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1
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Majster M, Almer S, Malmqvist S, Johannsen A, Lira‐Junior R, Boström EA. Salivary calprotectin and neutrophils in inflammatory bowel disease in relation to oral diseases. Oral Dis 2025; 31:286-297. [PMID: 38852161 PMCID: PMC11808171 DOI: 10.1111/odi.15036] [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: 12/10/2023] [Revised: 04/23/2024] [Accepted: 05/23/2024] [Indexed: 06/11/2024]
Abstract
OBJECTIVE Calprotectin is elevated in saliva from inflammatory bowel disease (IBD) patients, but it is also affected by oral disease. We assessed the salivary concentration of calprotectin in IBD patients, in relation to intestinal and oral diseases. Furthermore, we investigated the phenotype of salivary neutrophils from IBD patients, and their ability to secrete calprotectin. MATERIALS AND METHODS Thirty IBD patients and 26 controls were orally examined and sampled for stimulated saliva. Twenty-five IBD patients provided fresh fecal samples. Calprotectin concentrations in saliva and feces were determined by an enzyme-linked immunosorbent assay. Expression of CD11b, CD15, and CD16 on oral neutrophils was assessed by flow cytometry. Secretion of calprotectin was evaluated in cultured oral neutrophils. RESULTS Calprotectin was significantly elevated in saliva of IBD patients compared to controls, particularly in Crohn's disease, irrespective of caries or periodontitis. Salivary calprotectin did not correlate to fecal calprotectin. CD11b expression was significantly reduced in salivary neutrophils from IBD patients. Salivary neutrophils from IBD patients tended to secrete more calprotectin than controls. CONCLUSIONS Salivary calprotectin is elevated in IBD regardless of oral diseases. Furthermore, salivary neutrophils secrete calprotectin, and display lower CD11b expression in IBD.
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Affiliation(s)
- Mirjam Majster
- Division of Oral Diagnostics and Rehabilitation, Department of Dental MedicineKarolinska InstitutetStockholmSweden
| | - Sven Almer
- Department of Medicine SolnaKarolinska InstitutetStockholmSweden
- Division of Gastroenterology, Department of Gastroenterology, Dermatology and RheumatologyKarolinska University HospitalStockholmSweden
| | - Sebastian Malmqvist
- Division of Oral Diseases, Department of Dental MedicineKarolinska InstitutetStockholmSweden
| | - Annsofi Johannsen
- Division of Oral Diseases, Department of Dental MedicineKarolinska InstitutetStockholmSweden
| | - Ronaldo Lira‐Junior
- Division of Oral Diagnostics and Rehabilitation, Department of Dental MedicineKarolinska InstitutetStockholmSweden
| | - Elisabeth Almer Boström
- Division of Oral Diagnostics and Rehabilitation, Department of Dental MedicineKarolinska InstitutetStockholmSweden
- Department of Orofacial MedicineFolktandvården Stockholms Län ABStockholmSweden
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2
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Tanwar H, Gnanasekaran JM, Allison D, Chuang LS, He X, Aimetti M, Baima G, Costalonga M, Cross RK, Sears C, Mehandru S, Cho J, Colombel JF, Raufman JP, Thumbigere-Math V. Unravelling the Oral-Gut Axis: Interconnection Between Periodontitis and Inflammatory Bowel Disease, Current Challenges, and Future Perspective. J Crohns Colitis 2024; 18:1319-1341. [PMID: 38417137 PMCID: PMC11324343 DOI: 10.1093/ecco-jcc/jjae028] [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: 08/21/2023] [Revised: 12/04/2023] [Accepted: 02/27/2024] [Indexed: 03/01/2024]
Abstract
As the opposite ends of the orodigestive tract, the oral cavity and the intestine share anatomical, microbial, and immunological ties that have bidirectional health implications. A growing body of evidence suggests an interconnection between oral pathologies and inflammatory bowel disease [IBD], implying a shift from the traditional concept of independent diseases to a complex, reciprocal cycle. This review outlines the evidence supporting an 'oral-gut' axis, marked by a higher prevalence of periodontitis and other oral conditions in IBD patients and vice versa. We present an in-depth examination of the interconnection between oral pathologies and IBD, highlighting the shared microbiological and immunological pathways, and proposing a 'multi-hit' hypothesis in the pathogenesis of periodontitis-mediated intestinal inflammation. Furthermore, the review underscores the critical need for a collaborative approach between dentists and gastroenterologists to provide holistic oral-systemic healthcare.
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Affiliation(s)
- Himanshi Tanwar
- Division of Periodontology, University of Maryland School of Dentistry, Baltimore, MD, USA
| | | | - Devon Allison
- Division of Periodontology, University of Maryland School of Dentistry, Baltimore, MD, USA
| | - Ling-shiang Chuang
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Xuesong He
- Department of Microbiology, The Forsyth Institute, Cambridge, MA, USA
| | - Mario Aimetti
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
| | - Giacomo Baima
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
| | - Massimo Costalonga
- Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USA
| | - Raymond K Cross
- Division of Gastroenterology & Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Cynthia Sears
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Saurabh Mehandru
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Judy Cho
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jean-Pierre Raufman
- Division of Gastroenterology & Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Vivek Thumbigere-Math
- Division of Periodontology, University of Maryland School of Dentistry, Baltimore, MD, USA
- National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA
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3
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Dongiovanni P, Meroni M, Casati S, Goldoni R, Thomaz DV, Kehr NS, Galimberti D, Del Fabbro M, Tartaglia GM. Salivary biomarkers: novel noninvasive tools to diagnose chronic inflammation. Int J Oral Sci 2023; 15:27. [PMID: 37386003 PMCID: PMC10310701 DOI: 10.1038/s41368-023-00231-6] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 05/23/2023] [Accepted: 06/05/2023] [Indexed: 07/01/2023] Open
Abstract
Several chronic disorders including type 2 diabetes (T2D), obesity, heart disease and cancer are preceded by a state of chronic low-grade inflammation. Biomarkers for the early assessment of chronic disorders encompass acute phase proteins (APP), cytokines and chemokines, pro-inflammatory enzymes, lipids and oxidative stress mediators. These substances enter saliva through the blood flow and, in some cases, there is a close relation between their salivary and serum concentration. Saliva can be easily collected and stored with non-invasive and cost-saving procedures, and it is emerging the concept to use it for the detection of inflammatory biomarkers. To this purpose, the present review aims to discuss the advantages and challenges of using standard and cutting-edge techniques to discover salivary biomarkers which may be used in diagnosis/therapy of several chronic diseases with inflammatory consequences with the pursuit to possibly replace conventional paths with detectable soluble mediators in saliva. Specifically, the review describes the procedures used for saliva collection, the standard approaches for the measurement of salivary biomarkers and the novel methodological strategies such as biosensors to improve the quality of care for chronically affected patients.
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Affiliation(s)
- Paola Dongiovanni
- Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Marica Meroni
- Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Sara Casati
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
| | - Riccardo Goldoni
- Department of Electronics, Information and Bioengineering (DEIB), Politecnico di Milano, Milan, Italy
- Istituto di Elettronica e di Ingegneria dell'Informazione e delle Telecomunicazioni, CNR, Pisa, Italy
| | - Douglas Vieira Thomaz
- Laboratory of Medicinal Pharmaceutical Chemistry, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil
| | - Nermin Seda Kehr
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- Department of Chemistry, İzmir Institute of Technology, Gülbahçe Kampüsü, Urla İzmir, Turkey
| | - Daniela Galimberti
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- Neurology-Neurodegenerative Diseases, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Massimo Del Fabbro
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- UOC Maxillo-Facial Surgery and Dentistry Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Gianluca M Tartaglia
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- UOC Maxillo-Facial Surgery and Dentistry Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy
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4
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Haraikawa M, Shibuya T, Kurosawa T, Ito K, Nomura K, Haga K, Nomura O, Takeda T, Fukushima H, Murakami T, Ishikawa D, Hojo M, Yao T, Nagahara A. Differential diagnosis of ulcerative colitis with increased diarrhea; collagenous colitis or irritable bowel syndrome? A case report. J Int Med Res 2022; 50:3000605221140686. [PMID: 36474409 PMCID: PMC9732797 DOI: 10.1177/03000605221140686] [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: 06/27/2022] [Accepted: 11/04/2022] [Indexed: 12/12/2022] Open
Abstract
A 50-year-old man with a 20-year history of left-sided ulcerative colitis (UC) presented to our hospital with sudden onset of watery diarrhea. To this point, he had been treated with mesalazine 2.0 g/day for UC and had maintained remission. We considered that the UC had worsened. We immediately performed surveillance colonoscopy, which revealed a normal mucous membrane. The results of blood laboratory examinations were normal. Histopathology of colonic biopsies revealed new-onset collagenous colitis (CC), with a thickened subepithelial collagen band (SECB) and inactive UC. We herein report the importance of random colonic biopsies to diagnose CC even when the endoscopic appearance of the colon is normal in patients with inflammatory bowel disease with worsened diarrhea.
