-
Journal of Integrative Neuroscience Aug 2023Periodontitis is one of the most common chronic inflammatory disorders in adults. Although clinical studies have suggested a causal relationship between periodontitis...
BACKGROUND
Periodontitis is one of the most common chronic inflammatory disorders in adults. Although clinical studies have suggested a causal relationship between periodontitis and major depression (MD), the biological mechanisms by which periodontitis instigates MD are unknown. We investigated whether a systemic administration of lipopolysaccharide (LPS) from (), a major Gram-negative pathogen of periodontitis, causes depressive-like behavior and glial activation in the hippocampus and the prefrontal cortex (PFC), which are MD-related brain regions.
MATERIALS AND METHODS
Eight-week-old male Sprague Dawley rats were randomly divided into a behavioral test group and an immunohistochemistry group. The rats in each group were further assigned to the sham injection (saline) and -lipopolysaccharide (-LPS) injection protocols. The rats received an intraperitoneal injection of saline or -LPS with gradually increasing doses (day 1: 0.5, day 2: 0.5, day 3: 0.75, day 4: 0.75, day 5: 1.0, day 6: 1.0, and day 7: 1.0 mg/kg of body weight) for seven consecutive days. After the systemic administration, the behavior test group underwent the forced swimming test (FST) and Y-maze test. For the immunohistochemistry group, we quantified the immunoreactivity for microglial Iba-1 (ionized calcium-binding adapter molecule 1) and astrocytic glial fibrillary acidic protein (GFAP) in the hippocampus (dentate gyrus [DG], cornu ammonis [CA1 and CA3]) and PFC (prelimbic [PrL] and the infralimbic [IL]) areas.
RESULTS
The FST immobility time in the -LPS group was significantly longer than that in the sham group. In the Y-maze test, a significant decline in spontaneous alternation behavior was observed in the -LPS group compared to the sham group. The peripheral administration of -LPS significantly increased the immunoreactivity for Iba-1 in the CA3 and PrL. -LPS injection significantly increased the immunoreactivity for GFAP in the DG, CA1, and CA3.
CONCLUSIONS
The major result of this study is that a repeated systemic administration of -LPS caused depressive-like behavior and both microglial and astrocytic activation in rats. This finding may comprise biological evidence of a causal relationship between periodontitis and MD.
Topics: Male; Rats; Animals; Rats, Sprague-Dawley; Lipopolysaccharides; Porphyromonas gingivalis; Depressive Disorder, Major; Hippocampus
PubMed: 37735127
DOI: 10.31083/j.jin2205120 -
BMC Microbiology Apr 2024Oral microbiota imbalance is associated with the progression of various lung diseases, including lung cancer. Pulmonary nodules (PNs) are often considered a critical...
BACKGROUND
Oral microbiota imbalance is associated with the progression of various lung diseases, including lung cancer. Pulmonary nodules (PNs) are often considered a critical stage for the early detection of lung cancer; however, the relationship between oral microbiota and PNs remains unknown.
METHODS
We conducted a 'Microbiome with pulmonary nodule series study 1' (MCEPN-1) where we compared PN patients and healthy controls (HCs), aiming to identify differences in oral microbiota characteristics and discover potential microbiota biomarkers for non-invasive, radiation-free PNs diagnosis and warning in the future. We performed 16 S rRNA amplicon sequencing on saliva samples from 173 PN patients and 40 HCs to compare the characteristics and functional changes in oral microbiota between the two groups. The random forest algorithm was used to identify PN salivary microbial markers. Biological functions and potential mechanisms of differential genes in saliva samples were preliminarily explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of Orthologous Groups (COG) analyses.
RESULTS
The diversity of salivary microorganisms was higher in the PN group than in the HC group. Significant differences were noted in community composition and abundance of oral microorganisms between the two groups. Neisseria, Prevotella, Haemophilus and Actinomyces, Porphyromonas, Fusobacterium, 7M7x, Granulicatella and Selenomonas were the main differential genera between the PN and HC groups. Fusobacterium, Porphyromonas, Parvimonas, Peptostreptococcus and Haemophilus constituted the optimal marker sets (area under curve, AUC = 0.80), which can distinguish between patients with PNs and HCs. Further, the salivary microbiota composition was significantly correlated with age, sex, and smoking history (P < 0.001), but not with personal history of cancer (P > 0.05). Bioinformatics analysis of differential genes showed that patients with PN showed significant enrichment in protein/molecular functions related to immune deficiency and energy metabolisms, such as the cytoskeleton protein RodZ, nicotinamide adenine dinucleotide phosphate dehydrogenase (NADPH) dehydrogenase, major facilitator superfamily transporters and AraC family transcription regulators.
