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ABSTRACT Clusters of similar or dissimilar objects are encountered in many fields. Frequently used approaches treat each cluster's central object as latent. Yet, often objects of one or more types cluster around objects of another type. Such arrangements are common in biomedical images of cells, in which nearby cell types likely interact. Quantifying spatial relationships may elucidate biological mechanisms. Parent‐offspring statistical frameworks can be usefully applied even when central objects (“parents”) differ from peripheral ones (“offspring”). We propose the novel multivariate cluster point process (MCPP) to quantify multi‐object (e.g., multi‐cellular) arrangements. Unlike commonly used approaches, the MCPP exploits locations of the central parent object in clusters. It accounts for possibly multilayered, multivariate clustering. The model formulation requires specification of which object types function as cluster centers and which reside peripherally. If such information is unknown, the relative roles of object types may be explored by comparing fit of different models via the deviance information criterion (DIC). In simulated data, we compared a series of models' DIC; the MCPP correctly identified simulated relationships. It also produced more accurate and precise parameter estimates than the classical univariate Neyman–Scott process model. We also used the MCPP to quantify proposed configurations and explore new ones in human dental plaque biofilm image data. MCPP models quantified simultaneous clustering of Streptococcus and Porphyromonas around Corynebacterium and of Pasteurellaceae around Streptococcus and successfully captured hypothesized structures for all taxa. Further exploration suggested the presence of clustering between Fusobacterium and Leptotrichia, a previously unreported relationship. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Design Setting Population Methods Main Outcome Measures Results Conclusions To identify a microbial signature for endometriosis for use as a diagnostic non‐invasive biomarker.Prospective cohort pilot study.Nepean Hospital and UNSW Microbiome Research Centre, Australia.Sixty‐four age‐ and sex‐matched subjects (n = 19 healthy control (HC); n = 24 non‐endometriosis (N‐ENDO) and n = 21 confirmed endometriosis (ENDO)). All study participants, besides healthy controls, underwent laparoscopic surgical assessment for endometriosis, and histology was performed on excised lesions.Oral, stool and, vaginal samples were self‐collected at a single time point for healthy controls, and preoperatively for patients undergoing laparoscopy. Samples underwent 16S rRNA amplicon sequencing, followed by bioinformatics analysis.Compositional differences between cohorts as identified by diversity analyses, and differentially abundant microbial taxa, as identified by LEfSE analysis.The composition of the oral (adjusted p = 0.003), and stool (adjusted p = 0.042) microbiota is different between the three cohorts. Differentially abundant taxa are present within each cohort as identified by LEfSE analysis. Particularly, Fusobacterium was enriched in the oral samples of patients with moderate/severe endometriosis.Taxonomic and compositional differences were found between the microbiota in the mouth, gut and, vagina of patients with and without endometriosis and healthy controls. Fusobacterium was enriched in patients with moderate/severe endometriosis. Fusobacterium is noted as a key pathogen in periodontal disease, a common comorbidity in endometriosis. These findings suggest a role for the oral, stool and, vaginal microbiome in endometriosis, and present potential for microbial‐based treatments and the design of a diagnostic swab. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence suggests a significant role of the gut microbiota in the development and progression of colorectal cancer (CRC). In particular, an over-representation of oral pathogens has been linked to CRC. The aim of this study was to further investigate the faecal microbial landscape of CRC patients, with a focus on the oral pathogens Parvimonas micra and Fusobacterium nucleatum. Methods: In this study, 16S rRNA sequencing was conducted using faecal samples from CRC patients (n = 275) and controls without pathological findings (n = 95). Results: We discovered a significant difference in microbial composition depending on tumour location and microsatellite instability (MSI) status, with P. micra, F. nucleatum, and Peptostreptococcus stomatis found to be more abundant in patients with MSI tumours. Moreover, P. micra and F. nucleatum were associated with a cluster of CRC-related bacteria including Bacteroides fragilis as well as with other oral pathogens such as P. stomatis and various Porphyromonas species. This cluster was distinctly different in the control group, suggesting its potential linkage with CRC. Conclusions: Our results suggest a similar distribution of several CRC-associated bacteria within CRC patients, underscoring the importance of considering the concomitant presence of bacterial species in studies investigating the mechanisms of CRC development and progression. [ABSTRACT FROM AUTHOR]

The family Fusobacteriaceae is a large family within the phylum Fusobacteriota. The reclassification of F. naviforme as Zandiella naviformis gen. nov., comb. nov. is proposed because of the separate and distinct phylogenetic situation on the basis of the results of 16S rRNA gene sequence analysis, the genetic and genomic differences from all other species and subspecies in the Fusobacteriaceae family. The type strain is ATCC 25832; CCUG 50052; NCTC 13121. In phylogenetic trees drawn using complete genome sequences and 16S rRNA gene sequences, F. necrophorum subsp. funduliforme and F. equinum were clades together with F. necrophorum subsp. necrophorum and F. gonidiaformans, respectively. The average nucleotide identity, average amino acid identity, and digital DNA–DNA hybridization values between themes exceeded the cut-off values for species delineation. Based on these results, F. necrophorum subsp. funduliforme and F. equinum should be reclassified as later heterotypic synonyms of F. necrophorum subsp. necrophorum and F. gonidiaformans, respectively. [ABSTRACT FROM AUTHOR]

Lemierre's syndrome, a forgotten clinical entity, is characterised by septic thrombophlebitis of the internal jugular vein due to oropharyngeal infection. In the past, it was mainly associated with Fusobacterium necrophorum infections. We present a unique case report of Lemierre's syndrome due to Klebsiella pneumoniae. Patient reported with progressive swelling involving right side of the neck that eventually increased in size. After confirming the diagnosis through CECT, patient was managed through combined medical and surgical therapy in the form of incision and drainage, targeted antibiotic therapy, glycaemic control and anticoagulation therapy. This case report highlights the association of poor glycaemic control in the pathogenesis and the isolation of Klebsiella pneumoniae as the rare organism of Lemierre's syndrome. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer of unknown primary site is a group of cancers in which metastases are found, and the primary tumor is not detected with available diagnostic methods. The aim of this study was to evaluate prognostic factors, clinical features including the microbiome, and treatment outcomes in patients with CUP. Diagnosis and treatment of patients with CUP is difficult due to the lack of consensus on this issue. The clinical value of the influence of the microbiome on the development and treatment of cancer is becoming important. The microbiome may become a marker of response to anticancer treatment and the risk of its complications. Fusobacterium and Porphyromonas seem to be the bacteria most important for the development of cancer, also worsening the prognosis by increasing the risk of complications of radiotherapy and shortening the survival rate of patients. Streptococcus and Lactobacillus seem to be bacteria that reduce the risk of cancer. Introductions: cancer of unknown primary site (CUP) is a heterogeneous group of cancers in which metastases are found, and the primary tumor is not detected with available diagnostic methods. CUP is a disease that has not been fully researched, and its biology is unclear. The clinical characteristics of CUP are variable, but the prognosis of patients is usually unfavorable, and the possibilities of radical treatment are limited. The microbiome is the genes and gene products of microorganisms residing in a human body. In recent years, thanks to the use of next-generation sequencing, it is possible to assess the impact of the microbiome on human body functions. Head and neck cancers, due to the rich microbiome of this area, are influenced by it, and dysbiosis may be a risk factor for the development of cancer. Objective of this work: the aim of this study was to evaluate prognostic factors, clinical features including the microbiome, and treatment outcomes in patients with cancer of unknown primary site. Results: in the study group, increased numbers of bacteria of the phyla Bacteroides, Fusobacteria, Bacillota, Actinomycetota, Actinobacteria, and Candidatus were detected, while Firmicutes and Proteobacteria were detected in smaller numbers. Independent predictors of CUP occurrence were the following: leukocyte count of at most 6.49 × 103/mm, bacteria from the Proteobacteria phylum in the microbiome below 11.6%, Firmicutes below 22.1%, and Actinobacteria at least 11.0%. Increased numbers of Porphyromonas and Fusobacterium bacteria were associated with the risk of radiotherapy complications and shortened survival rate. Conclusions: clinical diagnosis and treatment of patients with CUP is complicated and difficult due to the lack of consensus on this issue. Treatment and prognosis of patients with CUP is unsatisfactory. The clinical value of the influence of the microbiome on the development, course, and treatment of cancer is becoming increasingly important. The microbiome may become a marker of response to anticancer treatment and the risk of its complications. Immunity modulation with the microbiome provides opportunities for further research on improving the effectiveness of oncological treatment. Fusobacterium and Porphyromonas seem to be the bacteria most important for the development of cancer, also worsening the prognosis of patients by increasing the risk of complications of radiotherapy and shortening the survival rate of patients. Streptococcus and Lactobacillus seem to be bacteria that reduce the risk of cancer, reduce the risk of complications, and improve the prognosis of patients. Total protein deficiency and elevated inflammatory markers are also important predictors of cancer risk. [ABSTRACT FROM AUTHOR]

