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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 -
Microbiome Apr 2018Alterations of gut microbiota are associated with colorectal cancer (CRC) in different populations and several bacterial species were found to contribute to the...
BACKGROUND
Alterations of gut microbiota are associated with colorectal cancer (CRC) in different populations and several bacterial species were found to contribute to the tumorigenesis. The potential use of gut microbes as markers for early diagnosis has also been reported. However, cohort specific noises may distort the structure of microbial dysbiosis in CRC and lead to inconsistent results among studies. In this regard, our study targeted at exploring changes in gut microbiota that are universal across populations at species level.
RESULTS
Based on the combined analysis of 526 metagenomic samples from Chinese, Austrian, American, and German and French cohorts, seven CRC-enriched bacteria (Bacteroides fragilis, Fusobacterium nucleatum, Porphyromonas asaccharolytica, Parvimonas micra, Prevotella intermedia, Alistipes finegoldii, and Thermanaerovibrio acidaminovorans) have been identified across populations. The seven enriched bacterial markers classified cases from controls with an area under the receiver-operating characteristics curve (AUC) of 0.80 across the different populations. Abundance correlation analysis demonstrated that CRC-enriched and CRC-depleted bacteria respectively formed their own mutualistic networks, in which the latter was disjointed in CRC. The CRC-enriched bacteria have been found to be correlated with lipopolysaccharide and energy biosynthetic pathways.
CONCLUSIONS
Our study identified potential diagnostic bacterial markers that are robust across populations, indicating their potential universal use for non-invasive CRC diagnosis. We also elucidated the ecological networks and functional capacities of CRC-associated microbiota.
Topics: Aged; Bacteria; Cell Transformation, Neoplastic; Colorectal Neoplasms; Computational Biology; Female; Gastrointestinal Microbiome; Gene Ontology; Humans; Male; Metagenome; Metagenomics; Middle Aged
PubMed: 29642940
DOI: 10.1186/s40168-018-0451-2 -
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 -
Gut May 2017To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet.
OBJECTIVE
To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet.
DESIGN
We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like (), and . The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system.
RESULTS
Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated prior to the periodontal infection induced specific antibodies against and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from mimicked the impact of periodontitis on immune and metabolic parameters.
CONCLUSIONS
We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis.
Topics: Adaptive Immunity; Animals; Bacteroidaceae Infections; Cell Transplantation; Diet, High-Fat; Disease Models, Animal; Dysbiosis; Female; Gingiva; Hyperglycemia; Insulin Resistance; Interferon-gamma; Interleukin-6; Lipopolysaccharides; Lymph Nodes; Lymphocytes; Mice; Mice, Inbred C57BL; Microbiota; Periodontitis; Porphyromonas gingivalis; Random Allocation; Spleen; Vaccination
PubMed: 26838600
DOI: 10.1136/gutjnl-2015-309897 -
Virulence 2015As our knowledge of host-microbial interactions within the oral cavity increases, future treatments are likely to be more targeted. For example, efforts to target a... (Review)
Review
As our knowledge of host-microbial interactions within the oral cavity increases, future treatments are likely to be more targeted. For example, efforts to target a single species or key virulence factors that they produce, while maintaining the natural balance of the resident oral microbiota that acts to modulate the host immune response would be an advantage. Targeted approaches may be directed at the black-pigmented anaerobes, Porphyromonas gingivalis and Prevotella intermedia, associated with periodontitis. Such pigments provide an opportunity for targeted phototherapy with high-intensity monochromatic light. Functional inhibition approaches, including the use of enzyme inhibitors, are also being explored to control periodontitis. More general disruption of dental plaque through the use of enzymes and detergents, alone and in combination, shows much promise. The use of probiotics and prebiotics to improve gastrointestinal health has now led to an interest in using these approaches to control oral disease. More recently the potential of antimicrobial peptides and nanotechnology, through the application of nanoparticles with biocidal, anti-adhesive and delivery capabilities, has been explored. The aim of this review is to consider the current status as regards non-conventional treatment approaches for oral infections with particular emphasis on the plaque-related diseases.
Topics: Animals; Bacteria, Anaerobic; Dental Plaque; Detergents; Glycoside Hydrolases; Humans; Mouth; Nanoparticles; Periodontitis; Phototherapy; Porphyromonas gingivalis; Prebiotics; Prevotella intermedia; Probiotics; Protease Inhibitors
PubMed: 25668296
DOI: 10.4161/21505594.2014.983783 -
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 -
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