|
1
|
Ayati A, Khodabandelu S, Khaleghi S, Nourmohammadi A, Jafari F, Ahmadianghalehsorkh M, Vatani Z, Bashiri HS, Ahmadi M, Jafari M, Soltaninejad H, Rahmanian M. A systematic review and network meta-analysis of the association between periodontitis and inflammatory bowel diseases. BMC Oral Health 2025; 25:463. [PMID: 40165211 PMCID: PMC11956190 DOI: 10.1186/s12903-025-05830-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 03/17/2025] [Indexed: 04/02/2025] Open
Abstract
OBJECTIVES Several earlier studies have shown that IBD (including its two subtypes, ulcerative colitis (UC) and Crohn's disease (CD)) increases the risk of periodontal disease. This study aimed to evaluate the relevance among periodontitis and IBD subcategories. METHODS This study was conducted based on PRISMA guidelines. The Web of Science, PubMed, Google Scholar, and Scopus databases were searched up to February 2024 using pertinent keywords. Case series, review articles, and animal studies were excluded. The risk of bias in this research was evaluated through the Joanna Briggs Institute (JBI) criteria. The meta-analysis was conducted using R statistical software. RESULTS A total of 9134 patients within 13 studies after the screening process were evaluated. Our study has shown that periodontitis is significantly more prevalent among IBD patients (UC and CD). According to prior meta-analyses, PD morbidity was found to be significantly high among CD patients (OR: 4.30; 95% CI: 3.72-4.98; I2 = 0%). Similarly, UC elevated PD risk (OR: 4.55; 95% CI: 3.76-5.50; I2 = 0%). The risk of periodontitis was not significantly different between CD and UC patients (OR: 0.96; 95% CI: 0.65-1.43; I2 = 34%). CONCLUSIONS UC and CD patients were more likely to develop periodontitis, with low heterogeneity between studies, while the prevalence of periodontitis among UC and CD patients was not meaningfully different. CLINICAL RELEVANCE The higher risk of periodontitis in patients with IBD indicates the necessity of screening for periodontitis. Considering the various oral manifestations and poor quality of life associated with IBD, it is important to be aware of the symptoms of periodontitis.
Collapse
Affiliation(s)
- Ariyan Ayati
- School of Medicine, Shahid Beheshti University of Medical Sciences, Postal code, Tehran, 19839-63113, Iran
| | - Sajad Khodabandelu
- Department of Biostatistics and Epidemiology, Student Research Committee, School of Health, Mazandaran University of Medical Sciences, Postal code, Sari, 48175-866, Iran
| | - Sara Khaleghi
- Department of Biostatistics and Epidemiology, Student Research Committee, School of Health, Mazandaran University of Medical Sciences, Postal code, Sari, 48175-866, Iran
| | - Anita Nourmohammadi
- Faculty of Dentistry, Postal Code, Tehran Medical Sciences, Islamic Azad University, Tehran, 19468-53314, Iran
| | - Farnaz Jafari
- Oral and Dental Diseases Research Center, Kerman University of Medical Sciences, Postal code, Kerman, 1946853314, Iran
| | - Mina Ahmadianghalehsorkh
- Department of Pediatric Dentistry, Postal Code, Ilam University of Medical Sciences, Ilam, 6939177314, Iran
| | - Zahra Vatani
- School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, 6135715794, Iran
| | - Hanieh Sadat Bashiri
- Department of Public Health, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Postal code, Tehran, 19839-69411, Iran
| | - Mahta Ahmadi
- School of Dentistry, Shiraz University of Medical Sciences, Postal code, Shiraz, 71956-15878, Iran
| | | | - Hossein Soltaninejad
- Department of Stem Cells Technology and Tissue Regeneration, Faculty of Interdisciplinary Science and Technologies, Tarbiat Modares University, Tehran, Iran.
| | - Mohammad Rahmanian
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Postal Code, Tehran, 19839-63113, Iran.
| |
Collapse
|
|
2
|
Miyauchi S, Kawada-Matsuo M, Furusho H, Nishi H, Nakajima A, Phat PT, Shiba F, Kitagawa M, Ouhara K, Oda N, Tokuyama T, Okubo Y, Okamura S, Takasaki T, Takahashi S, Hiyama T, Kawaguchi H, Komatsuzawa H, Miyauchi M, Nakano Y. Atrial Translocation of Porphyromonas gingivalis Exacerbates Atrial Fibrosis and Atrial Fibrillation. Circulation 2025. [PMID: 40099365 DOI: 10.1161/circulationaha.124.071310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 02/21/2025] [Indexed: 03/19/2025]
Abstract
BACKGROUND Recent studies have indicated an association between periodontitis and atrial fibrillation (AF), although the underlying mechanisms remain unclear. Porphyromonas gingivalis is a causative agent of periodontal disease and is highly pathogenic. This study focused on P gingivalis and aimed to investigate the relationship among periodontitis, atrial translocation of P gingivalis, and atrial fibrosis and AF. METHODS An experiment was conducted using P gingivalis-infected C57BL/6J mice, in which P gingivalis was inoculated into the pulp of the molars. Immunohistochemistry was used to visualize the localization of P gingivalis, and loop-mediated isothermal amplification was employed to detect P gingivalis DNA in the left atrium. AF inducibility was examined by intracardiac stimulation. Moreover, left atrial appendage specimens were obtained from 68 patients with AF. A periodontal examination was conducted before the surgery, and the periodontal epithelial surface area and periodontal inflamed surface area, which are quantitative indices used to determine the clinical severity of periodontitis, were measured. The bacterial number of P gingivalis in human atrial tissue was analyzed via quantitative polymerase chain reaction. Atrial fibrosis was assessed using Azan-Mallory staining. RESULTS The translocation path of P gingivalis from the dental granuloma to the left atrium via the circulatory system was demonstrated by immunohistochemistry and loop-mediated isothermal amplification in P gingivalis-infected mice, which showed a higher degree of atrial fibrosis (21.9% versus 16.3%; P=0.0003) and a higher AF inducibility (30.0% versus 5.0%; P=0.04) than the control mice. Upregulation of GAL3 (galectin 3) and transforming growth factor-beta 1 in the left atrium was observed in P gingivalis-infected mice. Moreover, immunohistochemistry revealed that P gingivalis was also present in human atrial tissue. The number of P gingivalis in the human atrial tissue was positively correlated with periodontal epithelial surface area (ρ=0.35; P=0.004), periodontal inflamed surface area (ρ=0.52, P<0.0001), and the degree of atrial fibrosis (ρ=0.38; P=0.002). CONCLUSIONS P gingivalis translocation to the left atrium correlates with the clinical severity of periodontitis, which may exacerbate atrial fibrosis and AF. Atrial translocation of P gingivalis is a potential pathway explaining the causal relationship between periodontitis and AF.
Collapse
Affiliation(s)
- Shunsuke Miyauchi
- Departments of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (S.M., N.O., T. Tokuyama, Y.O., S.O., Y.N.)
- Division of Medicine, Health Service Center, Hiroshima University, 1-7-1 Kagamiyama, Higashihiroshima, Japan (S.M., T.H.)
| | - Miki Kawada-Matsuo
- Bacteriology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (M.K.-M., H. Komatsuzawa)
| | - Hisako Furusho
- Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (H.F., A.N., P.T.P., M.K., M.M.)
| | - Hiromi Nishi
- General Dentistry,Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (H.N., H. Kawaguchi))
| | - Ayako Nakajima
- Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (H.F., A.N., P.T.P., M.K., M.M.)
| | - Pham Trong Phat
- Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (H.F., A.N., P.T.P., M.K., M.M.)
| | - Fumie Shiba
- Collaborative Research Laboratory of Oral Inflammation Regulation (F.S., M.M.)
| | - Masae Kitagawa
- Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (H.F., A.N., P.T.P., M.K., M.M.)
| | - Kazuhisa Ouhara
- Periodontal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (K.O.)
| | - Noboru Oda
- Departments of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (S.M., N.O., T. Tokuyama, Y.O., S.O., Y.N.)
| | - Takehito Tokuyama
- Departments of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (S.M., N.O., T. Tokuyama, Y.O., S.O., Y.N.)
| | - Yousaku Okubo
- Departments of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (S.M., N.O., T. Tokuyama, Y.O., S.O., Y.N.)
| | - Sho Okamura
- Departments of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (S.M., N.O., T. Tokuyama, Y.O., S.O., Y.N.)
| | - Taiichi Takasaki
- Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (T. Takasaki, S.T.)
| | - Shinya Takahashi
- Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (T. Takasaki, S.T.)
| | - Toru Hiyama
- Division of Medicine, Health Service Center, Hiroshima University, 1-7-1 Kagamiyama, Higashihiroshima, Japan (S.M., T.H.)
| | - Hiroyuki Kawaguchi
- General Dentistry,Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (H.N., H. Kawaguchi))
| | - Hitoshi Komatsuzawa
- Bacteriology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (M.K.-M., H. Komatsuzawa)
| | - Mutsumi Miyauchi
- Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (H.F., A.N., P.T.P., M.K., M.M.)
- Collaborative Research Laboratory of Oral Inflammation Regulation (F.S., M.M.)
| | - Yukiko Nakano
- Departments of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan. (S.M., N.O., T. Tokuyama, Y.O., S.O., Y.N.)
| |
Collapse
|
|
3
|
Zhang J, Chen X, Huang D, Tan X. Impact of p. Gingivalis-induced chronic apical periodontitis on systemic iron homeostasis via the hepatic IL-6/STAT3/Hepcidin signaling pathway. Int Immunopharmacol 2025; 147:114002. [PMID: 39787762 DOI: 10.1016/j.intimp.2024.114002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 12/29/2024] [Accepted: 12/30/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND AND AIMS Chronic apical periodontitis (CAP), an inflammatory disease of the oral cavity caused by bacterial infections with Porphyromonas gingivalis (P. gingivalis) as a key pathogen, has been associated with systemic effects, potentially influencing distant organs including liver. The liver plays a key role in iron metabolism and immunity by hepcidin. This study aims to investigate the impact of P. gingivalis-induced CAP on liver and systemic iron metabolism, focusing on the role of the IL-6/STAT3 signaling pathway in hepatic hepcidin synthesis. METHODS A murine model of CAP was established by pulp chamber infection with P. gingivalis. Serum levels of IL-6, ferritin, and hepcidin were measured via ELISA. High-throughput sequencing was used to analyze hepatic gene expression, and immunohistochemistry with fluorescent staining was performed to validate protein expression in liver tissues. RESULTS CAP led to significant changes in serum iron, ferritin, and IL-6. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed enrichment in pathways like JAK/STAT signaling and acute-phase responses, and gene set enrichment analysis (GSEA) also indicated activation of IL-6/JAK/STAT3 signaling pathway. Iimmunofluorescence confirmed increased IL-6, p-STAT3, and hepcidin expression. These levels were alleviated by stattic treatment, mitigating CAP-induced inflammatory and iron-regulatory effects. CONCLUSION P. gingivalis-induced CAP triggered systemic inflammation and disrupts iron metabolism via the IL-6/STAT3 signaling pathway, potentially affecting liver function. Targeting this pathway may offer therapeutic strategies for managing iron dysregulation in chronic inflammatory diseases like CAP.
Collapse
Affiliation(s)
- Jinglan Zhang
- State Key Laboratory of Oral Diseases & National Center of Stomatology & National Clinical Research Center for Oral Diseases & Department of Operative Dentistry and Endodontics West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Xuan Chen
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China; Department of Endodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, Guangdong, China
| | - Dingming Huang
- State Key Laboratory of Oral Diseases & National Center of Stomatology & National Clinical Research Center for Oral Diseases & Department of Operative Dentistry and Endodontics West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
| | - Xuelian Tan
- State Key Laboratory of Oral Diseases & National Center of Stomatology & National Clinical Research Center for Oral Diseases & Department of Operative Dentistry and Endodontics West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
| |
Collapse
|
|
4
|
Ma L, Cao Z. Periodontopathogen-Related Cell Autophagy-A Double-Edged Sword. Inflammation 2025; 48:1-14. [PMID: 38762837 DOI: 10.1007/s10753-024-02049-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 05/08/2024] [Accepted: 05/08/2024] [Indexed: 05/20/2024]
Abstract
The periodontium is a highly organized ecosystem, and the imbalance between oral microorganisms and host defense leads to periodontal diseases. The periodontal pathogens, mainly Gram-negative anaerobic bacteria, colonize the periodontal niches or enter the blood circulation, resulting in periodontal tissue destruction and distal organ damage. This phenomenon links periodontitis with various systemic conditions, including cardiovascular diseases, malignant tumors, steatohepatitis, and Alzheimer's disease. Autophagy is an evolutionarily conserved cellular self-degradation process essential for eliminating internalized pathogens. Nowadays, increasing studies have been carried out in cells derived from periodontal tissues, immune system, and distant organs to investigate the relationship between periodontal pathogen infection and autophagy-related activities. On one hand, as a vital part of innate and adaptive immunity, autophagy actively participates in host resistance to periodontal bacterial infection. On the other, certain periodontal pathogens exploit autophagic vesicles or pathways to evade immune surveillance, therefore achieving survival within host cells. This review provides an overview of the autophagy process and focuses on periodontopathogen-related autophagy and their involvements in cells of different tissue origins, so as to comprehensively understand the role of autophagy in the occurrence and development of periodontal diseases and various periodontitis-associated systemic illnesses.
Collapse
Affiliation(s)
- Li Ma
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Periodontology, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Hongshan District, Wuhan, 430079, China
| | - Zhengguo Cao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
- Department of Periodontology, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Hongshan District, Wuhan, 430079, China.
| |
Collapse
|
|
5
|
Xu Q, Wang W, Li Y, Cui J, Zhu M, Liu Y, Liu Y. The oral-gut microbiota axis: a link in cardiometabolic diseases. NPJ Biofilms Microbiomes 2025; 11:11. [PMID: 39794340 PMCID: PMC11723975 DOI: 10.1038/s41522-025-00646-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 12/29/2024] [Indexed: 01/13/2025] Open
Abstract
The oral-gut microbiota axis plays a crucial role in cardiometabolic health. This review explores the interactions between these microbiomes through enteric, hematogenous, and immune pathways, resulting in disruptions in microbial balance and metabolic processes. These disruptions contribute to systemic inflammation, metabolic disorders, and endothelial dysfunction, which are closely associated with cardiometabolic diseases. Understanding these interactions provides insights for innovative therapeutic strategies to prevent and manage cardiometabolic diseases.
Collapse
Affiliation(s)
- Qian Xu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Wenting Wang
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Yiwen Li
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Jing Cui
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Mengmeng Zhu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Yanfei Liu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
- The Second Department of Geriatrics, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
- Key Laboratory of Disease and Syndrome Integration Prevention and Treatment of Vascular Aging, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Yue Liu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China.