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Affiliation(s)
- Mayuko Haraikawa
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Tomoyoshi Shibuya
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Taro Kurosawa
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Kentaro Ito
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Kei Nomura
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Keiichi Haga
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Osamu Nomura
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Tsutomu Takeda
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Hirofumi Fukushima
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Takashi Murakami
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Dai Ishikawa
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Mariko Hojo
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Takashi Yao
- Department of Human Pathology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
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5
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Li C, Wu Y, Xie Y, Zhang Y, Jiang S, Wang J, Luo X, Chen Q. Oral manifestations serve as potential signs of ulcerative colitis: A review. Front Immunol 2022; 13:1013900. [PMID: 36248861 PMCID: PMC9559187 DOI: 10.3389/fimmu.2022.1013900] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 09/14/2022] [Indexed: 11/23/2022] Open
Abstract
As an immune dysregulation-related disease, although ulcerative colitis (UC) primarily affects the intestinal tract, extraintestinal manifestations of the disease are evident, particularly in the oral cavity. Herein, we have reviewed the various oral presentations, potential pathogenesis, and treatment of oral lesions related to UC. The oral manifestations of UC include specific and nonspecific manifestations, with the former including pyostomatitis vegetans and the latter encompassing recurrent aphthous ulcers, atrophic glossitis, burning mouth syndrome, angular cheilitis, dry mouth, taste change, halitosis, and periodontitis. Although the aetiology of UC has not been fully determined, the factors leading to its development include immune system dysregulation, dysbiosis, and malnutrition. The principle of treating oral lesions in UC is to relieve pain, accelerate the healing of lesions, and prevent secondary infection, and the primary procedure is to control intestinal diseases. Systemic corticosteroids are the preferred treatment options, besides, topical and systemic administration combined with dietary guidance can also be applied. Oral manifestations of UC might accompany or precede the diagnosis of UC, albeit with the absence of intestinal symptoms; therefore, oral lesions, especially pyostomatitis vegetans, recurrent aphthous ulcer and periodontitis, could be used as good mucocutaneous signs to judge the occurrence and severity of UC, thus facilitating the early diagnosis and treatment of UC and avoiding severe consequences, such as colon cancer.
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Affiliation(s)
| | | | | | | | | | | | - Xiaobo Luo
- *Correspondence: Qianming Chen, ; Xiaobo Luo,
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6
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Komarova N, Panova O, Titov A, Kuznetsov A. Aptamers Targeting Cardiac Biomarkers as an Analytical Tool for the Diagnostics of Cardiovascular Diseases: A Review. Biomedicines 2022; 10:biomedicines10051085. [PMID: 35625822 PMCID: PMC9138532 DOI: 10.3390/biomedicines10051085] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/05/2022] [Accepted: 05/06/2022] [Indexed: 02/04/2023] Open
Abstract
The detection of cardiac biomarkers is used for diagnostics, prognostics, and the risk assessment of cardiovascular diseases. The analysis of cardiac biomarkers is routinely performed with high-sensitivity immunological assays. Aptamers offer an attractive alternative to antibodies for analytical applications but, to date, are not widely practically implemented in diagnostics and medicinal research. This review summarizes the information on the most common cardiac biomarkers and the current state of aptamer research regarding these biomarkers. Aptamers as an analytical tool are well established for troponin I, troponin T, myoglobin, and C-reactive protein. For the rest of the considered cardiac biomarkers, the isolation of novel aptamers or more detailed characterization of the known aptamers are required. More attention should be addressed to the development of dual-aptamer sandwich detection assays and to the studies of aptamer sensing in alternative biological fluids. The universalization of aptamer-based biomarker detection platforms and the integration of aptamer-based sensing to clinical studies are demanded for the practical implementation of aptamers to routine diagnostics. Nevertheless, the wide usage of aptamers for the diagnostics of cardiovascular diseases is promising for the future, with respect to both point-of-care and laboratory testing.
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7
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Nijakowski K, Rutkowski R, Eder P, Korybalska K, Witowski J, Surdacka A. Changes in Salivary Parameters of Oral Immunity after Biologic Therapy for Inflammatory Bowel Disease. Life (Basel) 2021; 11:life11121409. [PMID: 34947940 PMCID: PMC8708388 DOI: 10.3390/life11121409] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/14/2021] [Accepted: 12/15/2021] [Indexed: 12/30/2022] Open
Abstract
We previously observed that inflammatory bowel disease (IBD) may compromise oral host defense, as assessed by decreased salivary levels of immunoglobulin A (IgA) and myeloperoxidase (MPO). Biologic therapy with inhibitors of cytokines or adhesion molecules is increasingly used for patients with IBD. Little is known, however, about how this treatment modality affects the release and properties of saliva. Here, we aimed to determine how biologic therapy in patients who had not responded to previous standard treatment with conventional drugs affected the salivary concentration of IgA and MPO. To this end, unstimulated whole mixed saliva was collected before treatment or after 10-12 weeks of therapy from 27 patients with Crohn's disease (CD) and 24 patients with ulcerative colitis (UC). After the induction phase of therapy with biologics, salivary levels of IgA and MPO increased significantly in UC, but not in CD patients. These increases were approximately 8-fold and 6-fold, for IgA and MPO, respectively. Moreover, these effects occurred in UC patients who responded successfully to therapy, but not in those who failed to improve. Furthermore, the relative increases in salivary IgA and MPO correlated with the relative decrease in UC severity, as assessed by the Mayo scale. These data indicate that the successful therapy with biologics in UC patients results also in improved oral host defense. However, it remains to be determined why such an effect does not occur during therapy for CD.
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Affiliation(s)
- Kacper Nijakowski
- Department of Conservative Dentistry and Endodontics, Poznan University of Medical Sciences, 60-812 Poznan, Poland;
- Correspondence:
| | - Rafał Rutkowski
- Department of Pathophysiology, Poznan University of Medical Sciences, 60-806 Poznan, Poland; (R.R.); (K.K.); (J.W.)
| | - Piotr Eder
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, Poland;
| | - Katarzyna Korybalska
- Department of Pathophysiology, Poznan University of Medical Sciences, 60-806 Poznan, Poland; (R.R.); (K.K.); (J.W.)
| | - Janusz Witowski
- Department of Pathophysiology, Poznan University of Medical Sciences, 60-806 Poznan, Poland; (R.R.); (K.K.); (J.W.)
| | - Anna Surdacka
- Department of Conservative Dentistry and Endodontics, Poznan University of Medical Sciences, 60-812 Poznan, Poland;
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8
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Read E, Curtis MA, Neves JF. The role of oral bacteria in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2021; 18:731-742. [PMID: 34400822 DOI: 10.1038/s41575-021-00488-4] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/23/2021] [Indexed: 02/06/2023]
Abstract
Over the past two decades, the importance of the microbiota in health and disease has become evident. Pathological changes to the oral bacterial microbiota, such as those occurring during periodontal disease, are associated with multiple inflammatory conditions, including inflammatory bowel disease. However, the degree to which this association is a consequence of elevated oral inflammation or because oral bacteria can directly drive inflammation at distal sites remains under debate. In this Perspective, we propose that in inflammatory bowel disease, oral disease-associated bacteria translocate to the intestine and directly exacerbate disease. We propose a multistage model that involves pathological changes to the microbial and immune compartments of both the oral cavity and intestine. The evidence to support this hypothesis is critically evaluated and the relevance to other diseases in which oral bacteria have been implicated (including colorectal cancer and liver disease) are discussed.
