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Pathogens (Basel, Switzerland) Jan 2024Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. and , which are known periodontal pathogens,... (Review)
Review
Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. and , which are known periodontal pathogens, have emerged as extensively studied participants with potential pathogenic abilities in carcinogenesis. However, the complex dynamics arising from interactions between these two pathogens were less addressed. This narrative review aims to summarize the current knowledge on the prevalence and mechanism implications of and in the carcinogenesis of oral squamous cell carcinoma (OSCC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). In particular, it explores the clinical and experimental evidence on the interplay between and in affecting oral and gastrointestinal carcinogenesis. and , which are recognized as keystone or bridging bacteria, were identified in multiple clinical studies simultaneously. The prevalence of both bacteria species correlated with cancer development progression, emphasizing the potential impact of the collaboration. Regrettably, there was insufficient experimental evidence to demonstrate the synergistic function. We further propose a hypothesis to elucidate the underlying mechanisms, offering a promising avenue for future research in this dynamic and evolving field.
PubMed: 38276166
DOI: 10.3390/pathogens13010093 -
International Journal of Oral Science Sep 2023While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), the underlying mechanisms remain unclear....
While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), the underlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, including heart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment by periodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate the relationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes (NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagy inhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. This study also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomal sensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity than gingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wild-type P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-type P.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which are virulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms the strong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.
Topics: Mice; Rats; Animals; Porphyromonas gingivalis; Gingipain Cysteine Endopeptidases; Autophagosomes; Myocardium; Periodontal Diseases; Heart Rupture
PubMed: 37723152
DOI: 10.1038/s41368-023-00251-2 -
International Journal of Rheumatic... Mar 2024Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and pain, which can lead to the loss of normal joint function. Although the exact... (Review)
Review
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and pain, which can lead to the loss of normal joint function. Although the exact cause of the disease is not yet fully understood, both environmental factors and genetics may play a role in its development. Moreover, research suggests microbiota contributes to the onset and progression of RA. People with RA show higher quantities of bacteria such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella copri, Proteus mirabilis, and Lactobacillus salivarius compared to healthy individuals. Conversely, studies propose that Lactobacillus casei, a probiotic bacterium with immunomodulatory properties, has beneficial effects for RA in murine and human models. Therefore, this work reviews the potential role of the gut microbiota in the development of RA and explores the feasibility of using probiotic bacteria as a supplementary treatment for this disease.
Topics: Humans; Mice; Animals; Microbiota; Arthritis, Rheumatoid; Gastrointestinal Microbiome; Inflammation; Probiotics
PubMed: 38487975
DOI: 10.1111/1756-185X.15122 -
Journal of Periodontal Research Oct 2023To investigate the existence of any association between new putative periodontal pathogens and periodontitis. Two independent reviewers conducted electronic literature... (Meta-Analysis)
Meta-Analysis Review
To investigate the existence of any association between new putative periodontal pathogens and periodontitis. Two independent reviewers conducted electronic literature searches in the MEDLINE (PubMed), EMBASE, DOSS and Google Scholar databases as well as a manual search to identify eligible clinical studies prior to November 2022. Studies comparing the prevalence of microorganisms other than the already-known periodontal pathogens in subgingival plaque and/or saliva samples between subjects with periodontitis and subject with periodontal health were included. Meta-analyses were performed on data provided by the included studies. Fifty studies including a total of 2739 periodontitis subjects and 1747 subjects with periodontal health were included. The Archaea domain and 25 bacterial species (Anaeroglobus geminatus, Bacteroidales [G-2] bacterium HMT 274, Desulfobulbus sp. HMT 041, Dialister invisus, Dialister pneumosintes, Eubacterium brachy, Enterococcus faecalis, Eubacterium nodatum, Eubacterium saphenum, Filifactor alocis, Fretibacterium sp. HMT 360, Fretibacterium sp. HMT 362, Mogibacterium timidum, Peptoniphilaceae sp. HMT 113, Peptostreptococcus stomatis, Porphyromonas endodontalis, Slackia exigua, Streptococcus gordonii, Selenomonas sputigena, Treponema amylovorum, Treponema lecithinolyticum, Treponema maltophilum, Treponema medium, Treponema parvum and Treponema socranskii) were found to be statistically significantly associated with periodontitis. Network studies should be conducted to investigate the role of these newly identified periodontitis-associated microorganisms through interspecies interaction and host-microbe crosstalk analyses.
