and periodontitis have recently been related due to the higher incidence of CRC in periodontal patients and the involvement of periodontal...
Colorectal cancer (CRC) and periodontitis have recently been related due to the higher incidence of CRC in periodontal patients and the involvement of periodontal pathogens in carcinogenesis, suggesting that leakage from the oral cavity to the gut occurs. However, the magnitude of this pass-through in healthy individuals is controversial, and the effect that periodontitis could play in it is understudied. To evaluate the rate of bacterial leakage from the oral cavity to the gut, we analyzed the microbial composition of saliva, subgingival plaque, and fecal samples in healthy individuals without gastrointestinal disorders, including 20 periodontitis patients and 20 oral healthy controls, using PacBio full-length 16S rRNA gene sequencing. As expected, we observed a higher abundance of periodontal pathogens in the subgingival plaque and saliva of periodontal patients. In contrast, no significant differences were found between the fecal samples of both groups, implying that gut samples from periodontal patients were not enriched in periodontal pathogens. , a biomarker of CRC, was not found in the fecal samples of any participant. Our study does show a small leakage of some oral bacteria (mainly streptococci) to the gut, regardless of periodontal health status. Future studies should test whether other host factors and/or the preexistence of a gut disorder must be present in addition to periodontitis to promote the colonization of the gut by oral pathogens. The absence of periodontal pathogens in feces supports the idea that these bacteria could be used as biomarkers of intestinal disorders, including CRC.
Topics: Humans; RNA, Ribosomal, 16S; Periodontitis; Bacteria; Dental Plaque; Fusobacterium nucleatum
PubMed: 38193290
DOI: 10.1177/00220345231221709 -
Cancer Science Sep 2023Intratumor bacteria modify the tumor immune microenvironment and influence outcomes of various tumors. Periodontal pathogen Fusobacterium nucleatum has been detected in...
Intratumor bacteria modify the tumor immune microenvironment and influence outcomes of various tumors. Periodontal pathogen Fusobacterium nucleatum has been detected in pancreatic cancer tissues and is associated with poor prognosis. However, it remains unclear how F. nucleatum affects pancreatic cancer. Here, we compared clinical features with F. nucleatum colonization in pancreatic cancer tissues. F. nucleatum was detected in 15.5% (13/84) of pancreatic cancer patients. The tumor size was significantly larger in the F. nucleatum-positive group than in the negative group. To clarify the biological effect of intratumor F. nucleatum on pancreatic cancer progression, we performed migration/invasion assays and cytokine array analysis of cancer cells cocultured with F. nucleatum. F. nucleatum promoted CXCL1 secretion from pancreatic cancer cells, leading to cancer progression through autocrine signaling. Intratumor F. nucleatum suppressed tumor-infiltrating CD8 T cells by recruiting myeloid-derived suppressor cells (MDSCs) to the tumor in an F. nucleatum-injected subcutaneous pancreatic cancer mouse model, resulting in tumor progression. Furthermore, tumor growth accelerated by F. nucleatum was suppressed by MDSC depletion or cytokine inhibitors. Intratumor F. nucleatum promoted pancreatic cancer progression through autocrine and paracrine mechanisms of the CXCL1-CXCR2 axis. Blockade of the CXCL1-CXCR2 axis may be a novel therapeutic approach for patients with intratumor F. nucleatum-positive pancreatic cancer.
Topics: Animals; Mice; Fusobacterium nucleatum; CD8-Positive T-Lymphocytes; Colorectal Neoplasms; Pancreatic Neoplasms; Cytokines; Tumor Microenvironment
PubMed: 37438965
DOI: 10.1111/cas.15901