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Affiliation(s)
- Emily Read
- Centre for Host-Microbiome Interactions, King's College London, London, UK.,Wellcome Trust Cell Therapies and Regenerative Medicine PhD Programme, King's College London, London, UK
| | - Michael A Curtis
- Centre for Host-Microbiome Interactions, King's College London, London, UK
| | - Joana F Neves
- Centre for Host-Microbiome Interactions, King's College London, London, UK.
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9
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Potential Salivary Markers for Differential Diagnosis of Crohn's Disease and Ulcerative Colitis. Life (Basel) 2021; 11:life11090943. [PMID: 34575091 PMCID: PMC8469159 DOI: 10.3390/life11090943] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 08/19/2021] [Accepted: 09/08/2021] [Indexed: 12/21/2022] Open
Abstract
The properties of the saliva of patients with inflammatory bowel disease (IBD) are poorly recognized. Likewise, the diagnostic potential of saliva for differentiating various forms of IBD is largely unexplored. Therefore, we compared the concentrations of several parameters in unstimulated whole mixed saliva collected in a standardized manner from patients with active IBD unresponsive to conventional therapy. The samples were received from 27 patients with Crohn’s disease (CD), 24 patients with ulcerative colitis (UC), and 51 healthy individuals. Compared to the controls, the salivary concentrations of S100A8/calprotectin, myeloperoxidase, and IgA were significantly decreased in both CD and UC patients. In addition, patients with UC had decreased levels of TNF-R1 and decreased catalase activity. Interestingly, the concentrations of myeloperoxidase and TNF-R1 showed a high differentiation potential for CD and UC (AUC = 0.690 and 0.672, respectively). All these findings are discussed in the context of host defense in the oral cavity, patients’ prior treatment regimens, and smoking habits.
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10
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Hernandez J, Dandrieux JRS. From Bench Top to Clinics: How New Tests Can Be Helpful in Diagnosis and Management of Dogs with Chronic Enteropathies. Vet Clin North Am Small Anim Pract 2021; 51:137-153. [PMID: 33187620 DOI: 10.1016/j.cvsm.2020.09.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In this article, we review different tests that have been researched in dogs with chronic enteropathy. The usefulness of these tests either to assess etiology, to differentiate between treatment response, or to monitor treatment response is discussed. The tests are divided in those that are commercially available and those that hold promises for further development.
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Affiliation(s)
- Juan Hernandez
- Université Paris-Saclay, INRAE, AgroParisTech, UMR 1319 Micalis, Microbiota Interactions with Human and Animal Team (MIHA), F-78350, Jouy-en Josas, France; Department of Clinical Sciences, Nantes-Atlantic College of Veterinary Medicine and Food Sciences (Oniris), University of Nantes, 101 route de Gachet, Nantes 44300, France
| | - Julien Rodolphe Samuel Dandrieux
- Department of Veterinary Clinical Sciences, Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, U-Vet, 250 Princes Highway, Werribee, Victoria 3030, Australia.
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11
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Chandraiah SB, Ghosh S, Saha I, More SS, Annappa GS, Maiti AK. Substance P failed to reverse dextran sulfate sodium-induced murine colitis mediated by mitochondrial dysfunction: implications in ulcerative colitis. 3 Biotech 2021; 11:199. [PMID: 33927989 PMCID: PMC8006204 DOI: 10.1007/s13205-021-02755-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 03/20/2021] [Indexed: 12/31/2022] Open
Abstract
As controversy exists about the efficacy of substance P (SP) in treating ulcerative colitis (UC) with no previous study highlighting the impact of SP on mitochondrial dysfunction in this diseased condition, it became logical to perform the present study. C57BL/6 J mice were administered with DSS @ 3.5%/gm body weight for 3 cycles of 5 days each followed by i.v. dose of SP @ 5nmole per kg for consecutive 7 days. Histopathological features were noticed in the affected colon along with colonic mitochondrial dysfunction, alterations in mitochondrial stress variables and enhanced colonic cell death. Interestingly, SP failed to reverse colitic features and proved ineffective in inhibiting mitochondrial dysfunction. Unexpectedly SP alone seemed to impart detrimental effects on some of the mitochondrial functions, enhanced lipid peroxidation and increased staining intensities for caspases 3 and 9 in the normal colon. To substantiate in vivo findings and to assess free radical scavenging property of SP, Caco-2 cells were exposed to DSS with or without SP in the presence and absence of specific free radical scavengers and antioxidants. Interestingly, in vitro treatment with SP failed to restore mitochondrial functions and its efficacy proved below par compared to SOD and DMSO indicating involvement of O2 •- and •OH in the progression of UC. Besides, catalase, L-NAME and MEG proved ineffective indicating non-involvement of H2O2, NO and ONOO- in UC. Thus, SP may not be a potent anti-colitogenic agent targeting colonic mitochondrial dysfunction for maintenance of colon epithelial tract as it lacks free radical scavenging property.
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Affiliation(s)
- Spoorthi B. Chandraiah
- School of Basic and Applied Sciences, Dayananda Sagar University, SM Hills, Kumaraswamy Layout Campus, Bengaluru, Karnataka 560078 India
| | - Shashwati Ghosh
- Mitochondrial Biology and Experimental Therapeutics Laboratory, Department of Zoology, University of North Bengal, Raja Rammohunpur, Darjeeling, West Bengal 734013 India
| | - Ishita Saha
- Department of Physiology, Medical College Kolkata, 88, College Street, College Square, Kolkata, West Bengal 700073 India
| | - Sunil S. More
- School of Basic and Applied Sciences, Dayananda Sagar University, SM Hills, Kumaraswamy Layout Campus, Bengaluru, Karnataka 560078 India
| | - Gautham S. Annappa
- School of Basic and Applied Sciences, Dayananda Sagar University, SM Hills, Kumaraswamy Layout Campus, Bengaluru, Karnataka 560078 India
| | - Arpan K. Maiti
- School of Basic and Applied Sciences, Dayananda Sagar University, SM Hills, Kumaraswamy Layout Campus, Bengaluru, Karnataka 560078 India
- Mitochondrial Biology and Experimental Therapeutics Laboratory, Department of Zoology, University of North Bengal, Raja Rammohunpur, Darjeeling, West Bengal 734013 India
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12
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Salivary Stress/Immunological Markers in Crohn's Disease and Ulcerative Colitis. Int J Mol Sci 2020; 21:ijms21228562. [PMID: 33202858 PMCID: PMC7698267 DOI: 10.3390/ijms21228562] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 11/09/2020] [Accepted: 11/11/2020] [Indexed: 02/08/2023] Open
Abstract
There is continuous and growing interest in research into new alternatives to standard biomarkers to detect and follow-up disease, reducing physical and psychological stress in patients needing regular and invasive medical examinations for the evaluation of pathologies, including inflammatory bowel diseases (IBD). Saliva is one of the most promising body fluids in the research of new biomarkers, thanks to the large number of molecules it contains. Many molecules present in saliva are often directly correlated to their concentration in the blood but may be affected by the condition of the oral cavity. This means that a careful selection of a specific biomarker is required for each pathology, especially pathologies such as IBD, which may induce inflammation in the oral cavity. Here, we analyze the currently used and the proposed new salivary biomarkers (i.e., calprotectin, cytokines, IgA, cortisol, and oxidative stress markers) for the detection and follow-up of the main subtypes of IBD, known as ulcerative colitis and Crohn's disease.
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Sbeit W, Kadah A, Mahamid M, Karayanni H, Mari A, Tali S, Srouji S, Khoury T. Oral manifestations of inflammatory bowel disease: the neglected piece of the puzzle. Eur J Gastroenterol Hepatol 2020; 32:1422-1431. [PMID: 32925508 DOI: 10.1097/meg.0000000000001918] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing remitting autoimmune disease including Crohn's disease and ulcerative colitis. IBD is associated with various extra-intestinal manifestations including oral manifestation. To date, only limited studies addressing the characteristics of the oral manifestations are available. The aim of the present review is to report the oral manifestations and their characteristics in IBD. A Medline/PubMed and Embase databases search were conducted and all relevant studies were extracted and analyzed. Overall, the oral manifestations in IBD were mostly associated with Crohn's disease rather than Ulcerative colitis where their prevalence ranged from 8 to 50%. Specific lesions for Crohn's disease include mucosal tags, cobblestoning and deep linear ulcerations with vertical fissures, while for ulcerative colitis, pyostomatisis vegetans was more disease specific. Notably, most of the oral manifestations were unrelated to disease activity, however more data are needed to accurately assess this correlation. Oral manifestations among IBD patients are not uncommon as Crohn's disease account for most of them. More data are warranted to precisely characterize their prevalence and association to intestinal activity.