Topics: Humans; Bacteria; Periodontitis; Dental Plaque; Bacteroides; Eubacterium
PubMed: 37572051
DOI: 10.1111/jre.13173 -
Antibiotics (Basel, Switzerland) Nov 2023(1) Introduction: Current evidence shows that mechanical debridement augmented with systemic and topical antibiotics may be beneficial for the treatment of... (Review)
Review
(1) Introduction: Current evidence shows that mechanical debridement augmented with systemic and topical antibiotics may be beneficial for the treatment of peri-implantitis. The microbial profile of peri-implantitis plays a key role in identifying the most suitable antibiotics to be used for the treatment and prevention of peri-implantitis. This systematic review aimed to summarize and critically analyze the methodology and findings of studies which have utilized sequencing techniques to elucidate the microbial profiles of peri-implantitis. (2) Results: sp. are associated with peri-implantitis. sp. are associated with healthy implant sites and exhibit a reduced prevalence in deeper pockets and with greater severity of disease progression. sp. have been identified both in diseased and healthy sites. sp. have been associated with healthy implants and negatively correlate with the probing depth. Methanogens and AAGPRs were also detected in peri-implantitis sites. (3) Methods: The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023459266). The PRISMA criteria were used to select articles retrieved from a systematic search of the Scopus, Cochrane, and Medline databases until 1 August 2023. Title and abstract screening was followed by a full-text review of the included articles. Thirty-two articles were included in the final qualitative analysis. (4) Conclusions: A distinct microbial profile could not be identified from studies employing sequencing techniques to identify the microbiome. Further studies are needed with more standardization to allow a comparison of findings. A universal clinical parameter for the diagnosis of peri-implantitis should be implemented in all future studies to minimize confounding factors. The subject pool should also be more diverse and larger to compensate for individual differences, and perhaps a distinct microbial profile can be seen with a larger sample size.
PubMed: 37998812
DOI: 10.3390/antibiotics12111610 -
Oral Diseases Nov 2023Porphyromonas gingivalis (Pg) is thought to be involved in the progression of Alzheimer's disease (AD). Whether Pg or its contents can reach the brain and directly...
OBJECTIVE
Porphyromonas gingivalis (Pg) is thought to be involved in the progression of Alzheimer's disease (AD). Whether Pg or its contents can reach the brain and directly affect neuropathology is, however, unknown. Here, we investigated whether outer membrane vesicles (OMVs) of Pg translocate to the brain and induce the pathogenic features of AD.
MATERIAL AND METHODS
Pg OMVs were injected into the abdominal cavity of mice for 12 weeks. Pg OMV translocation to the brain was detected by immunohistochemistry using an anti-gingipain antibody. Tau protein and microglial activation in the mouse brain were examined by western blotting and immunohistochemistry. The effect of gingipains on inflammation was assessed by real-time polymerase chain reaction using human microglial HMC3 cells.
RESULTS
Gingipains were detected in the region around cerebral ventricles, choroid plexus, and ventricular ependymal cells in Pg OMV-administered mice. Tau and phosphorylated Tau protein increased and microglia were activated. Pg OMVs also increased the gene expression of proinflammatory cytokines in HMC3 cells in a gingipain-dependent manner.
CONCLUSION
Pg OMVs, including gingipains, can reach the cerebral ventricle and induce neuroinflammation by activating microglia. Pg OMVs may provide a better understanding of the implications of periodontal diseases in neurodegenerative conditions such as AD.