Objective: The impact of oral flora on intestinal micro-environment and related diseases has been widely reported, but its role in colorectal cancer (CRC) remains elusive. Methods: A Two-sample Mendelian Randomization (TSMR) analysis was conducted to explore the causal relationship between oral flora and CRC, with the Inverse-Variance Weighted (IVW) serving as the primary method for evaluating this causal relationship. Data on the oral flora were derived from human samples from the tongue and saliva, with all cohort populations originating from Asia. In addition, 2 independent external cohorts were used to validate the positive results and perform a meta-analysis of the final results. Lastly, to balance the effect of positive oral flora on CRC, a Multivariate Mendelian Randomization (MVMR) analysis was also performed. Results: The TSMR analysis revealed that 17 oral flora may have a causal relationship with CRC in the training cohort. Among them, s Haemophilus, g Fusobacterium, s Metamycoplasma salivarium, and s Mogibacterium pumilum were validated in two testing cohorts. Intriguingly, after integrating the results of the 3 cohorts for meta-analysis, 16 associations remained significant. In the training cohort, MVMR analysis demonstrated that s Capnocytophaga ochracea and s Metamycoplasma salivarium retained statistical significance. In one of the testing cohorts, s Metamycoplasma salivarium, s Streptococcus anginosus, and s Streptococcus sanguinis retained statistical significance. In the other testing cohort, s Metamycoplasma salivarium, s Haemophilus, and g Fusobacterium remained significant. Conclusion: s Haemophilus, g Fusobacterium, s Metamycoplasma salivarium, and s Mogibacterium pumilum have a solid causal relationship with the occurrence and development of CRC. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a common cancer that causes millions of deaths worldwide each year. At present, numerous studies have confirmed that intestinal microbes play a crucial role in the process of CRC. Additionally, studies have shown that CRC can be divided into several consensus molecular subtypes (CMS) based on tumor gene expression, and CRC microbiomes have been reported related to CMS. However, most previous studies on intestinal microbiome of CRC have only compared patients with healthy controls, without classifying of CRC patients based on intestinal microbial composition. Results: In this study, a CRC cohort including 339 CRC samples and 333 healthy controls was selected as the discovery set, and the CRC samples were divided into two subgroups (234 Subgroup1 and 105 Subgroup2) using PAM clustering algorithm based on the intestinal microbial composition. We found that not only the microbial diversity was significantly different (Shannon index, p-value < 0.05), but also 129 shared genera altered (p-value < 0.05) between the two CRC subgroups, including several marker genera in CRC, such as Fusobacterium and Bacteroides. A random forest algorithm was used to construct diagnostic models, which showed significantly higher efficiency when the CRC samples were divided into subgroups. Then an independent cohort including 187 CRC samples (divided into 153 Subgroup1 and 34 Subgroup2) and 123 healthy controls was chosen to validate the models, and confirmed the results. Conclusions: These results indicate that the divided CRC subgroups can improve the efficiency of disease diagnosis, with various microbial composition in the subgroups. [ABSTRACT FROM AUTHOR]

Purpose: Globally, colorectal cancer (CRC) is among the most prevalent cancers. One distinctive feature of colorectal cancer is its close relationship to the gut microbiota, which is a crucial component of the tumor microenvironment. Over the last ten years, research has demonstrated that colorectal cancer is accompanied with dysbiosis of gut bacteria, fungi, viruses, and Archaea, and that these alterations may be causal. Objectives: This study aimed to evaluate the disruption of the microorganism composition in the intestine, especially bacteria and to determine their relationship with colorectal cancer. Methods: An evaluation system for determining colorectal cancer (CRC) risk and prognosis can be established more easily with the help of accurate gut microbiota profiling. Stool samples from 14 CRC patients and 13 controls were collected and the flora relative abundance was measured using targeted quantitative PCR (qPCR) assays to evaluate diagnostic potential of selected biomarkers: Streptococcus gallolyticus and Enterococcus faecalis. Culture and MALDI-TOF mass spectrometry were coupled to identify the gut microbiota in both colorectal cancer and control groups. Results: Compared with controls, the gut microbiota of CRC patients showed an increase in the abundance of Enterococcus, Fusobacterium and Streptococcus. At the species level, the CRC enriched bacterium including Escherichia coli, Enterococcus faecalis, Fusobacterium nucleatum, Streptococcus gallolyticus, Flavoni fractorplautii and Eggerthella lenta acted as promising biomarkers for early detection of CRC. Conclusion: This study highlights the potential of gut microbiota biomarkers as a promising non-invasive tool for the accurate detection and distinction of individuals with CRC. [ABSTRACT FROM AUTHOR]

Background: Available descriptive studies on equine pneumonia are outdated or focus on specific horse or bacterial populations. Objectives: To describe the clinical presentation and bacterial isolates of adult horses with bacterial pneumonia and identify factors associated with death. Animals: One hundred sixteen horses >2 years old with bacterial pneumonia. Methods: Retrospective case series. Data regarding history, physical examination, clinicopathologic features, treatment, bacterial culture and sensitivity, and outcome were collected and analyzed retrospectively. Results: Historical risk factors were present for 60% of cases, whereas abnormal vital signs on intake were present for <50%. Most horses (58%) underwent at least 1 change of antimicrobial treatment, and 67% received the highest‐priority critically important antimicrobials. Streptococcus zooepidemicus was the most isolated bacteria (44%), followed by Escherichia coli (19%), Klebsiella spp. (18%), other Streptococcus species (17%), and Bacillus spp. (13%). Fusobacterium spp. were the most common anaerobic isolates (11%). Antimicrobial susceptibility varied widely. Survival to discharge was 73%. Heart rate at presentation (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.008‐1.17, P =.03) and higher creatinine (OR 14.1, 95% CI 1.56‐127.6, P =.02) increased the risk of death. Higher lymphocyte count (OR 0.27, 95% CI 0.08‐0.94, P =.04) reduced risk. Conclusions and Clinical Importance: Contrasting older literature, Fusobacterium spp. were the most common anaerobes. Streptococcus zooepidemicus remained the most common isolate and was predictably susceptible to penicillin. Antimicrobial susceptibility was otherwise variable and broad applicability is limited as this was a single‐center study. Increased risk of death associated with tachycardia and abnormally high serum creatinine concentration is consistent with previous studies. [ABSTRACT FROM AUTHOR]

Nano-mupirocin is a PEGylated nano-liposomal formulation of the antibiotic mupirocin, undergoing evaluation for treating infectious diseases and intratumor bacteria. Intratumoral microbiota play an important role in the regulation of tumor progression and therapeutic efficacy. However, antibiotic use to target intratumoral bacteria should be performed in a way that will not affect the gut microbiota, found to enable the efficacy of cancer treatments. Nano-mupirocin may offer such a selective treatment. Herein, we demonstrate the ability of Nano-mupirocin to successfully target tumor-residing Fusobacterium nucleatum without an immediate effect on the gut microbiome. In-depth characterization of this novel formulation was performed, and the main findings include: (i). the pharmacokinetic analysis of mupirocin administered as Nano-mupirocin vs mupirocin lithium (free drug) demonstrated that most of the Nano-mupirocin in plasma is liposome associated; (ii). microbiome analysis of rat feces showed no significant short-term difference between Nano-mupirocin, mupirocin lithium and controls; (iii). Nano-mupirocin was active against intratumoral F. nucleatum , a tumor promoting bacteria that accumulates in tumors of the AT3 mice model of breast cancer. These data suggest the ability of Nano-mupirocin to target tumor residing and promoting bacteria. Nano-mupirocin may offer a selective tumor-targeting antibiotic. Herein, we demonstrate the ability of Nano-mupirocin to successfully target tumor-residing Fusobacterium nucleatum without an immediate effect on the gut microbiome. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Fusobacterium nucleatum (F. nucleatum) is an integral component of supra‐ and subgingival biofilms, especially more prevalent in subgingival areas during both periodontal health and disease. Aims: In this review, we explore the physical, metabolic, and genetic interactions that influence the role of F. nucleatum in the formation of mixed oral biofilms. The role of F. nucleatum in antibiotic resistance in oral biofilms was discussed and some therapeutic strategies were proposed. Methods: PubMed, Scopus, Google Scholar, and the Web of Science were extensively searched for English‐language reports. Results: F. nucleatum‐derived proteins such as RadD, Fap2, FomA, and CmpA are involved in direct interactions contributing to biofilm formation, while autoinducer‐2 and putrescine are involved in metabolic interactions. Both groups are essential for the formation and persistence of oral biofilms. This study highlights the clinical relevance of targeted interactions of F. nucleatum in supra‐ and subgingival oral biofilms. Conclusions: By focusing on these interactions, researchers and clinicians can develop more effective strategies to prevent biofilm‐related disease and reduce the spread of antibiotic resistance. Further research in this area is warranted to explore the potential therapeutic interventions that can be derived from understanding the interactions of F. nucleatum in oral biofilm dynamics. [ABSTRACT FROM AUTHOR]

