Giacomo Baima, Shareef Dabdoub, Vivek Thumbigere-Math, Davide Giuseppe Ribaldone, Gian Paolo Caviglia, Leonardo Tenori, Linda Fantato, Alessia Vignoli, Mario Romandini, Ilario Ferrocino, Mario Aimetti
Aim: To characterize the impact of periodontitis and of Steps I-II of periodontal therapy on microbiome composition, function, and metabolic output across the oral and gut environments.
Methods: A multi-omics analysis was performed on saliva and stool samples collected from 50 systemically healthy individuals with and without Stage III-IV periodontitis. For participants with periodontitis, samples were analyzed both at baseline and 3 months after Steps I-II of periodontal therapy. High-throughput whole metagenome sequencing was used to profile microbial taxa and functional genes, NMR-based metabolomics profiled host-microbial metabolites. Single-omic differential abundance analysis between healthy samples and periodontitis samples was performed with MaAsLin2, while analysis between pre- and post-treatment was conducted with timeOmics. Variable selection and subsequent supervised multivariate analysis to determine group-separating markers utilized multi-level sparse Partial Least Squares Discriminant Analysis (sPLS-DA) through mixOmics. KEGG pathway enrichment was analyzed using clusterProfiler, whereas multi-omic data integration was performed with multi-block Partial Least Squares regression analysis.
Results: Periodontitis was associated with significant compositional and functional changes in both saliva and stool, with increased abundance of pathobionts and loss of health-associated taxa in both niches. A subset of species was shared across oral and gut habitats, with detectable differences across clinical groups. As functional potential, periodontitis enriched microbial pro-inflammatory pathways (lipopolysaccharide biosynthesis, bacterial motility) and depleted beneficial short-chain fatty acid (SCFA)- and vitamin-producing functions. Metabolomic profiles revealed reduced SCFAs and amino acids in periodontitis, with elevated pro-inflammatory metabolites (succinate, trimethylamine) in both saliva and stool. Following therapy, microbial communities and their metabolic output partially reverted toward health-associated profiles, particularly in saliva. Stool samples showed subtler but consistent shifts, including a decrease in some typically oral species and decreased succinate and methylamine and restoration of amino acid and SCFA-related metabolites.
Conclusions: Periodontitis is associated with coordinated microbial and metabolic signatures across the oral and gut environments. Non-surgical periodontal therapy promotes partial ecological restoration in both niches, supporting the view of oral health as a modifiable target for influencing systemic microbial homeostasis.
{"title":"Multi-Omics Signatures of Periodontitis and Periodontal Therapy on the Oral and Gut Microbiome.","authors":"Giacomo Baima, Shareef Dabdoub, Vivek Thumbigere-Math, Davide Giuseppe Ribaldone, Gian Paolo Caviglia, Leonardo Tenori, Linda Fantato, Alessia Vignoli, Mario Romandini, Ilario Ferrocino, Mario Aimetti","doi":"10.1111/jre.70055","DOIUrl":"https://doi.org/10.1111/jre.70055","url":null,"abstract":"<p><strong>Aim: </strong>To characterize the impact of periodontitis and of Steps I-II of periodontal therapy on microbiome composition, function, and metabolic output across the oral and gut environments.</p><p><strong>Methods: </strong>A multi-omics analysis was performed on saliva and stool samples collected from 50 systemically healthy individuals with and without Stage III-IV periodontitis. For participants with periodontitis, samples were analyzed both at baseline and 3 months after Steps I-II of periodontal therapy. High-throughput whole metagenome sequencing was used to profile microbial taxa and functional genes, NMR-based metabolomics profiled host-microbial metabolites. Single-omic differential abundance analysis between healthy samples and periodontitis samples was performed with MaAsLin2, while analysis between pre- and post-treatment was conducted with timeOmics. Variable selection and subsequent supervised multivariate analysis to determine group-separating markers utilized multi-level sparse Partial Least Squares Discriminant Analysis (sPLS-DA) through mixOmics. KEGG pathway enrichment was analyzed using clusterProfiler, whereas multi-omic data integration was performed with multi-block Partial Least Squares regression analysis.</p><p><strong>Results: </strong>Periodontitis was associated with significant compositional and functional changes in both saliva and stool, with increased abundance of pathobionts and loss of health-associated taxa in both niches. A subset of species was shared across oral and gut habitats, with detectable differences across clinical groups. As functional potential, periodontitis enriched microbial pro-inflammatory pathways (lipopolysaccharide biosynthesis, bacterial motility) and depleted beneficial short-chain fatty acid (SCFA)- and vitamin-producing functions. Metabolomic profiles revealed reduced SCFAs and amino acids in periodontitis, with elevated pro-inflammatory metabolites (succinate, trimethylamine) in both saliva and stool. Following therapy, microbial communities and their metabolic output partially reverted toward health-associated profiles, particularly in saliva. Stool samples showed subtler but consistent shifts, including a decrease in some typically oral species and decreased succinate and methylamine and restoration of amino acid and SCFA-related metabolites.