- Key Laboratory of Disease and Syndrome Integration Prevention and Treatment of Vascular Aging, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China.
| |
Collapse
|
|
6
|
Daidouji Y, Suzuki S, Wang X, Fahreza RR, Nemoto E, Yamada S. Periodontal inflammation potentially inhibits hepatic cytochrome P450 expression and disrupts the omega-3 epoxidation pathway in a murine model. J Dent Sci 2025; 20:444-451. [PMID: 39873042 PMCID: PMC11763211 DOI: 10.1016/j.jds.2024.05.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 05/23/2024] [Indexed: 01/30/2025] Open
Affiliation(s)
- Yoshino Daidouji
- Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Shigeki Suzuki
- Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Xiuting Wang
- Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Rahmad Rifqi Fahreza
- Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Eiji Nemoto
- Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Satoru Yamada
- Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, Japan
| |
Collapse
|
|
7
|
Hudson D, Ayares G, Taboun Z, Malhi G, Idalsoaga F, Mortuza R, Souyet M, Ramirez-Cadiz C, Díaz LA, Arrese M, Arab JP. Periodontal disease and cirrhosis: current concepts and future prospects. EGASTROENTEROLOGY 2025; 3:e100140. [PMID: 40160254 PMCID: PMC11950965 DOI: 10.1136/egastro-2024-100140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 02/05/2025] [Indexed: 04/02/2025]
Abstract
Periodontal diseases are prevalent among the general population and are associated with several systemic conditions, such as chronic kidney disease and type 2 diabetes mellitus. Chronic liver disease and cirrhosis have also been linked with periodontal disease, an association with complex underlying mechanisms, and with potential prognostic implications. Multiple factors can explain this relevant association, including nutritional factors, alcohol consumption, disruption of the oral-gut-liver axis and associated dysbiosis. Additionally, patients with liver disease have been observed to exhibit poorer oral hygiene practices compared with the general population, potentially predisposing them to the development of periodontal disease. Therefore, it is recommended that all patients with liver disease undergo screening and subsequent treatment for periodontal disease. Treatment of periodontal disease in patients with cirrhosis may help reduce liver-derived inflammatory damage, with recent research indicating a potential benefit in terms of reduced mortality. However, further studies on periodontal disease treatment in patients with liver disease are still warranted to determine optimal management strategies. This narrative review describes current concepts on the association between periodontal disease and chronic liver disease.
Collapse
Affiliation(s)
- David Hudson
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
| | - Gustavo Ayares
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Zahra Taboun
- Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Gurpreet Malhi
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
| | - Francisco Idalsoaga
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Rokhsana Mortuza
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
| | - Maite Souyet
- Escuela de Odontología, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Santiago, Chile
- Escuela de Odontología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Carolina Ramirez-Cadiz
- Department of Anesthesiology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Luis Antonio Díaz
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA
| | - Marco Arrese
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| |
Collapse
|
|
8
|
Rabiu L, Zhang P, Afolabi LO, Saliu MA, Dabai SM, Suleiman RB, Gidado KI, Ige MA, Ibrahim A, Zhang G, Wan X. Immunological dynamics in MASH: from landscape analysis to therapeutic intervention. J Gastroenterol 2024; 59:1053-1078. [PMID: 39400718 DOI: 10.1007/s00535-024-02157-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 10/01/2024] [Indexed: 10/15/2024]
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH), is a multifaceted liver disease characterized by inflammation and fibrosis that develops from simple steatosis. Immune and inflammatory pathways have a central role in the pathogenesis of MASH, yet, how to target immune pathways to treat MASH remains perplexed. This review emphasizes the intricate role that immune cells play in the etiology and pathophysiology of MASH and highlights their significance as targets for therapeutic approaches. It discusses both current strategies and novel therapies aimed at modulating the immune response in MASH. It also highlights challenges in liver-specific drug delivery, potential off-target effects, and difficulties in targeting diverse immune cell populations within the liver. This review is a comprehensive resource that integrates current knowledge with future perspectives in the evolving field of MASH, with the goal of driving forward progress in medical therapies designed to treat this complex liver disease.
Collapse
Affiliation(s)
- Lawan Rabiu
- Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China
- University of Chinese Academy of Sciences, Beijing, 100864, People's Republic of China
- Federal University Dutse, Jigawa, Nigeria
| | - Pengchao Zhang
- Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China
- University of Chinese Academy of Sciences, Beijing, 100864, People's Republic of China
| | - Lukman O Afolabi
- Department of Pediatrics, Indiana University School of Medicine, 1234 Notre Dame Ave, S Bend, IN, 46617, USA
| | - Muhammad A Saliu
- Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China
- University of Chinese Academy of Sciences, Beijing, 100864, People's Republic of China
| | - Salisu M Dabai
- Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China
- University of Chinese Academy of Sciences, Beijing, 100864, People's Republic of China
| | - Rabiatu B Suleiman
- Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China
- University of Chinese Academy of Sciences, Beijing, 100864, People's Republic of China
| | - Khalid I Gidado
- Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China
- University of Chinese Academy of Sciences, Beijing, 100864, People's Republic of China
| | - Mark A Ige
- Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China
- University of Chinese Academy of Sciences, Beijing, 100864, People's Republic of China
| | - Abdulrahman Ibrahim
- Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China
- University of Chinese Academy of Sciences, Beijing, 100864, People's Republic of China
| | - Guizhong Zhang
- Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China.
- University of Chinese Academy of Sciences, Beijing, 100864, People's Republic of China.
| | - Xiaochun Wan
- Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People's Republic of China.
- University of Chinese Academy of Sciences, Beijing, 100864, People's Republic of China.
| |
Collapse
|
|
9
|
Oue K, Yamawaki Y, Ouhara K, Imado E, Tamura T, Doi M, Shimizu Y, Yoshida M, Mizuno N, Morioka N, Kanematsu T, Irifune M, Ago Y. Oral administration of Porphyromonas gingivalis to mice with diet-induced obesity impairs cognitive function associated with microglial activation in the brain. J Oral Microbiol 2024; 16:2419155. [PMID: 39553478 PMCID: PMC11565673 DOI: 10.1080/20002297.2024.2419155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 01/04/2024] [Accepted: 10/16/2024] [Indexed: 11/19/2024] Open
Abstract
Objective Both periodontal disease and obesity are risk factors for dementia, but their links to 1brain function remain unclear. In this study, we examined the effects of oral infection with a periodontal pathogen on cognitive function in a mouse model of obesity, focusing on the roles of microglia. Methods To create a mouse model of diet-induced obesity and periodontitis, male C57BL/6 J mice were first fed a high-fat diet containing 60% lipid calories for 18 weeks, beginning at 12 weeks of age, to achieve diet-induced obesity. Then, Porphyromonas gingivalis administration in the oral cavity twice weekly for 6 weeks was performed to induce periodontitis in obese mice. Results Obese mice orally exposed to P. gingivalis showed cognitive impairment in the novel object recognition test. Increased expression levels of inflammatory cytokines (e.g. interleukin-1β and tumor necrosis factor-α) were observed in the hippocampus of P. gingivalis-treated obese mice. Immunohistochemical analysis revealed that microglia cell body size was increased in the hippocampus and prefrontal cortex of P. gingivalis-treated obese mice, indicating microglial activation. Furthermore, depletion of microglia by PLX3397, a colony-stimulating factor 1 receptor inhibitor, ameliorated cognitive dysfunction. Conclusion These results suggest that microglia mediate periodontal infection-induced cognitive dysfunction in obesity.
Collapse
Affiliation(s)
- Kana Oue
- Department of Dental Anesthesiology, Division of Oral and Maxillofacial Surgery and Oral Medicine, Hiroshima University Hospital, Hiroshima, Japan
| | - Yosuke Yamawaki
- Department of Advanced Pharmacology, Daiichi University of Pharmacy, Fukuoka, Japan
| | - Kazuhisa Ouhara
- Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Eiji Imado
- Department of Dental Anesthesiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tetsuya Tamura
- Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Mitsuru Doi
- Department of Dental Anesthesiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshitaka Shimizu
- Department of Dental Anesthesiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Mitsuhiro Yoshida
- Department of Dental Anesthesiology, Division of Oral and Maxillofacial Surgery and Oral Medicine, Hiroshima University Hospital, Hiroshima, Japan
- Department of Dental Anesthesiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Noriyoshi Mizuno
- Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Norimitsu Morioka
- Department of Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takashi Kanematsu
- Department of Cell Biology, Aging Science, and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Masahiro Irifune
- Department of Dental Anesthesiology, Division of Oral and Maxillofacial Surgery and Oral Medicine, Hiroshima University Hospital, Hiroshima, Japan
- Department of Dental Anesthesiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yukio Ago
- Department of Cellular and Molecular Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| |
Collapse
|
|
10
|
Ding C, Shen Z, Xu R, Liu Y, Xu M, Fan C, Hu D, Xing T. Exosomes derived from periodontitis induce hepatic steatosis through the SCD-1/AMPK signaling pathway. Biochim Biophys Acta Mol Basis Dis 2024; 1870:167343. [PMID: 38986822 DOI: 10.1016/j.bbadis.2024.167343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Revised: 06/29/2024] [Accepted: 07/04/2024] [Indexed: 07/12/2024]
Abstract
AIM To investigate the impact of exosomes released by Porphyromonas gingivalis-Lipopolysaccharide activated THP-1 macrophages and human periodontal ligament fibroblasts on hepatocyte fat metabolism. RESULTS The liver of rats with experimental periodontitis showed obvious steatosis and inflammation compared with control rats. The culture supernatant of macrophages and human periodontal ligament fibroblasts (hPDLFs), when stimulated with Pg-LPS, induced lipogenesis in HepG2 cells. Furthermore, the lipid-promoting effect was effectively inhibited by the addition of the exosome inhibitor GW4869. Subsequently, we isolated exosomes from cells associated with periodontitis. Exosomes released by Pg-LPS-stimulated macrophages and hPDLFs are taken up by hepatocytes, causing mRNA expression related to fat synthesis, promoting triglyceride synthesis, and aggravating NAFLD progression. Finally, two sets of exosomes were injected into mice through the tail vein. In vivo experiments have also demonstrated that periodontitis-associated exosomes promote the development of hepatic injury and steatosis, upregulate SCD-1 expression and inhibit the AMPK signaling pathway. CONCLUSIONS In conclusion, we found that exosomes associated with periodontitis promote hepatocyte adipogenesis by increasing the expression of SCD-1 and suppressing the AMPK pathway, which indicates that close monitoring of the progression of stomatopathy associated extra-oral disorders is important and establishes a theoretical foundation for the prevention and management of fatty liver disease linked to periodontitis.
Collapse
Affiliation(s)
- Chunmeng Ding
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei 230032, China
| | - Zhenguo Shen
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei 230032, China
| | - Ruonan Xu
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei 230032, China
| | - Yajing Liu
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei 230032, China
| | - Mengyue Xu
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei 230032, China
| | - Chenyu Fan
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei 230032, China
| | - Dongyue Hu
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei 230032, China
| | - Tian Xing
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei 230032, China.
| |
Collapse
|
|
11
|
Rotaru M, Singeap AM, Ciobica A, Huiban L, Stanciu C, Romila L, Burlui V, Mavroudis I, Trifan A. Oral Health and "Modern" Digestive Diseases: Pathophysiologic and Etiologic Factors. Biomedicines 2024; 12:1854. [PMID: 39200318 PMCID: PMC11351600 DOI: 10.3390/biomedicines12081854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 08/02/2024] [Accepted: 08/06/2024] [Indexed: 09/02/2024] Open
Abstract
In the contemporary era of medicine, exploring the complexity of the human body and its intricate interactions has become a central concern for health researchers. The main purpose of this article is to summarize the current understanding of relevant pathophysiological factors such as chronic inflammation, dysbiosis (microbial imbalance), and metabolic disorders, as well as etiological factors including dietary habits, lifestyle choices, obesity, metabolic syndrome, and genetic predispositions, as well as to emphasize potential avenues for upcoming studies and their medical significance. Additionally, this article aims to assess the potential impact of integrated treatment approaches on patient outcomes, emphasizing the need for interdisciplinary collaboration between gastroenterologists, dentists, and other healthcare professionals to develop comprehensive care plans that address both oral and digestive health issues simultaneously. Among the branches with a significant impact on general well-being are oral cavity health and digestive diseases, which have been the subject of intensive research in recent decades. In this context, analysis of the current state of knowledge on oral cavity disorders in relation to "modern" digestive diseases such as non-alcoholic fatty liver disease (NAFLD), small intestinal bacterial overgrowth (SIBO), inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS) becomes essential for a deeper understanding of the interconnections between oral and digestive health. The temporal overlap or succession, whether preceding or following, of oral manifestations and digestive disorders should be taken seriously by both gastroenterologists and dentists to facilitate early diagnosis and explain to patients the correlation between these two body systems. In summary, this article underscores the importance of understanding the intricate relationship between oral and digestive health, advocating for interdisciplinary approaches to improve patient outcomes and guide future research.
Collapse
Affiliation(s)
- Mihaela Rotaru
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Bd. Carol I No. 20A, 700505 Iasi, Romania; (M.R.); (A.C.)
| | - Ana-Maria Singeap
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (L.H.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
- CENEMED Platform for Interdisciplinary Research, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania
| | - Alin Ciobica
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Bd. Carol I No. 20A, 700505 Iasi, Romania; (M.R.); (A.C.)
- CENEMED Platform for Interdisciplinary Research, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania
- Centre of Biomedical Research, Romanian Academy, Bd. Carol I No. 8, 700506 Iasi, Romania
- Academy of Romanian Scientists, Splaiul Independentei Street No. 54, 050094 Bucharest, Romania
| | - Laura Huiban
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (L.H.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (L.H.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
- Centre of Biomedical Research, Romanian Academy, Bd. Carol I No. 8, 700506 Iasi, Romania
- Academy of Romanian Scientists, Splaiul Independentei Street No. 54, 050094 Bucharest, Romania
| | - Laura Romila
- “Ioan Haulica” Institute, Apollonia University, Pacurari Street No. 11, 700511 Iasi, Romania;
| | - Vasile Burlui
- “Ioan Haulica” Institute, Apollonia University, Pacurari Street No. 11, 700511 Iasi, Romania;
| | - Ioannis Mavroudis
- Department of Neuroscience, Leeds Teaching Hospitals, NHS Trust, Leeds LS2 9JT, UK;
- Third Department of Neurology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Anca Trifan
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (L.H.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
- CENEMED Platform for Interdisciplinary Research, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania
| |
Collapse
|
|
12
|
Ohno T, Kikuchi T, Suzuki Y, Goto R, Takeuchi D, Hayashi JI, Nishida E, Yamamoto G, Kondo S, Ono K, Nomoto S, Mitani A. Periodontitis promotes hepatocellular carcinoma in Stelic Animal model (STAM) mice. Sci Rep 2024; 14:17560. [PMID: 39080409 PMCID: PMC11289391 DOI: 10.1038/s41598-024-68422-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Accepted: 07/23/2024] [Indexed: 08/02/2024] Open
Abstract
Periodontitis is a prevalent oral inflammatory disease that leads to alveolar bone loss and may exert an adverse impact on systemic health. Periodontal disease may be associated with hepatocellular carcinoma (HCC); however, the mechanism of such an association is unknown. In this study, Stelic Animal model (STAM) mice, a model of nonalcoholic steatohepatitis (NASH)-HCC, were induced to develop periodontitis and subjected to histopathological and immunological analyses. HCC progression was greater in STAM mice with experimental periodontitis compared with that in STAM mice without experimental periodontitis. Tumor necrosis factor-α (TNFα), matrix metalloproteinase-9 (MMP9), collagen 1, and angiopoietin-like protein 2 (ANGPTL2) gene expression was significantly increased in the liver of the periodontitis group. ANGPTL2 was previously reported to be involved in the pathogenesis of periodontitis, and HCC and ANGPTL2 protein tended to be more abundant in the pocket epithelium of STAM mice with experimental periodontitis than in control STAM mice. ANGPTL2 levels in the serum of STAM mice with experimental periodontitis tended to be higher than in control STAM mice. Our results indicate that ANGPTL2 is produced in chronically inflamed periodontal tissue and then travels to the liver via the bloodstream where it accumulates to promote the progression of hepatocellular carcinoma.