Background: Subtypes of sinusitis have different symptoms and prognoses due to different pathogens. Odontogenic maxillary sinusitis (OMS) mainly occurs unilaterally and is different from chronic rhinosinusitis (CRS) usually occurring bilaterally in terms of clinical characteristics. However, comprehensive microbiological comparisons between OMS and CRS have never been systematically conducted and most comparisons are methodologically biased. This study aims to provide a comprehensive analysis of the microbiology associated with OMS and CRS through a meta-analysis approach in order to provide evidence for differential diagnosis of OMS and CRS from a microbiological perspective. Methods: The databases PubMed and CNKI were searched from their inception to July 2023. A random-effects model was employed to derive the pooled prevalence estimates of the identified bacterial species or genera. Results: The 17 represented studies included 6 concerning OMS, 12 concerning CRS, and 4 concerning normal sinus, yielding 191, 610, and 92 samples, respectively. Though not statistically significant, the prevalence of Peptostreptococcus and Prevotella was generally higher in OMS compared to CRS. Notably, Fusobacterium was identified as the only genus with a significantly higher prevalence in OMS compared to CRS. Conclusion: Fusobacterium was significantly more prevalent in OMS compared with CRS, while Staphylococcus aureus was more prevalent in CRS than in OMS. Such differences in bacterial profile may partly explain the distinct pathology observed and contribute to the development of novel strategies for diagnosis and therapeutic interventions in OMS. [ABSTRACT FROM AUTHOR]

Fusobacterium necrophorum is a Gram-negative anaerobic bacterium responsible for localized infections of the oropharynx that can evolve into bacteremia and/or septic thrombophlebitis of the jugular vein or peritonsillar vein, called Lemierre’s syndrome. To identify microbial genetic determinants associated with the severity of this life-threatening disease, 70 F. necrophorum strains were collected and grouped into two categories according to the clinical presentation: (i) localized infection, (ii) bacteremia with/without Lemierre’s syndrome. Comparative genomic analyses revealed two clades with distinct genetic content, one clade being significantly enriched with isolates from subjects with bacteremia. To identify genetic determinants contributing to F. necrophorum pathogenicity, genomic islands and virulence factor orthogroups (OVFs) were predicted. The presence/absence profiles of OVFs did not group isolates according to their clinical category, but rather according to their phylogeny. However, a variant of lktA, a key virulence factor, with a frameshift deletion that results in two open reading frames, was associated with bacteremia. Moreover, a genome-wide association study identified three orthogroups associated with bacteremic strains: (i) cas8a1, (ii) a sodium/solute symporter, and (iii) a POP1 domain-containing protein. Further studies must be performed to assess the functional impact of lktA mutation and of these orthogroups on the physiopathological mechanisms of F. necrophorum infections. [ABSTRACT FROM AUTHOR]

New insights in the urinary microbiome have led to a better understanding being built of the shifts in bacterial representations from health to disease; these hold promise as markers for diagnosis and therapeutic responses. Although several efforts have been made to identify a "core urinary microbiome", different fingerprints have been identified in men and women that shift with age. The main bacterial groups overall include Firmicutes, Actinobacteria, Fusobacteria, and Bacteroidetes. Although patients with bladder cancer have a microbiome that is similar to that of healthy individuals, differences have been observed at the species level with Fusobacterium nucleatum and Ralstonia, and at the genus level with Cutibacterium. Different bacterial representations may influence extracellular matrix composition, affecting tumor metastatic spreading and tumorigenic metalloproteinase expression. Furthermore, gene expression affecting targets of immune therapy, such as PD-L1, has been associated with changes in bacterial representations and therapeutic response to BCG. This comprehensive review aims to examine the influence of the urinary microbiome in bladder cancer. [ABSTRACT FROM AUTHOR]

Fusobacterium (F.) nucleatum is a carcinogenesis microbiota in colorectal cancer (CRC). Growing evidence shows that F. nucleatum contributes to chemoresistance. Ferroptosis is reported to restore the susceptibility of resistant cells to chemotherapy. However, the role of gut microbiota affecting ferroptosis in chemoresistance remains unclear. Here, we examined the CRC tissues of patients using 16S rRNA sequencing to investigate the possible connection between gut microbiota dysbiosis and the relapse of CRC. We found that a high abundance of F. nucleatum in CRC tissue is associated with relapse. We further demonstrated that F. nucleatum induced oxaliplatin resistance in vitro and in vivo. The transcriptome of an F. nucleatum -infected cell revealed ferroptosis was associated with F. nucleatum infection. We perform malondialdehyde, ferrous iron, and glutathione assays to verify the effect of F. nucleatum on ferroptosis under oxaliplatin treatment in vivo and in vitro. Mechanistically, F. nucleatum promoted oxaliplatin resistance by overexpressing GPX4 and then inhibiting ferroptosis. E-cadherin/β-catenin/TCF4 pathway conducted the GPX4 overexpression effect of F. nucleatum. The chromatin immuno-precipitation quantitative PCR (CHIP-qPCR) and dual-luciferase reporter assay showed that F. nucleatum promoted TCF4 binding with GPX4. We also determined the E-cadherin/β-catenin/TCF4/GPX4 axis related to tumor tissue F. nucleatum status and CRC relapse clinically. Here, we revealed the contribution of F. nucleatum to oxaliplatin resistance by inhibiting ferroptosis in CRC. Targeting F. nucleatum and ferroptosis will provide valuable insight into chemoresistance management and may improve outcomes for patients with CRC. Schematic diagram of the relationship amon g F. nucleatum , ferroptosis, and L-OHP resistance. [Display omitted] • F. nucleatum is associated with CRC relapse and can induce oxaliplatin resistance. • F. nucleatum can promote oxaliplatin resistance by inhibiting ferroptosis. • F. nucleatum promotes GPX4 expression via the E-cadherin/β-catenin/TCF4 pathway, ultimately leading to chemoresistance. • Targeting F. nucleatum and ferroptosis may be useful for chemoresistance management and improve outcomes for CRC patients. [ABSTRACT FROM AUTHOR]

Background: The adenoids, primary sites of microbial colonization in the upper airways, can influence the development of various conditions, including otitis media with effusion (OME). Alterations in the adenoid microbiota have been implicated in the pathogenesis of such conditions. Aim: This study aims to utilize 16S rRNA genetic sequencing to identify and compare the bacterial communities on the adenoid surfaces of children with OME and children with healthy middle ears. Additionally, we seek to assess the differences in bacterial diversity between these two groups. Materials and Methods: We collected adenoid surface swabs from forty children, divided into two groups: twenty samples from children with healthy middle ears and twenty samples from children with OME. The V3-V4 hypervariable region of the bacterial 16S rRNA gene was amplified and sequenced using the Illumina MiSeq platform. Alpha and beta diversity indices were calculated, and statistical analyses were performed to identify significant differences in bacterial composition. Results: Alpha diversity analysis, using Pielou's index, revealed significantly greater evenness in the bacterial communities on the adenoid surfaces of the healthy ear group compared with the OME group. Beta diversity analysis indicated greater variability in the microbial composition of the OME group. The most common bacterial genera in both groups were Haemophilus, Fusobacterium, Streptococcus, Moraxella, and Peptostreptococcus. The healthy ear group was primarily dominated by Haemophilus and Streptococcus, whereas the OME group showed higher abundance of Fusobacterium and Peptostreptococcus. Additionally, the OME group exhibited statistically significant higher levels of Alloprevotella, Peptostreptococcus, Porphyromonas, Johnsonella, Parvimonas, and Bordetella compared with the healthy ear group. Conclusion: Our study identified significant differences in the bacterial composition and diversity on the adenoid surfaces of children with healthy middle ears and those with OME. The OME group exhibited greater microbial variability and higher abundances of specific bacterial genera. These findings suggest that the adenoid surface microbiota may play a role in the pathogenesis of OME. Further research with larger sample sizes and control groups is needed to validate these results and explore potential clinical applications. [ABSTRACT FROM AUTHOR]

Abstract Background Colorectal cancer (CRC) is a common cancer that causes millions of deaths worldwide each year. At present, numerous studies have confirmed that intestinal microbes play a crucial role in the process of CRC. Additionally, studies have shown that CRC can be divided into several consensus molecular subtypes (CMS) based on tumor gene expression, and CRC microbiomes have been reported related to CMS. However, most previous studies on intestinal microbiome of CRC have only compared patients with healthy controls, without classifying of CRC patients based on intestinal microbial composition. Results In this study, a CRC cohort including 339 CRC samples and 333 healthy controls was selected as the discovery set, and the CRC samples were divided into two subgroups (234 Subgroup1 and 105 Subgroup2) using PAM clustering algorithm based on the intestinal microbial composition. We found that not only the microbial diversity was significantly different (Shannon index, p-value