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Affiliation(s)
- Wisam Sbeit
- Department of Gastroenterology, Galilee Medical Center, Nahariya
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed
| | - Anas Kadah
- Department of Gastroenterology, Galilee Medical Center, Nahariya
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed
| | - Mahmud Mahamid
- Faculty of medicine, Hebrew University of Jerusalem, Department of Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Hala Karayanni
- Oral and Maxillofacial Department, Medical Center, Nahariya, The Azrieli Faculty of Medicine, Bar-Ilan University, Ramat Gan
| | - Amir Mari
- Gastroenterology and endoscopy units, The Nazareth Hospital, EMMS, Nazareth, Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
| | - Shani Tali
- Oral and Maxillofacial Department, Medical Center, Nahariya, The Azrieli Faculty of Medicine, Bar-Ilan University, Ramat Gan
| | - Samer Srouji
- Oral and Maxillofacial Department, Medical Center, Nahariya, The Azrieli Faculty of Medicine, Bar-Ilan University, Ramat Gan
| | - Tawfik Khoury
- Department of Gastroenterology, Galilee Medical Center, Nahariya
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed
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Nijakowski K, Surdacka A. Salivary Biomarkers for Diagnosis of Inflammatory Bowel Diseases: A Systematic Review. Int J Mol Sci 2020; 21:ijms21207477. [PMID: 33050496 PMCID: PMC7589027 DOI: 10.3390/ijms21207477] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 10/05/2020] [Accepted: 10/06/2020] [Indexed: 12/15/2022] Open
Abstract
Saliva as a biological fluid has a remarkable potential in the non-invasive diagnostics of several systemic disorders. Inflammatory bowel diseases are chronic inflammatory disorders of the gastrointestinal tract. This systematic review was designed to answer the question “Are salivary biomarkers reliable for the diagnosis of inflammatory bowel diseases?”. Following the inclusion and exclusion criteria, eleven studies were included (according to PRISMA statement guidelines). Due to their heterogeneity, the potential salivary markers for IBD were divided into four groups: oxidative status markers, inflammatory cytokines, microRNAs and other biomarkers. Active CD patients manifest decreased activity of antioxidants (e.g., glutathione, catalase) and increased lipid peroxidation. Therefore, malondialdehyde seems to be a good diagnostic marker of CD. Moreover, elevated concentrations of proinflammatory cytokines (such as interleukin 1β, interleukin 6 or tumour necrosis factor α) are associated with the activity of IBD. Additionaly, selected miRNAs are altered in saliva (overexpressed miR-101 in CD; overexpressed miR-21, miR-31, miR-142-3p and underexpressed miR-142-5p in UC). Among other salivary biomarkers, exosomal PSMA7, α-amylase and calprotectin are detected. In conclusion, saliva contains several biomarkers which can be used credibly for the early diagnosis and regular monitoring of IBD. However, further investigations are necessary to validate these findings, as well as to identify new reliable salivary biomarkers.
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Majster M, Lira-Junior R, Höög CM, Almer S, Boström EA. Salivary and Serum Inflammatory Profiles Reflect Different Aspects of Inflammatory Bowel Disease Activity. Inflamm Bowel Dis 2020; 26:1588-1596. [PMID: 32725166 PMCID: PMC7500518 DOI: 10.1093/ibd/izaa190] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) can manifest both macroscopically and microscopically in the oral cavity; however, little is known about salivary changes in IBD. Therefore, this study aimed to assess salivary and circulatory inflammatory profiles in IBD and to compare their potential to reflect the presence and activity of IBD. METHODS We measured 92 known inflammatory proteins in serum and in unstimulated and stimulated whole saliva samples from patients with IBD with active intestinal inflammation (n = 21) and matched control patients (n = 22) by proximity extension assay. Fifteen of the patients with IBD returned 10 to 12 weeks after treatment escalation for resampling. RESULTS Sixty-seven of the proteins were detected in all 3 sample fluids but formed distinct clusters in serum and saliva. Twenty-one inflammatory proteins were significantly increased and 4 were significantly decreased in the serum of patients with IBD compared with that of the control patients. Two of the increased serum proteins, IL-6 and MMP-10, were also significantly increased in stimulated saliva of patients with IBD and correlated positively to their expressions in serum. None of the investigated proteins in serum or saliva were significantly altered by IBD treatment at follow-up. Overall, inflammatory proteins in serum correlated to biochemical status, and salivary proteins correlated positively to clinical parameters reflecting disease activity. CONCLUSIONS Saliva and serum inflammatory profiles in IBD share a similar composition but reflect different aspects of disease activity. The oral cavity reflects IBD through elevated IL-6 and MMP-10 in stimulated saliva.
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Affiliation(s)
- Mirjam Majster
- Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Ronaldo Lira-Junior
- Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Charlotte M Höög
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden,GHP Stockholm Gastro Center, Stockholm, Sweden
| | - Sven Almer
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden,Division of Gastroenterology, Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Elisabeth A Boström
- Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden,Address correspondence to: Elisabeth A. Boström, DDS, PhD, Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, SE-141 52, Huddinge, Sweden ()
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Conley S, Proctor DD, Lehner V, Jeon S, Redeker NS. The Feasibility of Measuring Sleep and Circadian Characteristics in Adults with Inflammatory Bowel Disease. West J Nurs Res 2020; 43:53-59. [PMID: 32517546 DOI: 10.1177/0193945920933926] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Interest in sleep and circadian research in inflammatory bowel disease (IBD) (Crohn's disease and ulcerative colitis) is growing; however, few studies have objectively measured sleep or circadian rhythms in people with these conditions. The purpose was to determine the feasibility of the use of wrist actigraphy, electronic sleep/activity diaries, and participant-collected saliva among adults with both active and inactive IBD. We conducted a 10-day feasibility study of adults aged 18 years to 60 years with IBD. We measured sleep and rest-activity rhythms with wrist actigraphy, self-reported sleep/activity using electronic diaries, and participant-collected saliva to compute salivary dim light melatonin onset. All 37 (100%) participants wore the wrist actigraphs, 91.8% (N = 34) participants completed at least 15 of the 18 electronic diaries, and 34 (91.9%) completed the saliva collection. It is feasible to use wrist actigraphy and electronic sleep/activity diaries in adult participants with inflammatory bowel disease.
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Majster M, Almer S, Boström EA. Salivary calprotectin is elevated in patients with active inflammatory bowel disease. Arch Oral Biol 2019; 107:104528. [PMID: 31442931 DOI: 10.1016/j.archoralbio.2019.104528] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 08/11/2019] [Accepted: 08/13/2019] [Indexed: 12/21/2022]
Abstract
OBJECTIVES To assess the concentration of calprotectin, a heterodimer of S100A8 and S100A9 implicated in inflammatory bowel disease (IBD), in saliva of IBD patients compared to controls. METHODS Unstimulated and stimulated saliva, and serum was collected from 23 IBD patients with active intestinal inflammation, verified by endoscopy. Fifteen patients were re-sampled after treatment. Saliva was collected from 15 controls for protocol validation and group comparisons. Calprotectin concentrations were measured by enzyme-linked immunosorbent assay, correlated to clinical data/indexes and routine laboratory parameters. RESULTS Calprotectin was 4.0-fold (median) elevated in stimulated saliva of IBD patients compared to controls and tended to be elevated in unstimulated saliva (P = 0.001, P = 0.090). Crohn's (CD) patients had significantly elevated calprotectin in both unstimulated and stimulated saliva compared to controls (P = 0.011, P = 0.002). Newly diagnosed, treatment naïve CD patients had 8.2-fold (median) higher calprotectin concentrations in unstimulated saliva and 1.5-fold in stimulated saliva, compared to CD patients with established disease (P = 0.059, P = 0.019). Calprotectin decreased in serum of IBD patients after treatment (P = 0.011), and in unstimulated saliva of newly diagnosed, treatment naïve CD patients (P = 0.046, P = 0.028). CONCLUSION Salivary calprotectin is elevated in IBD, which suggests subclinical inflammatory responses in the oral cavity as a manifestation of IBD.
