-
Journal of Integrative Neuroscience Mar 2022Alzheimer's disease (AD) is the leading cause of dementia worldwide. Individuals affected by the disease gradually lose their capacity for abstract thinking,... (Review)
Review
Alzheimer's disease (AD) is the leading cause of dementia worldwide. Individuals affected by the disease gradually lose their capacity for abstract thinking, understanding, communication and memory. As populations age, declining cognitive abilities will represent an increasing global health concern. While AD was first described over a century ago, its pathogenesis remains to be fully elucidated. It is believed that cognitive decline in AD is caused by a progressive loss of neurons and synapses that lead to reduced neural plasticity. AD is a multifactorial disease affected by genetic and environmental factors. The molecular hallmarks of AD include formation of extracellular β amyloid (Aβ) aggregates, neurofibrillary tangles of hyperphosphorylated tau protein, excessive oxidative damage, an imbalance of biothiols, dysregulated methylation, and a disproportionate inflammatory response. Recent reports have shown that viruses (e.g., Herpes simplex type 1, 2, 6A/B; human cytomegalovirus, Epstein-Barr virus, hepatitis C virus, influenza virus, and severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), bacteria (e.g., , , , , , , , , , and ), as well as eukaryotic unicellular parasites (e.g., ) may factor into cognitive decline within the context of AD. Microorganisms may trigger pathological changes in the brain that resemble and/or induce accumulation of Aβ peptides and promote tau hyperphosphorylation. Further, the mere presence of infectious agents is suspected to induce both local and systemic inflammatory responses promoting cellular damage and neuronal loss. Here we review the influence of infectious agents on the development of AD to inspire new research in dementia based on these pathogens.
Topics: Alzheimer Disease; COVID-19; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; SARS-CoV-2
PubMed: 35364661
DOI: 10.31083/j.jin2102073 -
Journal of Alzheimer's Disease : JAD 2020Microbial agents including periodontal pathogens have recently appeared as important actors in Alzheimer's disease (AD) pathology. We examined associations of clinical...
Microbial agents including periodontal pathogens have recently appeared as important actors in Alzheimer's disease (AD) pathology. We examined associations of clinical periodontal and bacterial parameters with incident all-cause and AD dementia as well as AD mortality among US middle-aged and older adults. Clinical [Attachment Loss (AL); probing pocket depth (PPD)] and bacterial [pathogen immunoglobulin G (IgG)] periodontal markers were investigated in relation to AD and all-cause dementia incidence and to AD mortality, using data from the third National Health and Nutrition Examination Surveys (NHANES III, 1988-1994) linked longitudinally with National Death Index and Medicare data through January 1, 2014, with up to 26 years of follow-up. Sex- and age-specific multivariable-adjusted Cox proportional hazards models were conducted. Among those ≥65 years, AD incidence and mortality were consistently associated with PPD, two factors and one cluster comprised of IgG titers against Porphyromonas gingivalis (P. gingivalis), Prevotella melaninogenica (P. melaninogenica) and Campylobacter rectus (C. rectus) among others. Specifically, AD incidence was linked to a composite of C. rectus and P. gingivalis titers (per SD, aHR = 1.22; 95% CI, 1.04-1.43, p = 0.012), while AD mortality risk was increased with another composite (per SD, aHR = 1.46; 95% CI, 1.09-1.96, p = 0.017) loading highly on IgG for P. gingivalis, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum, C. rectus, Streptococcus intermedius, Capnocylophaga Ochracea, and P. melaninogenica. This study provides evidence for an association between periodontal pathogens and AD, which was stronger for older adults. Effectiveness of periodontal pathogen treatment on reducing sequelae of neurodegeneration should be tested in randomized controlled trials.
Topics: Aged; Alzheimer Disease; Campylobacter rectus; Dementia; Female; Health Surveys; Humans; Incidence; Male; Middle Aged; Periodontitis; Porphyromonas gingivalis; Prevotella melaninogenica; United States
PubMed: 32280099
DOI: 10.3233/JAD-200064 -
Frontiers in Cellular and Infection... 2019The oral microbiota plays an important role in the human microbiome and human health, and imbalances between microbes and their hosts can lead to oral and systemic...