Background: Epidemiological studies have demonstrated that periodontitis is an independent risk factor for chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the association between these two diseases remains unclear. The lung microbiota shares similarities with the oral microbiota, and there is growing evidence to suggest that the lung microbiome could play a role in the pathogenesis of COPD. This study aimed to investigate whether periodontal pathogens could contribute to the pathogenesis of COPD in a mouse model. Methods: We established mouse models with oral infection by typical periodontal pathogens, porphyromonas gingivalis (Pg group) or fusobacterium nucleatum (Fn group), over a three-month period. Mice that did not receive oral infection were set as the control group (C group). We assessed the level of alveolar bone resorption, lung function, and histological changes in the lungs of the mice. Additionally, we measured the levels of inflammatory factors and tissue damage associated factors in the lung tissues. Results: Lung function indices, including airway resistance, peak inspiratory/expiratory flow and expiratory flow-50%, were significantly reduced in the Fn group compared to the C group. Additionally, histological examination revealed an increased number of inflammatory cells and bullae formation in the lung tissue sections of the Fn group. Meanwhile, levels of inflammatory factors such as IL-1β, IL-6, IFN-γ, and TNF-α, as well as tissue damage associated factors like matrix metalloproteinase-8 and neutrophil elastase, were significantly elevated in the lung tissue of the Fn group in comparison to the C group. The Pg group also showed similar but milder lung changes compared to the Fn group. Pg or Fn could be detected in the lungs of both oral infected groups. Conclusion: The results indicated that oral periodontal pathogens infection could induce COPD-like lung changes in mice, and they may play a biological role in the association between periodontitis and COPD. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that postbiotics possess bioactivities comparable to those of probiotics. Therefore, our experiment aimed to evaluate the effects of postbiotics derived from Enterococcus faecium on the growth performance and intestinal health of growing male minks. A total of 120 growing male minks were randomly assigned to 4 groups, each with 15 replicates of 2 minks. The minks in the 4 groups were fed a basal diet supplemented with 0 (control), 0.05, 0.1, and 0.15% postbiotics derived from E. faecium (PEF), respectively. Compared to the control, PEF improved feed/gain (F/G) during the first 4 weeks and the entire 8 weeks of the study (p < 0.05); in addition, 0.1% PEF improved average daily gain (ADG) during the first 4 weeks and the entire 8 weeks of the study (p < 0.05), while 0.15% PEF improved ADG during the first 4 weeks of the study (p < 0.05). Consequently, 0.1% PEF minks displayed greater body weight (BW) at weeks 4 and 8 (p < 0.05), and 0.15% PEF minks had greater BW at week 4 (p < 0.05) than minks in the control. Furthermore, compared to the control, both 0.05 and 0.1% PEF enhanced the apparent digestibility of crude protein (CP) and ether extract (EE) (p < 0.05) in the initial 4 weeks, while both 0.1 and 0.15% PEF enhanced the apparent digestibility of CP and DM in the final 4 weeks (p < 0.05). Additionally, trypsin activity was elevated in the 0.1 and 0.15% PEF groups compared to the control (p < 0.05). In terms of intestinal morphology, PEF increased the villus height and villus/crypt (V/C) in the jejunum (p < 0.05), and both 0.1 and 0.15% PEF decreased the crypt depth and increased the villus height and V/C in the duodenum (p < 0.05) compared to the control group. Supplementation with 0.1% PEF increased the SIgA levels but decreased the IL-2, IL-8, and TNF-a levels in the jejunum (p < 0.05). Compared to the control, E. faecium postbiotics decreased the relative abundances of Serratia and Fusobacterium (p < 0.05). In conclusion, the results indicate that the growth performance, digestibility, immunity, and intestine development of minks are considerably affected by E. faecium postbiotics. In particular, dietary supplementation with 0.1% E. faecium postbiotics provides greater benefits than supplementation with 0.05 and 0.15%. [ABSTRACT FROM AUTHOR]

Anti-angiogenesis has emerged a promising strategy against colorectal cancer (CRC). However, the efficacy of anti-angiogenic therapy is greatly compromised by the up-regulated autophagy levels resulting from the evolutionary resistance mechanism and the presence of Fusobacterium nucleatum (F. nucleatum) in CRC. Herein, we report a cationic polymer capable of blocking autophagic flux to deliver plasmid DNA (pDNA) encoding soluble FMS-like tyrosine kinase-1 (sFlt-1) for enhanced anti-angiogenic therapy against F. nucleatum -associated CRC. The autophagy-inhibiting cationic polymer, referred to as PNHCQ, is synthesized by conjugating hydroxychloroquine (HCQ) into 3,3′-diaminodipropylamine-pendant poly(β-benzyl-L-aspartate) (PAsp(Nors)), which can be assembled and electrostatically interacted with sFlt-1 plasmid to form PNHCQ/sFlt-1 polyplexes. Hydrophobic HCQ modification not only boosts transfection efficiency but confers autophagy inhibition activity to the polymer. Hyaluronic acid (HA) coating is further introduced to afford PNHCQ/sFlt-1@HA for improved tumor targeting without compromising on transfection. Consequently, PNHCQ/sFlt-1@HA demonstrates significant anti-tumor efficacy in F. nucleatum -colocalized HT29 mouse xenograft model by simultaneously exerting anti-angiogenic effects through sFlt-1 expression and down-regulating autophagy levels exacerbated by F. nucleatum challenge. The combination of anti-angiogenic gene delivery and overall autophagy blockade effectively sensitizes CRC tumors to anti-angiogenesis, providing an innovative approach for enhanced anti-angiogenic therapy against F. nucleatum -resident CRC. Up-regulated autophagy level within tumors is considered responsible for the impaired efficacy of clinic antiangiogenic therapy against CRC colonized with pathogenic F. nucleatum. To tackle this problem, an autophagy-inhibiting cationic polymer is developed to enable efficient intracellular delivery of plasmid DNA encoding soluble FMS-like tyrosine kinase-1 (sFlt-1) and enhance anti-angiogenic therapy against F. nucleatum -associated CRC. HA coating that can be degraded by tumor-enriching hyaluronidase is further introduced for improved tumor targeting without compromising transfection efficiency. The well-orchestrated polyplexes achieve considerable tumor accumulation, efficient in vivo transfection, and effectively reinforce the sensitivity of CRC to the sFlt-1-derived anti-angiogenic effects by significantly blocking overall autophagy flux exacerbated by F. nucleatum challenge, thus harvesting robust antitumor outcomes against F. nucleatum -resident CRC. [Display omitted] [ABSTRACT FROM AUTHOR]

Fusobacterium nucleatum, (F. nucleatum) as a known factor in inducing oncogenic, invasive, and inflammatory responses, can lead to an increase in the incidence and progression of colorectal cancer (CRC). Cancer-associated fibroblasts (CAF) are also one of the key components of the tumor microenvironment (TME), which lead to resistance to treatment, metastasis, and disease recurrence with their markers, secretions, and functions. This study aimed to investigate the effect of F. nucleatum on the invasive phenotype and function of fibroblast cells isolated from normal and cancerous colorectal tissue. F. nucleatum bacteria were isolated from deep periodontal pockets and confirmed by various tests. CAF cells from tumor tissue and normal fibroblasts (NF) from a distance of 10 cm of tumor tissue were isolated from 5 patients by the explant method and were exposed to secretions and ghosts of F. nucleatum. The expression level of two markers, fibroblast activation protein (FAP), and α-smooth muscle actin (α-SMA), and the amount of production of two cytokines TGF-β and IL-6 from fibroblast cells were measured by flow cytometry and ELISA test, respectively before and after exposure to different bacterial components. The expression of the FAP marker was significantly higher in CAF cells compared to NF cells (P < 0.05). Also, the expression of IL-6 in CAF cells was higher than that of NF cells. In investigating the effect of bacterial components on the function of fibroblastic cells, after comparing the amount of IL-6 produced between the normal tissue of each patient and his tumoral tissue under 4 treated conditions, it was found that the amount of IL-6 production from the CAF cells of patients in the control group, treated with heat-killed ghosts and treated with paraformaldehyde-fixed ghosts had a significant increase compared to NF cells (P < 0.05). Due to the significant increase in FAP marker expression in fibroblast cells of tumor tissue compared to normal tissue, it seems that FAP can be used as a very good therapeutic marker, especially in patients with high levels of CAF cells. Various components of F. nucleatum could affect fibroblast cells differentially and at least part of the effect of this bacterium in the TME is mediated by CAF cells. [ABSTRACT FROM AUTHOR]

Fusobacterium nucleatum, a gram‐negative anaerobic bacterium abundantly found in the human oral cavity, is widely recognized as a key pathobiont responsible for the initiation and progression of periodontal diseases due to its remarkable aggregative capabilities. Numerous clinical studies have linked F. nucleatum with unfavorable prognostic outcomes in various malignancies. In further research, scholars have partially elucidated the mechanisms underlying F. nucleatum’s impact on various types of cancer, thus gaining a certain comprehension of the role played by F. nucleatum in cancer. In this comprehensive review, we present an in‐depth synthesis of the interplay between F. nucleatum and different cancers, focusing on aspects such as tumor initiation, metastasis, chemoresistance, and modulation of the tumor immune microenvironment and immunotherapy. The implications for cancer diagnosis and treatment are also summarized. The objective of this review is to enhance our comprehension of the intricate relationship between F. nucleatum and oncogenic pathogenesis, while emphasizing potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

We have previously identified increased levels of distinct bacterial taxa within mucosal biopsies from colorectal cancer (CRC) patients. Following prior research, the aim of this study was to investigate the detection of the same CRC‐associated bacteria in fecal samples and to evaluate the suitability of fecal samples as a non‐invasive material for the detection of CRC‐associated bacteria. Next‐generation sequencing (NGS) of the 16S ribosomal RNA (rRNA) V4 region was performed to evaluate the detection of the CRC‐associated bacteria in the fecal microbiota of cancer patients, patients with adenomatous polyp and healthy controls. Furthermore, 19 novel species‐specific quantitative PCR (qPCR) assays were established to detect the CRC‐associated bacteria. Approximately, 75% of the bacterial taxa identified in biopsies were reflected in fecal samples. NGS failed to detect low‐abundance CRC‐associated taxa in fecal samples, whereas qPCR exhibited high sensitivity and specificity in identifying all targeted taxa. Comparison of fecal microbial composition between the different patient groups showed enrichment of Fusobacterium nucleatum, Parvimonas micra, and Gemella morbillorum in cancer patients. Our findings suggest that low‐abundance mucosa‐associated bacteria can be detected in fecal samples using sensitive qPCR assays. [ABSTRACT FROM AUTHOR]