Collapse
Affiliation(s)
- Tasuku Ohno
- Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan
| | - Takeshi Kikuchi
- Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan.
| | - Yuki Suzuki
- Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan
| | - Ryoma Goto
- Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan
| | - Daiki Takeuchi
- Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan
| | - Jun-Ichiro Hayashi
- Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan
| | - Eisaku Nishida
- Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan
| | - Genta Yamamoto
- Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan
| | - Shun Kondo
- Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan
| | - Kouta Ono
- Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan
| | - Shuji Nomoto
- Department of Surgery, School of Dentistry, Aichi Gakuin University, Nagoya, Japan
| | - Akio Mitani
- Department of Periodontology, School of Dentistry, Aichi Gakuin University, 2-11 Suemoridori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan
| |
Collapse
|
|
13
|
Chen X, Song J, Sun J, Zhang J, Chen X, Zeng C, Hu J, Chang X, Jin F, Luo S, Chen Z, Luo Y. Hepatitis B infection is associated with periodontitis: the national health and nutrition examination survey (2009-2014). BMC Oral Health 2024; 24:815. [PMID: 39020311 PMCID: PMC11256453 DOI: 10.1186/s12903-024-04489-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 06/17/2024] [Indexed: 07/19/2024] Open
Abstract
BACKGROUND Current research has been inconclusive regarding whether hepatitis B infection is associated with an increased risk of periodontitis. This study aims to test the null hypothesis that no association exists between hepatitis B infection and an increased risk of periodontitis using the National Health and Nutrition Examination Survey (2009-2014). METHODS We performed a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database (2009-2014) to assess the rate of the prevalence of periodontitis in patients with and without hepatitis B infection. Participants who had tested for hepatitis B and periodontitis were included. The included participants were divided into no/mild periodontitis and moderate/severe periodontitis groups according to their periodontal status. The association between hepatitis B infection and chronic periodontitis was evaluated by multivariable regression analyses adjusting for age, gender, race/ethnicity, education level, income-to-poverty ratio, smoking, alcohol, BMI, ALT, AST, creatinine, hypertension, and diabetes. RESULTS A total of 5957 participants were included and divided into two groups: inactive periodontitis group (n = 3444) and active periodontitis group (n = 2513). The results showed that participants with hepatitis B had a higher risk of periodontitis. After adjusting for covariables, adults with hepatitis B infection were 38% more likely to have periodontitis compared to those without hepatitis B infection (95% Confidence Interval [CI]:1.085-1.754). CONCLUSIONS In general, the results suggest that CHB is positively associated with the more severe periodontitis. These results suggest that people with hepatitis B infection should take good periodontal care measures to avoid the occurrence and development of periodontitis.
Collapse
Affiliation(s)
- XianRun Chen
- School of Stomatology, Zunyi Medical University, Zunyi, China
- Department of Prosthodontics, Guiyang Stomatological Hospital, Guiyang, China
| | - Jukun Song
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Guizhou Medical University, Guiyang, China
| | - JiangLing Sun
- Department of Endodontics, Guiyang Stomatological Hospital, Guiyang, China
| | - JiQin Zhang
- School of Stomatology, Zunyi Medical University, Zunyi, China
- Department of Prosthodontics, Guiyang Stomatological Hospital, Guiyang, China
| | - XingJin Chen
- School of Stomatology, Zunyi Medical University, Zunyi, China
- Department of Endodontics, Guiyang Stomatological Hospital, Guiyang, China
| | - ChongWen Zeng
- School of Stomatology, Zunyi Medical University, Zunyi, China
- Department of Endodontics, Guiyang Stomatological Hospital, Guiyang, China
| | - JiaXin Hu
- School of Stomatology, Zunyi Medical University, Zunyi, China
- Department of Prosthodontics, Guiyang Stomatological Hospital, Guiyang, China
| | - XingTao Chang
- School of Stomatology, Zunyi Medical University, Zunyi, China
- Department of Prosthodontics, Guiyang Stomatological Hospital, Guiyang, China
| | - FuQian Jin
- Department of Endodontics, Guiyang Stomatological Hospital, Guiyang, China
| | - SiYang Luo
- Department of Prosthodontics, Guiyang Stomatological Hospital, Guiyang, China
| | - Zhu Chen
- School of Stomatology, Zunyi Medical University, Zunyi, China.
- Department of Endodontics, Guiyang Stomatological Hospital, Guiyang, China.
| | - Yi Luo
- School of Stomatology, Zunyi Medical University, Zunyi, China.
- Department of Prosthodontics, Guiyang Stomatological Hospital, Guiyang, China.
| |
Collapse
|
|
14
|
Mei EH, Yao C, Chen YN, Nan SX, Qi SC. Multifunctional role of oral bacteria in the progression of non-alcoholic fatty liver disease. World J Hepatol 2024; 16:688-702. [PMID: 38818294 PMCID: PMC11135273 DOI: 10.4254/wjh.v16.i5.688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 02/26/2024] [Accepted: 04/07/2024] [Indexed: 05/22/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders of varying severity, ultimately leading to fibrosis. This spectrum primarily consists of NAFL and non-alcoholic steatohepatitis. The pathogenesis of NAFLD is closely associated with disturbances in the gut microbiota and impairment of the intestinal barrier. Non-gut commensal flora, particularly bacteria, play a pivotal role in the progression of NAFLD. Notably, Porphyromonas gingivalis, a principal bacterium involved in periodontitis, is known to facilitate lipid accumulation, augment immune responses, and induce insulin resistance, thereby exacerbating fibrosis in cases of periodontitis-associated NAFLD. The influence of oral microbiota on NAFLD via the "oral-gut-liver" axis is gaining recognition, offering a novel perspective for NAFLD management through microbial imbalance correction. This review endeavors to encapsulate the intricate roles of oral bacteria in NAFLD and explore underlying mechanisms, emphasizing microbial control strategies as a viable therapeutic avenue for NAFLD.
Collapse
Affiliation(s)
- En-Hua Mei
- Shanghai Medical College, Fudan University, Shanghai 200000, China
- Department of Prothodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
- Shanghai Key Laboratory of Craniomaxiofacial Development and Diseases, Fudan University, Shanghai 200000, China
| | - Chao Yao
- Department of Prothodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
- Shanghai Key Laboratory of Craniomaxiofacial Development and Diseases, Fudan University, Shanghai 200000, China
| | - Yi-Nan Chen
- Shanghai Medical College, Fudan University, Shanghai 200000, China
| | - Shun-Xue Nan
- Shanghai Medical College, Fudan University, Shanghai 200000, China
| | - Sheng-Cai Qi
- Department of Prothodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
- Shanghai Key Laboratory of Craniomaxiofacial Development and Diseases, Fudan University, Shanghai 200000, China.
| |
Collapse
|
|
15
|
Kuraji R, Ye C, Zhao C, Gao L, Martinez A, Miyashita Y, Radaic A, Kamarajan P, Le C, Zhan L, Range H, Sunohara M, Numabe Y, Kapila YL. Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis. NPJ Biofilms Microbiomes 2024; 10:3. [PMID: 38233485 PMCID: PMC10794237 DOI: 10.1038/s41522-024-00476-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Accepted: 01/02/2024] [Indexed: 01/19/2024] Open
Abstract
Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice. In the context of disease, nisin treatment significantly shifted the microbiome towards a new composition, commensurate with health while preventing the harmful inflammation in the small intestine concomitant with decreased villi structural integrity, and heightened hepatic exposure to bacteria and lipid and malondialdehyde accumulation in the liver. Validation with RNA Seq analyses, confirmed the significant infection-related alteration of several genes involved in mitochondrial dysregulation, oxidative phosphorylation, and metal/iron binding and their restitution following nisin treatment. In support of these in vivo findings indicating that periodontopathogens induce gastrointestinal and liver distant organ lesions, human autopsy specimens demonstrated a correlation between tooth loss and severity of liver disease. Nisin's ability to shift the gut and liver microbiome towards a new state commensurate with health while mitigating enteritis, represents a novel approach to treating NAFLD-steatohepatitis-associated periodontal disease.
Collapse
Affiliation(s)
- Ryutaro Kuraji
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Changchang Ye
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Periodontology, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Chuanjiang Zhao
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Department of Periodontology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Li Gao
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Department of Periodontology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - April Martinez
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
| | - Yukihiro Miyashita
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Allan Radaic
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Sections of Biosystems and Function and Periodontics, School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - Pachiyappan Kamarajan
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Sections of Biosystems and Function and Periodontics, School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - Charles Le
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
| | - Ling Zhan
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
| | - Helene Range
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Department of Periodontology, University of Rennes, UFR of Odontology; Service d'Odontologie, CHU de Rennes, Rennes, France
- INSERM CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer); CIC 1414, Rennes, France
| | - Masataka Sunohara
- Department of Anatomy, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yvonne L Kapila
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA.
- Sections of Biosystems and Function and Periodontics, School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA.
| |
Collapse
|
|
16
|
Lê S, Minty M, Boyer É, Blasco-Baque V, Bonnaure-Mallet M, Meuric V. [Oral microbiota and liver]. Med Sci (Paris) 2024; 40:42-48. [PMID: 38299902 DOI: 10.1051/medsci/2023194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2024] Open
Abstract
The liver has many important biological functions for the body, as it is involved in the storage and distribution of nutrients (carbohydrates to glycogen, lipids to triglycerides), the digestion of fats, the synthesis of blood proteins, and the detoxification of alcohol and drugs. The liver can be affected by various diseases such as viral or drug-induced hepatitis, fibrosis and cirrhosis, in which damaged hepatocytes are progressively replaced by scar tissue.
Collapse
Affiliation(s)
- Sylvie Lê
- Département dentaire, université Paul Sabatier III (UPS), Toulouse, France - Service d'odontologie Toulouse, CHU Toulouse, Toulouse, France - UMR1297 Inserm, équipe InCOMM (Intestine ClinicOmics Metabolism & Microbiota), Institut des maladies métaboliques et cardiovasculaires (I2MC), université Paul Sabatier, Toulouse, France
| | - Matthieu Minty
- Département dentaire, université Paul Sabatier III (UPS), Toulouse, France - Service d'odontologie Toulouse, CHU Toulouse, Toulouse, France - UMR1297 Inserm, équipe InCOMM (Intestine ClinicOmics Metabolism & Microbiota), Institut des maladies métaboliques et cardiovasculaires (I2MC), université Paul Sabatier, Toulouse, France
| | - Émile Boyer
- Inserm U1317, Inrae, université de Rennes, CHU de Rennes, site Pontchaillou-Villejean, Rennes, France
| | - Vincent Blasco-Baque
- Département dentaire, université Paul Sabatier III (UPS), Toulouse, France - Service d'odontologie Toulouse, CHU Toulouse, Toulouse, France - UMR1297 Inserm, équipe InCOMM (Intestine ClinicOmics Metabolism & Microbiota), Institut des maladies métaboliques et cardiovasculaires (I2MC), université Paul Sabatier, Toulouse, France
| | - Martine Bonnaure-Mallet
- Inserm U1317, Inrae, université de Rennes, CHU de Rennes, site Pontchaillou-Villejean, Rennes, France
| | - Vincent Meuric
- Inserm U1317, Inrae, université de Rennes, CHU de Rennes, site Pontchaillou-Villejean, Rennes, France
| |
Collapse
|
|
17
|
Aguiar ILS, Santos-Lins LS, Brasil-Oliveira R, Cotrim HP, Lins-Kusterer L. Non-alcoholic fatty liver disease and periodontal disease: A systematic review and meta-analysis of cross-sectional studies. Arab J Gastroenterol 2023; 24:198-203. [PMID: 37993376 DOI: 10.1016/j.ajg.2023.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 08/13/2022] [Accepted: 09/07/2023] [Indexed: 11/24/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, comprising hepatic steatosis, and non-alcoholic steatohepatitis. Periodontal disease (PD) may be a risk factor for the evolution of liver cirrhosis. This study aimed to evaluate the association between NAFLD and PD.We searched in Pubmed, Scopus, Cochrane, and Lilacs databases with descriptors (Non-alcoholic Fatty Liver Disease OR (non-alcoholic AND Fatty Liver AND disease) OR Nonalcoholic Steatohepatitis) AND (Periodontal Disease OR Gingivitis OR Periodontitis) from January 2021 to September 2021. We selected, by the abstract, cross-sectional, cohort (prospective and retrospective), and case-control studies that address periodontal disease in patients with Non-alcoholic Fatty Liver Disease, and aged ≥ 18 years. The search was without the restriction of language and publication time.The search resulted in 954 articles. After applying the selection criteria, five cross-sectional studies remained. A metanalysis combined the study estimates of periodontal disease in NAFLD, by using the random effects. The Odds Ratio (1.91; 95% CI 1.21-3.02; P = 0.006) indicates that the chance of presenting Periodontal disease is 91% higher in individuals with NAFLD when compared with individuals without NAFLD. There are few studies with appropriate methodology to produce sound evidence about the causal relationship between the use of NAFLD and PD, however, studies support the association. So, dental staff must be aware of this association for better management of periodontal disease in patients with NAFLD.
Collapse
Affiliation(s)
- Inácio Lima Silva Aguiar
- Program in Medicine and Health, School of Medicine, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Larissa Souza Santos-Lins
- Program in Medicine and Health, School of Medicine, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Rebeca Brasil-Oliveira
- Program in Medicine and Health, School of Medicine, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Helma Pinchemel Cotrim
- Program in Medicine and Health, School of Medicine, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Liliane Lins-Kusterer
- Program in Medicine and Health, School of Medicine, Federal University of Bahia, Salvador, Bahia, Brazil.
| |
Collapse
|
|
18
|
Chihara K, Okada K, Uchida F, Miura I, Komine S, Warabi E, Takayama T, Suzuki H, Matsuzaka T, Ishibashi-Kanno N, Yamagata K, Yanagawa T, Bukawa H, Shoda J. Macrophage specific restoration of the Nrf2 gene in whole-body knockout mice ameliorates steatohepatitis induced by lipopolysaccharide from Porphyromonas gingivalis through enhanced hepatic clearance. PLoS One 2023; 18:e0291880. [PMID: 37862331 PMCID: PMC10588835 DOI: 10.1371/journal.pone.0291880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 09/06/2023] [Indexed: 10/22/2023] Open
Abstract
Lipopolysaccharide (LPS) derived from Porphyromonas gingivalis (P.g.), which causes periodontal disease, contributes to the development of non-alcoholic steatohepatitis (NASH). We investigated the role of Nrf2, an antioxidative stress sensor, in macrophages in the development of NASH induced by LPS from P.g. We generated macrophage-specific Nrf2 gene rescue mice (Nrf2-mRes), which express Nrf2 only in macrophages, using the cre/loxp system. Wild-type (WT) mice, whole body Nrf2-knockout (Nrf2-KO) mice, and Nrf2-mRes mice were fed a high-fat diet for 18 weeks, and LPS from P.g. was administered intraperitoneally for the last 6 weeks. Nrf2-KO mice developed severe steatohepatitis with liver inflammation and fibrosis compared with WT mice, and steatohepatitis was ameliorated in Nrf2-mRes mice. The mRNA expressions of Toll-like receptor (Tlr)-2, which activates inflammatory signaling pathways after LPS binding, and α-smooth muscle actin (αSma), which promotes hepatic fibrosis, were reduced in Nrf2-mRes mice compared with Nrf2-KO mice. The protein levels of LPS-binding protein in livers were increased in Nrf2-KO mice compared with WT mice; however, the levels were reduced in Nrf2-mRes mice despite similar numbers of F4/80 positive cells, which reflect macrophage/Kupffer cell infiltration into the livers. Nrf2 in macrophages ameliorates NASH through the increased hepatic clearance of LPS.
