-
Exploration (Beijing, China) Feb 2024Colorectal cancer (CRC) is generally characterized by a high prevalence of (), a spindle-shaped, Gram-negative anaerobe pathogen derived from the oral cavity. This... (Review)
Review
Colorectal cancer (CRC) is generally characterized by a high prevalence of (), a spindle-shaped, Gram-negative anaerobe pathogen derived from the oral cavity. This tumor-resident microorganism has been closely correlated with the occurrence, progression, chemoresistance and immunosuppressive microenvironment of CRC. Furthermore, can specifically colonize CRC tissues through adhesion on its surface, forming biofilms that are highly resistant to commonly used antibiotics. Accordingly, it is crucial to develop efficacious non-antibiotic approaches to eradicate and its biofilms for CRC treatment. In recent years, various antimicrobial strategies, such as natural extracts, inorganic chemicals, organic chemicals, polymers, inorganic-organic hybrid materials, bacteriophages, probiotics, and vaccines, have been proposed to combat and biofilms. This review summarizes the latest advancements in anti- research, elucidates the antimicrobial mechanisms employed by these systems, and discusses the benefits and drawbacks of each antimicrobial technology. Additionally, this review also provides an outlook on the antimicrobial specificity, potential clinical implications, challenges, and future improvements of these antimicrobial strategies in the treatment of CRC.
PubMed: 38854496
DOI: 10.1002/EXP.20230092 -
BioRxiv : the Preprint Server For... May 2024Genetic factors and microbial imbalances play crucial roles in colorectal cancers (CRCs), yet the impact of infections on cancer initiation remains poorly understood....
BACKGROUND
Genetic factors and microbial imbalances play crucial roles in colorectal cancers (CRCs), yet the impact of infections on cancer initiation remains poorly understood. While bioinformatic approaches offer valuable insights, the rising incidence of CRCs creates a pressing need to precisely identify early CRC events. We constructed a network model to identify continuum states during CRC initiation spanning normal colonic tissue to pre-cancer lesions (adenomatous polyps) and examined the influence of microbes and host genetics.
METHODS
A Boolean network was built using a publicly available transcriptomic dataset from healthy and adenoma affected patients to identify an invariant Microbe-Associated Colorectal Cancer Signature (MACS). We focused on ( ), a CRC-associated microbe, as a model bacterium. MACS-associated genes and proteins were validated by RT-qPCR, RNA seq, ELISA, IF and IHCs in tissues and colon-derived organoids from genetically predisposed mice ( ) and patients (FAP, Lynch Syndrome, PJS, and JPS).
RESULTS
The MACS that is upregulated in adenomas consists of four core genes/proteins: CLDN2/Claudin-2 (leakiness), LGR5/leucine-rich repeat-containing receptor (stemness), CEMIP/cell migration-inducing and hyaluronan-binding protein (epithelial-mesenchymal transition) and IL8/Interleukin-8 (inflammation). MACS was induced upon infection, but not in response to infection with other enteric bacteria or probiotics. MACS induction upon infection was higher in organoids compared to WT controls. The degree of MACS expression in the patient-derived organoids (PDOs) generally corresponded with the known lifetime risk of CRCs.
CONCLUSIONS
Computational prediction followed by validation in the organoid-based disease model identified the early events in CRC initiation. MACS reveals that the CRC-associated microbes induce a greater risk in the genetically predisposed hosts, suggesting its potential use for risk prediction and targeted cancer prevention.
PubMed: 38853996
DOI: 10.1101/2024.05.26.595902 -
Ceramic conversion treated titanium implant abutments with gold for enhanced antimicrobial activity.Dental Materials : Official Publication... Jun 2024Peri-implantitis is an inflammatory process around dental implants that is characterised by bone loss that may jeopardize the long-term survival of osseo integrated...