Introduction: Fusobacterium nucleatum (F. nucleatum) is an anaerobic, gram-negative bacterium, morphologically an elongated bacillus with a sharp end belonging to the Bacteroidaceae. It is the normal flora of the mouth that is present in other organs in some diseases. Given the role of F. nucleatum in the creation and development of human diseases, it is very important to investigate its characteristics and functions. However, due to the obligate anaerobic nature of F. nucleatum, purification and long-term storage of the bacteria pose problems. The aim of this study is to find an optimal method for the purification of F. nucleatum to enable a detailed study of the functions and mechanisms of the bacteria to provide new therapeutic approaches to control or treat the diseases caused by F. nucleatum for future studies. Materials and Methods: Samples were taken from deep periodontal pockets of 16 patients using 40 size paper points with tryptic soy broth transfer medium (first method) and Columbia agar culture medium with gas pack type A and anaerobic jar (second method). The samples were then examined for the presence of F. nucleatum by macroscopic and microscopic observations, biochemical tests, PCR and sequencing. Results: The results showed that the tryptic soy broth transfer medium was not able to preserve and keep the bacteria alive, and the purified F. nucleatum was isolated by direct transfer to Columbia agar culture medium with gas pack type A and anaerobic jar. Discussion and Conclusion: Due to the obligate anaerobic nature of F. nucleatum, the use of transfer medium is not efficient for isolation due to the greater exposure of bacteria to air oxygen, and the optimal method for purification of F. nucleatum is the second sampling method. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis and Fusobacterium nucleatum are known to contribute to a variety of tumorigenic pathways linked to the progression of oral squamous cell carcinoma (OSCC). The growing global incidence of antibiotic resistance highlights the critical need to consider the use of antimicrobial peptides (AMPs) as a viable alternative to conventional antibiotics. The current study comprehensively tested Lactobacillus sp.−derived AMPs against bacterially exacerbated OSCC. A total of 52 AMPs were obtained from various databases, and an in silico analysis determined their potent antibacterial and anticancer characteristics after a rigorous screening and pruning approach. Twelve AMPs were tested for 3D structural alignment prediction and validation, with the GH12 synthetic AMP serving as a control. These candidate peptides were thoroughly screened against six important virulence proteins of P. gingivalis and four of F. nucleatum, with the lowest energy score of the docked complexes measuring binding affinity and interactions with active residues being chosen. plpl_18 was determined as the most efficient new AMP that interacted with the virulence protein RagB of P. gingivalis and Fap2 of F. nucleatum with docking scores of −238.24 and −254.27 kcal/mol, respectively. This AMP plpl_18 was docked against selective target OSCC regulatory proteins such as cytokines, metallomatrix proteinase, MAPK, E‐cadherin, and JAK‐1 proteins. Among these proteins, it docked against matrix metalloproteinase‐9 with the highest negative docking scores of −7.5, −260.956, and −1361.9 kcal/mol using AutoDock Vina, HPEPDOCK, and ClusPro 2.0, respectively. Molecular dynamic simulation was used to perform extrapolated validation. These computational studies provide an essential foundation for anticipated laboratory and clinical investigations concerning the possibility of adapting therapeutic peptides based on probiotics to combat the proliferation of OSCC, which is accelerated by F. nucleatum and P. gingivalis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fn was positively correlated with METTL3 expression in the ESCC tissues. • Fn-infection induced the upregulated-expression of METTL3 in ESCC. • Fn mediated METTL3/Myc axis to promote ESCC cells proliferation and migration in vitro. • Fn accelerates ESCC tumorigenesis and metastasis via METTL3-mediated c-Myc mRNA m6A modification in vivo. The tumor-associated microbiota plays a vital role in cancer development. Accumulating evidence shows that Fusobacterium nucleatum (Fn) participates in the progression of multiple tumor types. However, the underlying mechanisms remain unclear. This study examined the expression of methyltransferase-like protein 3 (METTL3) during Fn infection and elucidated the function and pathway of Fn-induced m6A methylation in esophageal squamous cell carcinoma (ESCC). The abundance of Fn in patient tissues was determined by qPCR. Western blot, qRT-PCR, and immunohistochemistry were performed to measure METTL3 expression in cells and tissues. METTL3 function was evaluated in vitro by colony formation and cell migration assays. MeRIP-qPCR was performed to determine the relationship between METTL3 and c-Myc. In addition, the half-lives of genes that are downstream of METTL3 were determined with RNA stability assays. Fn was enriched in hepatocellular carcinoma (HCC), breast cancer (BRCA), ESCC, and colorectal cancer (CRC) tumor tissues. METTL3 expression was positively associated with Fn abundance in ESCC tissues. Fn could survive and proliferation as well as increase METTL3 expression in ESCC, HCC, CRC, and BRCA cells. Moreover, METTL3 overexpression promoted ESCC cells proliferation, migration in vivo and in vitro. Mechanistically, Intracellular Fn infection increases METTL3 transcription. METTL3 promoted c-Myc mRNA methylation in the 3′-untranslated Region (3′-UTR) and enhanced its mRNA stability in a YTH N6-Methyladenosine RNA binding protein 1(YTHDF1)-dependent manner, which contributes to Fn induced ESCC proliferation and metastasis. This study indicates that intracellular Fn infection promotes ESCC development and metastasis, and eradicating Fn infection may be a promising strategy for treating ESCC. [ABSTRACT FROM AUTHOR]

Simple Summary: The presence of Bacteroidetes and Fusobacteria phyla are reported to decrease in dogs with chronic enteropathies, likely due to increased oxidative stress in the colon's inflammatory environment. Adherence to the colonic mucosa is considered an essential step for these bacteria to colonize and interact with the host's epithelium and immune system. No studies on dogs have investigated the adhesion of Bacteroides vulgatus and Fusobacterium varium on paraffin-embedded canine colonic mucosa. This study aims to examine the adhesion capacities of these bacterial species to paraffin-embedded colonic mucosa from healthy dogs and investigate their hydrophobicity properties to determine if this factor explains differences in adhesion capability. The results indicated that both canine B. vulgatus and F. varium adhered in high numbers to canine colonic mucosa; however, B. vulgatus had higher hydrophobicity but adhered in lower numbers than F. varium. In conclusion, both bacteria have probiotic potential, but further research is necessary to determine the efficacy and safety of the strains to be used, and other factors influencing attachment beyond hydrophobicity. The relative abundances of Bacteroidetes and Fusobacteria phyla have been reported to be decreased in dogs with chronic enteropathies. In colitis, obligate anaerobes (e.g., Bacteroides and Fusobacterium) are likely to vanish in response to the heightened oxidative stress in the colon's inflammatory environment. The ability to adhere to the colonic mucosa is viewed as an essential step for obligate anaerobic bacteria to colonize and subsequently interact with the host's epithelium and immune system. The reintroduction of a balanced community of obligate anaerobic bacteria using probiotics can restore the microbial function in the intestine. We found no studies on dogs regarding the adhesion properties of Bacteriodes vulgatus and Fusobacterium varium on paraffin-embedded canine colonic mucosa. Thus, the objective of this study is to investigate the adhesion capacities of these two bacterial species to paraffin-embedded colonic mucosa from healthy dogs. Additionally, we investigated their hydrophobicity properties to determine whether differences in adhesion capability can be explained by this factor. The results of our study showed that B. vulgatus adhered significantly lower than F. varium to the canine colonic mucosa (p = 0.002); however, B. vulgatus showed higher hydrophobicity (46.1%) than F. varium (12.6%). In conclusion, both bacteria have potential as probiotics, but further studies will be required to determine the efficacy and safety of the strains to be used, which strains to use, and the reasons other than hydrophobicity for attachment. [ABSTRACT FROM AUTHOR]

Fusobacterium nucleatum (F. nucleatum) is a commensal Gram‐negative anaerobic bacterium that lives in the oral cavity and gastrointestinal tract of humans. While it is a regular resident of the human oral cavity, F. nucleatum has been implicated in various infections and inflammatory conditions. This case report highlights an unusual association between F. nucleatum and isolated superior mesenteric vein (SMV) thrombosis. [ABSTRACT FROM AUTHOR]