The oral microbiota plays an important role in the human microbiome and human health, and imbalances between microbes and their hosts can lead to oral and systemic diseases and chronic inflammation, which is usually caused by bacteria and contributes to cancer. There may be a relationship between oral bacteria and oral squamous cell carcinoma (OSCC); however, this relationship has not been thoroughly characterized. Therefore, in this study, we compared the microbiota compositions between tumor sites and opposite normal tissues in buccal mucosal of 50 patients with OSCC using the 16S rDNA sequencing. Richness and diversity of bacteria were significantly higher in tumor sites than in the control tissues. Cancer tissues were enriched in six families (, and ) and 13 genera, including and . At the species level, the abundances of , and another five species were significantly increased, suggesting a potential association between these bacteria and OSCC. Furthermore, the functional prediction revealed that genes involved in bacterial chemotaxis, flagellar assembly and lipopolysaccharide (LPS) biosynthesis which are associated with various pathological processes, were significantly increased in the OSCC group. Overall, oral bacterial profiles showed significant difference between cancer sites and normal tissue of OSCC patients, which might be onsidered diagnostic markers and treatment targets. Our study has been registered in the Chinese clinical trial registry (ChiCTR1900025253, http://www.chictr.org.cn/index.aspx).
Topics: Bacteria; Carcinoma, Squamous Cell; DNA, Ribosomal; Female; Fusobacterium nucleatum; Humans; Lipopolysaccharides; Male; Microbiota; Middle Aged; Mouth; Mouth Mucosa; Peptostreptococcus; Prevotella intermedia; RNA, Ribosomal, 16S
PubMed: 32010645
DOI: 10.3389/fcimb.2019.00476 -
Acta Clinica Croatica Feb 2022Recent clinical and scientific evidence confirms the negative impact of long-term periodontitis on the clinical course and progression of various liver diseases.... (Review)
Review
Recent clinical and scientific evidence confirms the negative impact of long-term periodontitis on the clinical course and progression of various liver diseases. Periodontitis is a chronic, slow-progressing infectious disease of the tooth supporting tissues caused mainly by the gram-negative bacteria and These specific pathogens can be easily translocated from oral cavity to the intestine. Disruption of the intestine microbiota composition by orally derived periodontal pathogenic bacteria has recently been suggested to be a causal mechanism between periodontitis and liver disease. Furthermore, both diseases have the ability to induce an inflammatory response and lead to the creation of inflammatory mediators through which they may influence each other. Recent epidemiologic studies have demonstrated that individuals with liver cirrhosis have considerably poorer periodontal clinical parameters than those without cirrhosis. Periodontal therapy in cirrhosis patients favorably modulates oral and gut microbiome, the course of systemic inflammation, cirrhosis prognostic factors, and cognitive function. Therefore, future clinical researches should be focused on detailed examination of the biological mechanisms, strength and direction of the association between advanced liver disease and periodontitis.
Topics: Humans; Liver Cirrhosis; Periodontitis; Porphyromonas gingivalis
PubMed: 35282488
DOI: 10.20471/acc.2021.60.03.22 -
Journal of Biomedical Science Oct 2022Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in...
Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas.
BACKGROUND
Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin.
METHODS
Microbiota composition was determined through 16S rRNA V3-V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as "tri-part samples") in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria.
RESULTS
Prevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells.
CONCLUSION
This report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.
Topics: Humans; Fusobacterium nucleatum; Prevotella intermedia; RNA, Ribosomal, 16S; Culture Media, Conditioned; Adenoma; Colorectal Neoplasms; Cell Transformation, Neoplastic; Bacteria; Adenocarcinoma; Adenomatous Polyps
PubMed: 36303164
DOI: 10.1186/s12929-022-00869-0 -
Microbiology Spectrum Aug 2023Bacteria have to persist under low iron conditions in order to adapt to the nutritional immunity of a host. Since the knowledge of iron stimulon of is sparse, we...