INTRODUCTION
Peri-implantitis is an inflammatory process around dental implants that is characterised by bone loss that may jeopardize the long-term survival of osseo integrated dental implants. The aim of this study was to create a surface coating on titanium abutments that possesses cellular adhesion and anti-microbial properties as a post-implant placement strategy for patients at risk of peri-implantitis.
MATERIALS AND METHODSMETHODS
Titanium alloy Grade V stubs were coated with gold particles and then subjected to ceramic conversion treatment (CCT) at 620 °C for 3, 8 and 80 h. The surface characteristics and chemistry were assessed using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD) analysis. The leaching profile was investigated by inductively coupled plasma mass spectroscopy (ICP-MS) for all groups after 7, 14 and 28 days in contact with distilled water. A scratch test was conducted to assess the adhesion of the gold coating to the underlying titanium discs. Two bacterial species (Staphylococcus aureus (SA) & Fusobacterium nucleatum (FN)) were used to assess the antibacterial behaviour of the coated discs using a direct attachment assay test. The potential changes in surface chemistry by the bacterial species were investigated by grazing angle XRD.
RESULTS
The gold pre-coated titanium discs exhibited good stability of the coating especially after immersion in distilled water and after bacterial colonisation as evident by XRD analysis. Good surface adhesion of the coating was demonstrated for gold treated discs after scratch test analysis, especially titanium, following a 3-hour (3 H) ceramic conversion treatment. All coated discs exhibited significantly improved antimicrobial properties against both tested bacterial species compared to untreated titanium discs.
CONCLUSIONS
Ceramic conversion treated titanium with a pre-deposited gold layer showed improved antimicrobial properties against both SA and FN species than untreated Ti-C discs. Scratch test analysis showed good adherence properties of the coated discs the oxide layer formed is firmly adherent to the underlying titanium substrate, suggesting that this approach may have clinical efficacy for coating implant abutments.
PubMed: 38853104
DOI: 10.1016/j.dental.2024.05.029 -
BMC Oral Health Jun 2024Crohn's disease (CD)-associated periodontitis is common. However, the role of periodontal pathogens in the Coexistence of CD and periodontal disease remains unclear.
BACKGROUND
Crohn's disease (CD)-associated periodontitis is common. However, the role of periodontal pathogens in the Coexistence of CD and periodontal disease remains unclear.
METHODS
To investigate the potential relationship mediated by periodontal pathogens between periodontitis and CD, we collected salivary samples from healthy participants (H group, n = 12), patients with CD (Ch group, n = 10), patients with periodontitis (Ps group, n = 12), and patients with Coexistence of CD and periodontal disease (Cp group, n = 12) and analyzed them by 16 S rRNA sequencing.
RESULTS
Patients with Coexistence of CD and periodontal disease had increased levels of Fusobacterium, Actinomyces, Leptotrichia, and Prevotella, which correlated with the severity of periodontitis. Conversely, the levels of Streptococcus, Neisseria, Haemophilus, and Gemella, which decreased in Coexistence of CD and periodontal disease, were negatively correlated with the severity of periodontitis. To further investigate the role of periodontal pathogens in CD development, representative periodontal pathogens causing periodontitis, Porphyromonas gingivalis and Fusobacterium nucleatum, were administered to mice. These pathogens migrate to, and colonize, the gut, accelerating CD progression and aggravating colitis, and even systemic inflammation. In vitro experiments using a Caco-2/periodontal pathogen coculture revealed that P. gingivalis and F. nucleatum increased intestinal permeability by directly disrupting the tight junctions of intestinal epithelial cells.
CONCLUSION
Our findings strongly suggest that periodontal pathogens play a role in the relationship between periodontitis and CD. These results provide a basis for understanding the pathogenesis of Coexistence of CD and periodontal disease and may lead to the development of novel therapeutic strategies.