</p><p><strong>Conclusions: </strong>Periodontitis is associated with coordinated microbial and metabolic signatures across the oral and gut environments. Non-surgical periodontal therapy promotes partial ecological restoration in both niches, supporting the view of oral health as a modifiable target for influencing systemic microbial homeostasis.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identification number: NCT04826926.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Rong Hao Tay, Ashish C Kalhan, Upul Cooray, Gustavo G Nascimento
Aim: To examine the impact of emulated natural tooth preservation or dental rehabilitation scenarios on diet quality among older adults in the United States, assessing what diet quality would be if people's dentition or rehabilitation status were improved.
Methods: Data from 2606 participants aged ≥ 60 across four NHANES cycles (2011-2018) were analyzed. Dentition status and prosthetic rehabilitation were clinically assessed, and diet quality was measured using the Healthy Eating Index (HEI)-2020. The modified treatment policies (MTP) framework was used to emulate hypothetical interventions of retaining natural teeth or providing prosthetic rehabilitation. Odds ratios (OR) for achieving better diet quality under each scenario were estimated using doubly robust targeted maximum likelihood estimation (TMLE).
Results: If all participants retained ≥ 25 teeth, the likelihood of achieving better HEI scores increased by 51% (OR = 1.51, 95% CI: 1.32-1.69). In a pragmatic scenario where each dentition group was shifted up by one level (edentulous → 1-9 teeth, 1-9 teeth → 10-19 teeth, 10-19 teeth → 20-25 teeth, 1-9 teeth → ≥ 25 teeth), the population had a 20% higher likelihood of achieving better diet quality (OR = 1.22, 95% CI: 1.14-1.29). Prosthetic rehabilitation yielded comparatively smaller effects, with rehabilitation in individuals with < 25 teeth improving the likelihood of better diet quality by 8% (OR = 1.08, 95% CI: 1.03-1.12).
Conclusion: The present observational study suggests that preserving natural teeth has a stronger population-level impact on diet quality than prosthetic rehabilitation replacing missing teeth in older adults.
{"title":"Impact of Tooth Preservation or Replacement on Diet Quality: Modified Treatment Policies Approach.","authors":"John Rong Hao Tay, Ashish C Kalhan, Upul Cooray, Gustavo G Nascimento","doi":"10.1111/jre.70053","DOIUrl":"https://doi.org/10.1111/jre.70053","url":null,"abstract":"<p><strong>Aim: </strong>To examine the impact of emulated natural tooth preservation or dental rehabilitation scenarios on diet quality among older adults in the United States, assessing what diet quality would be if people's dentition or rehabilitation status were improved.</p><p><strong>Methods: </strong>Data from 2606 participants aged ≥ 60 across four NHANES cycles (2011-2018) were analyzed. Dentition status and prosthetic rehabilitation were clinically assessed, and diet quality was measured using the Healthy Eating Index (HEI)-2020. The modified treatment policies (MTP) framework was used to emulate hypothetical interventions of retaining natural teeth or providing prosthetic rehabilitation. Odds ratios (OR) for achieving better diet quality under each scenario were estimated using doubly robust targeted maximum likelihood estimation (TMLE).</p><p><strong>Results: </strong>If all participants retained ≥ 25 teeth, the likelihood of achieving better HEI scores increased by 51% (OR = 1.51, 95% CI: 1.32-1.69). In a pragmatic scenario where each dentition group was shifted up by one level (edentulous → 1-9 teeth, 1-9 teeth → 10-19 teeth, 10-19 teeth → 20-25 teeth, 1-9 teeth → ≥ 25 teeth), the population had a 20% higher likelihood of achieving better diet quality (OR = 1.22, 95% CI: 1.14-1.29). Prosthetic rehabilitation yielded comparatively smaller effects, with rehabilitation in individuals with < 25 teeth improving the likelihood of better diet quality by 8% (OR = 1.08, 95% CI: 1.03-1.12).</p><p><strong>Conclusion: </strong>The present observational study suggests that preserving natural teeth has a stronger population-level impact on diet quality than prosthetic rehabilitation replacing missing teeth in older adults.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Isabel Moreira, Tiago Caetano, Francisco Correia, Honorato Ribeiro-Vidal, Ricardo Faria Almeida
This RCT offers a nuanced understanding of nonsurgical peri-implantitis management (air polishing with erythritol versus ultrasonic instrumentation, in combination with systemic metronidazole), integrating both clinical and patient-centered outcomes. The results showed that the ultrasonic instrumentation reduced probing depth and bleeding on probing, throughout the 12-month period.