The study aimed to develop a quantitative colorimetric loop-mediated isothermal amplification technique using the phenol red indicator (QLAMP-PhR) for detecting Fusobacterium nucleatum (Fn) levels in colorectal cancer (CRC) patients and healthy individuals. QLAMP-PhR assays were conducted on 251 stool samples specific for the Fn FadA gene. Six primers were synthesized and utilized with master mix reagents, and a phenol red indicator was employed to enhance the QLAMP-PhR technique. A standard quantitative analysis curve was generated using a logarithmic function (absorbance vs. concentration) by serially diluting the copy number of genomic DNA templates (Fn ATCC25586). The CRC group exhibited a significantly higher abundance of Fn compared to the healthy control group (P < 0.001). These findings suggest that the QLAMP-PhR technique effectively identifies Fn specifically by its gene for the key virulence factor FadA. Additionally, ideas for developing a real-time QLAMP-PhR test were presented. Compared to the traditional polymerase chain reaction (PCR) technique, QLAMP-PhR offers several advantages including rapidity, simplicity, specificity, sensitivity, and cost-effectiveness method that can quantitatively screen for Fn presence in normal populations. The QLAMP-PhR method represents a sensitive and specific amplification assay for the rapid detection of the Fn pathogen. To the best of our knowledge, this study is the first to report the application of QLAMP-PhR for detecting FadA in Fn. [ABSTRACT FROM AUTHOR]

Introduction: Microbial community composition is closely associated with host disease onset and progression, underscoring the importance of understanding host-microbiota dynamics in various health contexts. Methods: In this study, we utilized full-length 16S rRNA gene sequencing to conduct species-level identification of the microorganisms in the oral cavity of a giant panda (Ailuropoda melanoleuca) with oral malignant fibroma. Results: We observed a significant difference between the microbial community of the tumor side and non-tumor side of the oral cavity of the giant panda, with the latter exhibiting higher microbial diversity. The tumor side was dominated by specific microorganisms, such as Fusobacterium simiae, Porphyromonas sp. feline oral taxon 110, Campylobacter sp. feline oral taxon 100, and Neisseria sp. feline oral taxon 078, that have been reported to be associated with tumorigenic processes and periodontal diseases in other organisms. According to the linear discriminant analysis effect size analysis, more than 9 distinct biomarkers were obtained between the tumor side and non-tumor side samples. Furthermore, the Kyoto Encyclopedia of Genes and Genomes analysis revealed that the oral microbiota of the giant panda was significantly associated with genetic information processing and metabolism, particularly cofactor and vitamin, amino acid, and carbohydrate metabolism. Furthermore, a significant bacterial invasion of epithelial cells was predicted in the tumor side. Discussion: This study provides crucial insights into the association between oral microbiota and oral tumors in giant pandas and offers potential biomarkers that may guide future health assessments and preventive strategies for captive and aging giant pandas. [ABSTRACT FROM AUTHOR]

Background: Legionella pneumonia is one of the most severe types of atypical pneumonia, impairing multiple organ systems, posing a threat to life. Diagnosing Legionella pneumonia is challenging due to difficulties in culturing the bacteria and limitations in immunoassay sensitivity and specificity. Case presentation: This paper reports a rare case of sepsis caused by combined infection with Legionella pneumophila and Fusobacterium necrophorum, leading to respiratory failure, acute kidney injury, acute liver injury, myocardial damage, and electrolyte disorders. In addition, we systematically reviewed literature on patients with combined Legionella infections, analyzing their clinical features, laboratory results and diagnosis. Conclusions: For pathogens that require prolonged incubation periods and are less sensitive to conventional culturing methods, metagenomic next-generation sequencing (mNGS) can be a powerful supplement to pathogen screening and plays a significant role in the auxiliary diagnosis of complex infectious diseases. [ABSTRACT FROM AUTHOR]

This article explores the relationship between genetic alterations in the ubiquitination pathway and the prevalence of Fusobacterium in oral cancer. The study analyzes samples from the TCGA-HNSC cohort and identifies mutations in specific genes that are associated with higher or lower levels of Fusobacterium. The researchers also plan to conduct further experiments using a co-culture model and spatial transcriptomics to investigate the impact of Fusobacterium on the oral cancer microenvironment. The study aims to provide valuable insights for the diagnosis and treatment of oral cancer. [Extracted from the article]

Objectives: Fusobacterium necrophorum is a common cause of pharyngotonsillitis. However, no guidelines exist on when to diagnose or treat it. We aimed to investigate associations between clinical criteria and F. necrophorum-positivity in pharyngotonsillitis and assess the predictive potential of a simple scoring system. Methods: Pharyngotonsillitis patients who were tested for F. necrophorum (PCR) and presented to hospitals in the Skåne Region, Sweden, between 2013–2020 were eligible. Data were retrieved from electronic chart reviews and registries. By logistic regression we investigated associations between F. necrophorum-positivity and pre-specified criteria: age 13–30 years, symptom duration ≤ 3 days, absence of viral symptoms (e.g. cough, coryza), fever, tonsillar swelling/exudate, lymphadenopathy and CRP ≥ 50 mg/L. In secondary analyses, associated variables were weighted by strength of association into a score and its predictive accuracy of F. necrophorum was assessed. Results: Among 561 cases included, 184 (33%) had F. necrophorum, which was associated with the following criteria: age 13–30, symptom duration ≤ 3 days, absence of viral symptoms, tonsillar swelling/exudate and CRP ≥ 50 mg/L. Age 13–30 had the strongest association (OR5.7 95%CI 3.7–8.8). After weighting, these five variables had a sensitivity and specificity of 68% and 71% respectively to predict F. necrophorum-positivity at the proposed cut-off. Conclusion: Our results suggest that F. necrophorum cases presenting to hospitals might be better distinguished from other pharyngotonsillitis cases by a simple scoring system presented, with age 13–30 being the strongest predictor for F. necrophorum. Prospective studies, involving primary care settings, are needed to evaluate generalisability of findings beyond cases presenting to hospitals. [ABSTRACT FROM AUTHOR]

Background: Metritis is a prevalent uterine disease that affects the welfare, fertility, and survival of dairy cows. The uterine microbiome from cows that develop metritis and those that remain healthy do not differ from calving until 2 days postpartum, after which there is a dysbiosis of the uterine microbiome characterized by a shift towards opportunistic pathogens such as Fusobacteriota and Bacteroidota. Whether these opportunistic pathogens proliferate and overtake the uterine commensals could be determined by the type of substrates present in the uterus. The objective of this study was to integrate uterine microbiome and metabolome data to advance the understanding of the uterine environment in dairy cows that develop metritis. Holstein cows (n = 104) had uterine fluid collected at calving and at the day of metritis diagnosis. Cows with metritis (n = 52) were paired with cows without metritis (n = 52) based on days after calving. First, the uterine microbiome and metabolome were evaluated individually, and then integrated using network analyses. Results: The uterine microbiome did not differ at calving but differed on the day of metritis diagnosis between cows with and without metritis. The uterine metabolome differed both at calving and on the day of metritis diagnosis between cows that did and did not develop metritis. Omics integration was performed between 6 significant bacteria genera and 153 significant metabolites on the day of metritis diagnosis. Integration was not performed at calving because there were no significant differences in the uterine microbiome. A total of 3 bacteria genera (i.e. Fusobacterium, Porphyromonas, and Bacteroides) were strongly correlated with 49 metabolites on the day of metritis diagnosis. Seven of the significant metabolites at calving were among the 49 metabolites strongly correlated with opportunistic pathogenic bacteria on the day of metritis diagnosis. The main metabolites have been associated with attenuation of biofilm formation by commensal bacteria, opportunistic pathogenic bacteria overgrowth, tissue damage and inflammation, immune evasion, and immune dysregulation. Conclusions: The data integration presented herein helps advance the understanding of the uterine environment in dairy cows with metritis. The identified metabolites may provide a competitive advantage to the main uterine pathogens Fusobacterium, Porphyromonas and Bacteroides, and may be promising targets for future interventions aiming to reduce opportunistic pathogenic bacteria growth in the uterus. [ABSTRACT FROM AUTHOR]

Periodontitis is linked to the onset and progression of oral squamous cell carcinoma (OSCC), an epidemiologically frequent and clinically aggressive malignancy. In this context, Fusobacterium (F.) nucleatum and Porphyromonas (P.) gingivalis, two bacteria that cause periodontitis, are found in OSCC tissues as well as in oral premalignant lesions, where they exert pro-tumorigenic activities. Since the two bacteria are present also in endodontic diseases, playing a role in their pathogenesis, here we analyze the literature searching for information on the impact that endodontic infection by P. gingivalis or F. nucleatum could have on cellular and molecular events involved in oral carcinogenesis. Results from the reviewed papers indicate that infection by P. gingivalis and/or F. nucleatum triggers the production of inflammatory cytokines and growth factors in dental pulp cells or periodontal cells, affecting the survival, proliferation, invasion, and differentiation of OSCC cells. In addition, the two bacteria and the cytokines they induce halt the differentiation and stimulate the proliferation and invasion of stem cells populating the dental pulp or the periodontium. Although most of the literature confutes the possibility that bacteria-induced endodontic inflammatory diseases could impact on oral carcinogenesis, the papers we have analyzed and discussed herein recommend further investigations on this topic. [ABSTRACT FROM AUTHOR]