Topics: Humans; Crohn Disease; Periodontitis; Animals; Mice; Male; Female; Adult; Porphyromonas gingivalis; Fusobacterium nucleatum; Caco-2 Cells; Saliva; RNA, Ribosomal, 16S
PubMed: 38849764
DOI: 10.1186/s12903-024-04425-0 -
BMC Microbiology Jun 2024Emerging evidence emphasized the role of oral microbiome in oral lichen planus (OLP). To date, no dominant pathogenic bacteria have been identified consistently. It is...
BACKGROUND
Emerging evidence emphasized the role of oral microbiome in oral lichen planus (OLP). To date, no dominant pathogenic bacteria have been identified consistently. It is noteworthy that a decreased abundance of Streptococcus, a member of lactic acid bacteria (LAB) in OLP patients has been commonly reported, indicating its possible effect on OLP. This study aims to investigate the composition of LAB genera in OLP patients by high-throughput sequencing, and to explore the possible relationship between them.
METHODS
We collected saliva samples from patients with OLP (n = 21) and healthy controls (n = 22) and performed 16 S rRNA gene high-throughput sequencing. In addition, the abundance of LAB genera was comprehensively analyzed and compared between OLP and HC group. To verify the expression of Lactococcus lactis, real time PCR was conducted in buccal mucosa swab from another 14 patients with OLP and 10 HC. Furthermore, the correlation was conducted between clinical severity of OLP and LAB.
RESULTS
OLP and HC groups showed similar community richness and diversity. The members of LAB, Lactococcus and Lactococcus lactis significantly decreased in saliva of OLP cases and negatively associated with OLP severity. In addition, Lactococcus and Lactococcus lactis showed negative relationship with Fusobacterium and Aggregatibacter, which were considered as potential pathogens of OLP. Similarly, compared with healthy controls, the amount of Lactococcus lactis in mucosa lesion of OLP patients was significantly decreased.
CONCLUSIONS
A lower amount of Lactococcus at genus level, Lactococcus lactis at species level was observed in OLP cases and associated with disease severity. Further studies to verify the relationship between LAB and OLP, as well as to explore the precise mechanism is needed.
Topics: Humans; Saliva; Female; Male; Lichen Planus, Oral; Middle Aged; Lactobacillales; RNA, Ribosomal, 16S; Microbiota; Adult; High-Throughput Nucleotide Sequencing; Aged; Mouth Mucosa; Case-Control Studies; DNA, Bacterial; Lactococcus lactis
PubMed: 38849732
DOI: 10.1186/s12866-024-03350-0 -
Infectious Medicine Jun 2024brain abscesses are relatively rare. Here, we report our treatment of an anaerobic brain abscess caused by a mixed infection of , and diagnosed by metagenomic...
brain abscesses are relatively rare. Here, we report our treatment of an anaerobic brain abscess caused by a mixed infection of , and diagnosed by metagenomic next-generation sequencing (mNGS). This is the first reported case of in a brain abscess. This case highlights the possibility that oral anaerobic microbes can cause a brain abscess and demonstrates that mNGS has the potential to be deployed to provide rapid infection diagnosis and rationalize antimicrobial therapy for brain abscesses.
PubMed: 38846345
DOI: 10.1016/j.imj.2024.100109 -
Frontiers in Cellular and Infection... 2024Trimethylamine-N-oxide (TMAO) is produced by hepatic flavin-containing monooxygenase 3 (FMO3) from trimethylamine (TMA). High TMAO level is a biomarker of cardiovascular...
BACKGROUND
Trimethylamine-N-oxide (TMAO) is produced by hepatic flavin-containing monooxygenase 3 (FMO3) from trimethylamine (TMA). High TMAO level is a biomarker of cardiovascular diseases and metabolic disorders, and it also affects periodontitis through interactions with the gastrointestinal microbiome. While recent findings indicate that periodontitis may alter systemic TMAO levels, the specific mechanisms linking these changes and particular oral pathogens require further clarification.