Topics: Humans; Animals; Mice; Gingipain Cysteine Endopeptidases; Microglia; tau Proteins; Porphyromonas gingivalis; Alzheimer Disease; Cerebral Ventricles
PubMed: 36266256
DOI: 10.1111/odi.14413 -
International Journal of Molecular... Mar 2024Rheumatoid arthritis (RA) is a chronic, autoimmune disease with a complex outset. Besides the genetic susceptibility in its pathogenesis, various environmental factors... (Review)
Review
Rheumatoid arthritis (RA) is a chronic, autoimmune disease with a complex outset. Besides the genetic susceptibility in its pathogenesis, various environmental factors also participate. Of these, in recent years, there have been increasing reports of the involvement of bacteria in the disease's outset and development, especially gut microbiota and oral pathogens. Most recent reports about bacteria participation in RA pathogenesis focus on and . There are also reports about the involvement of respiratory and urinary tract pathogens. The exact mechanisms leading to RA development used by bacteria are not well known; however, some mechanisms by which bacteria can interact with the immune system are known and can potentially lead to RA development. The aim of this study is to provide a comprehensive review of the potential bacteria participating in RA development and the mechanism involved in that process.
Topics: Humans; Arthritis, Rheumatoid; Porphyromonas gingivalis; Gastrointestinal Microbiome; Communicable Diseases; Genetic Predisposition to Disease
PubMed: 38542357
DOI: 10.3390/ijms25063386 -
Complementary Therapies in Medicine Dec 2023This study examined the role of gut microbiome changes in mediating the effects of a dietary intervention on the frequency and severity of postmenopausal vasomotor... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study examined the role of gut microbiome changes in mediating the effects of a dietary intervention on the frequency and severity of postmenopausal vasomotor symptoms METHODS: Postmenopausal women (n = 84) reporting ≥2 moderate-to-severe hot flashes daily were randomly assigned, in 2 successive cohorts, to an intervention including a low-fat, vegan diet and cooked soybeans (½ cup [86 g] daily) or to stay on their usual diet. Over a 12-week period, frequency and severity of hot flashes were recorded with a mobile application. In a subset of 11 women, gut microbiome was analyzed at baseline and after 12 weeks of the dietary intervention (low-fat vegan diet with soybeans), using deep shotgun metagenomic sequencing. Differences in the microbiome between baseline and 12 weeks were assessed by comparing alpha diversity with Wilcoxon signed rank tests, beta diversity with permanovaFL, and taxon abundance with Wilcoxon signed rank tests. Pearson correlations were used to assess the association between changes in hot flashes and gut bacteria.
RESULTS
In the subset for which microbiome testing was done, total hot flashes decreased by 95 % during the dietary intervention (p = 0.007); severe hot flashes disappeared (from 0.6 to 0.0/day; p = 0.06); and moderate-to-severe hot flashes decreased by 96 % (p = 0.01). Daytime and nighttime hot flashes were reduced by 96 % (p = 0.01) and 94 % (p = 0.004), respectively. Alpha and beta diversity did not significantly differ in the intervention group between baseline and 12 weeks. Two families (Enterobacteriaceae and Veillonellaceae), 5 genera (Erysipelatoclostridium, Fusicatenibacter, Holdemanella, Intestinimonas, and Porphyromonas), and 6 species (Clostridium asparagiforme, Clostridium innocuum, Bacteroides thetaiotaomicron, Fusicatenibacter saccharivorans, Intestinimonas butyriciproducens, Prevotella corporis, and Streptococcus sp.) were differentially abundant, but after correction for multiple comparisons, these differences were no longer significant. Changes in the relative abundance of Porphyromonas and Prevotella corporis were associated with the reduction in severe day hot flashes both unadjusted (r = 0.61; p = 0.047; and r = 0.69; p = 0.02), respectively), and after adjustment for changes in body mass index (r = 0.63; p = 0.049; and r = 0.73; p = 0.02), respectively). Changes in relative abundance of Clostridium asparagiforme were associated with the reduction in total severe hot flashes (r = 0.69; p = 0.019) and severe night hot flashes (r = 0.82; p = 0.002) and the latter association remained significant after adjustment for changes in body mass index (r = 0.75; p = 0.01).
CONCLUSIONS
This exploratory analysis revealed potential associations between changes in vasomotor symptoms in response to a diet change and changes in the gut microbiome. Larger randomized clinical trials are needed to investigate these findings.