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Affiliation(s)
- Mirjam Majster
- Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Sven Almer
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Division of Gastroenterology, Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Elisabeth A Boström
- Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden; Medical Dentistry, Public Dental Health Services, Folktandvården, Stockholm, Sweden.
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Gug IT, Tertis M, Hosu O, Cristea C. Salivary biomarkers detection: Analytical and immunological methods overview. Trends Analyt Chem 2019. [DOI: 10.1016/j.trac.2019.02.020] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Nam Y, Kim YY, Chang JY, Kho HS. Salivary biomarkers of inflammation and oxidative stress in healthy adults. Arch Oral Biol 2018; 97:215-222. [PMID: 30399508 DOI: 10.1016/j.archoralbio.2018.10.026] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 10/16/2018] [Accepted: 10/22/2018] [Indexed: 12/27/2022]
Abstract
OBJECTIVES Diagnostic value of saliva depends on the reproducibility of data in repeatedly collected samples and predictable correlations between saliva and blood. We aimed to investigate the reliability, blood reflectance, and influence of blood contamination in the analysis of inflammatory and oxidative stress biomarkers in saliva samples. DESIGN In total, 37 healthy young male participants (26.7 ± 2.2 years) were included. Unstimulated whole saliva and blood samples were collected on the first visit, and saliva samples were collected again after 2-3 days. The concentrations of total protein and inflammatory [C-reactive protein (CRP), IL-1β, IL-6, and TNF-α] and oxidative stress [8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and total antioxidant capacity (TAC)] biomarkers in saliva and blood, and as well as blood contamination biomarkers (transferrin and hemoglobin) in saliva were analyzed. RESULTS The intra-class correlations of all examined biomarkers except TNF-α were fair to excellent. Significant positive correlations between CRP and IL-6 and between total protein and TAC were stable in the saliva samples collected on different days. Notably, IL-6 was the only biomarker that showed a significant correlation between saliva and blood. As the concentration of salivary transferrin increased, the saliva/blood ratios of total protein and TAC also increased. The concentration of salivary hemoglobin did not affect the saliva/blood ratios of biomarkers. CONCLUSIONS The findings of this study are limited to healthy young males. For clinical applications, studies on salivary diagnostics should be performed for individual disease and health conditions, demographic characteristics, and biomarkers.
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Affiliation(s)
- Yoon Nam
- Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
| | - Yoon-Young Kim
- Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
| | - Ji-Youn Chang
- Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
| | - Hong-Seop Kho
- Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea; Institute on Aging, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
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Hwang DY, Kim S, Hong HS. Substance-P Ameliorates Dextran Sodium Sulfate-Induced Intestinal Damage by Preserving Tissue Barrier Function. Tissue Eng Regen Med 2017; 15:63-73. [PMID: 30603535 DOI: 10.1007/s13770-017-0085-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Revised: 08/30/2017] [Accepted: 09/11/2017] [Indexed: 02/07/2023] Open
Abstract
Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease. Thus, the modulation of intestinal integrity and immune responses in IBD can be the critical factor to be considered to reduce the severity of damages. Substance-P (SP), endogenous peptide to be involved in cell proliferation, migration and immune modulation, can exert the therapeutic effect on diverse diseases including cornea damage, rheumatoid arthritis and diabetic complications. SP was found to elevate expression of junctional molecule. Considering the function of SP reported previously, it was inferred that SP is capable of exert the beneficial effect of SP on intestinal diseases by controlling intestinal structure as well as immune responses. In this study, we explored the therapeutic effect of SP on dextran sodium sulfate-induced intestine damage by injecting SP. The effects of SP were evaluated by analyzing crypt structures, proliferating cell pool and infiltration of immune cells. DSS treatment provoked abnormal immune response and disruption of intestine epithelial barrier. However, co-treatment of SP obviously blocked the development of intestinal damages by declining inflammatory responses and sustaining intestinal structure more intact. The treatment of SP to chronic damages also promoted intestinal regeneration by preserving the integrity of colon tissue. Moreover, DSS-induced reduction of epithelial junctional molecule was obviously inhibited by SP treatment in vitro. Taken together, our data indicate that SP can reduce intestinal damages, possibly by modulating barrier structure and immune response. Our results propose SP as candidate therapeutics in intestinal damages.
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Affiliation(s)
- Dae Yeon Hwang
- 1Department of Medicine, Graduate School, Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447 Republic of Korea
| | - Suna Kim
- 2Graduate School of Biotechnology and Department of Genetic Engineering, College of Life Science, Kyung Hee University Global Campus, 1732 Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17104 Republic of Korea
| | - Hyun Sook Hong
- 3College of Medicine/East-West Medical Research Institute, Kyung Hee University, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447 Republic of Korea
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21
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Hassona Y, Scully C. Salivary changes in oral mucosal diseases. Periodontol 2000 2017; 70:111-27. [PMID: 26662486 DOI: 10.1111/prd.12102] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2015] [Indexed: 12/17/2022]
Abstract
Saliva is a unique biological fluid that can be easily collected and analyzed with low cost and low morbidity. Therefore, there is a growing attention for using salivary biomarkers in the diagnosis and monitoring of disease progress and response to treatment. Salivary changes have been described in relation to oral mucosal diseases. This article discusses the causes and consequences of salivary hypofunction and presents a review of the literature related to changes in salivary parameters in various oral mucosal diseases and in systemic diseases with possible oral mucosal involvement.
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Vasovic M, Gajovic N, Brajkovic D, Jovanovic M, Zdravkovaic N, Kanjevac T. The relationship between the immune system and oral manifestations of inflammatory bowel disease: a review. Cent Eur J Immunol 2016; 41:302-310. [PMID: 27833449 PMCID: PMC5099388 DOI: 10.5114/ceji.2016.63131] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Accepted: 07/28/2015] [Indexed: 12/15/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) are chronic, relapsing inflammatory diseases characterized by exacerbations and remissions of the gastrointestinal tract, clinically manifested as Crohn's disease and ulcerative colitis. The etiology of IBDs is considered to be multi factorial, comprising environmental, immune, microbial and genetic factors. Clinical signs may include abdominal pain, frequent bloody diarrheas, mucorrhea, vomiting, fever, fatigue or weight loss. Changes in the oral cavity often precede intestinal symptoms. Inflammatory bowel disease leads to a significant deterioration of oral health, which indicates that cooperation between the dentist and the gastroenterologist is necessary when considering patients' welfare. Patients with IBD have an altered immune response, but microorganisms of the oral cavity may also be responsible for its modification. This review paper discusses the correlation between the immune system and inflammatory bowel disease manifestations in the oral cavity.
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Affiliation(s)
- Miroslav Vasovic
- Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Nevena Gajovic
- Center for Molecular Medicine and Stem Cells Research, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Denis Brajkovic
- Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Marina Jovanovic
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Natasa Zdravkovaic
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Tatjana Kanjevac
- Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Serbia
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Lira-Junior R, Figueredo CM. Periodontal and inflammatory bowel diseases: Is there evidence of complex pathogenic interactions? World J Gastroenterol 2016; 22:7963-7972. [PMID: 27672291 PMCID: PMC5028810 DOI: 10.3748/wjg.v22.i35.7963] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 06/29/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
Periodontal disease and inflammatory bowel disease (IBD) are both chronic inflammatory diseases. Their pathogenesis is mediated by a complex interplay between a dysbiotic microbiota and the host immune-inflammatory response, and both are influenced by genetic and environmental factors. This review aimed to provide an overview of the evidence dealing with a possible pathogenic interaction between periodontal disease and IBD. There seems to be an increased prevalence of periodontal disease in patients with IBD when compared to healthy controls, probably due to changes in the oral microbiota and a higher inflammatory response. Moreover, the induction of periodontitis seems to result in gut dysbiosis and altered gut epithelial cell barrier function, which might contribute to the pathogenesis of IBD. Considering the complexity of both periodontal disease and IBD, it is very challenging to understand the possible pathways involved in their coexistence. In conclusion, this review points to a complex pathogenic interaction between periodontal disease and IBD, in which one disease might alter the composition of the microbiota and increase the inflammatory response related to the other. However, we still need more data derived from human studies to confirm results from murine models. Thus, mechanistic studies are definitely warranted to clarify this possible bidirectional association.
