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Trends in Molecular Medicine Oct 2023Recent work by Muraoka and colleagues reports that the Gram-negative anaerobic bacterium Fusobacterium nucleatum is detected in the uterus of 64% of women with...
Recent work by Muraoka and colleagues reports that the Gram-negative anaerobic bacterium Fusobacterium nucleatum is detected in the uterus of 64% of women with endometriosis. Fusobacterium infection causes macrophage infiltration, transforming growth factor-β production, and transgelin upregulation in human and mouse endometria as well as endometriotic lesion development in a mouse model of endometriosis.
Topics: Animals; Mice; Female; Humans; Fusobacterium; Base Composition; Endometriosis; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 37599125
DOI: 10.1016/j.molmed.2023.08.003 -
Periodontology 2000 Jun 2021Ecologists have long recognized the importance of spatial scale in understanding structure-function relationships among communities of organisms within their... (Review)
Review
Ecologists have long recognized the importance of spatial scale in understanding structure-function relationships among communities of organisms within their environment. Here, we review historical and contemporary studies of dental plaque community structure in the context of three distinct scales: the micro (1-10 µm), meso (10-100 µm) and macroscale (100 µm to ≥1 cm). Within this framework, we analyze the compositional nature of dental plaque at the macroscale, the molecular interactions of microbes at the microscale, and the emergent properties of dental plaque biofilms at the mesoscale. Throughout our analysis of dental plaque across spatial scales, we draw attention to disease and health-associated structure-function relationships and include a discussion of host immune involvement in the mesoscale structure of periodontal disease-associated biofilms. We end with a discussion of two filamentous organisms, Fusobacterium nucleatum and Corynebacterium matruchotii, and their relevant contributions in structuring dental plaque biofilms.
Topics: Biofilms; Corynebacterium; Dental Plaque; Fusobacterium nucleatum; Humans; Microbiota
PubMed: 33690940
DOI: 10.1111/prd.12364 -
Archives of Oral Biology Dec 2021The tongue microbiome has emerged as a non-invasive diagnostic and tracking prognostic tool in the detection of diseases mainly cancer. This scoping review aimed to... (Review)
Review
OBJECTIVE
The tongue microbiome has emerged as a non-invasive diagnostic and tracking prognostic tool in the detection of diseases mainly cancer. This scoping review aimed to identify the association between tongue microbiome and pre-cancer or cancer lesions.
DESIGN
A comprehensive electronic database search including PubMed, Web of Science, and Scopus was undertaken up to March 2021, without language or date restrictions. This review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guideline. All observational studies that compared microbial community on the dorsal surface of the tongue between cancer or precancerous cases and healthy controls using NGS techniques were included.
RESULTS
Of 274 records identified, nine studies were eligible to be included. Despite the inconsistent observations in terms of diversity and richness, most studies reported alteration in bacterial communities between pre-cancer or cancer cases and control groups. The bacterial profile among cases was so far correlated at the phylum level with a noticeable diverse degree at the genus level. The majority of included studies reported a higher abundance of certain kinds of microorganisms as compared to healthy participants including Firmicutes, Fusobacteria and Actinobacteria at phyla level as well as Streptococcus, Actinomyces, Leptotrichia, Campylobacter, and Fusobacterium at the genus level.
CONCLUSION
The alteration of the tongue microbial community has been associated with several diseases mainly cancer. So, the tongue microbiome may serve as a promising diagnostic tool or as a long-term monitor in precancerous or cancer cases.
Topics: Bacteria; Fusobacterium; Humans; Microbiota; Neoplasms; Tongue
PubMed: 34610507
DOI: 10.1016/j.archoralbio.2021.105271 -
Frontiers in Cellular and Infection... 2022There is an urgent need to search for new screening methods that allow early detection of esophageal cancer and thus achieve better clinical outcomes. Nowadays, it is... (Review)
Review
There is an urgent need to search for new screening methods that allow early detection of esophageal cancer and thus achieve better clinical outcomes. Nowadays, it is known that the esophagus is not a sterile part of the gastrointestinal tract. It is colonized with various microorganisms therefore a "healthy" esophageal microbiome exists. The dysbiotic changes of esophageal microbiome can lead to the development of esophageal diseases including esophageal cancer. There is a strong consensus in the literature that the intestinal microbiome may be involved in esophageal carcinogenesis. Recently, emphasis has also been placed on the relationship between the oral microbiome and the occurrence of esophageal cancer. According to recent studies, some of the bacteria present in the oral cavity, such as , , , , and may contribute to the development of this cancer. Moreover, the oral microbiome of patients with esophageal cancer differs significantly from that of healthy individuals. This opens new insights into the search for a microbiome-associated marker for early identification of patients at high risk for developing this cancer.
Topics: Humans; Gastrointestinal Microbiome; Esophageal Neoplasms; Microbiota; Fusobacterium nucleatum; Mouth
PubMed: 36467733
DOI: 10.3389/fcimb.2022.1057668 -
Bone & Joint Research Apr 2022Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut...
