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Gut Pathogens Feb 2024Colorectal cancer (CRC) poses a significant healthcare challenge, accounting for nearly 6.1% of global cancer cases. Early detection, facilitated by population screening...
BACKGROUND
Colorectal cancer (CRC) poses a significant healthcare challenge, accounting for nearly 6.1% of global cancer cases. Early detection, facilitated by population screening utilizing innovative biomarkers, is pivotal for mitigating CRC incidence. This study aims to scrutinize the fecal and salivary microbiomes of CRC-positive individuals (CPs) in comparison to CRC-negative counterparts (CNs) to enhance early CRC diagnosis through microbial biomarkers.
MATERIAL AND METHODS
A total of 80 oral and stool samples were collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, encompassing both CPs and CNs undergoing screening. Microbial profiling was conducted using 16S rRNA sequencing assays, employing the Nextera XT Index Kit on an Illumina NovaSeq platform.
RESULTS
Distinct microbial profiles were observed in saliva and stool samples of CPs, diverging significantly from those of CNs at various taxonomic levels, including phylum, family, and species. Saliva samples from CPs exhibited abundance of Calothrix parietina, Granulicatella adiacens, Rothia dentocariosa, and Rothia mucilaginosa, absent in CNs. Additionally, Lachnospiraceae and Prevotellaceae were markedly higher in CPs' feces, while the Fusobacteria phylum was significantly elevated in CPs' saliva. Conversely, the non-pathogenic bacterium Akkermansia muciniphila exhibited a significant decrease in CPs' fecal samples compared to CNs.
CONCLUSION
Through meticulous selection of saliva and stool microbes based on Mean Decrease GINI values and employing logistic regression for saliva and support vector machine models for stool, we successfully developed a microbiota test with heightened sensitivity and specificity for early CRC detection.
PubMed: 38378690
DOI: 10.1186/s13099-024-00604-0 -
BMC Infectious Diseases Feb 2024Fusobacterium nucleatum (F. nucleatum) belongs to the genus Fusobacterium, which is a gram-negative obligate anaerobic bacterium. Bacteremia associated with F. nucleatum... (Review)
Review
BACKGROUND
Fusobacterium nucleatum (F. nucleatum) belongs to the genus Fusobacterium, which is a gram-negative obligate anaerobic bacterium. Bacteremia associated with F. nucleatum is a serious complication, which is not common in clinic, especially when it is combined with other intracranial pathogenic microorganism infection. We reported for the first time a case of F. nucleatum bacteremia combined with intracranial Porphyromonas gingivalis (P. gingivalis) and herpes simplex virus type 1(HSV-1) infection.
CASE PRESENTATION
A 60-year-old woman was admitted to our hospital with a headache for a week that worsened for 2 days. Combined with history, physical signs and examination, it was characterized as ischemic cerebrovascular disease (ICVD). F. nucleatum was detected in blood by matrix-assisted laser desorption/ionization time-offight mass spectrometry (MALDI-TOF-MS). Meanwhile, P. gingivalis and HSV-1 in cerebrospinal fluid (CSF) were identified by metagenome next generation sequencing (mNGS). After a quick diagnosis and a combination of antibiotics and antiviral treatment, the patient recovered and was discharged.
CONCLUSION
To our knowledge, this is the first report of intracranial P. gingivalis and HSV-1 infection combined with F. nucleatum bacteremia.
Topics: Female; Humans; Middle Aged; Porphyromonas gingivalis; Fusobacterium nucleatum; Herpesvirus 1, Human; Base Composition; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Herpes Simplex; Bacteremia; Fusobacterium Infections
PubMed: 38378498
DOI: 10.1186/s12879-024-09078-6 -
Journal of Infection in Developing... Jan 2024A 22-year-old male, with a history of recreational drug use, was admitted with a 24-hour history of sore throat, bilateral otalgia, fever, chills, sweats, and pain in...
A 22-year-old male, with a history of recreational drug use, was admitted with a 24-hour history of sore throat, bilateral otalgia, fever, chills, sweats, and pain in the upper chest. The blood cultures were positive for Fusobacterium necrophorum. A thoracic and neck soft tissue computed tomography (CT) scan revealed an intratonsillar abscess and pulmonary septic emboli. Initial treatment with Piperacillin-tazobactam and Clindamycin was de-escalated after 5 days. The patient made a complete recovery after 22 days of antibiotic treatment.