Fusobacterium nucleatum, a gram-negative oral bacterium, has been consistently validated as a strong contributor to the progression of several types of cancer, including colorectal (CRC) and pancreatic cancer. While previous in vitro studies have shown that intracellular F. nucleatum enhances malignant phenotypes such as cell migration, the dependence of this regulation on features of the tumor microenvironment (TME) such as oxygen levels are wholly uncharacterized. Here we examine the influence of hypoxia in facilitating F. nucleatum invasion and its effects on host responses focusing on changes in the global epigenome and transcriptome. Using a multiomic approach, we analyze epigenomic alterations of H3K27ac and global transcriptomic alterations sustained within a hypoxia and normoxia conditioned CRC cell line HCT116 at 24 h following initial infection with F. nucleatum. Our findings reveal that intracellular F. nucleatum activates signaling pathways and biological processes in host cells similar to those induced upon hypoxia conditioning in the absence of infection. Furthermore, we show that a hypoxic TME favors F. nucleatum invasion and persistence and therefore infection under hypoxia may amplify malignant transformation by exacerbating the effects induced by hypoxia alone. These results motivate future studies to investigate host-microbe interactions in tumor tissue relevant conditions that more accurately define parameters for targeted cancer therapies. Multiomic study reveals that tumor microenvironmental factors such as hypoxia influence intracellular infection of Fusobacterium nucleatum in colorectal cancer cells and provides clues to malignant transformation of infected cells. [ABSTRACT FROM AUTHOR]

Pneumatosis cystoides intestinalis, or intestinal emphysema, is a condition characterized by the presence of multiple cystic structures within the gut wall and on the serosal surface of the intestine. Intestinal emphysema represents an accidental finding in swine, although it can be clinically relevant in humans. Its etiology is unknown, and many theories have been proposed. Among them, a bacterial etiology is considered the most likely. Therefore, in this study, the V3-V4 region of the 16S rRNA gene was sequenced from 19 swine ileal tracts, 12 with intestinal emphysema and 7 without lesions, to detect a possible bacterial agent. In parallel, prevalence was estimated. Escherichia–Shigella (13.15%), Clostridium_sensu_stricto_1; s__uncultured_bacterium (7.09%), and Fusobacterium; s_uncultured bacterium (6.60%) were the most abundant species identified. No statistically relevant differences were observed between the pathological and physiological groups. Prevalence ranged from 1.25 to 5.12% depending on the batch. Our results suggest that the gut wall bacterial microbiota greatly match the normal gut microbiota, and that the etiological agent of intestinal emphysema may be (1) undetectable due to the chronicity of the lesions, (2) not considered statistically relevant in comparing the two groups (p < 0.05) and likewise in causing lesions, and (3) undetectable due to contamination. Regarding prevalence, the condition is moderately frequent. [ABSTRACT FROM AUTHOR]

Background: A case of retropharyngeal abscess complicated by both artery and nerve injury has rarely been reported. Methods: A 36‐year‐old woman suddenly presented with right eye visual loss, dilated pupil, reduced direct light reflex, ptosis and ocular motility disorder on the side of inflammation progression, and was diagnosed with retropharyngeal abscess due to Fusobacterium necrophorum. The patient was treated only with antibiotics and, no further surgery was necessary but tracheotomy. Four months later, MRA showed right ICA occlusion and left ICA stenosis. MRI revealed continuous spread of inflammation due to the abscess from the retropharyngeal to the intracranial space. Results: These severe complications would be attributed to an endothelial damage to the arterial wall and an ischemic neuropathy caused by inflammation and thrombogenesis due to Fusobacterium necrophorum. Conclusions: This case should provide a better understanding of the mechanism of vascular and cranial nerve injury due to retropharyngeal infections, and highlights the need for early antibiotic therapy and repeated vascular evaluation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the antibacterial effectiveness of a combination of ε-poly-L-lysine (ε-PL), funme peptide (FP) as well as domiphen against oral pathogens, and assess the efficacy of a BOP® mouthwash supplemented with this combination in reducing halitosis and supragingival plaque in a clinical trial. Materials and methods: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the compound against Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were determined by the gradient dilution method. Subsequently, the CCK-8 assay was used to detect the toxicity of mouthwash on human gingival fibroblastst, and the effectiveness in reducing halitosis and supragingival plaque of the mouthwash supplemented with the combination was analyzed by a randomized, double-blind, parallel-controlled clinical trial. Results: The combination exhibited significant inhibitory effects on tested oral pathogens with the MIC < 1.56% (v/v) and the MBC < 3.13% (v/v), and the mouthwash containing this combination did not inhibit the viability of human gingival fibroblasts at the test concentrations. The clinical trial showed that the test group displayed notably lower volatile sulfur compounds (VSCs) at 0, 10, 24 h, and 7 d post-mouthwash (P < 0.05), compared with the baseline. After 7 days, the VSC levels of the and control groups were reduced by 50.27% and 32.12%, respectively, and notably cutting severe halitosis by 57.03% in the test group. Additionally, the Plaque Index (PLI) of the test and control group decreased by 54.55% and 8.38%, respectively, and there was a significant difference in PLI between the two groups after 7 days (P < 0.01). Conclusions: The combination of ε-PL, FP and domiphen demonstrated potent inhibitory and bactericidal effects against the tested oral pathogens, and the newly formulated mouthwash added with the combination exhibited anti-dental plaque and anti-halitosis properties in a clinical trial and was safe. Trial registration: The randomized controlled clinical trial was registered on Chinese Clinical Trial Registry (No. ChiCTR2300073816, Date: 21/07/2023). [ABSTRACT FROM AUTHOR]

A bioinformatic analysis is a promising approach to understand the relationship between the vast tumor microbiome and cancer development. In the present study, we studied the relationships between the intratumoral microbiome and classical clinical risk factors using bioinformatics analysis of the Cancer Genome Atlas (TCGA) and the Cancer Microbiome Atlas (TCMA) datasets. We used TCMA database and investigated the abundance of microbes at the genus level in solid normal tissue (n = 22) and the primary tumors of patients with head and neck squamous cell carcinoma (HNSCC) (n = 154) and identified three major tumor microbiomes, Fusobacterium, Prevotella, and Streptococcus. The tissue level of Fusobacterium was higher in primary tumors than in solid normal tissue. However, univariate and multivariate analyses of these 3 microbes showed no significant effects on patient survival. We then extracted 43, 55, or 59 genes that were differentially expressed between the over and under the median groups for Fusobacterium, Prevotella, or Streptococcus using the criteria of >2.5, >1.5, or >2.0 fold and p

Purpose: Antibiotics play an important role in treating periodontal diseases. Due to the effectiveness of antibiotic therapies, their usage in dentistry has significantly increased. The aim of this study focused on the in-vitro susceptibility of different gram-negative oral bacteria species -- which are associated with periodontal diseases (Fusobacterium spp., Capnocytophaga spp. and Leptotrichia buccalis) and have different geographical origins (Asia and Europe) -- against antimicrobials that are clinically relevant in dental therapy. Materials and Methods: A total of 45 strains were tested (29 Fusobacterium spp., 13 Capnocytophaga spp. and 3 L. buccalis) that were either isolated from Chinese patients or were obtained from different strain collections. Their antimicrobial susceptibility to the antimicrobial agents benzylpenicillin, amoxicillin, amoxicillin-clavulanic acid, ciprofloxacin, moxifloxacin, clindamycin, doxycycline, tetracycline and metronidazole was tested using the E-Test. Strains with particular resistance to penicillin, clindamycin and metronidazole were further analysed for resistance genes. Results: All tested bacterial isolates were sensitive to amoxicillin, amoxicillin-clavulanic acid, doxycycline and tetracycline, but showed variable sensitivity towards other antibiotics such as benzylpenicillin, ciprofloxacin, moxifloxacin, clindamycin and metronidazole. Conclusion: The results of the present study suggest that certain periodontal disease-related bacterial strains can be resistant towards antimicrobial agents commonly used in adjuvant periodontal therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the inhibitory effects of Streptococcus salivarius K12 and M18 strains on the growth of six oral pathogens as well as their release of volatile sulfur compounds (VSCs), and whether these probiotics can inhibit the expression of arginine-specific gingipain A (RgpA), a protease secreted by Porphyromonas gingivalis. Materials and Methods: After six halitogenic oral pathogens (P. gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum, Parvimonas micra, and Eikenella corrodens) were cultured with or without S. salivarius K12 and M18, the concentration of two VSCs was measured. Moreover, the antimicrobial activity of S. salivarius K12 and M18 against these pathogens and the suppressive effect on RgpA release by P. gingivalis were assessed. Results: In the co-culture of S. salivarius K12 or M18 with oral pathogenic bacteria, the growth of all six oral pathogens was significantly inhibited (p < 0.01). Additionally, S. salivarius K12 and M18 had an inhibitory effect on the production of the halitogenic substances H2S and CH3SH (p < 0.01) as well as the expression of P. gingivalis RgpA. Finally, we demonstrated that the addition of only culture supernatants of the two strains K12/M18 to oral pathogen cultures was sufficient to mimic the effects of K12/M18 co-cultures upon VSCs production and protease expression. Conclusions: S. salivarius K12 and M18 inhibited VSC release by all six of the major oral pathogens that were assayed and reduced the expression of RgpA. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of Fusobacterium nucleatum and Capnocytophaga species in dental plaque, cord blood, pericrevicular vaginal samples, and adverse pregnancy outcomes in gestational diabetic mellitus (GDM) women with and without periodontitis stage II. Method and materials: In this prospective cohort study, 415 pregnant women were screened and 60 primigravidae with diagnosis of GDM were recruited. Glycosylated hemoglobin (HbA1c) was recorded at weeks 24, 28, and 32, and at parturition. Subgingival plaque sample, cord blood, and pericrevicular vaginal swab were taken immediately postpartum from both the groups. Identification of F nucelatum and Capnocytophaga species was done using polymerase chain reaction. Adverse pregnancy outcomes such as preterm birth, low birth weight, and macrosomia were prospectively checked in all the recruited individuals. Results: Incidence of adverse pregnancy outcomes was significantly higher in the GDM with periodontitis group (48%) than the nonperiodontitis GDM group (14%) with P < .07. There was a moderate positive correlation (r = 0.429) between Gingival Index and HbA1c and microorganisms in the three samples at parturition. Macrosomia was seen in equal percentages in both groups. Conclusion: Concomitant existence of F nucleatum and Capnocytophaga species in all three samples was shown to be associated with increased incidence of adverse pregnancy outcomes in the GDM with periodontitis group. Of the adverse outcomes, preterm birth and low birth weight were more closely related to the periodontitis group than macrosomia. [ABSTRACT FROM AUTHOR]