AIMS
Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive.
METHODS
A total of 18 eight-week Sprague-Dawley rats were assigned into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and the destabilization of the medial meniscus (DMM). Treadmill-walking (15 m/min, 30 min/d, five days/week for eight weeks) was employed in the PTOA/TW group. The response of cartilage, subchondral bone, serology, and gut microbiome and their correlations were assessed.
RESULTS
Eight-week treadmill-walking was effective at maintaining the integrity of cartilage-subchondral bone unit and reducing the elevated systematic inflammation factors and microbiome-derived metabolites. Furthermore, 16S ribosomal ribonucleic acid (rRNA) sequencing showed disease-relevant microbial shifts in PTOA animals, characterized by the decreased abundance of phylum and the increase of phylum . At the genus level, the abundance of , , , and were increased in the PTOA animals, while the increase of and was weakened as a response to exercise. The correlation analysis showed that genus and were correlated to the structural OA phenotypes, while phylum and genus may contribute to the effects of exercise on the diminishment of serological inflammatory factors.
CONCLUSION
Exercise is effective at maintaining the integrity of cartilage-subchondral bone unit, and the exercise-induced modification of disease-relevant microbial shifts is potentially involved in the mechanisms of exercise-induced amelioration of PTOA. Cite this article: 2022;11(4):214-225.
PubMed: 35382556
DOI: 10.1302/2046-3758.114.BJR-2021-0192.R1 -
Revista de Gastroenterologia de Mexico... 2022
Topics: Colorectal Neoplasms; Fusobacterium nucleatum; Humans
PubMed: 35623988
DOI: 10.1016/j.rgmxen.2022.01.003 -
Anaerobe Apr 2023We set out to identify and characterize prophages within genomes of published Fusobacterium strains, and to develop qPCR-based methods to characterize intra- and...
OBJECTIVES
We set out to identify and characterize prophages within genomes of published Fusobacterium strains, and to develop qPCR-based methods to characterize intra- and extra-cellular induction of prophage replication in a variety of environmental contexts.
METHODS
Various in silico tools were used to predict prophage presence across 105 Fusobacterium spp. Genomes. Using the example of the model pathogen, Fusobacterium nucleatum subsp. animalis strain 7-1, qPCR was used with DNase I treatment to determine induction of its 3 predicted prophages ɸFunu1, ɸFunu2, and ɸFunu3, across several conditions.
RESULTS
116 predicted prophage sequences were found and analyzed. An emerging association between the phylogenetic history of a Fusobacterium prophage and that of its host was detected, as was the presence of genes encoding putative host fitness factors (e.g. ADP-ribosyltransferases) in distinct subclusters of prophage genomes. For strain 7-1, a pattern of expression for ɸFunu1, ɸFunu2, and ɸFunu3 was established indicating that ɸFunu1 and ɸFunu2 are capable of spontaneous induction. I Salt and mitomycin C exposure were able to promote induction of ɸFunu2. A range of other biologically relevant stressors, including exposure to pH, mucin and human cytokines showed no or minimal induction of these same prophages. ɸFunu3 induction was not detected under tested conditions.
CONCLUSION
The heterogeneity of Fusobacterium strains is matched by their prophages. While the role of Fusobacterium prophages in host pathogenicity remains unclear, this work provides the first overview of clustered prophage distribution among this enigmatic genus and describes an effective assay for quantifying mixed samples of prophages that cannot be detected by plaque assay.
Topics: Humans; Prophages; Phylogeny; Fusobacterium
PubMed: 36801248
DOI: 10.1016/j.anaerobe.2023.102718 -
Nature Reviews. Microbiology Oct 2022
Topics: Biofilms; Fusobacterium; Fusobacterium nucleatum
PubMed: 35915254
DOI: 10.1038/s41579-022-00787-w -
Microbiology Spectrum Aug 2023Fusobacterium nucleatum is a Gram-negative bacterium that has been identified as an important pathogenic gut bacterium associated with colorectal cancer. Compared with...