METHODS
In this study, we established a C57BL/6J male mouse model by orally administering (, ), (, ), (, ) and PBS was used as a control. We conducted LC-MS/MS analysis to quantify the concentrations of TMAO and its precursors in the plasma and cecal contents of mice. The diversity and composition of the gut microbiome were analyzed using 16S rRNA sequencing. TMAO-related lipid metabolism and enzymes in the intestines and liver were assessed by qPCR and ELISA methods. We further explored the effect of on FMO3 expression and lipid molecules in HepG2 cells by stimulating the cells with -LPS .
RESULTS
The three oral pathogenic bacteria were orally administered to the mice for 5 weeks. The group showed a marked increase in plasma TMAO, betaine, and creatinine levels, whereas no significant differences were observed in the gut TMAO level among the four groups. Further analysis showed similar diversity and composition in the gut microbiomes of both the and groups, which were different from the and control groups. The profiles of TMA-TMAO pathway-related genera and gut enzymes were not significantly different among all groups. The group showed significantly higher liver FMO3 levels and elevated lipid factors (IL-6, TG, TC, and NEFA) in contrast to the other groups. experiments confirmed that stimulation of HepG2 cells with -LPS upregulated the expression of FMO3 and increased the lipid factors TC, TG, and IL-6.
CONCLUSION
This study conclusively demonstrates that , compared to and , plays a critical role in elevating plasma TMAO levels and significantly influences the TMA-TMAO pathway, primarily by modulating the expression of hepatic FMO3 and directly impacting hepatic lipid metabolism.
Topics: Animals; Male; Methylamines; Humans; Gastrointestinal Microbiome; Mice; Mice, Inbred C57BL; Oxygenases; Porphyromonas gingivalis; Fusobacterium nucleatum; Metabolic Networks and Pathways; Hep G2 Cells; Lipid Metabolism; Disease Models, Animal; Periodontitis; Liver; RNA, Ribosomal, 16S; Tandem Mass Spectrometry; Mouth
PubMed: 38836053
DOI: 10.3389/fcimb.2024.1413787 -
Frontiers in Oncology 2024Intratumoral microbes play an important role in the development of colorectal cancer (CRC). However, studying intratumoral microbes in CRC faces technical challenges, as...
INTRODUCTION
Intratumoral microbes play an important role in the development of colorectal cancer (CRC). However, studying intratumoral microbes in CRC faces technical challenges, as tumor microbe communities are often contaminated by fecal microbes due to the structure of the gut folds and villi. The present study aimed to develop a new method for isolating tumor cell-associated microbiota and comparing microbial populations from different compartments.
MATERIALS AND METHODS
The distribution of intestinal bacteria was detected using immunohistochemistry combined with 5R-16s rRNA gene sequencing to explore the effects of the sampling site and number of washes on the detection of microbiota. The 5R-16s rRNA gene sequencing was performed using 44 samples from 11 patients with CRC, including CRC tumor tissues (TT), normal tissues adjacent to CRC (NT), tumor cells (TC), and normal cells (NC). TC and NC were obtained from the TT and NT using an enzymatic digestion method. The microbiota and their potential functions in the four groups were analyzed and compared to determine the differential microbiota related to CRC.
RESULTS
Bacteria were mainly distributed in the feces covering intestinal tissues and in the epithelial cells and macrophages within the tissues. Different sampling sites and number of washes led to detection of different microbiota distributions. Although the cleaning method could be controlled, sampling sites varied and led to different microbiota distributions. The phyla of Firmicutes and Bacteroidetes were highly abundant in the conventionally used tissue samples, whereas Proteobacteria was the most abundant phyla in the cell samples isolated with the new method (i.e., after cell enzymatic hydrolysis). Detection of CRC cell-associated microbiota using a cell enzymatic digestion method showed that some bacteria, such as , and , were more abundant in TT than NT, whereas the abundance of was lower in TT than NT. The tumor/normal ratios of some bacteria, such as , and , were different between the cell and tissue samples.
CONCLUSION
The cell enzymatic digestion method reduced fecal bacterial contamination, enabling low biomass intratumoral microbiota to be detected and allowing prediction of bacterial distributions.