Topics: Male; Humans; Young Adult; Adult; Fusobacterium necrophorum; Abscess; Fusobacterium Infections; Bacteremia; Substance-Related Disorders
PubMed: 38377084
DOI: 10.3855/jidc.18268 -
BMC Infectious Diseases Feb 2024Fusobacterium necrophorum (F. necrophorum)-induced necrotizing pneumonia is a rare but severe pulmonary infection. Insufficient microbiological detection methods can...
BACKGROUND
Fusobacterium necrophorum (F. necrophorum)-induced necrotizing pneumonia is a rare but severe pulmonary infection. Insufficient microbiological detection methods can lead to diagnostic difficulties.
METHODS
We report a case of F. necrophorum lung abscess diagnosed by next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF).
RESULTS
BALF-NGS detected F. necrophorum, guiding subsequent targeted antibiotic therapy. With active drainage and metronidazole treatment, the patient's condition was effectively treated.
CONCLUSION
BALF-NGS is a valuable tool for the rapid diagnosis of infections caused by difficult-to-culture bacteria. It played a decisive role in the early identification of F. necrophorum, enabling timely and targeted antibiotic intervention. Early diagnosis and appropriate treatment are crucial for the management of F. necrophorum pneumonia.
Topics: Humans; Fusobacterium; Bronchoalveolar Lavage Fluid; Lung Abscess; Fusobacterium Infections; Anti-Bacterial Agents; Fusobacterium necrophorum; High-Throughput Nucleotide Sequencing
PubMed: 38373919
DOI: 10.1186/s12879-024-09087-5 -
Anaerobe Apr 2024Tonsillar Fusobacterium necrophorum PCR Ct-values were higher in participants with asymptomatic tonsillar carriage than patients with pharyngeal infections. However,...
Tonsillar Fusobacterium necrophorum PCR Ct-values were higher in participants with asymptomatic tonsillar carriage than patients with pharyngeal infections. However, Ct-values were not associated with severity of disease or predictive of development of complications and hence lacked clinical usefulness. The reporting of F. necrophorum Ct-values in clinical samples is not recommended.
Topics: Humans; Fusobacterium necrophorum; Fusobacterium Infections; Male; Polymerase Chain Reaction; Female; Adult; Middle Aged; Palatine Tonsil; Young Adult; Adolescent; Aged; Tomography, X-Ray Computed; Carrier State
PubMed: 38369049
DOI: 10.1016/j.anaerobe.2024.102831 -
Molecular Oncology May 2024The incidence of colorectal cancer (CRC) has increased worldwide, and early diagnosis is crucial to reduce mortality rates. Therefore, new noninvasive biomarkers for CRC...
The incidence of colorectal cancer (CRC) has increased worldwide, and early diagnosis is crucial to reduce mortality rates. Therefore, new noninvasive biomarkers for CRC are required. Recent studies have revealed an imbalance in the oral and gut microbiomes of patients with CRC, as well as impaired gut vascular barrier function. In the present study, the microbiomes of saliva, crevicular fluid, feces, and non-neoplastic and tumor intestinal tissue samples of 93 CRC patients and 30 healthy individuals without digestive disorders (non-CRC) were analyzed by 16S rRNA metabarcoding procedures. The data revealed that Parvimonas, Fusobacterium, and Bacteroides fragilis were significantly over-represented in stool samples of CRC patients, whereas Faecalibacterium and Blautia were significantly over-abundant in the non-CRC group. Moreover, the tumor samples were enriched in well-known periodontal anaerobes, including Fusobacterium, Parvimonas, Peptostreptococcus, Porphyromonas, and Prevotella. Co-occurrence patterns of these oral microorganisms were observed in the subgingival pocket and in the tumor tissues of CRC patients, where they also correlated with other gut microbes, such as Hungatella. This study provides new evidence that oral pathobionts, normally located in subgingival pockets, can migrate to the colon and probably aggregate with aerobic bacteria, forming synergistic consortia. Furthermore, we suggest that the group composed of Fusobacterium, Parvimonas, Bacteroides, and Faecalibacterium could be used to design an excellent noninvasive fecal test for the early diagnosis of CRC. The combination of these four genera would significantly improve the reliability of a discriminatory test with respect to others that use a single species as a unique CRC biomarker.
Topics: Humans; Colorectal Neoplasms; Fusobacterium; Male; Female; Bacteroides; Middle Aged; Feces; Biomarkers, Tumor; Faecalibacterium; Aged; RNA, Ribosomal, 16S; Gastrointestinal Microbiome; Saliva; Adult
PubMed: 38366793
DOI: 10.1002/1878-0261.13604 -
PloS One 2024Fusobacterium nucleatum (Fn) and enterotoxigenic Bacteroides fragilis (ETBF) are two pathobionts consistently enriched in the gut microbiomes of patients with colorectal...