Fusobacterium nucleatum is a Gram-negative bacterium that has been identified as an important pathogenic gut bacterium associated with colorectal cancer. Compared with the normal intestine, the pH value of the tumor microenvironment is weakly acidic. The metabolic changes of F. nucleatum in the tumor microenvironment, especially the protein composition of its outer membrane vesicles, remain unclear. Here, we systematically analyzed the effect of environmental pH on the proteome of outer membrane vesicles (OMVs) from F. nucleatum by tandem mass tag (TMT) labeling-high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. A total of 991 proteins were identified in acidic OMVs (aOMVs) and neutral OMVs (nOMVs), including known virulence proteins and putative virulence proteins. Finally, 306 upregulated proteins and 360 downregulated proteins were detected in aOMVs, and approximately 70% of the expression of OMV proteins was altered under acidic conditions. A total of 29 autotransporters were identified in F. nucleatum OMVs, and 13 autotransporters were upregulated in aOMVs. Interestingly, three upregulated autotransporters (D5REI9, D5RD69, and D5RBW2) show homology to the known virulence factor Fap2, suggesting that they may be involved in various pathogenic pathways such as the pathway for binding with colorectal cancer cells. Moreover, we found that more than 70% of MORN2 domain-containing proteins may have toxic effects on host cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that a number of proteins were significantly enriched in multiple pathways involving fatty acid synthesis and butyrate synthesis. Seven metabolic enzymes involved in fatty acid metabolism pathways were identified in the proteomic data, of which 5 were upregulated and 2 were downregulated in aOMVs, while 14 metabolic enzymes involved in the butyric acid metabolic pathway were downregulated in aOMVs. In conclusion, we found a key difference in virulence proteins and pathways in the outer membrane vesicles of F. nucleatum between the tumor microenvironment pH and normal intestinal pH, which provides new clues for the prevention and treatment of colorectal cancer. F. nucleatum is an opportunistic pathogenic bacterium that can be enriched in colorectal cancer tissues, affecting multiple stages of colorectal cancer development. OMVs have been demonstrated to play key roles in pathogenesis by delivering toxins and other virulence factors to host cells. By employing quantitative proteomic analysis, we found that the pH conditions could affect the protein expression of the outer membrane vesicles of F. nucleatum. Under acidic conditions, approximately 70% of the expression of proteins in OMVs was altered. Several virulence factors, such as type 5a secreted autotransporter (T5aSSs) and membrane occupation and recognition nexus (MORN) domain-containing proteins, were upregulated under acidic conditions. A large number of proteins showed significant enrichments in multiple pathways involving fatty acid synthesis and butyrate synthesis. Proteomics analysis of the outer membrane vesicles secreted by pathogenic bacteria in the acidic tumor microenvironment is of great significance for elucidating the pathogenicity mechanism and its application in vaccine and drug delivery vehicles.
Topics: Humans; Fusobacterium nucleatum; Proteomics; Type V Secretion Systems; Chromatography, Liquid; Tandem Mass Spectrometry; Virulence Factors; Membrane Proteins; Colorectal Neoplasms; Fatty Acids; Bacterial Outer Membrane Proteins; Tumor Microenvironment
PubMed: 37341631
DOI: 10.1128/spectrum.00394-23 -
Cancer Research Communications Nov 2022() is a gram-negative oral anaerobe and prevalent in colorectal cancer. encodes a unique amyloid-like adhesin, FadA complex (FadAc), consisting of intact pre-FadA and...
UNLABELLED
() is a gram-negative oral anaerobe and prevalent in colorectal cancer. encodes a unique amyloid-like adhesin, FadA complex (FadAc), consisting of intact pre-FadA and cleaved mature FadA, to promote colorectal cancer tumorigenesis. We aimed to evaluate circulating anti-FadAc antibody levels as a biomarker for colorectal cancer. Circulating anti-FadAc IgA and IgG levels were measured by ELISA in two study populations. In study 1, plasma samples from patients with colorectal cancer ( = 25) and matched healthy controls ( = 25) were obtained from University Hospitals Cleveland Medical Center. Plasma levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer (mean ± SD: 1.48 ± 1.07 μg/mL) compared with matched healthy controls (0.71 ± 0.36 μg/mL; = 0.001). The increase was significant in both early (stages I and II) and advanced (stages III and IV) colorectal cancer. In study 2, sera from patients with colorectal cancer ( = 50) and patients with advanced colorectal adenomas ( = 50) were obtained from the Weill Cornell Medical Center biobank. Anti-FadAc antibody titers were stratified according to the tumor stage and location. Similar as study 1, serum levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer (2.06 ± 1.47 μg/mL) compared with patients with colorectal adenomas (1.49 ± 0.99 μg/mL; = 0.025). Significant increase was limited to proximal cancers, but not distal tumors. Anti-FadAc IgG was not increased in either study population, suggesting that likely translocates through the gastrointestinal tract and interact with colonic mucosa. Anti-FadAc IgA, but not IgG, is a potential biomarker for early detection of colorectal neoplasia, especially for proximal tumors.
SIGNIFICANCE
, an oral anaerobe highly prevalent in colorectal cancer, secretes the amyloid-like FadAc to promote colorectal cancer tumorigenesis. We report that circulating levels of anti-FadAc IgA, but not IgG, are increased in patients with both early and advanced colorectal cancer compared with the healthy controls, and especially in those with proximal colorectal cancer. Anti-FadAc IgA may be developed into a serological biomarker for early detection of colorectal cancer.
Topics: Humans; Fusobacterium nucleatum; Colorectal Neoplasms; Adhesins, Bacterial; Carcinogenesis; Cell Transformation, Neoplastic; Biomarkers; Adenoma
PubMed: 36970057
DOI: 10.1158/2767-9764.CRC-22-0248