PubMed: 38835371
DOI: 10.3389/fonc.2024.1374769 -
Heliyon May 2024Disturbances in the oral microbiota may be due to several mechanisms and factors, such as smoking. An imbalance in oral bacteria may result in changes to the innate...
Disturbances in the oral microbiota may be due to several mechanisms and factors, such as smoking. An imbalance in oral bacteria may result in changes to the innate immune system and the development of periodontal disease. This study aimed to investigate the distribution of oral microbiota in smokers and non-smokers in a South African population using subgingival plaque samples. From the 128 recruited participants, 57 were identified as smokers (serum cotinine: >15 ng/ml). Analysis of 16S rRNA gene sequencing demonstrated significant differences between the two groups with a reduced abundance of Actinobacteria in smokers. Fusobacterium and Campylobacter were found in higher abundance, while a lower abundance of Leptotrichia, Actinomyces, Corynebacterium, and Lautropia were observed. This study highlighted significant differences in the oral microbiota of smokers, indicating an abundance of anaerobic gram-negative bacteria. These findings suggest that smoking allows certain oral microorganisms to gain dominance, thereby predisposing individuals to periodontal disease development and progression.
PubMed: 38831830
DOI: 10.1016/j.heliyon.2024.e31559 -
BMC Microbiology Jun 2024HIV-infected persons demonstrate notable disturbances in their intestinal microbiota; however, the impact of intestinal microbiota on HIV susceptibility in men who have...
BACKGROUND
HIV-infected persons demonstrate notable disturbances in their intestinal microbiota; however, the impact of intestinal microbiota on HIV susceptibility in men who have sex with men (MSM), as well as the effects of HIV and antiretroviral therapy (ART) on their gut microbiota, remains under active study. Thus, our research focuses on clarifying the distinctions in intestinal microbiota composition among uninfected MSM and non-MSM healthy controls, investigating the alterations in early-stage intestinal microbial communities following HIV infection, and assessing how ART affects the intestinal microbiota.
METHODS
This study enrolled four participant groups: uninfected MSM, Recent HIV-1 infection (RHI) MSM, MSM on ART, and non-MSM healthy controls, with 30 individuals in each group. We utilized 16S ribosomal DNA (16S rDNA) amplicon sequencing to analyze fecal microbiota and employed Luminex multiplex assays to measure plasma markers for microbial translocation (LBP, sCD14) and the inflammatory marker CRP.
FINDINGS
Comparing uninfected MSM to non-MSM healthy controls, no substantial variances were observed in α and β diversity. Uninfected MSM had higher average relative abundances of Bacteroidetes, Prevotella, and Alloprevotella, while Bacteroides, Firmicutes, and Faecalibacterium had lower average relative abundances. MSM on ART had lower intestinal microbiota diversity than RHI MSM and uninfected MSM. In MSM on ART, Megasphaera and Fusobacterium increased, while Faecalibacterium and Roseburia decreased at genus level. Additionally, treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) led to significant alterations in intestinal microbiota diversity and composition compared to RHI MSM. The random forest model showed that HIV infection biomarkers effectively distinguished between newly diagnosed HIV-infected MSM and HIV-negative MSM, with an ROC AUC of 76.24% (95% CI: 61.17-91.31%).
CONCLUSIONS
MSM showed early intestinal microbiota imbalances after new HIV infection. MSM on ART experienced worsened dysbiosis, indicating a combined effect of HIV and ART. NNRTI-based treatment notably changed intestinal microbiota, suggesting a potential direct impact of NNRTI drugs on intestinal microbiota.
Topics: Humans; Male; Gastrointestinal Microbiome; HIV Infections; Homosexuality, Male; Adult; RNA, Ribosomal, 16S; Bacteria; Feces; Middle Aged; HIV-1; Dysbiosis
PubMed: 38831399
DOI: 10.1186/s12866-024-03351-z