Bacteria have to persist under low iron conditions in order to adapt to the nutritional immunity of a host. Since the knowledge of iron stimulon of is sparse, we examined oral (Porphyromonas gingivalis and Prevotella intermedia) and gut (Bacteroides thataiotaomicron) representatives for their ability to adapt to iron deplete and iron replete conditions. Our transcriptomics and comparative genomics analysis show that many iron-regulated mechanisms are conserved within the phylum. They include genes upregulated in low iron, as follows: (flavodoxin), (hemin uptake operon), and loci encoding ABC transporters. Downregulated genes were (ferredoxin), (rubrerythrin), (succinate dehydrogenase/fumarate reductase), (oxoglutarate oxidoreductase/dehydrogenase), and (pyruvate:ferredoxin/flavodoxin oxidoreductase). Some genus-specific mechanisms, such as the of B. thetaiotaomicron coding for carbohydrate metabolism and the coding for xenosiderophore utilization were also identified. While all bacteria tested in our study had the operon coding for nitrite reduction and were able to reduce nitrite levels present in culture media, the expression of the operon was iron dependent only in B. thetaiotaomicron. It is noteworthy that we identified a significant overlap between regulated genes found in our study and the B. thetaiotaomicron colitis study (W. Zhu, M. G. Winter, L. Spiga, E. R. Hughes et al., Cell Host Microbe 27:376-388, 2020, http://dx.doi.org/10.1016/j.chom.2020.01.010). Many of those commonly regulated genes were also iron regulated in the oral bacterial genera. Overall, this work points to iron being the master regulator enabling bacterial persistence in the host and paves the way for a more generalized investigation of the molecular mechanisms of iron homeostasis in . are an important group of anaerobic bacteria abundant both in the oral and gut microbiomes. Although iron is a required nutrient for most living organisms, the molecular mechanisms of adaptation to the changing levels of iron are not well known in this group of bacteria. We defined the iron stimulon of by examination of the transcriptomic response of Porphyromonas gingivalis and Prevotella intermedia (both belong to the oral microbiome) and Bacteroidetes thetaiotaomicron (belongs to the gut microbiome). Our results indicate that many of the iron-regulated operons are shared among the three genera. Furthermore, using bioinformatics analysis, we identified a significant overlap between our studies and transcriptomic data derived from a colitis study, thus underscoring the biological significance of our work. Defining the iron-dependent stimulon of can help to identify the molecular mechanisms of iron-dependent regulation as well as better understand the persistence of the anaerobes in the human host.
Topics: Humans; Bacteroidetes; Ferredoxins; Flavodoxin; Nitrites; Porphyromonas gingivalis; Iron; Iron Deficiencies; Colitis; Inflammation
PubMed: 37314331
DOI: 10.1128/spectrum.04733-22 -
Journal of Oral Microbiology 2022Oral are known as anaerobic commensals on oral mucosae and in dental plaques from early life onwards, including pigmented and and non-pigmented species. Many... (Review)
Review
Oral are known as anaerobic commensals on oral mucosae and in dental plaques from early life onwards, including pigmented and and non-pigmented species. Many species contribute to oral inflammatory processes, being frequent findings in dysbiotic biofilms of periodontal diseases (), cariotic lesions ( (formerly ) ), endodontic infections (), and other clinically relevant oral conditions. Over the years, several novel species have been recovered from the oral cavity without knowledge of their clinical relevance. Within this wide genus, virulence properties and other characteristics like biofilm formation seemingly vary in a species- and strain-dependent manner, as shown for the group organisms (, and ). Oral species are identified in various non-oral infections and chronic pathological conditions. Here, we have updated the knowledge of the genus and the role of species as residents and infectious agents of the oral cavity, as well as their detection in non-oral infections, but also gathered information on their potential link to cancers of the head and neck, and other systemic disorders.
PubMed: 36393976
DOI: 10.1080/20002297.2022.2079814 -
Frontiers in Microbiology 2023Gut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of...
OBJECTIVE
Gut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of CRC-associated microbes. Multiple studies have identified gut and fecal microbiome-derived biomarkers for precursors lesions of CRC detection. However, few studies have used salivary samples to predict colorectal polyps. Therefore, in order to find new noninvasive colorectal polyp biomarkers, we searched into the differences in fecal and salivary microbiota between patients with colorectal polyps and healthy controls.
METHODS
In this case-control study, we collected salivary and fecal samples from 33 patients with colorectal polyps (CP) and 22 healthy controls (HC) between May 2021 and November 2022. All samples were sequenced using full-length 16S rRNA sequencing and compared with the Nucleotide Sequence Database. The salivary and fecal microbiota signature of colorectal polyps was established by alpha and beta diversity, Linear discriminant analysis Effect Size (LEfSe) and random forest model analysis. In addition, the possibility of microbiota in identifying colorectal polyps was assessed by Receiver Operating Characteristic Curve (ROC).
RESULTS
In comparison to the HC group, the CP group's microbial diversity increased in saliva and decreased in feces ( < 0.05), but there was no significantly difference in microbiota richness ( > 0.05). The principal coordinate analysis revealed significant differences in β-diversity of salivary and fecal microbiota between the CP and HC groups. Moreover, LEfSe analysis at the species level identified and as the major contributors to the salivary microbiota, and and to the fecal microbiota of patients with polyps. Salivary and fecal bacterial biomarkers showed Area Under ROC Curve of 0.8167 and 0.8051, respectively, which determined the potential of diagnostic markers in distinguishing patients with colorectal polyps from controls, and it increased to 0.8217 when salivary and fecal biomarkers were combined.