{"title":"Air-Polishing Versus Ultrasonic Instrumentation for Nonsurgical Treatment of Peri-Implantitis: A Randomized Clinical Trial.","authors":"Ana Isabel Moreira, Tiago Caetano, Francisco Correia, Honorato Ribeiro-Vidal, Ricardo Faria Almeida","doi":"10.1111/jre.70054","DOIUrl":"10.1111/jre.70054","url":null,"abstract":"<p><p>This RCT offers a nuanced understanding of nonsurgical peri-implantitis management (air polishing with erythritol versus ultrasonic instrumentation, in combination with systemic metronidazole), integrating both clinical and patient-centered outcomes. The results showed that the ultrasonic instrumentation reduced probing depth and bleeding on probing, throughout the 12-month period.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145541198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>The introduction and recognition of the domain of “Periodontal Medicine” can be regarded as one of the greatest paradigm shifts in the realm of periodontology. The explosion of journal articles in the last four decades on the links between periodontitis, systemic diseases, systemic consequences and related pathophysiological pathways, is overwhelming to date. Also, the number of scientific articles on periodontal medicine related subjects published in medical and non-dental journals has increased importantly in the same period. We have come to the point that the traditional separation between medicine and dentistry is fading where the obvious interrelationship between mouth and body is gaining momentum beyond doubt. We can consider periodontitis now a medical condition in its own right [<span>1</span>]. At the occasion of the 60th anniversary of the Journal of Periodontal Research, we present here a short perspective on the past, the present, the future of periodontal medicine.</p><p>At the beginning of the 20th century, the doctrine of ‘focal infection’ promoted the belief that oral infections were the root cause of many systemic diseases, to the extent that extracting all teeth was often recommended as a preventive measure [<span>2, 3</span>]. In the decades that followed, this concept was largely abandoned, and oral diseases came to be regarded as disconnected from the rest of the body. It was not until the 1980s and 1990s, that this assumption of disconnection was convincingly refuted. In short, the scientific evolution of understanding much better biological and pathophysiological concepts, the understanding that all organs and bodily tissues are interconnected, as well as clearly common sense, made the focal infection theory untenable. The scientific world began to rely to a much larger extent on modern evidence-based frameworks rather than observational research. Biostatistics became an important scientific aspect in our scientific publications. The fields of epidemiology, microbiology, immunology and the understanding of systemic inflammation (e.g., in atherosclerotic cardiovascular diseases [ACVD]), underwent methodological revolutions that enabled the redefinition of the field. Thus first, several European studies demonstrated that periodontitis and poor oral health could be associated with ACVD [<span>4, 5</span>]. In 1996, Steven Offenbacher introduced the term “periodontal medicine” [<span>6</span>], signifying the need to view the mouth as an integral part of systemic health. Offenbacher and colleagues suggested that periodontitis should be considered alongside other major noncommunicable diseases such as diabetes mellitus, rheumatoid arthritis, Crohn's disease and ACVD. A well-remembered symposium in 1997 in Chapel Hill, North Carolina, USA, further consolidated the concept of periodontal medicine. It provided greater clarity on the associations between periodontitis and multiple systemic conditions, including diabetes mellitus