Introduction: Pyogenic liver abscess is a noteworthy health concern in North America, characterized by a mortality rate ranging from 2 to 12%. This condition is often polymicrobial, with Streptococcus species and Escherichia coli as the predominant causal pathogens in Western countries. Fusobacterium species, typically commensals of gastrointestinal, genital, and oral flora, have been implicated in the rare formation of tonsillar abscesses and Lemierre syndrome, including its gastrointestinal variant known as pylephlebitis. Case Presentation: We present the case of an immunocompetent male with a 2-week history of abdominal distention and pain. Abdominal magnetic resonance imaging revealed multiseptated cystic hepatic masses and portal vein thrombosis. A subsequent liver biopsy confirmed Fusobacterium nucleatum etiology. The patient was initiated on intravenous cefepime and oral metronidazole antibiotics. Unfortunately, the patient succumbed to cardiac arrest before a final diagnosis could be established. Conclusion: Fusobacterium species-associated liver abscess, coupled with the rare gastrointestinal variant of Lemierre syndrome (pylephlebitis), poses a significant mortality risk. This case underscores the rarity and clinical challenges associated with these conditions. Increased awareness among clinicians is crucial for early diagnosis and prompt intervention, potentially improving outcomes in such cases.

Abstract Background Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by cancer-associated bacteria (CAB) that impair tumor suppressor functions. Our previous research found that Mycoplasma fermentans DnaK, a chaperone protein, impairs p53 activities, which are essential for most anti-cancer chemotherapeutic responses. Methods To investigate the role of DnaK in chemotherapy, we treated cancer cell lines with M. fermentans DnaK and then with commonly used p53-dependent anti-cancer drugs (cisplatin and 5FU). We evaluated the cells’ survival in the presence or absence of a DnaK-binding peptide (ARV-1502). We also validated our findings using primary tumor cells from a novel DnaK knock-in mouse model. To provide a broader context for the clinical significance of these findings, we investigated human primary cancer sequencing datasets from The Cancer Genome Atlas (TCGA). We identified F. nucleatum as a CAB carrying DnaK with an amino acid composition highly similar to M. fermentans DnaK. Therefore, we investigated the effect of F. nucleatum DnaK on the anti-cancer activity of cisplatin and 5FU. Results Our results show that both M. fermentans and F. nucleatum DnaKs reduce the effectiveness of cisplatin and 5FU. However, the use of ARV-1502 effectively restored the drugs' anti-cancer efficacy. Conclusions Our findings offer a practical framework for designing and implementing novel personalized anti-cancer strategies by targeting specific bacterial DnaKs in patients with poor response to chemotherapy, underscoring the potential for microbiome-based personalized cancer therapies.

Background IgA nephropathy (IgAN) is intimately linked to mucosal immune responses, with nasopharyngeal and intestinal lymphoid tissues being crucial for its abnormal mucosal immunity. The specific pathogenic bacteria in these sites associated with IgAN, however, remain elusive. Our study employs 16S rRNA sequencing and machine learning (ML) approaches to identify specific pathogenic bacteria in these locations and to investigate common pathogens that may exacerbate IgAN.Methods In this cross-sectional analysis, we collected pharyngeal swabs and stool specimens from IgAN patients and healthy controls. We applied 16SrRNA sequencing to identify differential microbial populations. ML algorithms were then used to classify IgAN based on these microbial differences. Spearman correlation analysis was employed to link key bacteria with clinical parameters.Results We observed a reduced microbial diversity in IgAN patients compared to healthy controls. In the gut microbiota of IgAN patients, increases in Bacteroides, Escherichia-Shigella, and Parabacteroides, and decreases in Parasutterella, Dialister, Faecalibacterium, and Subdoligranulum were notable. In the respiratory microbiota, increases in Neisseria, Streptococcus, Fusobacterium, Porphyromonas, and Ralstonia, and decreases in Prevotella, Leptotrichia, and Veillonella were observed. Post-immunosuppressive therapy, Oxalobacter and Butyricoccus levels were significantly reduced in the gut, while Neisseria and Actinobacillus levels decreased in the respiratory tract. Veillonella and Fusobacterium appeared to influence IgAN through dual immune loci, with Fusobacterium abundance correlating with IgAN severity.Conclusions This study revealing that changes in flora structure could provide important pathological insights for identifying therapeutic targets, and ML could facilitate noninvasive diagnostic methods for IgAN.

ABSTRACTThe anaerobic bacterium Fusobacterium nucleatum is significantly associated with human colorectal cancer (CRC) and is considered a significant contributor to the disease. The mechanisms underlying the promotion of intestinal tumor formation by F. nucleatum have only been partially uncovered. Here, we showed that F. nucleatum releases a metabolite into the microenvironment that strongly activates NF-κB in intestinal epithelial cells via the ALPK1/TIFA/TRAF6 pathway. Furthermore, we showed that the released molecule had the biological characteristics of ADP-heptose. We observed that F. nucleatum induction of this pathway increased the expression of the inflammatory cytokine IL-8 and two anti-apoptotic genes known to be implicated in CRC, BIRC3 and TNFAIP3. Finally, it promoted the survival of CRC cells and reduced 5-fluorouracil chemosensitivity in vitro. Taken together, our results emphasize the importance of the ALPK1/TIFA pathway in Fusobacterium induced-CRC pathogenesis, and identify the role of ADP-H in this process.

Objective: This study aimed to assess the cause of acute pharyngitis and determine the duration of severe and moderate symptoms based on the aetiology. Design: Prospective observational study. Site: One urban health care centre. Participants: Patients aged 15 or older with acute pharyngitis were included. Interventions: Bacterial identification was carried out in the microbiology lab using MALDI-TOF in two throat samples. Patients received a symptom diary to return after one week. Main measurements: Number of days with severe symptoms, scoring 5 or more in any of the symptoms included in the symptom diary, and moderate symptoms, scoring 3 or more. Results: Among the 149 patients recruited, beta-haemolytic streptococcus group A (GABHS) was the most common aetiology. Symptoms and signs alone as well as the mean Centor score cannot distinguish between GABHS and other bacterial causes in patients with acute pharyngitis. However, there was a trend indicating that infections caused by Streptococcus dysgalactiae and Streptococcus agalactiae presented more severe symptoms, whereas infections attributed to the Streptococcus anginosus group, Fusobacterium spp., and those where oropharyngeal microbiota was isolated tended to have milder symptoms. S. dysgalactiae infections showed a trend towards longer severe and moderate symptom duration. Conclusion: GABHS was the most prevalent, but group C streptococcus caused more severe and prolonged symptoms. Resumen: Objetivo: Evaluar la etiología de los episodios de faringitis aguda y determinar la duración de los síntomas graves y moderados según la etiología. Métodos: Estudio observacional prospectivo. Emplazamiento: Un centro de salud urbano. Participantes: Se incluyeron pacientes de 15 años o más con faringitis aguda. Intervenciones: Se realizó identificación bacteriana en el laboratorio de microbiología utilizando MALDI-TOF en 2 muestras faríngeas. Los pacientes recibieron un diario de síntomas que devolvieron a la semana. Medidas prinicpales: Número de días con síntomas graves, aquellas puntuaciones de 5 o más en cualquiera de los síntomas del diario de síntomas, y síntomas moderados con puntuaciones de 3 o más. Resultados: Entre los 149 pacientes incluidos, el estreptococo beta-hemolítico del grupo A (EBHGA) fue la etiología más común. Tanto los síntomas y signos como la puntuación media de la escala de Centor no permiten distinguir la infección de EBHGA de las otras causas bacterianas en pacientes con faringitis aguda. Sin embargo, se observó una tendencia en que las infecciones por S. dysgalactiae y agalactiae presentaban síntomas más graves, mientras que S. grupo anginosus, Fusobacterium spp. y aquellos con microbiota orofaringea solían presentar síntomas más leves. Las infecciones por S. dysgalactiae mostraron una tendencia hacia una mayor duración de síntomas graves y moderados. Conclusión: El EBHGA es el más prevalente, pero el estreptococo del grupo C causa síntomas más graves y prolongados.