Fusobacterium nucleatum (Fn) and enterotoxigenic Bacteroides fragilis (ETBF) are two pathobionts consistently enriched in the gut microbiomes of patients with colorectal cancer (CRC) compared to healthy counterparts and frequently observed for their direct association within tumors. Although several molecular mechanisms have been identified that directly link these organisms to features of CRC in specific cell types, their specific effects on the epithelium and local immune compartment are not well-understood. To fill this gap, we leveraged single-cell RNA sequencing (scRNA-seq) on wildtype mice and mouse model of CRC. We find that Fn and ETBF exacerbate cancer-like transcriptional phenotypes in transit-amplifying and mature enterocytes in a mouse model of CRC. We also observed increased T cells in the pathobiont-exposed mice, but these pathobiont-specific differences observed in wildtype mice were abrogated in the mouse model of CRC. Although there are similarities in the responses provoked by each organism, we find pathobiont-specific effects in Myc-signaling and fatty acid metabolism. These findings support a role for Fn and ETBF in potentiating tumorigenesis via the induction of a cancer stem cell-like transit-amplifying and enterocyte population and the disruption of CTL cytotoxic function.
Topics: Humans; Mice; Animals; Colorectal Neoplasms; Bacterial Infections; Fusobacterium nucleatum; Carcinogenesis; Bacteroides fragilis
PubMed: 38363784
DOI: 10.1371/journal.pone.0297897 -
Journal of Nanobiotechnology Feb 2024A large number of Fusobacterium nucleatum (Fn) are present in colorectal cancer (CRC) tissues of patients who relapse after chemotherapy, and Fn has been reported to...
BACKGROUND
A large number of Fusobacterium nucleatum (Fn) are present in colorectal cancer (CRC) tissues of patients who relapse after chemotherapy, and Fn has been reported to promote oxaliplatin and 5-FU chemoresistance in CRC. Pathogens such as bacteria and parasites stimulate exosome production in tumor cells, and the regulatory mechanism of exosomal circRNA in the transmission of oxaliplatin and 5-FU chemotherapy resistance in Fn-infected CRC remains unclear.
METHODS
Hsa_circ_0004085 was screened by second-generation sequencing of CRC tissues. The correlation between hsa_circ_0004085 and patient clinical response to oxaliplatin/5-FU was analyzed. Exosome tracing experiments and live imaging systems were used to test the effect of Fn infection in CRC on the distribution of hsa_circ_0004085. Colony formation, ER tracking analysis and immunofluorescence were carried out to verify the regulatory effect of exosomes produced by Fn-infected CRC cells on chemotherapeutic resistance and ER stress. RNA pulldown, LC-MS/MS analysis and RIP were used to explore the regulatory mechanism of downstream target genes by hsa_circ_0004085.
RESULTS
First, we screened out hsa_circ_0004085 with abnormally high expression in CRC clinical samples infected with Fn and found that patients with high expression of hsa_circ_0004085 in plasma had a poor clinical response to oxaliplatin/5-FU. Subsequently, the circular structure of hsa_circ_0004085 was identified. Fn infection promoted hsa_circ_0004085 formation by hnRNP L and packaged hsa_circ_0004085 into exosomes by hnRNP A1. Exosomes produced by Fn-infected CRC cells transferred hsa_circ_0004085 between cells and delivered oxaliplatin/5-FU resistance to recipient cells by relieving ER stress. Hsa_circ_0004085 enhanced the stability of GRP78 mRNA by binding to RRBP1 and promoted the nuclear translocation of ATF6p50 to relieve ER stress.
CONCLUSIONS
Plasma levels of hsa_circ_0004085 are increased in colon cancer patients with intracellular Fn and are associated with a poor response to oxaliplatin/5-FU. Fn infection promoted hsa_circ_0004085 formation by hnRNP L and packaged hsa_circ_0004085 into exosomes by hnRNP A1. Exosomes secreted by Fn-infected CRC cells deliver hsa_circ_0004085 between cells. Hsa_circ_0004085 relieves ER stress in recipient cells by regulating GRP78 and ATF6p50, thereby delivering resistance to oxaliplatin and 5-FU.
Topics: Humans; Oxaliplatin; Fusobacterium nucleatum; Heterogeneous Nuclear Ribonucleoprotein A1; Colorectal Neoplasms; Exosomes; Chromatography, Liquid; Endoplasmic Reticulum Chaperone BiP; Heterogeneous-Nuclear Ribonucleoprotein L; Tandem Mass Spectrometry; Colonic Neoplasms; Fluorouracil; MicroRNAs; Cell Proliferation
PubMed: 38360615
DOI: 10.1186/s12951-024-02331-9 -
Clinical Oral Investigations Feb 2024This study aimed to describe the effects of two single-file systems on the diversity of the endodontic microbiome of teeth with primary asymptomatic apical periodontitis.