CONCLUSION
The composition and diversity of the salivary and fecal microbiota were significantly different in colorectal polyp patients compared to healthy controls, with an increased abundance of harmful bacteria and a decreased abundance of beneficial bacteria. A promising non-invasive tool for the detection of colorectal polyps can be provided by potential biomarkers based on the microbiota of the saliva and feces.
PubMed: 37655344
DOI: 10.3389/fmicb.2023.1182346 -
Virulence Dec 2022readily colonizes healthy dental biofilm and is associated with periodontal diseases. The viscous exopolysaccharide (EPS)-producing capability is known as a major...
readily colonizes healthy dental biofilm and is associated with periodontal diseases. The viscous exopolysaccharide (EPS)-producing capability is known as a major virulence factor of 17 (Pi17). However, the inter-strain difference in regarding virulence-associated phenotype is not well studied. We compared virulence and whole genome sequences using five wild-type strains: ATCC 49046 (Pi49046), ATCC 15032 (Pi15032), ATCC 15033 (Pi15033), ATCC 25611 (Pi25611), and Pi17. Non-EPS producing Pi25611 was the least virulent in insect and mammalian models. Unexpectedly, Pi49046 did not produce viscous EPS but was the most virulent, followed by Pi17. Genomes of the five strains were quite similar but revealed subtle differences such as copy number variations and single nucleotide polymorphisms. Variations between strains were found in genes encoding glycosyltransferases and genes involved in the acquisition of carbohydrates and iron/haem. Based on these genetic variations, further analyses were performed. Phylogenetic and structural analyses discovered phosphoglycosyltransferases of Pi49046 and Pi17 have evolved to contain additional loops that may confer substrate specificity. Pi17, Pi15032, and Pi15033 displayed increased growth by various carbohydrates. Meanwhile, Pi49046 exhibited the highest activities for haemolysis and haem accumulation, as well as co-aggregation with harbouring type II, which is more tied to periodontitis than other types. Collectively, subtle genetic differences related to glycosylation and acquisition of carbohydrates and iron/haem may contribute to the diversity of virulence and phenotypic traits among strains. These variations may also reflect versatile strategies for within-host adaptation of
Topics: Animals; Carbohydrates; DNA Copy Number Variations; Genomics; Heme; Iron; Mammals; Phylogeny; Prevotella intermedia; Virulence
PubMed: 35791444
DOI: 10.1080/21505594.2022.2095718 -
Medicina (Kaunas, Lithuania) Nov 2023: More than a billion people worldwide suffer from chronic periodontitis. The primary etiological factor of periodontal diseases is dental plaque and the bacteria it... (Review)
Review
: More than a billion people worldwide suffer from chronic periodontitis. The primary etiological factor of periodontal diseases is dental plaque and the bacteria it contains, particularly , , , , and . Zinc, owing to its antibacterial properties, can be employed in periodontology. The objective of this review was to analyze scientific literature that examines the effects of zinc on periopathogens. : A systematic review protocol of scientific literature was designed following PRISMA recommendations. Data search was conducted in PubMed, Web of Science, and ScienceDirect databases. Full-text articles in English that examine the effects of zinc on periopathogens and were published between 2011 and 2021 were included. Fifteen articles were included in the analysis based on inclusion criteria. ZnO exhibited antibacterial activity against and ( < 0.001). The minimum inhibitory concentration against was 10 μg/mL. ZnO demonstrated a significant antibacterial effect, as evidenced by inhibition zones of 15.10 mm for , 13.36 mm for , 12.98 mm for , and 14.01 mm for Zn (II)-based polymers inhibited the and genes of . Titanium dental implants coated with ZnO effectively disrupted the cell walls of and . ZnO inhibited the growth of within 2 h and the growth of and within 3 h. ZnO exhibited nontoxic effects, and concentrations up to 0.8 mg/L increased cell survival rates by up to 90%. The analysis of the literature confirms the antibacterial action of zinc against periodontal pathogenic bacteria. At low concentrations, these substances do not exhibit cytotoxic effects on fibroblasts.
Topics: Humans; Anti-Bacterial Agents; Anti-Infective Agents; Chronic Periodontitis; Organic Chemicals; Porphyromonas gingivalis; Systematic Reviews as Topic; Zinc; Zinc Oxide
PubMed: 38138191
DOI: 10.3390/medicina59122088