{"title":"Periodontal Medicine: The Past, the Present, the Future","authors":"Bruno G. Loos, Magda Feres","doi":"10.1111/jre.70052","DOIUrl":"10.1111/jre.70052","url":null,"abstract":"<p>The introduction and recognition of the domain of “Periodontal Medicine” can be regarded as one of the greatest paradigm shifts in the realm of periodontology. The explosion of journal articles in the last four decades on the links between periodontitis, systemic diseases, systemic consequences and related pathophysiological pathways, is overwhelming to date. Also, the number of scientific articles on periodontal medicine related subjects published in medical and non-dental journals has increased importantly in the same period. We have come to the point that the traditional separation between medicine and dentistry is fading where the obvious interrelationship between mouth and body is gaining momentum beyond doubt. We can consider periodontitis now a medical condition in its own right [<span>1</span>]. At the occasion of the 60th anniversary of the Journal of Periodontal Research, we present here a short perspective on the past, the present, the future of periodontal medicine.</p><p>At the beginning of the 20th century, the doctrine of ‘focal infection’ promoted the belief that oral infections were the root cause of many systemic diseases, to the extent that extracting all teeth was often recommended as a preventive measure [<span>2, 3</span>]. In the decades that followed, this concept was largely abandoned, and oral diseases came to be regarded as disconnected from the rest of the body. It was not until the 1980s and 1990s, that this assumption of disconnection was convincingly refuted. In short, the scientific evolution of understanding much better biological and pathophysiological concepts, the understanding that all organs and bodily tissues are interconnected, as well as clearly common sense, made the focal infection theory untenable. The scientific world began to rely to a much larger extent on modern evidence-based frameworks rather than observational research. Biostatistics became an important scientific aspect in our scientific publications. The fields of epidemiology, microbiology, immunology and the understanding of systemic inflammation (e.g., in atherosclerotic cardiovascular diseases [ACVD]), underwent methodological revolutions that enabled the redefinition of the field. Thus first, several European studies demonstrated that periodontitis and poor oral health could be associated with ACVD [<span>4, 5</span>]. In 1996, Steven Offenbacher introduced the term “periodontal medicine” [<span>6</span>], signifying the need to view the mouth as an integral part of systemic health. Offenbacher and colleagues suggested that periodontitis should be considered alongside other major noncommunicable diseases such as diabetes mellitus, rheumatoid arthritis, Crohn's disease and ACVD. A well-remembered symposium in 1997 in Chapel Hill, North Carolina, USA, further consolidated the concept of periodontal medicine. It provided greater clarity on the associations between periodontitis and multiple systemic conditions, including diabetes mellitus ","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":"60 10","pages":"943-946"},"PeriodicalIF":3.4,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jre.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlo Galli, Chiara Moretti, Elena Calciolari, Nikolaos Donos
While periodontitis is globally recognized as a significant public health problem, its common definition as a plaque-based inflammatory condition is incomplete. Disease progression, personal experience, and treatment are shaped by social, economic, and structural forces largely invisible in clinical practice and policy. A lens from medical anthropology helps us see periodontitis as more than a clinical diagnosis; it is a lived experience, deeply entangled with a person's social world. The physical reality of inflammation translates into profound emotional distress-from the shame and stigma of bleeding gums and gingival recession to the tangible fear of tooth loss. This personal suffering is often intensified by a societal focus on individual blame, which masks systemic barriers like poor insurance coverage and the simple lack of local care. Ultimately, the cultural language and assumptions surrounding oral health-what anthropologists term explanatory models and semantic networks-powerfully influence everything from a patient's decisions to the public's perception of the disease itself. We argue for a more culturally attuned approach to periodontal health-one that prioritizes prevention, centers the patient's lived experience, and confronts the systemic roots of oral health inequities. By integrating the insights of anthropology with the science of periodontics, we believe we can build a more complete model of care that leads to equitable health outcomes, creating policies and practices that acknowledge both microbial causes and patients' lived realities.