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Exum NG, Pisanic N, Granger DA, Schwab KJ, Detrick B, Kosek M, Egorov AI, Griffin SM, Heaney CD. Use of Pathogen-Specific Antibody Biomarkers to Estimate Waterborne Infections in Population-Based Settings. Curr Environ Health Rep 2016; 3:322-34. [PMID: 27352014 PMCID: PMC5424709 DOI: 10.1007/s40572-016-0096-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW This review discusses the utility of pathogen-specific antibody biomarkers for improving estimates of the population burden of waterborne infections, assessing the fraction of infections that can be prevented by specific water treatments, and understanding transmission routes and the natural history and ecology of disease in different populations (including asymptomatic infection rates). RECENT FINDINGS We review recent literature on the application of pathogen-specific antibody response data to estimate incidence and prevalence of acute infections and their utility to assess the contributions of waterborne transmission pathways. Advantages and technical challenges associated with the use of serum versus minimally invasive salivary antibody biomarkers in cross-sectional and prospective surveys are discussed. We highlight recent advances and challenges and outline future directions for research, development, and application of antibody-based and other immunological biomarkers of waterborne infections.
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Affiliation(s)
- Natalie G Exum
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Nora Pisanic
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Douglas A Granger
- Institute for Interdisciplinary Salivary Bioscience Research, University of California Irvine, Irvine, CA, USA
- Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
- Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
- Department of Acute and Chronic Care, School of Nursing, Johns Hopkins University, Baltimore, Maryland, USA
| | - Kellogg J Schwab
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Barbara Detrick
- Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
| | - Margaret Kosek
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Andrey I Egorov
- National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina, USA
| | - Shannon M Griffin
- National Exposure Research Laboratory, US Environmental Protection Agency, Cincinnati, Ohio, USA
| | - Christopher D Heaney
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Room W7033B, 615 North Wolfe Street, Baltimore, Maryland, 21205-2179, USA.
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25
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Jaedicke KM, Preshaw PM, Taylor JJ. Salivary cytokines as biomarkers of periodontal diseases. Periodontol 2000 2015; 70:164-83. [DOI: 10.1111/prd.12117] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/07/2015] [Indexed: 12/15/2022]
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Goodson JM, Kantarci A, Hartman ML, Denis GV, Stephens D, Hasturk H, Yaskell T, Vargas J, Wang X, Cugini M, Barake R, Alsmadi O, Al-Mutawa S, Ariga J, Soparkar P, Behbehani J, Behbehani K, Welty F. Metabolic disease risk in children by salivary biomarker analysis. PLoS One 2014; 9:e98799. [PMID: 24915044 PMCID: PMC4051609 DOI: 10.1371/journal.pone.0098799] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2014] [Accepted: 05/07/2014] [Indexed: 12/04/2022] Open
Abstract
Objective The study of obesity-related metabolic syndrome or Type 2 diabetes (T2D) in children is particularly difficult because of fear of needles. We tested a non-invasive approach to study inflammatory parameters in an at-risk population of children to provide proof-of-principle for future investigations of vulnerable subjects. Design and Methods We evaluated metabolic differences in 744, 11-year old children selected from underweight, normal healthy weight, overweight and obese categories by analyzing fasting saliva samples for 20 biomarkers. Saliva supernatants were obtained following centrifugation and used for analyses. Results Salivary C-reactive protein (CRP) was 6 times higher, salivary insulin and leptin were 3 times higher, and adiponectin was 30% lower in obese children compared to healthy normal weight children (all P<0.0001). Categorical analysis suggested that there might be three types of obesity in children. Distinctly inflammatory characteristics appeared in 76% of obese children while in 13%, salivary insulin was high but not associated with inflammatory mediators. The remaining 11% of obese children had high insulin and reduced adiponectin. Forty percent of the non-obese children were found in groups which, based on biomarker characteristics, may be at risk for becoming obese. Conclusions Significantly altered levels of salivary biomarkers in obese children from a high-risk population, suggest the potential for developing non-invasive screening procedures to identify T2D-vulnerable individuals and a means to test preventative strategies.
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Affiliation(s)
- J. Max Goodson
- Department of Applied Oral Sciences, the Forsyth Research Institute, Cambridge, Massachusetts, United States of America
- * E-mail:
| | - Alpdogan Kantarci
- Department of Applied Oral Sciences, the Forsyth Research Institute, Cambridge, Massachusetts, United States of America
| | - Mor-Li Hartman
- Department of Applied Oral Sciences, the Forsyth Research Institute, Cambridge, Massachusetts, United States of America
| | - Gerald V. Denis
- Cancer Research Center, Boston University School of Medicine, Boston, Massachusetts, United States of America
| | - Danielle Stephens
- Department of Applied Oral Sciences, the Forsyth Research Institute, Cambridge, Massachusetts, United States of America
| | - Hatice Hasturk
- Department of Applied Oral Sciences, the Forsyth Research Institute, Cambridge, Massachusetts, United States of America
| | - Tina Yaskell
- Department of Applied Oral Sciences, the Forsyth Research Institute, Cambridge, Massachusetts, United States of America
| | - Jorel Vargas
- Department of Applied Oral Sciences, the Forsyth Research Institute, Cambridge, Massachusetts, United States of America
| | - Xiaoshan Wang
- Department of Applied Oral Sciences, the Forsyth Research Institute, Cambridge, Massachusetts, United States of America
| | - Maryann Cugini
- Department of Applied Oral Sciences, the Forsyth Research Institute, Cambridge, Massachusetts, United States of America
| | - Roula Barake
- The Dasman Diabetes Institute, Kuwait City, Kuwait
| | | | | | | | - Pramod Soparkar
- Department of Applied Oral Sciences, the Forsyth Research Institute, Cambridge, Massachusetts, United States of America
| | - Jawad Behbehani
- Faculty of Dentistry, Kuwait University, Kuwait City, Kuwait
| | | | - Francine Welty
- Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America
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Byrne ML, O'Brien-Simpson NM, Reynolds EC, Walsh KA, Laughton K, Waloszek JM, Woods MJ, Trinder J, Allen NB. Acute phase protein and cytokine levels in serum and saliva: a comparison of detectable levels and correlations in a depressed and healthy adolescent sample. Brain Behav Immun 2013; 34:164-75. [PMID: 23999491 DOI: 10.1016/j.bbi.2013.08.010] [Citation(s) in RCA: 107] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 08/15/2013] [Accepted: 08/23/2013] [Indexed: 12/23/2022] Open
Abstract
Recent research has examined associations between inflammation and mental health, and has increasingly focused on utilising younger samples to characterise the temporal relationship between inflammatory responses and the emergence of other symptoms. These studies have typically used blood to measure inflammation, although rates of detection for many inflammatory markers appear to be low. Saliva is a safe and low-cost alternative, and adult research has shown that levels of some salivary markers correlate well with those in serum. However, no research has examined this association in young people. This study examined 16 inflammatory markers in serum and saliva in 17 depressed adolescents and 18 healthy controls, aged 13-18 years. In general, detection rates were higher in saliva compared to in serum. When non-detectable levels were excluded, serum levels of C-reactive protein (CRP) correlated with salivary CRP (r=0.424, p=0.015), and this correlation appeared to only exist for those individuals with high levels of serum CRP (r=0.599, p=0.014). However, when non-detectable levels were included as zero, salivary levels of CRP, interleukin (IL)-2, IL-12p70, and interferon (IFN)-γ correlated with their serum counterparts. No significant clinical group differences in any acute phase proteins or cytokines were present. This study suggests that saliva can be used to measure inflammation in studies with adolescent participants, especially CRP, as it appears to correlate with systemic inflammation for those individuals who are expected to have high levels of inflammation. Implications for future directions in research on salivary inflammatory markers are discussed.