CONCLUSIONS
Our study provides the first evidence that the salivary microbiota can serve as potential biomarkers for identifying PN. We observed a significant association between changes in the oral microbiota and PNs, indicating the potential of salivary microbiota as a new non-invasive biomarker for PNs.
TRIAL REGISTRATION
Clinical trial registration number: ChiCTR2200062140; Date of registration: 07/25/2022.
Topics: Humans; Saliva; RNA, Ribosomal, 16S; Microbiota; Biomarkers; Lung Neoplasms; Oxidoreductases
PubMed: 38643115
DOI: 10.1186/s12866-024-03280-x -
The Japanese Dental Science Review Dec 2023The mechanisms modulated by periodontal pathogens in atherosclerosis are not fully understood. Aim: to perform an integrative analysis of gene and protein expression... (Review)
Review
UNLABELLED
The mechanisms modulated by periodontal pathogens in atherosclerosis are not fully understood. Aim: to perform an integrative analysis of gene and protein expression modulated by periodontal pathogens in cells and animal models for atherosclerosis.
METHODS
Cochrane, PRISMA and AMSTAR2 guidelines for systematic reviews were followed. Data search was conducted in Pub-med, LILACS and Science Direct databases. Gene and protein expression data were collected from the included papers to perform an overrepresentation analysis using the Reactome Pathway Analysis tool and the KEGG database.
RESULTS
Thirty-two papers were included in the review, they analyzed the effect of , , , , , and or/and their virulent factors on gene and protein expression in human cells and animal models of atherosclerosis. Some of the modulated pathways include the immune system, programmed cell death, cellular responses to external stimuli, transport of small molecules, and signal transduction (p < 0.05). Those pathways are known to be involved in different stages of atherosclerosis progression.
CONCLUSION
Based on the performed analysis, it is possible to state that periodontal pathogens have the potential to be a contributing factor for atherosclerosis even in absence of a high-fat diet or high shear stress.
PubMed: 36654677
DOI: 10.1016/j.jdsr.2022.12.001 -
Frontiers in Immunology 2024There exists a bidirectional relationship between oral health and general well-being, with an imbalance in oral symbiotic flora posing a threat to overall human health.... (Review)
Review
There exists a bidirectional relationship between oral health and general well-being, with an imbalance in oral symbiotic flora posing a threat to overall human health. Disruptions in the commensal flora can lead to oral diseases, while systemic illnesses can also impact the oral cavity, resulting in the development of oral diseases and disorders. and , known as pathogenic bacteria associated with periodontitis, play a crucial role in linking periodontitis to accompanying systemic diseases. In periodontal tissues, these bacteria, along with their virulence factors, can excessively activate the host immune system through local diffusion, lymphatic circulation, and blood transmission. This immune response disruption contributes to an imbalance in osteoimmune mechanisms, alveolar bone resorption, and potential systemic inflammation. To restore local homeostasis, a deeper understanding of microbiota-host interactions and the immune network phenotype in local tissues is imperative. Defining the immune network phenotype in periodontal tissues offers a promising avenue for investigating the complex characteristics of oral plaque biofilms and exploring the potential relationship between periodontitis and associated systemic diseases. This review aims to provide an overview of the mechanisms underlying - and -induced alveolar bone resorption, as well as the immunophenotypes observed in host periodontal tissues during pathological conditions.
Topics: Humans; Periodontitis; Alveolar Bone Loss; Porphyromonas gingivalis; Inflammation; Fusobacterium nucleatum
PubMed: 38455060
DOI: 10.3389/fimmu.2024.1254516 -
Journal of Oral Microbiology 2023Acute pancreatitis (AP) is a common abdomen clinical emergency. Most APs have mild clinical symptoms and a good prognosis. However, about 20% of patients develop severe...
Acute pancreatitis (AP) is a common abdomen clinical emergency. Most APs have mild clinical symptoms and a good prognosis. However, about 20% of patients develop severe acute pancreatitis (SAP), increasing morbidity and mortality. The microbiome's impact on AP pathophysiology has received increasing attention. Hence, to explore changes in oral microbial composition in acute pancreatitis, we collected clinical information and oral saliva samples from 136 adult participants: 47 healthy controls, 43 acute mild AP (MAP), 29 moderate AP (MSAP), and 17 severe AP (SAP). Using 16S rRNA gene sequencing, 663,175 high-quality sequences were identified. The relative abundance and diversity of oral microorganisms in AP patients increased, with decreased beneficial bacteria such as , , and , and increased , and in the AP group. Further changes in microbial composition occurred with increasing disease severity, including a decreased abundance of beneficial bacteria such as , and in MSAP and SAP compared to MAP. Moreover, the Lefse analysis showed that , and were better microbial markers for AP. Therefore, oral microbiome changes could distinguish AP from healthy individuals and serve as an early novel predictor of disease severity in AP patients.