OBJECTIVES
This study aimed to describe the effects of two single-file systems on the diversity of the endodontic microbiome of teeth with primary asymptomatic apical periodontitis.
MATERIALS AND METHODS
The root canals from single-rooted teeth with apical periodontitis were prepared using either the Reciproc Blue (RB) or the XP-endo Shaper (XPS) instrument system. The latter was followed by a supplementary step with the XP-endo Finisher (XPF) instrument. For irrigation, 5.25% sodium hypochlorite was used. Root canal samples were taken at the baseline (S1), after preparation (S2), and after the supplementary step (S3). DNA was extracted and subjected to high-throughput sequencing using the MiSeq Illumina platform.
RESULTS
Samples from 10 teeth from the RB and 7 from the XPS group were subjected to DNA sequencing. Initial samples differed significantly from post-preparation samples in bacterial diversity, with no significant difference when comparing the two instrument systems. The most dominant phyla in S2 were Bacteroidetes, Proteobacteria, Firmicutes, Fusobacteria, and Actinobacteria. The same phyla were found to dominate baseline samples and samples taken after using XPF, but with differences in the ranking of the most dominant ones. At the genus level, the most dominant genera identified after RB instrumentation were Bacteroidaceae [G-1], Fusobacterium, and Staphylococcus, while the most dominant genera after XPS instrumentation were Fusobacterium and Porphyromonas. These genera were also dominant in the initial samples.
CONCLUSIONS
Both treatment protocols had measurable effects on the root canal microbial diversity, with no significant differences between them. Most of the dominant taxa involved in the primary infection and probably in the aetiology of apical periodontitis were eliminated or substantially reduced.
CLINICAL RELEVANCE
The most dominant taxa that persisted after instrumentation were Fusobacterium, Porphyromonas, Staphylococcus, and Bacteroidaceae [G-1].
Topics: Humans; Root Canal Preparation; Dental Pulp Cavity; Root Canal Therapy; Periapical Periodontitis; Bacteria
PubMed: 38332365
DOI: 10.1007/s00784-024-05544-2 -
American Journal of Translational... 2024The prevalence of allergic rhinitis (common allergies) has increased in the last fifty years, from less than one percent to more than twenty-six percent of the...
The prevalence of allergic rhinitis (common allergies) has increased in the last fifty years, from less than one percent to more than twenty-six percent of the population. Today, more than one hundred million people in the US suffer seasonal or yearlong allergies. The hygiene hypothesis was proposed 30 years ago as a potential explanation for this phenomenon, and we built on it with the specific oral hygiene hypothesis. Our longitudinal pilot study suggested that oral probiotic deficiency is the cause of allergic rhinitis. This clinical trial served to verify our theory and evaluate the effectiveness of AllerPops for allergy relief. We carried out a phase II, randomized, double-blind, controlled, single-center 21-day study to investigate the efficacy of AllerPops to reduce nasal symptoms in 72 adult volunteers with seasonal/year-long nasal allergies and its impact on oral microbiome using amplicon sequencing of 16S ribosome RNA genes. The volunteers were randomly separated into two equally sized groups: a control group and an investigational group. Both groups were given at least three doses of AllerPops, taken every other day, and asked to answer questions about observed allergy symptoms. Volunteers in the investigational group cleaned their mouths before taking a dose and slowly dissolve the lozenge, while those in the control did not. Through this trial, we show that AllerPops prebiotic supplements are effective in providing sustained allergy relief (P = 0.002) and can modulate oral beneficial bacteria that produce short-chain fatty acids (SCFA), such as Fusobacteria, Butyrivibrio, and Peptostreptococcus. The clinical improvements correlated with changes in the relative abundance of probiotics significantly: Fusobacteria (R = 0.32, P = 0.009), Butyrivibrio (R = 0.25, P = 0.044), and Peptostreptococcus (R = 0.34, P = 0.005). These results point to the root cause of allergic rhinitis: the lack of oral probiotics that produce SCFA to pacify the immune systems. Future study of AllerPops' theory will help society redefine the best oral hygiene practice to protect oral probiotics so that we may prevent allergic and autoimmune diseases and dental/gum infections. The trial was retrospectively registered at clinicaltrials.com, with registration number NCT05956691, on 21/07/2023.
PubMed: 38322553
DOI: 10.62347/JWOU4205