Collapse
Affiliation(s)
- Kanako Chihara
- Department of Oral and Maxillofacial Surgery, Institute of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
- Doctoral Program in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
| | - Kosuke Okada
- Division of Medical Sciences, Institute of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
| | - Fumihiko Uchida
- Department of Oral and Maxillofacial Surgery, Institute of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
| | - Ikuru Miura
- Faculty of Sports and Health Science, Fukuoka University, Fukuoka-shi, Fukuoka, Japan
| | - Shoichi Komine
- Department of Acupuncture and Moxibustion, Faculty of Human Care, Teikyo Heisei University, Toshima-ku, Tokyo, Japan
| | - Eiji Warabi
- Division of Biomedical Sciences, Institute of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
| | - Takako Takayama
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
| | - Hideo Suzuki
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
| | - Takashi Matsuzaka
- Transborder Medical Research Center, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
| | - Naomi Ishibashi-Kanno
- Department of Oral and Maxillofacial Surgery, Institute of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
| | - Kenji Yamagata
- Department of Oral and Maxillofacial Surgery, Institute of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
| | - Toru Yanagawa
- Department of Oral and Maxillofacial Surgery, Institute of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
| | - Hiroki Bukawa
- Department of Oral and Maxillofacial Surgery, Institute of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
| | - Junichi Shoda
- Division of Medical Sciences, Institute of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
| |
Collapse
|
|
19
|
Wang S, Friedman SL. Found in translation-Fibrosis in metabolic dysfunction-associated steatohepatitis (MASH). Sci Transl Med 2023; 15:eadi0759. [PMID: 37792957 PMCID: PMC10671253 DOI: 10.1126/scitranslmed.adi0759] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 09/15/2023] [Indexed: 10/06/2023]
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is a severe form of liver disease that poses a global health threat because of its potential to progress to advanced fibrosis, leading to cirrhosis and liver cancer. Recent advances in single-cell methodologies, refined disease models, and genetic and epigenetic insights have provided a nuanced understanding of MASH fibrogenesis, with substantial cellular heterogeneity in MASH livers providing potentially targetable cell-cell interactions and behavior. Unlike fibrogenesis, mechanisms underlying fibrosis regression in MASH are still inadequately understood, although antifibrotic targets have been recently identified. A refined antifibrotic treatment framework could lead to noninvasive assessment and targeted therapies that preserve hepatocellular function and restore the liver's architectural integrity.
Collapse
Affiliation(s)
- Shuang Wang
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029
| | - Scott L. Friedman
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029
| |
Collapse
|
|
20
|
Sato S, Iino C, Chinda D, Sasada T, Tateda T, Kaizuka M, Nomiya H, Igarashi G, Sawada K, Mikami T, Nakaji S, Sakuraba H, Fukuda S. Effect of Liver Fibrosis on Oral and Gut Microbiota in the Japanese General Population Determined by Evaluating the FibroScan-Aspartate Aminotransferase Score. Int J Mol Sci 2023; 24:13470. [PMID: 37686272 PMCID: PMC10487682 DOI: 10.3390/ijms241713470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/18/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023] Open
Abstract
The association between liver fibrosis and oral or gut microbiota has been studied before. However, epidemiological studies in the general population are limited owing to the difficulty of noninvasive liver-fibrosis assessment. FibroScan-asparate aminotransferase (FAST) scores can be used to accurately and non-invasively evaluate liver fibrosis. This study aimed to determine the association between liver fibrosis and oral or gut microbiota using the FAST score in the general population. After propensity score matching of 1059 participants based on sex, age, body mass index, homeostasis model assessment of insulin resistance, and triglyceride levels, 125 (non-liver-fibrosis group, 100; liver fibrosis group, 25) were included. The diversity of gut microbiota differed significantly between the two groups; however, no significant differences were noted in their oral microbiota. The liver fibrosis group showed an increase in the relative abundance of Fusobacteria strains and a decrease in the relative abundance of Faecalibacterium, with the presence of Fusicatenibacter in the gut microbiota. Feacalibacterium was not identified as an independent factor of liver fibrosis in adjusting the fatty liver index. In the general population, gut microbiota may be more involved in liver fibrosis than oral microbiota.
Collapse
Affiliation(s)
- Satoshi Sato
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (S.S.); (T.S.); (T.T.); (M.K.); (H.N.); (G.I.); (H.S.); (S.F.)
| | - Chikara Iino
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (S.S.); (T.S.); (T.T.); (M.K.); (H.N.); (G.I.); (H.S.); (S.F.)
| | - Daisuke Chinda
- Division of Endoscopy, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Takafumi Sasada
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (S.S.); (T.S.); (T.T.); (M.K.); (H.N.); (G.I.); (H.S.); (S.F.)
| | - Tetsuyuki Tateda
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (S.S.); (T.S.); (T.T.); (M.K.); (H.N.); (G.I.); (H.S.); (S.F.)
| | - Masatoshi Kaizuka
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (S.S.); (T.S.); (T.T.); (M.K.); (H.N.); (G.I.); (H.S.); (S.F.)
| | - Hiroki Nomiya
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (S.S.); (T.S.); (T.T.); (M.K.); (H.N.); (G.I.); (H.S.); (S.F.)
| | - Go Igarashi
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (S.S.); (T.S.); (T.T.); (M.K.); (H.N.); (G.I.); (H.S.); (S.F.)
| | - Kaori Sawada
- Department of Preemptive Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (K.S.); (T.M.)
| | - Tatsuya Mikami
- Department of Preemptive Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (K.S.); (T.M.)
| | - Shigeyuki Nakaji
- Center of Healthy Aging Innovation, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan;
| | - Hirotake Sakuraba
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (S.S.); (T.S.); (T.T.); (M.K.); (H.N.); (G.I.); (H.S.); (S.F.)
| | - Shinsaku Fukuda
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; (S.S.); (T.S.); (T.T.); (M.K.); (H.N.); (G.I.); (H.S.); (S.F.)
| |
Collapse
|
|
21
|
Ishida E, Furusho H, Renn TY, Shiba F, Chang HM, Oue H, Terayama R, Ago Y, Tsuga K, Miyauchi M. Mouse maternal odontogenic infection with Porphyromonas gingivalis induces cognitive decline in offspring. Front Pediatr 2023; 11:1203894. [PMID: 37635786 PMCID: PMC10450928 DOI: 10.3389/fped.2023.1203894] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 07/24/2023] [Indexed: 08/29/2023] Open
Abstract
Introduction Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, causes intrauterine infection/inflammation. Offspring exposed to intrauterine infection/inflammation have an increased risk of neurological disorders, regardless of gestational age. However, the relationship between maternal periodontitis and offspring functional/histological changes in the brain has not yet been elucidated. Methods In this study, we used a gestational mouse model to investigate the effects of maternal odontogenic infection of P. gingivalis on offspring behavior and brain tissue. Results The step-through passive avoidance test showed that the latency of the acquisition trial was significantly shorter in the P. gingivalis group (p < 0.05), but no difference in spontaneous motor/exploratory parameters by open-field test. P. gingivalis was diffusely distributed throughout the brain, especially in the hippocampus. In the hippocampus and amygdala, the numbers of neuron cells and cyclic adenosine monophosphate response element binding protein-positive cells were significantly reduced (p < 0.05), whereas the number of ionized calcium binding adapter protein 1-positive microglia was significantly increased (p < 0.05). In the hippocampus, the number of glial fibrillary acidic protein-positive astrocytes was also significantly increased (p < 0.05). Discussion The offspring of P. gingivalis-infected mothers have reduced cognitive function. Neurodegeneration/neuroinflammation in the hippocampus and amygdala may be caused by P. gingivalis infection, which is maternally transmitted. The importance of eliminating maternal P. gingivalis-odontogenic infection before or during gestation in maintenance healthy brain function in offspring should be addressed in near future.
Collapse
Affiliation(s)
- Eri Ishida
- Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hisako Furusho
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ting-Yi Renn
- Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Fumie Shiba
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hung-Ming Chang
- Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Hiroshi Oue
- Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ryuji Terayama
- Department of Maxillofacial Anatomy and Neuroscience, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yukio Ago
- Department of Cellular and Molecular Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kazuhiro Tsuga
- Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Mutsumi Miyauchi
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| |
Collapse
|
|
22
|
Liu Y, He M, Yin T, Zheng Z, Fang C, Peng S. Association of severely damaged endodontically infected tooth with carotid plaque and abnormal carotid intima-media thickness: a retrospective analysis. Clin Oral Investig 2023; 27:4677-4686. [PMID: 37294352 DOI: 10.1007/s00784-023-05094-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 05/22/2023] [Indexed: 06/10/2023]
Abstract
OBJECTIVE We investigated the association of severely damaged endodontically infected tooth with carotid artery plaque and abnormal mean carotid intima-media thickness (CIMT) ≥ 1.0 mm. METHODS A retrospective analysis of 1502 control participants and 1552 participants with severely damaged endodontically infected tooth who received routine medical and dental checkup in Health Management Center, Xiangya Hospital was performed. Carotid plaque and CIMT were measured with B-mode tomographic ultrasound. Data were analyzed using logistic and linear regression. RESULTS Severely damaged endodontically infected tooth group had a significantly higher prevalence of carotid plaque (41.62%) compared to 32.22% of carotid plaque in control group. Participants with severely damaged endodontically infected tooth had a significantly higher prevalence of abnormal CIMT (16.17%) and a significantly increased level of CIMT (0.79 ± 0.16 mm) in comparison to 10.79% of abnormal CIMT and 0.77 ± 0.14 mm CIMT in control participants. Severely damaged endodontically infected tooth was significantly related with formation of carotid plaque [1.37(1.18-1.60), P < 0.001], top quartile length [1.21(1.02-1.44), P = 0.029] and top quartile thickness [1.27(1.08-1.51), P = 0.005] of carotid plaque and abnormal CIMT [1.47(1.18-1.83), P < 0.001]. Severely damaged endodontically infected tooth was significantly associated with both single [1.277(1.056-1.546), P = 0.012] and multiple carotid plaques [1.488(1.214-1.825), P < 0.001] and instable carotid plaques [1.380(1.167-1.632), P < 0.001]. Presence of severely damaged endodontically infected tooth increased 0.588 mm of carotid plaque length (P = 0.001), 0.157 mm of carotid plaque thickness (P < 0.001) and 0.015 mm of CIMT (P = 0.005). CONCLUSION Severely damaged endodontically infected tooth was associated with carotid plaque and abnormal CIMT. CLINICAL RELEVANCE Early treatment of endodontically infected tooth is warranted.
Collapse
Affiliation(s)
- Yundong Liu
- Health Management Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
| | - Mi He
- Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China
| | - Tao Yin
- Changsha Health Vocational College, Changsha, Hunan, 410605, People's Republic of China
| | - Ziran Zheng
- Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China
| | - Changyun Fang
- Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China
| | - Shifang Peng
- Department of Infectious Diseases, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
| |
Collapse
|
|
23
|
Jia S, Li X, Du Q. Host insulin resistance caused by Porphyromonas gingivalis-review of recent progresses. Front Cell Infect Microbiol 2023; 13:1209381. [PMID: 37520442 PMCID: PMC10373507 DOI: 10.3389/fcimb.2023.1209381] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 06/27/2023] [Indexed: 08/01/2023] Open
Abstract
Porphyromonas gingivalis (P. gingivalis) is a Gram-negative oral anaerobic bacterium that plays a key role in the pathogenesis of periodontitis. P. gingivalis expresses a variety of virulence factors that disrupt innate and adaptive immunity, allowing P. gingivalis to survive and multiply in the host and destroy periodontal tissue. In addition to periodontal disease, P.gingivalis is also associated with systemic diseases, of which insulin resistance is an important pathological basis. P. gingivalis causes a systemic inflammatory response, disrupts insulin signaling pathways, induces pancreatic β-cell hypofunction and reduced numbers, and causes decreased insulin sensitivity leading to insulin resistance (IR). In this paper, we systematically review the studies on the mechanism of insulin resistance induced by P. gingivalis, discuss the association between P. gingivalis and systemic diseases based on insulin resistance, and finally propose relevant therapeutic approaches. Overall, through a systematic review of the mechanisms related to systemic diseases caused by P. gingivalis through insulin resistance, we hope to provide new insights for future basic research and clinical interventions for related systemic diseases.
Collapse
Affiliation(s)
- Shuxian Jia
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Xiaobing Li
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Qin Du
- Department of Stomatology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| |
Collapse
|
|
24
|
Sakamoto S, Nagasaki A, Shrestha M, Shintani T, Watanabe A, Furusho H, Chayama K, Takata T, Miyauchi M. Porphyromonas gingivalis-odontogenic infection is the potential risk for progression of nonalcoholic steatohepatitis-related neoplastic nodule formation. Sci Rep 2023; 13:9350. [PMID: 37291206 PMCID: PMC10250332 DOI: 10.1038/s41598-023-36553-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 06/06/2023] [Indexed: 06/10/2023] Open
Abstract
Porphyromonas gingivalis (P.g.), a major periodontal pathogen is a known risk factor for various systemic diseases. However, the relationship between P.g. and nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is unclear. Thus, we aimed to elucidate whether P.g.-odontogenic infection promotes NASH-related HCC development/progression and to clarify its mechanism. Using high-fat diet (HFD)-induced NASH mouse model, P.g. was infected odontogenically. After 60 weeks of infection, tumor profiles were examined. Chow diet (CD) groups were also prepared at 60 weeks. Nodule formation was only seen in HFD-mice. P.g.-odontogenic infection significantly increased the mean nodule area (P = 0.0188) and tended to promote histological progression score after 60 weeks (P = 0.0956). Interestingly, P.g. was detected in the liver. HFD-P.g. (+) showed numerous TNF-α positive hepatic crown-like structures and 8-OHdG expression in the non-neoplastic liver. In P.g.-infected hepatocytes, phosphorylation of integrin β1 signaling molecules (FAK/ERK/AKT) was upregulated in vitro. In fact, total AKT in the liver of HFD-P.g. (+) was higher than that of HFD-P.g. (-). P.g.-infected hepatocytes showed increased cell proliferation and migration, and decreased doxorubicin-mediated apoptosis. Integrin β1 knockdown inhibited these phenotypic changes. P.g.-odontogenic infection may promote the progression of neoplastic nodule formation in an HFD-induced NASH mouse model via integrin signaling and TNF-α induced oxidative DNA damage.