{"title":"From Disease to Illness: Reframing Periodontitis Through an Anthropological Lens.","authors":"Carlo Galli, Chiara Moretti, Elena Calciolari, Nikolaos Donos","doi":"10.1111/jre.70051","DOIUrl":"https://doi.org/10.1111/jre.70051","url":null,"abstract":"<p><p>While periodontitis is globally recognized as a significant public health problem, its common definition as a plaque-based inflammatory condition is incomplete. Disease progression, personal experience, and treatment are shaped by social, economic, and structural forces largely invisible in clinical practice and policy. A lens from medical anthropology helps us see periodontitis as more than a clinical diagnosis; it is a lived experience, deeply entangled with a person's social world. The physical reality of inflammation translates into profound emotional distress-from the shame and stigma of bleeding gums and gingival recession to the tangible fear of tooth loss. This personal suffering is often intensified by a societal focus on individual blame, which masks systemic barriers like poor insurance coverage and the simple lack of local care. Ultimately, the cultural language and assumptions surrounding oral health-what anthropologists term explanatory models and semantic networks-powerfully influence everything from a patient's decisions to the public's perception of the disease itself. We argue for a more culturally attuned approach to periodontal health-one that prioritizes prevention, centers the patient's lived experience, and confronts the systemic roots of oral health inequities. By integrating the insights of anthropology with the science of periodontics, we believe we can build a more complete model of care that leads to equitable health outcomes, creating policies and practices that acknowledge both microbial causes and patients' lived realities.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-07-19DOI: 10.1111/jre.70019
Nahrain Warda, Ryan Noh, J E Davies
A pre-clinical rabbit study shows peri-implant tissue contains mono- and multinucleate tartrate-resistant acid phosphatase (TRAP) + cells and a plethora of punctate extracellular TRAP staining. The latter provides a putative extracellular vesicular trafficking mechanism by which these cells drive early osseointegration.
{"title":"Tartrate-Resistant Acid Phosphatase-Positive Cells: Putative Mediators of Peri-Implant Bone Healing.","authors":"Nahrain Warda, Ryan Noh, J E Davies","doi":"10.1111/jre.70019","DOIUrl":"10.1111/jre.70019","url":null,"abstract":"<p><p>A pre-clinical rabbit study shows peri-implant tissue contains mono- and multinucleate tartrate-resistant acid phosphatase (TRAP) + cells and a plethora of punctate extracellular TRAP staining. The latter provides a putative extracellular vesicular trafficking mechanism by which these cells drive early osseointegration.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":"60 11","pages":"1171-1173"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2024-12-12DOI: 10.1111/jre.13372
Jiayi Liu, Haoyang Tian, Jinhong Ju, Fujiao Nie, Qiuyue Yin, Jingjing Zhao, Suli Wang, Hongmei Guo, Pishan Yang
Aim: To investigate whether trained immunity occurs in gingival fibroblasts (GFs) and its relationship to the persistence of inflammation in periodontitis.
Methods: Periodontally healthy and inflammatory gingival fibroblasts (HGFs and IGFs) were cultured through continuous adherence subculture of tissue blocks. Trained immunity in HGFs was evaluated via a classic in vitro model, with relevant markers assessed via enzyme-linked immunosorbent assay, lactate content assay, glycolytic rate assay, and chromatin immunoprecipitation. A histone methyltransferase blocker and a PI3K inhibitor were added to investigate the mechanisms underlying trained immunity. The relationship between trained immunity and periodontitis was further examined via immunofluorescence staining and chromatin immunoprecipitation on IGFs.
Results: Compared with untrained cells, GFs trained with Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS) exhibited a significant increase in IL-6 and TNF-α secretion, enhanced glycolytic metabolism, and enriched mono-methylation of lysine 4 on histone H3 (H3K4me1) at the enhancer regions of TNF-α and IL-6. The addition of a histone methyltransferase blocker and a PI3K inhibitor greatly reduced trained immunity. Additionally, the response of IGFs to P. gingivalis-LPS stimulation and their epigenetic modifications were similar to those observed in trained HGFs.
Conclusion: This study novelly discovered that both P. gingivalis-LPS-stimulated HGFs and IGFs in periodontitis acquired trained immunity. Following P. gingivalis-LPS stimulation, HGFs underwent metabolic and epigenetic changes via the PI3K/AKT pathway, with these epigenetic changes also observed in IGFs. This finding suggests that trained immunity in GFs may be a key mechanism underlying the recurrence and persistence of periodontitis.