PubMed: 37808891
DOI: 10.1080/20002297.2023.2264619 -
Life (Basel, Switzerland) Nov 2023Alzheimer's disease (AD) has become one of the leading causes of health problems in the elderly, and studying its causes and treatments remains a serious challenge for... (Review)
Review
Alzheimer's disease (AD) has become one of the leading causes of health problems in the elderly, and studying its causes and treatments remains a serious challenge for researchers worldwide. The two main pathological features of Alzheimer's disease are the extracellular deposition of β-amyloid (Aβ) to form senile plaques and the intracellular aggregation of hyperphosphorylated Tau protein to form neurofibrillary tangles (NFTs). Researchers have proposed several hypotheses to elucidate the pathogenesis of AD, but due to the complexity of the pathophysiologic factors involved in the development of AD, no effective drugs have been found to stop the progression of the disease. Currently, the mainstay drugs used to treat AD can only alleviate the patient's symptoms and do not have a therapeutic effect. As researchers explore interactions among diseases, much evidence suggests that there is a close link between periodontitis and AD, and that periodontal pathogenic bacteria can exacerbate Aβ deposition and Tau protein hyperphosphorylation through neuroinflammatory mechanisms, thereby advancing the pathogenesis of AD. This article reviews recent advances in the pathogenesis of AD, available therapeutic agents, the relevance of periodontitis to AD, and mechanisms of action.
PubMed: 38004343
DOI: 10.3390/life13112203 -
Scientific Reports Jul 2023The Arg-specific gingipains of Porphyromonas gingivalis RgpA and RgpB have 97% identical sequences in their catalytic domains yet their propeptides are only 76%...
The Arg-specific gingipains of Porphyromonas gingivalis RgpA and RgpB have 97% identical sequences in their catalytic domains yet their propeptides are only 76% identical. RgpA isolates as a proteinase-adhesin complex (HRgpA) which hinders direct kinetic comparison of RgpA as a monomer with monomeric RgpB. We tested modifications of rgpA identifying a variant that enabled us to isolate histidine-tagged monomeric RgpA (rRgpAH). Kinetic comparisons between rRgpAH and RgpB used benzoyl-L-Arg-4-nitroanilide with and without cysteine and glycylglycine acceptor molecules. With no glycylglycine, values of K, V, k and k/K for each enzyme were similar, but with glycylglycine K decreased, V increased and k increased ~ twofold for RgpB but ~ sixfold for rRgpAH. The k/K for rRgpAH was unchanged whereas that of RgpB more than halved. Recombinant RgpA propeptide inhibited rRgpAH and RgpB with K 13 nM and 15 nM K respectively slightly more effectively than RgpB propeptide which inhibited rRgpAH and RgpB with K 22 nM and 29 nM respectively (p < 0.0001); a result that may be attributable to the divergent propeptide sequences. Overall, the data for rRgpAH reflected observations previously made by others using HRgpA, indicating rRgpAH fidelity and confirming the first production and isolation of functional affinity tagged RgpA.
Topics: Gingipain Cysteine Endopeptidases; Cysteine Endopeptidases; Peptide Hydrolases; Adhesins, Bacterial; Catalytic Domain; Porphyromonas gingivalis; Hemagglutinins
PubMed: 37402780
DOI: 10.1038/s41598-023-37534-x -
Bioactive Materials Feb 2024Cementum, a thin layer of mineralized tissue covering tooth root surface, is recognized as the golden standard in periodontal regeneration. However, current efforts...
Cementum, a thin layer of mineralized tissue covering tooth root surface, is recognized as the golden standard in periodontal regeneration. However, current efforts mainly focus on alveolar bone regeneration rather than cementum regeneration, and rarely take (Pg), the keystone pathogen responsible for periodontal tissue destruction, into consideration. Though M2 macrophage-derived exosomes (M2-EXO) show promise in tissue regeneration, the exosome-producing M2 macrophages are induced by exogenous cytokines with transitory and unstable effects, restricting the regeneration potential of M2-EXO. Here, exosomes derived from genetically engineered M2-like macrophages are constructed by silencing of casein kinase 2 interacting protein-1 (Ckip-1), a versatile player involved in various biological processes. Ckip-1 silencing is proved to be an effective gene regulation strategy to obtain permanent M2-like macrophages with mineralization-promoting effect. Further, exosomes derived from Ckip-1-silenced macrophages (sh-Ckip-1-EXO) rescue Pg-suppressed cementoblast mineralization and cementogenesis. Mechanismly, sh-Ckip-1-EXO delivers targeting and silencing Ckip-1, a negative regulator also for cementum formation and cementoblast mineralization. More deeply, downregulation of Ckip-1 in cementoblasts by exosomal activates PGC-1α-dependent mitochondrial biogenesis. In all, this study provides a new strategy of genetically engineered M2-like macrophage-derived exosomes for cementum regeneration under Pg-dominated inflammation.