Collapse
Affiliation(s)
- Shinnichi Sakamoto
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Hiroshima, 734-8551, Japan
- Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Japan
| | - Atsuhiro Nagasaki
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Hiroshima, 734-8551, Japan
- Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Madhu Shrestha
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Hiroshima, 734-8551, Japan
- Department of Diagnostic Sciences, Texas A&M University School of Dentistry, Dallas, TX, USA
| | - Tomoaki Shintani
- Center of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima, Japan
| | - Atsushi Watanabe
- Laboratory of Research Advancement, National Center for Geriatrics and Gerontology, Research Institute, Obu, Japan
| | - Hisako Furusho
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Hiroshima, 734-8551, Japan
| | - Kazuaki Chayama
- Collaborative Research Laboratory of Medical Innovation, Hiroshima University, Hiroshima, Japan
- Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Takashi Takata
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Hiroshima, 734-8551, Japan.
- Shunan University, 843-4-2 Gakuendai, Shunan, Japan.
| | - Mutsumi Miyauchi
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Hiroshima, 734-8551, Japan.
| |
Collapse
|
|
25
|
Tan X, Wang Y, Gong T. The interplay between oral microbiota, gut microbiota and systematic diseases. J Oral Microbiol 2023; 15:2213112. [PMID: 37200866 PMCID: PMC10187086 DOI: 10.1080/20002297.2023.2213112] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 05/02/2023] [Accepted: 05/08/2023] [Indexed: 05/20/2023] Open
Abstract
Over the past two decades, the importance of microbiota in health and disease has become evident. The human gut microbiota and oral microbiota are the largest and second-largest microbiome in the human body, respectively, and they are physically connected as the oral cavity is the beginning of the digestive system. Emerging and exciting evidence has shown complex and important connections between gut microbiota and oral microbiota. The interplay of the two microbiomes may contribute to the pathological processes of many diseases, including diabetes, rheumatoid arthritis, nonalcoholic fatty liver disease, inflammatory bowel disease, pancreatic cancer, colorectal cancer, and so on. In this review, we discuss possible routes and factors of oral microbiota to affect gut microbiota, and the contribution of this interplay between oral and gut microbiota to systemic diseases. Although most studies are association studies, recently, there have been increasing mechanistic investigations. This review aims to enhance the interest in the connection between oral and gut microbiota, and shows the tangible impact of this connection on human health.
Collapse
Affiliation(s)
- Xiujun Tan
- Stomatological Hospital of Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Yizhong Wang
- Department of Research & Development, Zhejiang Charioteer Pharmaceutical CO. LTD, Taizhou, China
| | - Ting Gong
- Stomatological Hospital of Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| |
Collapse
|
|
26
|
Kobayashi T, Iwaki M, Nogami A, Honda Y, Ogawa Y, Imajo K, Saito S, Nakajima A, Yoneda M. Involvement of Periodontal Disease in the Pathogenesis and Exacerbation of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis: A Review. Nutrients 2023; 15:1269. [PMID: 36904268 PMCID: PMC10004797 DOI: 10.3390/nu15051269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 02/23/2023] [Accepted: 02/28/2023] [Indexed: 03/08/2023] Open
Abstract
The increasing incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), along with global lifestyle changes, requires further in-depth research to elucidate the mechanisms and develop new treatment strategies. In addition, the number of patients with periodontal disease has increased recently, suggesting that periodontal disease is sometimes associated with systemic conditions. In this review, we summarize recent studies linking periodontal disease and NAFLD, the concept of the mouth-gut-liver axis, oral and intestinal microbiota, and liver disease. We suggest new research directions toward a detailed mechanistic understanding and novel targets for treatment and prevention. Forty years have passed since the concepts of NAFLD and NASH were first proposed. however, no effective prevention or treatment has been established. We also found that the pathogenesis of NAFLD/NASH is not limited to liver-related diseases but has been reported to be associated with various systemic diseases and an increasing number of causes of death. In addition, changes in the intestinal microbiota have been shown to be a risk factor for periodontal diseases, such as atherosclerosis, diabetes, rheumatoid arthritis, nonalcoholic fatty liver disease, and obesity.
Collapse
Affiliation(s)
- Takashi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa, Yokohama 236-0004, Japan
| | - Michihiro Iwaki
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa, Yokohama 236-0004, Japan
| | - Asako Nogami
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa, Yokohama 236-0004, Japan
| | - Yasushi Honda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa, Yokohama 236-0004, Japan
| | - Yuji Ogawa
- National Hospital Organization Yokohama Medical Center, Gastroenterology Division, 3-60-2 Harajyuku, Yokohama 245-8575, Japan
| | - Kento Imajo
- Department of Gastroenterology, Shin-Yurigaoka General Hospital, 255 Tsuko, Furusawa, Kawasaki 215-0026, Japan
| | - Satoru Saito
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa, Yokohama 236-0004, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa, Yokohama 236-0004, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa, Yokohama 236-0004, Japan
| |
Collapse
|
|
27
|
Pischke S, Shiprov A, Peters U, Schulze Zur Wiesch J, Kluwe J, Westphal T, Fischer F, Mader M, Fründt T, Horvatits K, Horvatits T, Aarabi G, Beikler T. High prevalence of periodontal disease in patients with NASH- possible association of poor dental health with NASH severity. Ann Hepatol 2023; 28:100887. [PMID: 36646168 DOI: 10.1016/j.aohep.2022.100887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 11/28/2022] [Accepted: 12/14/2022] [Indexed: 01/18/2023]
Abstract
INTRODUCTION AND OBJECTIVES Recent translational research indicated a bidirectional relationship between NASH (non-alcoholic steatohepatitis) and periodontitis; however, few clinical cohorts have studied this in detail. Thus we investigated this assumed association in a well-defined cohort. MATERIALS AND METHODS Data were generated prospectively for 132 patients (32 patients with NASH and 100 unselected, consecutively collected, anonymized controls from a local dental practice): detailed periodontal parameters, i.e., pocket-probing-depths (PPD), bleeding-on-probing (BOP), plaque-index, and utilization of dental care were assessed and correlated with relevant hepatic parameters (liver stiffness via fibroscan, AST, ALT, bilirubin, and MELD-score). Gingiva samples were tested for Porphyromonas gingvalis (P.g.) and Actinobacillus actinomyctemcomitans (A.a.) by PCR. RESULTS 87.5% of NASH patients and 47% of controls suffered from moderate to severe periodontitis (p=0.01). Liver stiffness was significantly correlated with elevated PPD (p=0.02) and BOP (p=0.03). 34 % of the NASH patients did not make use of regular dental health care. In these patients, AST (p=0.04), MELD score (p<0.01), and liver stiffness (p=0.01) were significantly elevated compared to those who see a dentist regularly. The severity of NASH was not associated with the intraoral detection of P.g. and A.a. CONCLUSIONS The present study suggests that NASH might be associated with periodontitis, irrespective of the intraoral presence of P.g. and A.a. Moreover, regular dental care utilization might mitigate the course of NASH, and patients should be reminded by their hepatologists of the importance of regular dental visits. Future studies should investigate the role of regular dental care and additional anti-inflammatory treatments of the oral cavity.
Collapse
Affiliation(s)
- Sven Pischke
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner Sites, Germany.
| | - Anita Shiprov
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Periodontics, Preventive and Restorative Dentistry, University Medical Centre Hamburg-Eppendorf, Germany
| | - Ulrike Peters
- Department of Periodontics, Preventive and Restorative Dentistry, University Medical Centre Hamburg-Eppendorf, Germany
| | - Julian Schulze Zur Wiesch
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner Sites, Germany
| | - Johannes Kluwe
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Tim Westphal
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Frank Fischer
- Department of Periodontics, Preventive and Restorative Dentistry, University Medical Centre Hamburg-Eppendorf, Germany
| | - Maria Mader
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Thorben Fründt
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Karoline Horvatits
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Thomas Horvatits
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ghazal Aarabi
- Department of Periodontics, Preventive and Restorative Dentistry, University Medical Centre Hamburg-Eppendorf, Germany
| | - Thomas Beikler
- Department of Periodontics, Preventive and Restorative Dentistry, University Medical Centre Hamburg-Eppendorf, Germany
| |
Collapse
|
|
28
|
Liu L, Geng Y, Xiong C. Impact of Porphyromonas gingivalis-odontogenic infection on the pathogenesis of non-alcoholic fatty liver disease. Ann Med 2023; 55:2255825. [PMID: 37708866 PMCID: PMC10503456 DOI: 10.1080/07853890.2023.2255825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 06/15/2023] [Accepted: 09/01/2023] [Indexed: 09/16/2023] Open
Abstract
Aim: Non-alcoholic fatty liver disease is characterized by diffuse hepatic steatosis and has quickly risen to become the most prevalent chronic liver disease. Its incidence is increasing yearly, but the pathogenesis is still not fully understood. Porphyromonas gingivalis (P. gingivalis) is a major pathogen widely prevalent in periodontitis patients. Its infection has been reported to be a risk factor for developing insulin resistance, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and metabolic syndrome. The aim of this review is to evaluate the association between P. gingivalis infection and NAFLD, identify the possible etiopathogenetic mechanisms, and raise public awareness of oral health to prevent and improve NAFLD.Methods: After searching in PubMed and Web of Science databases using 'Porphyromonas gingivalis', 'non-alcoholic fatty liver disease', and 'hepatic steatosis' as keywords, studies related were compiled and examined.Results: P. gingivalis infection is a direct risk factor for NAFLD based on clinical and basic research. Moreover, it induces systematic changes and systemic abnormalities by disrupting metabolic, inflammatory, and immunologic homeostasis.Conclusion: P. gingivalis-odontogenic infection promotes the occurrence and development of NAFLD. Further concerns are needed to emphasize oral health and maintain good oral hygiene for the prevention and treatment of NAFLD.
Collapse
Affiliation(s)
- Linbo Liu
- Department of Clinical Laboratory, Yulin No.2 Hospital, Yulin, Shaanxi, China
| | - Yan Geng
- Department of Clinical Laboratory, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Chaoliang Xiong
- Department of Clinical Laboratory, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| |
Collapse
|
|
29
|
Equisetum arvense Inhibits Alveolar Bone Destruction in a Rat Model with Lipopolysaccharide (LPS)-Induced Periodontitis. Int J Dent 2022; 2022:7398924. [PMID: 36794024 PMCID: PMC9925265 DOI: 10.1155/2022/7398924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 10/31/2022] [Accepted: 11/08/2022] [Indexed: 12/31/2022] Open
Abstract
Background and Aims Equisetum arvense extract (EA) exerts various biological effects, including anti-inflammatory activity. The effect of EA on alveolar bone destruction has not been reported; therefore, we aimed to determine whether EA could inhibit alveolar bone destruction associated with periodontitis in a rat model in which periodontitis was induced using lipopolysaccharide from Escherichia coli (E. coli-LPS). Methods Physiological saline or E. coli-LPS or E. coli-LPS/EA mixture was topically administered into the gingival sulcus of the upper molar region of the rats. After 3 days, periodontal tissues of the molar region were collected. Immunohistochemistry was performed for cathepsin K, receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG). The cathepsin K-positive osteoclasts along the alveolar bone margin were counted. EA effects on the expression of the factors regulating osteoclastogenesis in osteoblasts with E. coli-LPS-stimulation were also examined in vitro. Results Treatment with EA significantly reduced the number of osteoclasts by decreasing the RANKL-expression and increasing OPG-expression in the periodontal ligament in the treatment group compared to the E. coli-LPS group. The in vitro study showed that the upregulation of p-IκB kinase α and β (p-IKKα/β), p-NF-κB p65, TNF-α, interleukin-6, and RANKL and downregulation of semaphorin 3A (Sema3A), β-catenin, and OPG in the osteoblasts with E. coli-LPS-stimulation improved with EA-treatment. Conclusion These findings demonstrated that topical EA suppressed alveolar bone resorption in the rat model with E. coli-LPS-induced periodontitis by maintaining a balance in RANKL/OPG ratio via the pathways of NF-κB, Wnt/β-catenin, and Sema3A/Neuropilin-1. Therefore, EA possesses the potential to prevent bone destruction through inhibiting osteoclastogenesis attributed to cytokine burst under plaque accumulation.
Collapse
|
|
30
|
Li C, Yu R, Ding Y. Association between Porphyromonas Gingivalis and systemic diseases: Focus on T cells-mediated adaptive immunity. Front Cell Infect Microbiol 2022; 12:1026457. [PMID: 36467726 PMCID: PMC9712990 DOI: 10.3389/fcimb.2022.1026457] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 10/25/2022] [Indexed: 12/01/2023] Open
Abstract
The association between periodontal disease and systemic disease has become a research hotspot. Porphyromonas gingivalis (P. gingivalis), a crucial periodontal pathogen, affects the development of systemic diseases. The pathogenicity of P. gingivalis is largely linked to interference with the host's immunity. This review aims to discover the role of P. gingivalis in the modulation of the host's adaptive immune system through a large number of virulence factors and the manipulation of cellular immunological responses (mainly mediated by T cells). These factors may affect the cause of large numbers of systemic diseases, such as atherosclerosis, hypertension, adverse pregnancy outcomes, inflammatory bowel disease, diabetes mellitus, non-alcoholic fatty liver disease, rheumatoid arthritis, and Alzheimer's disease. The point of view of adaptive immunity may provide a new idea for treating periodontitis and related systemic diseases.
Collapse
Affiliation(s)
- Cheng Li
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| | - Ran Yu
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| | - Yumei Ding
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| |
Collapse
|
|
31
|
Sato S, Kamata Y, Kessoku T, Shimizu T, Kobayashi T, Kurihashi T, Takashiba S, Hatanaka K, Hamada N, Kodama T, Higurashi T, Taguri M, Yoneda M, Usuda H, Wada K, Nakajima A, Morozumi T, Minabe M. A cross-sectional study assessing the relationship between non-alcoholic fatty liver disease and periodontal disease. Sci Rep 2022; 12:13621. [PMID: 35948584 PMCID: PMC9365789 DOI: 10.1038/s41598-022-17917-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 08/02/2022] [Indexed: 11/09/2022] Open
Abstract
The risk factors for non-alcoholic fatty liver disease (NAFLD) progression are not completely known. Porphyromonas gingivalis infection is a risk factor for systemic diseases. We investigated the association of P. gingivalis infection with the risk of non-alcoholic steatohepatitis progression. Here, hematological tests, periodontal examination, and saliva collection were performed for 164 patients with NAFLD. P. gingivalis was identified in saliva using polymerase chain reaction. Hepatic steatosis and stiffness were evaluated using vibration-controlled transient elastography (VCTE) and magnetic resonance imaging. In patients with NAFLD, P. gingivalis positivity (P. gingivalis ratio ≥ 0.01%) in saliva correlated with liver stiffness determined using magnetic resonance elastography (MRE; p < 0.0001). A P. gingivalis ratio of 0.01% corresponds to 100,000 cells/mL and indicates the proportion of P. gingivalis in the total number of bacteria in the oral cavity. Patients with NAFLD and advanced fibrosis on MRE showed significantly elevated endotoxin activity; those who had > 10 periodontal pockets with depths ≥ 4 mm had significantly increased hepatic stiffness on both VCTE and MRE.