{"title":"Porphyromonas gingivalis-Lipopolysaccharide Induced Gingival Fibroblasts Trained Immunity Sustains Inflammation in Periodontitis.","authors":"Jiayi Liu, Haoyang Tian, Jinhong Ju, Fujiao Nie, Qiuyue Yin, Jingjing Zhao, Suli Wang, Hongmei Guo, Pishan Yang","doi":"10.1111/jre.13372","DOIUrl":"10.1111/jre.13372","url":null,"abstract":"<p><strong>Aim: </strong>To investigate whether trained immunity occurs in gingival fibroblasts (GFs) and its relationship to the persistence of inflammation in periodontitis.</p><p><strong>Methods: </strong>Periodontally healthy and inflammatory gingival fibroblasts (HGFs and IGFs) were cultured through continuous adherence subculture of tissue blocks. Trained immunity in HGFs was evaluated via a classic in vitro model, with relevant markers assessed via enzyme-linked immunosorbent assay, lactate content assay, glycolytic rate assay, and chromatin immunoprecipitation. A histone methyltransferase blocker and a PI3K inhibitor were added to investigate the mechanisms underlying trained immunity. The relationship between trained immunity and periodontitis was further examined via immunofluorescence staining and chromatin immunoprecipitation on IGFs.</p><p><strong>Results: </strong>Compared with untrained cells, GFs trained with Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS) exhibited a significant increase in IL-6 and TNF-α secretion, enhanced glycolytic metabolism, and enriched mono-methylation of lysine 4 on histone H3 (H3K4me1) at the enhancer regions of TNF-α and IL-6. The addition of a histone methyltransferase blocker and a PI3K inhibitor greatly reduced trained immunity. Additionally, the response of IGFs to P. gingivalis-LPS stimulation and their epigenetic modifications were similar to those observed in trained HGFs.</p><p><strong>Conclusion: </strong>This study novelly discovered that both P. gingivalis-LPS-stimulated HGFs and IGFs in periodontitis acquired trained immunity. Following P. gingivalis-LPS stimulation, HGFs underwent metabolic and epigenetic changes via the PI3K/AKT pathway, with these epigenetic changes also observed in IGFs. This finding suggests that trained immunity in GFs may be a key mechanism underlying the recurrence and persistence of periodontitis.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"1156-1167"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: To investigate the role of lipopolysaccharide (LPS) from Porphyromonas gingivalis and miR-155-5p-enriched exosomes in the formation of foam cells and the occurrence of carotid atherosclerosis (CAS).
Methods: The CAS tissue samples and plasma from the healthy control group or patients undergoing periodontitis without CAS and with CAS were collected at the Xuanwu Hospital, Capital Medical University. The expression level of miR-155-5p was evaluated by immunofluorescent analysis and qRT-PCR. Oil red O staining and lipid accumulation assays were performed to explore the effects of LPS and miR-155-5p on mouse macrophage Raw264.7 and human monocytes THP-1. The expression levels of lipid-regulated genes were detected by qRT-PCR. Dual-luciferase reporter gene assay and DET1 overexpressed or inhibited Raw264.7 cells were used to verify the target gene of exosomal miR-155-5p. ApoE-/- mice were used to confirm the auxo-action of atherosclerosis from exosomal miR-155-5p in vivo, and LAL assay was used to detect the LPS content.
Results: miR-155-5p was higher in patients with periodontitis and CAS plasma exosomes than those in patients without CAS. The expression of miR-155-5p was significantly increased in CAS tissues compared with Normal tissues, and the expression level of miR-155-5p was associated with lipid-regulated genes in CAS tissues. MiR-155-5p-enriched exosomes accelerated lipid accumulation in macrophage-like cells and promoted the activity of lipid-accumulation genes by targeting DET1. In ApoE-/- mice, circulating miR-155-5p-enriched exosomes captured LPS, and the LPS-laden exosomes conferred plasma access for LPS, triggering the formation of foam cells and the occurrence of CAS.
Conclusion: miR-155-5p enriched exosomes capture and escort LPS to the atherosclerotic sites, licensing the formation of foam cells and thus promoting CAS.