PubMed: 37965240
DOI: 10.1016/j.bioactmat.2023.10.009 -
Molecular Medicine Reports Mar 2024Periodontitis is a common chronic inflammatory and destructive disease in the mouth and is considered to be associated with systemic diseases. Accumulating evidence has... (Review)
Review
Periodontitis is a common chronic inflammatory and destructive disease in the mouth and is considered to be associated with systemic diseases. Accumulating evidence has suggested that periodontitis is a risk factor for pulmonary diseases such as pneumonia, chronic obstructive pulmonary disease (COPD), asthma, coronavirus disease 2019 (COVID‑19) and lung cancer. The presence of common periodontal pathogens has been detected in samples from a variety of pulmonary diseases. Periodontal pathogens can be involved in lung diseases by promoting the adhesion and invasion of respiratory pathogens, regulating the apoptosis of respiratory epithelium and inducing overexpression of mucin and disrupting the balance of immune systemin respiratory epithelium cells. Additionally, measures to control plaque and maintain the health of periodontal tissue can decrease the incidence of respiratory adverse events. This evidence suggests a close association between periodontitis and pulmonary diseases. The present study aimed to review the clinical association between periodontitis and pneumonia, COPD, asthma, COVID‑19 and lung cancer, and propose a possible mechanism and potential role of periodontal pathogens in linking periodontal disease and lung disease. This could provide a direction for further research on the association between periodontitis and lung disease and provide novel ideas for the clinical diagnosis and treatment management of these two diseases.
Topics: Humans; Asthma; COVID-19; Fusobacterium nucleatum; Lung Neoplasms; Periodontitis; Pneumonia; Porphyromonas gingivalis; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases
PubMed: 38240101
DOI: 10.3892/mmr.2024.13166 -
Frontiers in Cardiovascular Medicine 2023Periodontitis (PD) and cardiovascular diseases (CVD) rank among the most prevalent pathologies worldwide, and their correlation has been a subject of prolonged...
BACKGROUND
Periodontitis (PD) and cardiovascular diseases (CVD) rank among the most prevalent pathologies worldwide, and their correlation has been a subject of prolonged investigation. Numerous studies suggest shared etiological factors; however, a definitive causal connection remains unestablished. The objective of this study was to employ bibliometric and visual analyses in order to comprehensively examine the overarching characteristics, focal areas of research, and prospective trends pertaining to the PD-CVD relationship.
METHODS
We sourced articles, reviews, and online publications on PD- and CVD- research from the Web of Science Core Collection (WoSCC) spanning from January 1, 1993, to May 15, 2023. A triad of analytical tools (R-Bibliometrix, VOSviewer 1.6.19, and CiteSpace 6.2.R3) were utilized to facilitate collaboration network analysis, co-citation analysis, co-occurrence analysis, and citation burst detection.
RESULTS
Out of the 1,116 publications that fulfilled the eligibility criteria in the WoSCC database, the comprehensive characteristics analysis divulged a sustained growth trend in publication frequency. In the cluster analysis of reference co-citation and keyword co-occurrence, prominent themes such as "periodontitis", "cardiovascular diseases", "inflammation", "", and "atherosclerosis" consistently emerged. Contemporary topics such as "peri-implantitis," "COVID-19", "cardiovascular risk factors," and "endocarditis" were pinpointed as burgeoning research hotspots.
CONCLUSION
Based on this bibliometric study, in the field of association studies between PD and CVD, the etiologic mechanisms of both diseases have been intensively studied in the last three decades. Periodontal pathogens might serve as potential initiating factors linking PD and CVD. Inflammation may constitute a significant etiological factor shared by both diseases. Several emerging topics, such as COVID-19 and peri-implantitis, exhibit promising potential. This exhaustive overview casts light on pivotal research arenas, augmenting the field's understanding and stimulating further scholarly investigations.
PubMed: 37745126
DOI: 10.3389/fcvm.2023.1255722