Collapse
Affiliation(s)
- Satsuki Sato
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Yohei Kamata
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan.
| | - Takaomi Kessoku
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Tomoko Shimizu
- Department of Highly Advanced Oral Stomatology, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Takashi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Takeo Kurihashi
- Department of Internal Medicine, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Shogo Takashiba
- Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan
| | - Kazu Hatanaka
- Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan
| | - Nobushiro Hamada
- Division of Microbiology, Department of Oral Science Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Toshiro Kodama
- Department of Implantology and Periodontology, Graduate School of Dentistry, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan
| | - Takuma Higurashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Masataka Taguri
- Department of Biostatistics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Haruki Usuda
- Department of Pharmacology, Shimane University School of Medicine, 89-1 Enya-cho Izumo, Shimane, 693-0581, Japan
| | - Koichiro Wada
- Department of Pharmacology, Shimane University School of Medicine, 89-1 Enya-cho Izumo, Shimane, 693-0581, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Toshiya Morozumi
- Division of Periodontology, Department of Oral Interdisciplinary Medicine, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Masato Minabe
- Division of Periodontology, Department of Oral Interdisciplinary Medicine, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| |
Collapse
|
|
32
|
Teraoka Y, Sugimoto J, Konishi H, Miyoshi H, Furusho H, Miyauchi M, Kajioka S, Koh I, Kudo Y. Progesterone Suppresses Uterine Contraction by Reducing Odontogenic Porphyromonas gingivalis Induced Chronic Inflammation in Mice. Biomolecules 2022; 12:biom12081029. [PMID: 35892338 PMCID: PMC9332501 DOI: 10.3390/biom12081029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/22/2022] [Accepted: 07/22/2022] [Indexed: 12/10/2022] Open
Abstract
Preterm birth is one of the most significant obstetric complications. Inflammation reportedly promotes uterine contraction and weakening of the fetal membrane, which induces preterm birth. Previous studies using animal models of lipopolysaccharide-induced acute inflammation have shown that progesterone (P4) promotes uterine quiescence. However, this effect is not fully understood in chronic inflammation. This study aimed to investigate the effects of P4 on uterine contractility and inflammation of the fetal membrane in mice infected with Porphyromonas gingivalis (P.g.), a major periodontal pathogen as a model of preterm birth caused by chronic inflammation. Mice were injected with 1 mg of P4 from day 15.5 to 17.5. P4 prolonged the mean gestation period of P.g mice from 18.3 to 20.4 days, and no reduction in the gestation period was observed. P4 treatment suppressed spontaneous uterine contractility and decreased oxytocin sensitivity. In addition, the expression of inflammatory cytokines in the fetal membrane was significantly reduced. Thus, P4 prevented preterm birth by suppressing enhanced uterine contractility induced by chronic inflammation in this model. This result describes the effects of P4 in a chronic inflammation model, which may lead to a better understanding of the efficacy of P4 in preventing preterm birth in humans.
Collapse
Affiliation(s)
- Yuko Teraoka
- Department of Obstetrics and Gynecology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (J.S.); (I.K.); (Y.K.)
- Correspondence:
| | - Jun Sugimoto
- Department of Obstetrics and Gynecology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (J.S.); (I.K.); (Y.K.)
| | - Haruhisa Konishi
- Department of Obstetrics and Gynecology, Miyoshi Central Hospital, Miyoshi 728-8502, Japan;
| | - Hiroshi Miyoshi
- Department of Obstetrics and Gynecology, Hiroshima Prefectural Hospital, Hiroshima 734-0004, Japan;
| | - Hisako Furusho
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (H.F.); (M.M.)
| | - Mutsumi Miyauchi
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (H.F.); (M.M.)
| | - Shunichi Kajioka
- Department of Pharmaceutical Sciences, School of Pharmacy at Fukuoka, International University of Health Welfare, Fukuoka 812-8582, Japan;
| | - Iemasa Koh
- Department of Obstetrics and Gynecology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (J.S.); (I.K.); (Y.K.)
| | - Yoshiki Kudo
- Department of Obstetrics and Gynecology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (J.S.); (I.K.); (Y.K.)
| |
Collapse
|
|
33
|
Xu W, Zhang Z, Yao L, Xue B, Xi H, Wang X, Sun S. Exploration of Shared Gene Signatures and Molecular Mechanisms Between Periodontitis and Nonalcoholic Fatty Liver Disease. Front Genet 2022; 13:939751. [PMID: 35836570 PMCID: PMC9273910 DOI: 10.3389/fgene.2022.939751] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 05/16/2022] [Indexed: 12/28/2022] Open
Abstract
Background: Periodontitis is associated with periodontal tissue damage and teeth loss. Nonalcoholic fatty liver disease (NAFLD) has an intimate relationship with periodontitis. Nevertheless, interacted mechanisms between them have not been clear. This study was intended for the exploration of shared gene signatures and latent therapeutic targets in periodontitis and NAFLD. Methods: Microarray datasets of periodontitis and NAFLD were obtained from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network analysis (WGCNA) was utilized for the acquisition of modules bound up with NAFLD and periodontitis. We used ClueGO to carry out biological analysis on shared genes to search their latent effects in NAFLD and periodontitis. Another cohort composed of differential gene analysis verified the results. The common microRNAs (miRNAs) in NAFLD and periodontitis were acquired in the light of the Human microRNA Disease Database (HMDD). According to miRTarbase, miRDB, and Targetscan databases, latent target genes of miRNAs were forecasted. Finally, the miRNAs–mRNAs network was designed. Results: Significant modules with periodontitis and NAFLD were obtained via WGCNA. GO enrichment analysis with GlueGo indicated that damaged migration of dendritic cells (DCs) might be a common pathophysiologic feature of NAFLD and periodontitis. In addition, we revealed common genes in NAFLD and periodontitis, including IGK, IGLJ3, IGHM, MME, SELL, ENPP2, VCAN, LCP1, IGHD, FCGR2C, ALOX5AP, IGJ, MMP9, FABP4, IL32, HBB, FMO1, ALPK2, PLA2G7, MNDA, HLA-DRA, and SLC16A7. The results of differential analysis in another cohort were highly accordant with the findings of WGCNA. We established a comorbidity model to explain the underlying mechanism of NAFLD secondary to periodontitis. Finally, the analysis of miRNA pointed out that hsa-mir-125b-5p, hsa-mir-17-5p, and hsa-mir-21-5p might provide potential therapeutic targets. Conclusion: Our study initially established a comorbidity model to explain the underlying mechanism of NAFLD secondary to periodontitis, found that damaged migration of DCs might be a common pathophysiological feature of NAFLD and periodontitis, and provided potential therapeutic targets.
Collapse
Affiliation(s)
- Wanqiu Xu
- Department of Dentistry, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhengwei Zhang
- Ward 7, Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lihong Yao
- Department of Dentistry, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Bing Xue
- Department of Dentistry, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hualei Xi
- Department of Dentistry, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiumei Wang
- Department of Dentistry, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
- *Correspondence: Xiumei Wang, ; Shibo Sun,
| | - Shibo Sun
- Ward 7, Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
- *Correspondence: Xiumei Wang, ; Shibo Sun,
| |
Collapse
|
|
34
|
Bai L, Wang YL, Chen YL, Li HX, Zhu SW, Liu Y, Song ZC, Duan SZ. The combination of experimental periodontitis and oral microbiota from periodontitis patients aggravates liver fibrosis in mice. J Clin Periodontol 2022; 49:1067-1078. [PMID: 35713233 DOI: 10.1111/jcpe.13682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 04/22/2022] [Accepted: 06/10/2022] [Indexed: 11/29/2022]
Abstract
AIM Periodontitis (PD) is the sixth most prevalent disease around the world and is involved in the development and progression of multiple systemic diseases. Previous studies have reported that PD may aggravate liver injuries. The objective of this study was to investigate whether and how PD affects liver fibrosis. MATERIALS AND METHODS Ligature-induced PD (LIP) was induced in male C57/B6J mice, and sub-gingival plaques (PL) from patients with PD were applied to mouse teeth. Liver fibrosis was induced by carbon tetrachloride (CCl4 ) injection. The mice were randomly divided into six groups: Oil, Oil+LIP, Oil+LIP+PL, CCl4 , CCl4 +LIP, and CCl4 +LIP+PL. Alveolar bone resorption was evaluated by methylene blue staining. Hepatic function was analysed by serum alanine aminotransferase and hepatic hydroxyproline. Picrosirius red and α-smooth muscle actin (SMA) staining were used to evaluate the fibrotic area. RNA sequencing and quantitative RT-PCR were used to measure gene expression. Western blotting was used to measure protein levels. Flow cytometry was used to analyse the accumulation of immune cells. Mouse microbiota were analysed using 16S rRNA gene sequencing. RESULTS Mice in the CCl4 +LIP+PL group displayed higher serum alanine aminotransferase and hepatic hydroxyproline as well as more Picrosirius red-positive and α-SMA-positive areas in liver samples than those of the CCl4 group, suggesting that PD (LIP+PL) aggravated CCl4 -induced hepatic dysfunction and liver fibrosis. Consistently, the expression of fibro-genic genes and the protein levels of transforming growth factor β were much higher in the CCl4 +LIP+PL group than in the CCl4 group. Flow cytometry revealed that PD increased the accumulation of immune cells, including Kupffer cells, B cells, and Th17 cells, in the liver of mice with CCl4 treatment. PD also increased the expression of inflammatory genes and activated pro-inflammatory nuclear factor-kappa B pathway in the livers of CCl4 -injected mice. Moreover, PD altered both oral and liver microbiota in CCl4 -injected mice. CONCLUSIONS PD aggravates CCl4 -induced hepatic dysfunction and fibrosis in mice, likely through the increase of inflammation and alteration of microbiota in the liver.
Collapse
Affiliation(s)
- Lan Bai
- Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Yong-Li Wang
- Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Yan-Lin Chen
- Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hu-Xiao Li
- Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Shi-Wei Zhu
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yan Liu
- Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Zhong-Chen Song
- Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Sheng-Zhong Duan
- Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| |
Collapse
|
|
35
|
Wu L, Shi R, Bai H, Wang X, Wei J, Liu C, Wu Y. Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk. Front Cell Infect Microbiol 2022; 12:776996. [PMID: 35360107 PMCID: PMC8961321 DOI: 10.3389/fcimb.2022.776996] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 02/17/2022] [Indexed: 11/13/2022] Open
Abstract
Porphyromonas gingivalis, a keystone periodontal pathogen, has emerged as a risk factor for systemic chronic diseases, including non-alcoholic fatty liver disease (NAFLD). To clarify the mechanism by which this pathogen induces such diseases, we simultaneously analyzed the transcriptome of intracellular P. gingivalis and infected host cells via dual RNA sequencing. Pathway analysis was also performed to determine the differentially expressed genes in the infected cells. Further, the infection-induced notable expression of P. gingivalis livk and livh genes, which participate in branched-chain amino acid (BCAA) transfer, was also analyzed. Furthermore, given that the results of recent studies have associated NAFLD progression with elevated serum BCAA levels, which reportedly, are upregulated by P. gingivalis, we hypothesized that this pathogen may induce increases in serum BCAA levels and exacerbate liver injury via livh/livk. To verify this hypothesis, we constructed P. gingivalis livh/livk-deficient strains (Δlivk, Δlivh) and established a high-fat diet (HFD)-fed murine model infected with P. gingivalis. Thereafter, the kinetic growth and exopolysaccharide (EPS) production rates as well as the invasion efficiency and in vivo colonization of the mutant strains were compared with those of the parental strain. The serum BCAA and fasting glucose levels of the mice infected with either the wild-type or mutant strains, as well as their liver function were also further investigated. It was observed that P. gingivalis infection enhanced serum BCAA levels and aggravated liver injury in the HFD-fed mice. Additionally, livh deletion had no effect on bacterial growth, EPS production, invasion efficiency, and in vivo colonization, whereas the Δlivk strain showed a slight decrease in invasion efficiency and in vivo colonization. More importantly, however, both the Δlivk and Δlivh strains showed impaired ability to upregulate serum BCAA levels or exacerbate liver injury in HFD-fed mice. Overall, these results suggested that P. gingivalis possibly aggravates NAFLD progression in HFD-fed mice by increasing serum BCAA levels, and this effect showed dependency on the bacterial BCAA transport system.
Collapse
Affiliation(s)
- Leng Wu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Department of Periodontics, Sichuan University, Chengdu, China
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rui Shi
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Department of Periodontics, Sichuan University, Chengdu, China
- Department of Periodontics and Oral Mucosal Diseases, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, China
| | - Huimin Bai
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Department of Periodontics, Sichuan University, Chengdu, China
| | - Xingtong Wang
- Department of Hematology, Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Jian Wei
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chengcheng Liu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Department of Periodontics, Sichuan University, Chengdu, China
- *Correspondence: Chengcheng Liu, ; Yafei Wu,
| | - Yafei Wu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Department of Periodontics, Sichuan University, Chengdu, China
- *Correspondence: Chengcheng Liu, ; Yafei Wu,
| |
Collapse
|
|
36
|
Albuquerque-Souza E, Sahingur SE. Periodontitis, chronic liver diseases, and the emerging oral-gut-liver axis. Periodontol 2000 2022; 89:125-141. [PMID: 35244954 PMCID: PMC9314012 DOI: 10.1111/prd.12427] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The liver carries out a wide range of functions ranging from the control of metabolites, nutrient storage, and detoxification to immunosurveillance. While inflammation is essential for the tissue remodeling and maintenance of homeostasis and normal liver physiology, constant exposure to dietary and microbial products creates a niche for potentially prolonged immune activation and unresolved inflammation in susceptible host. Failure to restrain inflammation can lead to development of chronic liver diseases characterized by fibrosis, cirrhosis and eventually liver failure. The liver maintains close interactions with numerous organs which can influence its metabolism and physiology. It is also known that oral cavity microenvironment can influence the physiological conditions of other organs and emerging evidence implicates that this could be true for the liver as well. Presence of chronic inflammation and dysbiotic microbiota is a common feature leading to clinical pathology both in periodontitis and chronic liver diseases (CLDs). In fact, known CLDs appear to have some relationship with periodontitis, which impacts the onset or progression of these conditions in a bidirectional crosstalk. In this review, we explore the emerging association between oral‐gut‐liver axis focusing on periodontitis and common CLDs including nonalcoholic fatty liver disease, chronic viral hepatitis, liver cirrhosis, and hepatocellular cancer. We highlight the immune pathways and oral microbiome interactions which can link oral cavity and liver health and offer perspectives for future research.