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Affiliation(s)
- Michelle L Byrne
- Melbourne School of Psychological Sciences, The University of Melbourne, Victoria 3010, Australia
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Rychlik A, Nieradka R, Kander M, Nowicki M, Wdowiak M, Kołodziejska-Sawerska A. The effectiveness of natural and synthetic immunomodulators in the treatment of inflammatory bowel disease in dogs. Acta Vet Hung 2013; 61:297-308. [PMID: 23921342 DOI: 10.1556/avet.2013.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The aim of the study was to evaluate the usefulness of immunomodulators in the treatment of inflammatory bowel disease (IBD) in dogs. Twenty-eight dogs diagnosed with IBD took part in the study. The animals received a food containing extruded immunomodulators: β-1,3/1,6-D-glucan, β-hydroxy-β-methyl-butyrate (HMB) and levamisole for 42 days. Whole blood samples were analysed before and after therapy assessing changes in phagocyte activity (respiratory burst activity, RBA and potential killing activity, PKA), evaluation of proliferation response of mitogen-stimulated lymphocytes and serum gamma globulin levels, lysozyme activity, ceruloplasmin levels and interleukin activity (IL-6 and IL-10). In this experiment, β-1,3/1,6-D-glucan delivered the highest level of treatment efficacy by producing the quickest therapeutic effect, lowering Canine Inflammatory Bowel Disease Activity Index (CIBDAI) values to below 3, improving histopathological parameters, decreasing IL-6 levels, increasing IL-10 concentrations, and producing remission periods longer than six months. HMB and levamisole were also effective in lowering CIBDAI scores, but the abatement of clinical symptoms was slower and less pronounced in comparison with β-1,3/1,6-D-glucan. The results indicate that β-1,3/1,6-D-glucan can be useful in the treatment of canine IBD.
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Affiliation(s)
- Andrzej Rychlik
- 1 University of Warmia and Mazury in Olsztyn Department of Clinical Diagnostics, Faculty of Veterinary Medicine Oczapowskiego 14 10-957 Olsztyn Poland
| | - Renata Nieradka
- 1 University of Warmia and Mazury in Olsztyn Department of Clinical Diagnostics, Faculty of Veterinary Medicine Oczapowskiego 14 10-957 Olsztyn Poland
| | - Małgorzata Kander
- 1 University of Warmia and Mazury in Olsztyn Department of Clinical Diagnostics, Faculty of Veterinary Medicine Oczapowskiego 14 10-957 Olsztyn Poland
| | - Marcin Nowicki
- 1 University of Warmia and Mazury in Olsztyn Department of Clinical Diagnostics, Faculty of Veterinary Medicine Oczapowskiego 14 10-957 Olsztyn Poland
| | - Michał Wdowiak
- 1 University of Warmia and Mazury in Olsztyn Department of Clinical Diagnostics, Faculty of Veterinary Medicine Oczapowskiego 14 10-957 Olsztyn Poland
| | - Anna Kołodziejska-Sawerska
- 1 University of Warmia and Mazury in Olsztyn Department of Clinical Diagnostics, Faculty of Veterinary Medicine Oczapowskiego 14 10-957 Olsztyn Poland
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Brandtzaeg P. Secretory immunity with special reference to the oral cavity. J Oral Microbiol 2013; 5:20401. [PMID: 23487566 PMCID: PMC3595421 DOI: 10.3402/jom.v5i0.20401] [Citation(s) in RCA: 199] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Revised: 01/29/2013] [Accepted: 02/15/2013] [Indexed: 11/14/2022] Open
Abstract
The two principal antibody classes present in saliva are secretory IgA (SIgA) and IgG; the former is produced as dimeric IgA by local plasma cells (PCs) in the stroma of salivary glands and is transported through secretory epithelia by the polymeric Ig receptor (pIgR), also named membrane secretory component (SC). Most IgG in saliva is derived from the blood circulation by passive leakage mainly via gingival crevicular epithelium, although some may be locally produced in the gingiva or salivary glands. Gut-associated lymphoid tissue (GALT) and nasopharynx-associated lymphoid tissue (NALT) do not contribute equally to the pool of memory/effector B cells differentiating to mucosal PCs throughout the body. Thus, enteric immunostimulation may not be the best way to activate the production of salivary IgA antibodies although the level of specific SIgA in saliva may still reflect an intestinal immune response after enteric immunization. It remains unknown whether the IgA response in submandibular/sublingual glands is better related to B-cell induction in GALT than the parotid response. Such disparity is suggested by the levels of IgA in submandibular secretions of AIDS patients, paralleling their highly upregulated intestinal IgA system, while the parotid IgA level is decreased. Parotid SIgA could more consistently be linked to immune induction in palatine tonsils/adenoids (human NALT) and cervical lymph nodes, as supported by the homing molecule profile observed after immune induction at these sites. Several other variables influence the levels of antibodies in salivary secretions. These include difficulties with reproducibility and standardization of immunoassays, the impact of flow rate, acute or chronic stress, protein loss during sample handling, and uncontrolled admixture of serum-derived IgG and monomeric IgA. Despite these problems, saliva is an easily accessible biological fluid with interesting scientific and clinical potentials.
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Affiliation(s)
- Per Brandtzaeg
- Per Brandtzaeg, Department of Pathology, Oslo University Hospital, Rikshospitalet, PO Box 4950 Oslo, NO-0424 Norway. Tel: +47-23072743, Fax: 47-23071511.
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Hiratsuka T, Inomata M, Hagiwara S, Kono Y, Shiraishi N, Noguchi T, Kitano S. Bolus injection of newly synthesized vitamin E derivative ETS-GS for the treatment of acute severe ulcerative colitis in a mouse model. New vitamin E derivative for acute severe UC. Int J Colorectal Dis 2013; 28:305-11. [PMID: 22847605 DOI: 10.1007/s00384-012-1502-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/09/2012] [Indexed: 02/04/2023]
Abstract
PURPOSE Vitamin E with its antioxidant action has therapeutic effects on ulcerative colitis (UC), but use of vitamin E is limited because of its insolubility in water. We developed ETS-GS (γ-L-glutamyl-S-[2-[[[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltri-decyl)-2 H-1-benzopyran-6-yl]oxy]carbonyl]-3-oxo-3-[(2-sulfoethyl)amino]propyl]-L-cysteinylglycine sodium salt), a newly synthesized soluble vitamin E derivative with strong antioxidant action. We evaluated the therapeutic effects of bolus injection of ETS-GS on acute severe UC in a mouse model. METHODS An animal model of acute severe UC was induced by feeding mice 5 % dextran sulfate sodium (DSS) for 5 days, followed by 1 % DSS on days 5-8, the experimental period. ETS-GS or saline was administered by subcutaneous bolus injection during the experimental period. We examined disease activity index (DAI) score, histological score, colon length, colon weight, and serum cytokines in the mice. RESULTS The following results at day 8 in the DSS + ETS-GS group were significantly lower than those in the DSS + Saline group: DAI score, 2.6 ± 0.6 vs. 3.1 ± 0.5; histological score, 2.1 ± 1.0 vs. 3.1 ± 0.8; serum interleukin (IL)-6, 15 ± 9.4 vs. 39 ± 23 pg/ml; and keratinocyte-derived chemokine (KC), 122 ± 61 vs. 228 ± 66 pg/ml (P < 0.05). Colon length, colon weight, and serum IL-10 in the DSS + ETS-GS group were significantly higher than those in the DSS + Saline group (88 ± 12 vs. 75 ± 5.7 mm, 0.48 ± 0.09 vs. 0.38 ± 0.05 g, and 55 ± 18 vs. 31 ± 10 pg/ml, respectively; P < 0.05). CONCLUSIONS Bolus injection of ETS-GS may be one therapeutic modality for acute severe UC. Its effects are associated with suppression of serum IL-6 and serum KC and promotion of serum IL-10.
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Affiliation(s)
- Takahiro Hiratsuka
- Department of Gastroenterological Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-city, Oita 879-5593, Japan.