Topics: Female; Humans; Hot Flashes; Postmenopause; Gastrointestinal Microbiome; Menopause
PubMed: 37949415
DOI: 10.1016/j.ctim.2023.103002 -
Journal of Endodontics Jul 2023This scoping review aimed to map the evidence about the microbiota found in persistent endodontic infections. (Review)
Review
INTRODUCTION
This scoping review aimed to map the evidence about the microbiota found in persistent endodontic infections.
METHODS
The study protocol was prospectively registered and is available at https://osf.io/3g2cp. The electronic search was performed in MEDLINE via PubMed, Lilacs, BBO, Scopus, Web of Science, Cochrane Library, and Embase. The eligibility criteria were based on the PCC acronym, where P (Population) represents patients with teeth presenting persistent endodontic infection, C (Concept) represents microbial profile, and C (Context) represents undergoing endodontic retreatment. Clinical studies that evaluated the microbial profile of samples collected from root canals of teeth undergoing retreatment, using classical or molecular methods, were included. Studies that did not show a minimum period of 1 year between primary endodontic treatment and retreatment or did not radiographically evaluate the quality of primary root canal filling were excluded. Two reviewers independently selected the articles and collected data.
RESULTS
From a total of 957 articles, 161 were read in full, and 32 studies were included. The most prevalent species were Enterococcus faecalis, Parvimonas micra, Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella intermedia, Dialister invisus, Propionibacterium acnes, Tannerella forsythia, and Treponema denticola. Cases with symptomatology or inadequate root canal filling presented an increase in specific bacterial species compared to those with no symptomatology or adequate filling. A greater number of microorganisms was observed in teeth with inadequate coronal restoration compared to those with adequate restoration.
CONCLUSIONS
Persistent endodontic infections have a polymicrobial profile identified by the commonly used methods for bacterial detection/identification and are subject to the limitations present in each of those methods.
Topics: Humans; Dental Pulp Cavity; Porphyromonas gingivalis; Prevotella intermedia; Porphyromonas endodontalis
PubMed: 37211309
DOI: 10.1016/j.joen.2023.05.010 -
NPJ Biofilms and Microbiomes Aug 2023Immune responses can have opposing effects in colorectal cancer (CRC), the balance of which may determine whether a cancer regresses, progresses, or potentially...
Immune responses can have opposing effects in colorectal cancer (CRC), the balance of which may determine whether a cancer regresses, progresses, or potentially metastasizes. These effects are evident in CRC consensus molecular subtypes (CMS) where both CMS1 and CMS4 contain immune infiltrates yet have opposing prognoses. The microbiome has previously been associated with CRC and immune response in CRC but has largely been ignored in the CRC subtype discussion. We used CMS subtyping on surgical resections from patients and aimed to determine the contributions of the microbiome to the pleiotropic effects evident in immune-infiltrated subtypes. We integrated host gene-expression and meta-transcriptomic data to determine the link between immune characteristics and microbiome contributions in these subtypes and identified lipopolysaccharide (LPS) binding as a potential functional mechanism. We identified candidate bacteria with LPS properties that could affect immune response, and tested the effects of their LPS on cytokine production of peripheral blood mononuclear cells (PBMCs). We focused on Fusobacterium periodonticum and Bacteroides fragilis in CMS1, and Porphyromonas asaccharolytica in CMS4. Treatment of PBMCs with LPS isolated from these bacteria showed that F. periodonticum stimulates cytokine production in PBMCs while both B. fragilis and P. asaccharolytica had an inhibitory effect. Furthermore, LPS from the latter two species can inhibit the immunogenic properties of F. periodonticum LPS when co-incubated with PBMCs. We propose that different microbes in the CRC tumor microenvironment can alter the local immune activity, with important implications for prognosis and treatment response.
Topics: Humans; Lipopolysaccharides; Leukocytes, Mononuclear; Tumor Microenvironment; Bacteria; Colorectal Neoplasms; Cytokines; Immunity
PubMed: 37612266
DOI: 10.1038/s41522-023-00429-w