Collapse
Affiliation(s)
- Emmanuel Albuquerque-Souza
- Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Sinem E Sahingur
- Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| |
Collapse
|
|
37
|
Pussinen PJ, Kopra E, Pietiäinen M, Lehto M, Zaric S, Paju S, Salminen A. Periodontitis and cardiometabolic disorders: The role of lipopolysaccharide and endotoxemia. Periodontol 2000 2022; 89:19-40. [PMID: 35244966 PMCID: PMC9314839 DOI: 10.1111/prd.12433] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Lipopolysaccharide is a virulence factor of gram-negative bacteria with a crucial importance to the bacterial surface integrity. From the host's perspective, lipopolysaccharide plays a role in both local and systemic inflammation, activates both innate and adaptive immunity, and can trigger inflammation either directly (as a microbe-associated molecular pattern) or indirectly (by inducing the generation of nonmicrobial, danger-associated molecular patterns). Translocation of lipopolysaccharide into the circulation causes endotoxemia, which is typically measured as the biological activity of lipopolysaccharide to induce coagulation of an aqueous extract of blood cells of the assay. Apparently healthy subjects have a low circulating lipopolysaccharide activity, since it is neutralized and cleared rapidly. However, chronic endotoxemia is involved in the pathogenesis of many inflammation-driven conditions, especially cardiometabolic disorders. These include atherosclerotic cardiovascular diseases, obesity, liver diseases, diabetes, and metabolic syndrome, where endotoxemia has been recognized as a risk factor. The main source of endotoxemia is thought to be the gut microbiota. However, the oral dysbiosis in periodontitis, which is typically enriched with gram-negative bacterial species, may also contribute to endotoxemia. As endotoxemia is associated with an increased risk of cardiometabolic disorders, lipopolysaccharide could be considered as a molecular link between periodontal microbiota and cardiometabolic diseases.
Collapse
Affiliation(s)
- Pirkko J Pussinen
- Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Elisa Kopra
- Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Milla Pietiäinen
- Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Markku Lehto
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Clinical and Molecular Metabolism, Faculty of Medicine Research Programs, University of Helsinki, Helsinki, Finland
| | - Svetislav Zaric
- Faculty of Dentistry, Oral & Craniofacial Sciences, Kings College London, London, UK
| | - Susanna Paju
- Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Aino Salminen
- Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| |
Collapse
|
|
38
|
Simas AM, Kramer CD, Genco CA. Diet-Induced Non-alcoholic Fatty Liver Disease and Associated Gut Dysbiosis Are Exacerbated by Oral Infection. FRONTIERS IN ORAL HEALTH 2022; 2:784448. [PMID: 35141703 PMCID: PMC8820505 DOI: 10.3389/froh.2021.784448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 12/29/2021] [Indexed: 11/13/2022] Open
Abstract
Increasing evidence indicates that chronic inflammation due to periodontal disease is associated with progression of non-alcoholic fatty liver disease (NAFLD) caused by a Western diet. NAFLD has also been associated with oral infection with the etiological agent of periodontal disease, Porphyromonas gingivalis. P. gingivalis oral infection has been shown to induce cardiometabolic disease features including hepatic lipid accumulation while also leading to dysbiosis of the gut microbiome. However, the impact of P. gingivalis infection on the gut microbiota of mice with diet-induced NAFLD and the potential for those changes to mediate NAFLD progression has yet to be determined. In the current study, we have demonstrated that P. gingivalis infection induced sustained alterations of the gut microbiota composition and predicted functions, which was associated with the promotion of NAFLD in steatotic mice. Reduced abundance of short-chain fatty acid-producing microbiota was observed after both acute and chronic P. gingivalis infection. Collectively, our findings demonstrate that P. gingivalis infection produces a persistent change in the gut microbiota composition and predicted functions that promotes steatosis and metabolic disease.
Collapse
Affiliation(s)
- Alexandra M. Simas
- Gerald J. and Dorothy R. Friedman School of Nutrition and Science Policy, Graduate Program in Biochemical and Molecular Nutrition, Tufts University, Boston, MA, United States
- Department of Immunology, Tufts University School of Medicine, Boston, MA, United States
| | - Carolyn D. Kramer
- Department of Immunology, Tufts University School of Medicine, Boston, MA, United States
| | - Caroline A. Genco
- Department of Immunology, Tufts University School of Medicine, Boston, MA, United States
- Graduate Program in Immunology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA, United States
- Graduate Program in Molecular Microbiology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA, United States
- *Correspondence: Caroline A. Genco
| |
Collapse
|
|
39
|
Oral Health and Liver Disease: Bidirectional Associations—A Narrative Review. Dent J (Basel) 2022; 10:dj10020016. [PMID: 35200242 PMCID: PMC8870998 DOI: 10.3390/dj10020016] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/11/2022] [Accepted: 01/18/2022] [Indexed: 12/04/2022] Open
Abstract
Several links between chronic liver disease and oral health have been described and are discussed in this narrative review. Oral manifestations such as lichen planus, ulcers, xerostomia, erosion and tongue abnormalities seem to be particularly prevalent among patients with chronic liver disease. These may be causal, coincidental, secondary to therapeutic interventions, or attributable to other factors commonly observed in liver disease patients. In addition, findings from both experimental and epidemiological studies suggest that periodontitis can induce liver injury and contribute to the progression of chronic liver disease through periodontitis-induced systemic inflammation, endotoxemia, and gut dysbiosis with increased intestinal translocation. This has brought forward the hypothesis of an oral-gut-liver axis. Preliminary clinical intervention studies indicate that local periodontal treatments may lead to beneficial liver effects, but more human studies are needed to clarify if treatment of periodontitis truly can halt or reverse progression of liver disease and improve liver-related outcomes.
Collapse
|
|
40
|
The Periodontopathic Pathogen, Porphyromonas gingivalis, Involves a Gut Inflammatory Response and Exacerbates Inflammatory Bowel Disease. Pathogens 2022; 11:pathogens11010084. [PMID: 35056032 PMCID: PMC8779656 DOI: 10.3390/pathogens11010084] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 01/07/2022] [Accepted: 01/08/2022] [Indexed: 12/13/2022] Open
Abstract
Periodontal disease (PD) is one of the most prevalent disorders globally and is strongly associated with many other diseases. Inflammatory bowel disease (IBD), an inflammatory condition of the colon and the small intestine, is reported to be associated with PD through undetermined mechanisms. We analyzed taxonomic assignment files from the Crohn’s Disease Viral and Microbial Metagenome Project (PRJEB3206). The abundance of Porphyromonadaceae in fecal samples was significantly different between patients with Crohn’s disease and control volunteers. Dextran sulfate sodium was used to induce colitis in mice to reveal the effect of this periodontopathic pathogen in vivo. After intrarectal implantation of Porphyromonas gingivalis (Pg)—the primary pathogen causing PD—the disease activity index score, colonic epithelial loss, and inflammatory cell infiltration were intensified. In addition, tumor necrosis factor-α and interleukin-6 showed the highest levels in Pg-infected colons. This revealed the importance of Pg in the exacerbation of IBD. Thus, simultaneous treatment of PD should be considered for people with IBD. Moreover, implantation of Pg in the rectum worsened the clinical symptoms of colitis in mice. Because Pg participates in the pathogenesis of IBD, reducing the chances of it entering the intestine might prevent the worsening of this disorder.
Collapse
|
|
41
|
Thalla S, Kamaraj R, Kavitha A. Increasing risk factors of non-alcoholic fatty liver disease, a look into chronic periodontitis and insulin resistance. Endocr Metab Immune Disord Drug Targets 2022; 22:807-814. [PMID: 34983354 DOI: 10.2174/1871530322666220104095534] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 10/21/2021] [Accepted: 10/27/2021] [Indexed: 11/22/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is marked by the excessive intrusion of triglycerides into hepatocytes without any role of alcohol consumption. Various risk factors have been attributed to this disease pathogenesis which involves metabolic disorders, immune response, and even an intricate relationship between the two. The role of insulin resistance (IR) in NAFLD has long been known; however, the molecular basis of disease progression under this metabolic backdrop is still being investigated. Similarly, the periodontitis-mediated immune response is another major factor involved in NAFLD manifestation which has generated huge interest. The prevalence of pathogenic bacteria elicits a strong immune response which according to studies shows a strong correlation with NAFLD state. Such pre-existing conditions have a strong probability of explaining the disease onset. Additionally, increasing reports of inflammatory response and its links to insulin resistance have further increased the scope of understanding NAFLD. Through this review, we aim to elaborate on these factors explaining their role in the disease progression.
Collapse
Affiliation(s)
- Sreenu Thalla
- Department of Pharmacology, SRM College of Pharmacy, SRMIST, Kattankalathur, Tamil Nadu - 603203
| | - Kamaraj R
- SRM College of Pharmacy, SRMIST, Kattankalathur, Tamil Nadu - 603203
| | - Kavitha A
- Department of Gastroenterology, Guntur Medical College & Government General Hospital, Guntur, Andhra Pradesh - 522004
| |
Collapse
|
|
42
|
Wang T, Ishikawa T, Sasaki M, Chiba T. Oral and Gut Microbial Dysbiosis and Non-alcoholic Fatty Liver Disease: The Central Role of Porphyromonas gingivalis. Front Med (Lausanne) 2022; 9:822190. [PMID: 35308549 PMCID: PMC8924514 DOI: 10.3389/fmed.2022.822190] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/19/2022] [Indexed: 02/05/2023] Open
Abstract
Gut microbiota play many important roles, such as the regulation of immunity and barrier function in the intestine, and are crucial for maintaining homeostasis in living organisms. The disruption in microbiota is called dysbiosis, which has been associated with various chronic inflammatory conditions, food allergies, colorectal cancer, etc. The gut microbiota is also affected by several other factors such as diet, antibiotics and other medications, or bacterial and viral infections. Moreover, there are some reports on the oral-gut-liver axis indicating that the disruption of oral microbiota affects the intestinal biota. Non-alcoholic fatty liver disease (NAFLD) is one of the systemic diseases caused due to the dysregulation of the oral-gut-liver axis. NAFLD is the most common liver disease reported in the developed countries. It includes liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and cancer. Recently, accumulating evidence supports an association between NAFLD and dysbiosis of oral and gut microbiota. Periodontopathic bacteria, especially Porphyromonas gingivalis, have been correlated with the pathogenesis and development of NAFLD based on the clinical and basic research, and immunology. P. gingivalis was detected in the liver, and lipopolysaccharide from this bacteria has been shown to be involved in the progression of NAFLD, thereby indicating a direct role of P. gingivalis in NAFLD. Moreover, P. gingivalis induces dysbiosis of gut microbiota, which promotes the progression of NAFLD, through disrupting both metabolic and immunologic pathways. Here, we review the roles of microbial dysbiosis in NAFLD. Focusing on P. gingivalis, we evaluate and summarize the most recent advances in our understanding of the relationship between oral-gut microbiome symbiosis and the pathogenesis and progression of non-alcoholic fatty liver disease, as well as discuss novel strategies targeting both P. gingivalis and microbial dysbiosis.
Collapse
Affiliation(s)
- Ting Wang
- Division of Internal Medicine, Department of Oral Medicine, Iwate Medical University, Morioka, Japan
- Ting Wang
| | - Taichi Ishikawa
- Division of Molecular Microbiology, Department of Microbiology, Iwate Medical University, Morioka, Japan
| | - Minoru Sasaki
- Division of Molecular Microbiology, Department of Microbiology, Iwate Medical University, Morioka, Japan
| | - Toshimi Chiba
- Division of Internal Medicine, Department of Oral Medicine, Iwate Medical University, Morioka, Japan
- *Correspondence: Toshimi Chiba
| |
Collapse
|
|
43
|
Chen X, Dou J, Fu Z, Qiu Y, Zou L, Huang D, Tan X. Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis. J Appl Oral Sci 2022; 30:e20220316. [DOI: 10.1590/1678-7757-2022-0316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 10/17/2022] [Indexed: 11/22/2022] Open
|
|
44
|
Zhang L, Xie Z, Yu H, Du H, Wang X, Cai J, Qiu Y, Chen R, Jiang X, Liu Z, Li Y, Chen T. TLR2 inhibition ameliorates the amplification effect of LPS on lipid accumulation and lipotoxicity in hepatic cells. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1429. [PMID: 34733981 PMCID: PMC8506759 DOI: 10.21037/atm-21-4012] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 09/10/2021] [Indexed: 12/04/2022]
Abstract
Background Gut microbiome dysbiosis is related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD), and the role of toll-like receptor 2 (TLR2) in its molecular mechanism is controversial. Here, we investigated the effects and mechanisms of Escherichia coli-derived lipopolysaccharide (LPS) on lipid accumulation and lipotoxicity in palmitic acid (PA)-treated L02 cell as an NAFLD cell model, and the role of TLR2 in this process. Methods Oil red O staining assay and free fatty acid (FFA) content test were performed to determine the effects of LPS on lipid accumulation in a PA-induced NAFLD cell model with or without TLR2 inhibition. The levels of IL-6 and TNF-α were measured to investigate inflammation conditions. Hoechst 33342 staining assay and Caspase-3 activity assay were used to test cell apoptosis, and the expression levels of proteins in the IRS1/PI3K/AKT signaling pathway, TLR2/MyD88/IKKα/NF-κB signaling pathway, and mitochondrion-dependent apoptotic signaling pathway were detected using Western blot. Results Lipid accumulation, pro-inflammatory cytokine release, and cell apoptosis with high levels were observed in the PA-induced NAFLD cell model, and LPS aggravated these processes. Whereas TLR2 inhibition could significantly ameliorate PA-induced and LPS-amplified lipid accumulation, inflammatory, and cell apoptosis, it had no significant effect on L02 cells treated with LPS alone. Conclusions These results were confirmed by activation or inhibition of the IRS1/PI3K/AKT signaling pathway, TLR2/MyD88/IKKα/NF-κB signaling pathway, and mitochondrion-dependent apoptotic signaling pathway, and were reflected by changes on their proteins expression. TLR2 is involved in PA-induced lipid accumulation and lipotoxicity in L02 cells, which could be aggravated by LPS, although LPS-induced amplification might not be through direct interaction with TLR2.