{"title":"Exosomal miR-155-5p Facilitates Lipopolysaccharide Transport and Foam Cell Formation: A Novel Link Between Periodontitis and Atherosclerosis.","authors":"Wen-Wen Yang, Qing-Xiang Li, Fei Wang, Xin-Ran Zhang, Xian-Li Zhang, Meng Wang, Dong Xue, Ying Zhao, Lu Tang","doi":"10.1111/jre.13369","DOIUrl":"10.1111/jre.13369","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the role of lipopolysaccharide (LPS) from Porphyromonas gingivalis and miR-155-5p-enriched exosomes in the formation of foam cells and the occurrence of carotid atherosclerosis (CAS).</p><p><strong>Methods: </strong>The CAS tissue samples and plasma from the healthy control group or patients undergoing periodontitis without CAS and with CAS were collected at the Xuanwu Hospital, Capital Medical University. The expression level of miR-155-5p was evaluated by immunofluorescent analysis and qRT-PCR. Oil red O staining and lipid accumulation assays were performed to explore the effects of LPS and miR-155-5p on mouse macrophage Raw264.7 and human monocytes THP-1. The expression levels of lipid-regulated genes were detected by qRT-PCR. Dual-luciferase reporter gene assay and DET1 overexpressed or inhibited Raw264.7 cells were used to verify the target gene of exosomal miR-155-5p. ApoE<sup>-/-</sup> mice were used to confirm the auxo-action of atherosclerosis from exosomal miR-155-5p in vivo, and LAL assay was used to detect the LPS content.</p><p><strong>Results: </strong>miR-155-5p was higher in patients with periodontitis and CAS plasma exosomes than those in patients without CAS. The expression of miR-155-5p was significantly increased in CAS tissues compared with Normal tissues, and the expression level of miR-155-5p was associated with lipid-regulated genes in CAS tissues. MiR-155-5p-enriched exosomes accelerated lipid accumulation in macrophage-like cells and promoted the activity of lipid-accumulation genes by targeting DET1. In ApoE<sup>-/-</sup> mice, circulating miR-155-5p-enriched exosomes captured LPS, and the LPS-laden exosomes conferred plasma access for LPS, triggering the formation of foam cells and the occurrence of CAS.</p><p><strong>Conclusion: </strong>miR-155-5p enriched exosomes capture and escort LPS to the atherosclerotic sites, licensing the formation of foam cells and thus promoting CAS.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"1132-1142"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-07-10DOI: 10.1111/jre.70010
Lucia Schiavon, Leonardo Mancini, Eugenia Settecase, Ronald E Jung, Tim Joda
Aim: This systematic review and network meta-analysis aimed to answer the PICO question: In patients undergoing immediate implant placement (IIP) [P], does Computer-Assisted Implant Surgery (CAIS) [I] lead to higher accuracy [O] compared to free-hand (FH) [C] implant placement?
Methods: A systematic search of MEDLINE, Scopus, and Cochrane databases was conducted for randomized clinical trials (RCTs) published between January 2014 and September 2024, comparing accuracy of CAIS and FH for IIP. Two reviewers screened the studies and extracted data for a network meta-analysis.
Results: Of 2064 records screened, 7 RCTs (338 implants and 291 patients) met the inclusion criteria. These RCTs evaluated FH and dynamic, full static, and partial static CAIS for single or partial implant placement. No RCTs analyzing robotic-assisted implant surgery (RAIS) were found. In 71.4% of the studies, IIP was performed in the anterior maxilla using a flapless approach. Accuracy was assessed by angular, cervical, and apical deviations between planned and real implant positions. All CAIS methods demonstrated significantly higher accuracy than FH (p < 0.05), but no significant differences were observed between CAIS approaches.
Conclusions: CAIS significantly improves IIP accuracy, enhancing 3D implant positioning and prosthetic outcomes. All CAIS techniques revealed comparable accuracy, allowing clinicians to select the most suitable approach for each patient.
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Pub Date : 2025-11-01Epub Date: 2025-12-22DOI: 10.1111/jre.70061
Tord Berglundh
{"title":"Peri-Implant Diseases: The Past, the Present, the Future.","authors":"Tord Berglundh","doi":"10.1111/jre.70061","DOIUrl":"10.1111/jre.70061","url":null,"abstract":"","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"1059-1066"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}