Collapse
Affiliation(s)
- Liting Zhang
- State Key Laboratory of Cryospheric Science, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou, China.,University of Chinese Academy of Sciences, Beijing, China.,Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, China
| | - Zehui Xie
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Hongmiao Yu
- Children's Hospital and Institute of Biomedical Sciences, Fudan University, Shanghai, China
| | - Haoxuan Du
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Xuqiao Wang
- School/Hospital of Stomatology, Lanzhou University, Lanzhou, China
| | - Jiazheng Cai
- School/Hospital of Stomatology, Lanzhou University, Lanzhou, China
| | - Yingfei Qiu
- School/Hospital of Stomatology, Lanzhou University, Lanzhou, China
| | - Rui Chen
- School/Hospital of Stomatology, Lanzhou University, Lanzhou, China
| | - Xiaofeng Jiang
- School/Hospital of Stomatology, Lanzhou University, Lanzhou, China
| | - Zelin Liu
- School/Hospital of Stomatology, Lanzhou University, Lanzhou, China
| | - Yi Li
- State Key Laboratory of Cryospheric Science, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou, China.,School/Hospital of Stomatology, Lanzhou University, Lanzhou, China
| | - Tuo Chen
- State Key Laboratory of Cryospheric Science, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou, China.,University of Chinese Academy of Sciences, Beijing, China
| |
Collapse
|
|
45
|
Ezhilarasan D. Deciphering the toxicological role of Porphyromonas gingivalis derived endotoxins in liver diseases. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2021; 88:103755. [PMID: 34662732 DOI: 10.1016/j.etap.2021.103755] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 10/08/2021] [Accepted: 10/11/2021] [Indexed: 06/13/2023]
Abstract
Periodontitis is a most prevalent and infectious multifactorial inflammatory disease and is characterized by the progressive destruction of the tooth-supporting tissues. Porphyromonas gingivalis, a Gram‑negative oral anaerobe, mainly causes periodontitis and it is one of the most important risk factors responsible for aggravation of existing systemic diseases. Several experimental and clinical studies have shown the positive association between periodontitis and different forms of liver disease. Periodontal diseases increase the prevalence of non-alcoholic fatty liver diseases and cirrhosis. Infected periodontium and pathogens in the periodontal microenvironments release pathogen-associated molecular patterns such as peptidoglycan, lipopolysaccharides, gingipain, fimbria, bacterial DNA, etc, and damage-associated molecular patterns such as interleukins-1α, β, - 8, and galectin-3, etc. These virulence factors and cytokines enter the bloodstream, disseminate into the whole body, and induce a variety of systemic pathological effects, including liver diseases (steatosis and fibrosis). Maintaining oral hygiene by scaling and root planning significantly improves liver damage in patients with periodontitis. Dentists and physicians should have more awareness in understanding the bidirectional nature of the relationship between oral and systemic diseases. Importantly, periodontitis condition aggravates simple fatty liver into fibrotic disease and therefore, the aim of this review is to understand the possible link between periodontitis and liver diseases.
Collapse
Affiliation(s)
- Devaraj Ezhilarasan
- Department of Pharmacology, The Blue Lab, Molecular Medicine and Toxicology Division, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 600 077, India.
| |
Collapse
|
|
46
|
Kuraji R, Sekino S, Kapila Y, Numabe Y. Periodontal disease-related nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: An emerging concept of oral-liver axis. Periodontol 2000 2021; 87:204-240. [PMID: 34463983 PMCID: PMC8456799 DOI: 10.1111/prd.12387] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Periodontal disease, a chronic inflammatory disease of the periodontal tissues, is not only a major cause of tooth loss, but it is also known to exacerbate/be associated with various metabolic disorders, such as obesity, diabetes, dyslipidemia, and cardiovascular disease. Recently, growing evidence has suggested that periodontal disease has adverse effects on the pathophysiology of liver disease. In particular, nonalcoholic fatty liver disease, a hepatic manifestation of metabolic syndrome, has been associated with periodontal disease. Nonalcoholic fatty liver disease is characterized by hepatic fat deposition in the absence of a habitual drinking history, viral infections, or autoimmune diseases. A subset of nonalcoholic fatty liver diseases can develop into more severe and progressive forms, namely nonalcoholic steatohepatitis. The latter can lead to cirrhosis and hepatocellular carcinoma, which are end‐stage liver diseases. Extensive research has provided plausible mechanisms to explain how periodontal disease can negatively affect nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, namely via hematogenous or enteral routes. During periodontitis, the liver is under constant exposure to various pathogenic factors that diffuse systemically from the oral cavity, such as bacteria and their by‐products, inflammatory cytokines, and reactive oxygen species, and these can be involved in disease promotion of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Also, gut microbiome dysbiosis induced by enteral translocation of periodontopathic bacteria may impair gut wall barrier function and promote the transfer of hepatotoxins and enterobacteria to the liver through the enterohepatic circulation. Moreover, in a population with metabolic syndrome, the interaction between periodontitis and systemic conditions related to insulin resistance further strengthens the association with nonalcoholic fatty liver disease. However, most of the pathologic links between periodontitis and nonalcoholic fatty liver disease in humans are provided by epidemiologic observational studies, with the causal relationship not yet being established. Several systematic and meta‐analysis studies also show conflicting results. In addition, the effect of periodontal treatment on nonalcoholic fatty liver disease has hardly been studied. Despite these limitations, the global burden of periodontal disease combined with the recent nonalcoholic fatty liver disease epidemic has important clinical and public health implications. Emerging evidence suggests an association between periodontal disease and liver diseases, and thus we propose the term periodontal disease–related nonalcoholic fatty liver disease or periodontal disease–related nonalcoholic steatohepatitis. Continued efforts in this area will pave the way for new diagnostic and therapeutic approaches based on a periodontologic viewpoint to address this life‐threatening liver disease.
Collapse
Affiliation(s)
- Ryutaro Kuraji
- Department of Life Science Dentistry, The Nippon Dental University, Tokyo, Japan.,Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan.,Department of Orofacial Sciences, University of California San Francisco School of Dentistry, San Francisco, California, USA
| | - Satoshi Sekino
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yvonne Kapila
- Department of Orofacial Sciences, University of California San Francisco School of Dentistry, San Francisco, California, USA
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| |
Collapse
|
|
47
|
Bregaint S, Boyer E, Fong SB, Meuric V, Bonnaure-Mallet M, Jolivet-Gougeon A. Porphyromonas gingivalis outside the oral cavity. Odontology 2021; 110:1-19. [PMID: 34410562 DOI: 10.1007/s10266-021-00647-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 07/31/2021] [Indexed: 12/14/2022]
Abstract
Porphyromonas gingivalis, a Gram-negative anaerobic bacillus present in periodontal disease, is considered one of the major pathogens in periodontitis. A literature search for English original studies, case series and review articles published up to December 2019 was performed using the MEDLINE, PubMed and GoogleScholar databases, with the search terms "Porphyromonas gingivalis" AND the potentially associated condition or systemic disease Abstracts and full text articles were used to make a review of published research literature on P. gingivalis outside the oral cavity. The main points of interest of this narrative review were: (i) a potential direct action of the bacterium and not the systemic effects of the inflammatory acute-phase response induced by the periodontitis, (ii) the presence of the bacterium (viable or not) in the organ, or (iii) the presence of its virulence factors. Virulence factors (gingipains, capsule, fimbriae, hemagglutinins, lipopolysaccharide, hemolysin, iron uptake transporters, toxic outer membrane blebs/vesicles, and DNA) associated with P. gingivalis can deregulate certain functions in humans, particularly host immune systems, and cause various local and systemic pathologies. The most recent studies linking P. gingivalis to systemic diseases were discussed, remembering particularly the molecular mechanisms involved in different infections, including cerebral, cardiovascular, pulmonary, bone, digestive and peri-natal infections. Recent involvement of P. gingivalis in neurological diseases has been demonstrated. P. gingivalis modulates cellular homeostasis and increases markers of inflammation. It is also a factor in the oxidative stress involved in beta-amyloid production.
Collapse
Affiliation(s)
- Steeve Bregaint
- Microbiology, INSERM, INRAE, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), Université de Rennes, U1241, 2, avenue du Professeur Léon Bernard, 35043, Rennes, France
| | - Emile Boyer
- Microbiology, INSERM, INRAE, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), Université de Rennes, U1241, 2, avenue du Professeur Léon Bernard, 35043, Rennes, France.,Teaching Hospital Pontchaillou, 2 rue Henri Le Guilloux, 35033, Rennes, France
| | - Shao Bing Fong
- Microbiology, INSERM, INRAE, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), Université de Rennes, U1241, 2, avenue du Professeur Léon Bernard, 35043, Rennes, France
| | - Vincent Meuric
- Microbiology, INSERM, INRAE, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), Université de Rennes, U1241, 2, avenue du Professeur Léon Bernard, 35043, Rennes, France.,Teaching Hospital Pontchaillou, 2 rue Henri Le Guilloux, 35033, Rennes, France
| | - Martine Bonnaure-Mallet
- Microbiology, INSERM, INRAE, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), Université de Rennes, U1241, 2, avenue du Professeur Léon Bernard, 35043, Rennes, France.,Teaching Hospital Pontchaillou, 2 rue Henri Le Guilloux, 35033, Rennes, France
| | - Anne Jolivet-Gougeon
- Microbiology, INSERM, INRAE, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), Université de Rennes, U1241, 2, avenue du Professeur Léon Bernard, 35043, Rennes, France. .,Teaching Hospital Pontchaillou, 2 rue Henri Le Guilloux, 35033, Rennes, France.
| |
Collapse
|
|
48
|
Nagasaki A, Sakamoto S, Arai T, Kato M, Ishida E, Furusho H, Fujii M, Takata T, Miyauchi M. Elimination of Porphyromonas gingivalis inhibits liver fibrosis and inflammation in NASH. J Clin Periodontol 2021; 48:1367-1378. [PMID: 34250613 DOI: 10.1111/jcpe.13523] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 06/25/2021] [Indexed: 12/23/2022]
Abstract
AIM Non-alcoholic steatohepatitis (NASH) is a critical liver disease showing potential progression to liver cirrhosis/cancer. Previously, we had reported that odontogenic infection of Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, exacerbates fibrosis in NASH through the production of fibrosis mediators such as transforming growth factor-β1 (TGF-β1) and galectin-3. In this study, we determined the effects of therapeutic interventions using antibiotics on NASH progression induced by P. gingivalis odontogenic infection. MATERIALS AND METHODS To eliminate P. gingivalis infection, the macrolide antibiotic [azithromycin (AZM)] was applied locally and/or systemically to a high-fat-diet-induced NASH mouse model with P. gingivalis odontogenic infection. After treatment with AZM, liver and periodontal tissues were analysed with focus on inflammation markers such as tumour necrosis factor-α (TNF-α)/Tnf-α and interleukin-1β (IL-1β)/Il-1β, and fibrosis markers such as galectin-3, phosphorylated Smad2 (pSmad2; key signalling molecule of TGF-β1), and the number of hepatic crown-like structures (hCLSs). Further, Non-alcoholic Fatty Liver Disease Activity Score (NAS), a common histological scoring system, and fibrosis area were evaluated. RESULTS P. gingivalis odontogenic infection significantly increased the expression of Tnf-α, Il-1β, galectin-3, and pSmad2, the number of hCLSs, and NAS score, whereas the elimination of P. gingivalis odontogenic infection, especially local with or without systemic application, significantly inhibited them. CONCLUSION This study suggests that elimination of P. gingivalis odontogenic infection inhibited NASH progression induced by the infection.
Collapse
Affiliation(s)
- Atsuhiro Nagasaki
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shinnichi Sakamoto
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Toshiki Arai
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Minami Kato
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Eri Ishida
- Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hisako Furusho
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Makiko Fujii
- Department of Global Dental Medicine & Molecular Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takashi Takata
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.,Tokuyama University, Yamaguchi, Japan
| | - Mutsumi Miyauchi
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| |
Collapse
|
|
49
|
Cintra LTA, Gomes MS, da Silva CC, Faria FD, Benetti F, Cosme-Silva L, Samuel RO, Pinheiro TN, Estrela C, González AC, Segura-Egea JJ. Evolution of endodontic medicine: a critical narrative review of the interrelationship between endodontics and systemic pathological conditions. Odontology 2021; 109:741-769. [PMID: 34240297 DOI: 10.1007/s10266-021-00636-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 07/04/2021] [Indexed: 12/12/2022]
Abstract
Endodontics has gained emphasis in the scientific community in recent years due to the increase in clinical and in animal models studies focused on endodontic medicine, which aims to evaluate the interrelationship between systemic and periapical tissues pathological conditions. These studies have shown that systemic changes can boost the pathogenesis of endodontic infection, favoring its development and progression. A contrary relationship is reported in numerous studies that affirm the potential of endodontic infection to trigger systemic damage and may lead to the worsening of pre-existing pathologies. Recently, the potential of filling materials to develop systemic changes such as neurological alterations had been evaluated, also showing that systemic diseases can negatively influence tissue responses to filling materials after endodontic treatment. Despite advances in endodontic medicine studies, there are still gaps in knowledge on the mechanisms of interactions between apical periodontitis (AP) and systemic diseases and much research to be done. In this sense, this critical narrative literature review aimed to show the evolution of studies in endodontic medicine to help the endodontist to know the role of systemic diseases in the pathogenesis of AP and the possible interference in the repair of periapical tissues after endodontic treatment, as well as to evidence the systemic complications that can be triggered or aggravated in the presence of endodontic infection.
Collapse
Affiliation(s)
- Luciano Tavares Angelo Cintra
- Department of Preventive and Restorative Dentistry, Endodontic Section, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, CEP 16015-050, Brazil. .,Dental Assistance Center for Disabled Persons (CAOE) of the São Paulo State University (Unesp), School of Dentistry, Araçatuba, SP, Brazil.
| | - Maximiliano Schünke Gomes
- Departament of Odontology, School of Dentistry and Medical and Dental Center, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Cristiane Cantiga da Silva
- Department of Preventive and Restorative Dentistry, Endodontic Section, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, CEP 16015-050, Brazil
| | - Flávio Duarte Faria
- Department of Preventive and Restorative Dentistry, Endodontic Section, School of Dentistry, São Paulo State University (Unesp), José Bonifácio, 1193, Vila Mendonça, Araçatuba, SP, CEP 16015-050, Brazil
| | - Francine Benetti
- Department of Restorative Dentistry, School of Dentistry, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | - Leopoldo Cosme-Silva
- Department of Clinics and Surgery, School of Dentistry, Federal University of Alfenas (Unifal), Alfenas, MG, Brazil
| | - Renata Oliveira Samuel
- Department of Clinical Dentistry, Dental School, Universidade de Uberaba, Uberaba, MG, Brazil
| | - Tiago Novaes Pinheiro
- Department of Oral Pathology and Oral Medicine, Dental School of Amazonas State University, Manaus, AM, Brazil
| | - Carlos Estrela
- Department of Stomatologic Sciences, School of Dentistry, Federal University of Goiás (UFG), Goiânia, GO, Brazil
| | | | - Juan José Segura-Egea
- Department of Stomatology, School of Dentistry, University of Sevilla, Sevilla, Spain
| |
Collapse
|
|
50
|
Imai J, Kitamoto S, Kamada N. The pathogenic oral-gut-liver axis: new understandings and clinical implications. Expert Rev Clin Immunol 2021; 17:727-736. [PMID: 34057877 DOI: 10.1080/1744666x.2021.1935877] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Oral health is closely related to extra-oral disease status, as may be represented by the manifestations of gastrointestinal and liver diseases. AREAS COVERED This review focuses on the roles that the oral-gut or the oral-gut-liver axis play in the pathogenesis of inflammatory bowel disease, colorectal cancer, metabolic fatty liver disease, and nonalcoholic steatohepatitis. The discussion will begin with clinical data, including data from preclinical animal models, to elucidate mechanisms. We will also discuss ways to target oral dysbiosis and oral inflammation to treat gastrointestinal and liver diseases. EXPERT OPINION Several studies have demonstrated that oral pathobionts can translocate to the gastrointestinal tract where they contribute to inflammation and tumorigenesis. Furthermore, oral bacteria that migrate to the gastrointestinal tract can disseminate to the liver and cause hepatic disease. Thus, oral bacteria that ectopically colonize the intestine may serve as biomarkers for gastrointestinal and liver diseases. Also, understanding the characteristics of the oral-gut and oral-gut-liver microbial and immune axes will provide new insights into the pathogenesis of these diseases.
Collapse
Affiliation(s)
- Jin Imai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Sho Kitamoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Nobuhiko Kamada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
| |
Collapse
|