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Zhao C, Wang XM, Wang JH, Hua XG, Yao Y. Effect of moxibustion on the expressions of protein KGF-1, KGF-2 and IL-6 in colon of rats with ulcerative colitis. JOURNAL OF ACUPUNCTURE AND TUINA SCIENCE 2012. [DOI: 10.1007/s11726-012-0590-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Zhou LF, Miao YL. Progress in research of biological activity markers for inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2011; 19:3229-3236. [DOI: 10.11569/wcjd.v19.i31.3229] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The incidence of inflammatory bowel disease (IBD) has been increasing in recent years. The clinical manifestations of IBD are complicated, and both intestinal and extraintestinal symptoms may develop. Due to the lack of specific index, IBD is easy to be misdiagnosed, and evaluating disease activity is more difficult. Radiology, endoscopic and histological biopsy for diagnosis are expensive. Currently, there is an urgent need of a simple, noninvasive, sensitive, economic, and highly specific method for diagnosis of IBD. Biological activity markers may meet this demand. In this paper, the clinical applicability of biological activity markers, which come from both ulcerative colitis (UC) and Crohn's disease (CD), in identifying the presence or extent of inflammatory response, is reviewed.
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Schapher M, Wendler O, Gröschl M. Salivary cytokines in cell proliferation and cancer. Clin Chim Acta 2011; 412:1740-8. [PMID: 21736875 DOI: 10.1016/j.cca.2011.06.026] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2011] [Revised: 06/19/2011] [Accepted: 06/21/2011] [Indexed: 01/08/2023]
Abstract
While the presence of multiple systemic steroids, amines and peptides in saliva has been reported, other hormones of the circulation do not appear in saliva. Substances present within saliva may be classified in different groups: first, those which passively display blood plasma concentrations and constitute a promising alternative to evaluate certain systemic parameters. Second, molecules which seem to play a more active, regulatory role within the upper gastrointestinal tract. Concerning the latter, a growing awareness, especially with regards to salivary peptides has been established. Up to now, understanding the distinct effects of salivary peptides known so far is in its infancy. Various publications, however, emphasize important effects of their presence. Salivary peptides can influence inflammatory processes and cell proliferation in epithelia of the upper digestive tract. These include transforming growth factors (TGFs), epidermal growth factors (EGFs), vascular endothelial growth factors (VEGFs) as well as amines such as melatonin. Of those, candidate cytokines like interleukin 8, tumor necrosis factors (TNFs) and leptin are involved in neoplastic activities of salivary glands and the oral cavity. The exact mechanisms of action are not yet completely understood, but their presence can be utilized for diagnostic purposes. Salivary gland tumors in patients may, in certain circumstances, be identified by saliva diagnostics. Saliva samples of the concerned patients, for instance, reveal significantly higher leptin concentrations than those of healthy individuals. Numerous studies postulate that, beside single indicators, the establishment of salivary hormone profiles may assist clinicians and researchers in detecting tumors and other pathologies of the oral cavity, including adjacent tissues, with high sensitivity and specificity.
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Affiliation(s)
- Mirco Schapher
- University of Erlangen-Nuremberg, Department of Otorhinolaryngology, Head and Neck Surgery, Germany.
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Wang X, Chen Y, Song Y, Zhang S, Xie X, Wang X. Activated Syndecan-1 shedding contributes to mice colitis induced by dextran sulfate sodium. Dig Dis Sci 2011; 56:1047-56. [PMID: 20936359 DOI: 10.1007/s10620-010-1398-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2010] [Accepted: 08/12/2010] [Indexed: 12/21/2022]
Abstract
BACKGROUND Syndecan-1(Sdc1) plays important roles in many steps of inflammatory responses. In ulcerative colitis patients, decreased Sdc1 expression was observed and Sdc1 analogue heparin could improve the disease course. A better understanding of how Sdc1 functions in colitis will benefit the disease intervention. AIMS To evaluate the role of Sdc1 in dextran sulfate sodium (DSS)-induced colitis. METHODS BALB/c mice were grouped randomly into control, DSS, and heparin+DSS. The DSS group was given 4% DSS orally and heparin+DSS group was given 4% DSS with heparin (enoxaparin) subcutaneously, while the control was given distilled water orally. All mice were killed at day 7. Disease activities, histopathological changes, membrane-bound and free Sdc1 level and mRNA expression of Sdc1, IL-1, and IL-10 in colon mucosa were detected. RESULTS Significant colitis was observed in the DSS group, but disease activity index and histological score showed significant lower in the heparin+DSS group than those in the DSS group. Compared to the control group, decreased Sdc1 protein expression was detected in colon mucosa of DSS-induced colitis while Sdc1 ectodomain level in serum was much higher. Inhibited Sdc1 ectodomain shedding was detected in the heparin+DSS group compared to the DSS group. RT-PCR demonstrated that both IL-1 and IL-10 expression were up-regulated in DSS-induced colitis while heparin lessened the up-regulation extent. CONCLUSIONS Sdc1 shedding is activated in DSS-induced colitis and heparin, which mimics Sdc1 functions, relieves colitis severity by inhibiting Sdc1 shedding and down-regulating cytokines expression.
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Affiliation(s)
- Xia Wang
- Guangdong Provincial Key Laboratory of Gastroenterology and Department of Digestive Diseases, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.
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Vallières M, du Souich P. Modulation of inflammation by chondroitin sulfate. Osteoarthritis Cartilage 2010; 18 Suppl 1:S1-6. [PMID: 20399900 DOI: 10.1016/j.joca.2010.02.017] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2009] [Revised: 02/16/2010] [Accepted: 02/18/2010] [Indexed: 02/02/2023]
Abstract
OBJECTIVE AND METHODS To evaluate the immune-modulator effect of chondroitin sulfate (CS) by means of the review of the literature. RESULTS Inflammatory reactions are primarily originated by infectious agents, immune reactions and by sterile tissue lesions that activate membrane receptors by means of pathogen-associated molecular patterns, tissue breakdown products and cytokines. The activation of membrane receptors triggers the phosphorylation of mitogen activated protein kinases and of the nuclear factor kappaB (NF-kappaB). The binding of NF-kappaB to the promoter of target genes enhances the expression of pro-inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase 2, phospholipase A2, and matrix metalloproteases, proteins that contribute to tissue damage and to the inflammatory reaction. The activation of NF-kappaB has a key role in the immune homeostasis and the inflammatory response and therefore, in the pathogenesis of numerous diseases. Chondroitin sulfate (CS) is able to diminish NF-kappaB activation and nuclear translocation in chondrocytes and synovial membrane, effects that may explain the benefits of CS in osteoarthritis. In addition, systemic CS reduces NF-kappaB nuclear translocation in macrophages and hepatocytes, raising the hypothesis that CS might be of benefit to treat other diseases with a strong inflammatory component. There is preliminary evidence in humans that CS improves moderate to severe psoriasis. Moreover, experimental and clinical data suggest that CS might be a useful therapeutic agent in diseases such as inflammatory bowel diseases, atherosclerosis, Parkinson's and Alzheimer's diseases, multiple sclerosis, amyotrophic lateral sclerosis, rheumatoid arthritis and systemic lupus erythematosus. DISCUSSION These results urge for double blinded placebo-controlled trials to confirm the utility of CS in diseases with immune and inflammatory components.
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Affiliation(s)
- M Vallières
- Department of Pharmacology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada H3C 3J7
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Kriel M, Sayers A, Fraser WD, Williams AM, Koch A, Zacharowski K, Probert CS, Tobias JH. IL-6 may modulate the skeletal response to glucocorticoids during exacerbations of inflammatory bowel disease. Calcif Tissue Int 2010; 86:375-81. [PMID: 20229252 DOI: 10.1007/s00223-010-9345-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2009] [Accepted: 01/31/2010] [Indexed: 10/19/2022]
Abstract
Whether inflammatory cytokines affect the skeletal response to glucocorticoid (GC) treatment is unclear. Our objectives were to (1) identify the cytokine(s) elevated during exacerbations of inflammatory bowel disease (IBD); (2) determine whether the cytokine(s) identified in this way is related to systemic GC sensitivity; and (3) examine whether cytokines and/or measures of GC sensitivity are related to changes in bone formation or resorption following GC therapy. We designed a combined cross-sectional and prospective study, including patients with active (n = 31) and inactive (n = 34) IBD as well as controls (n = 29). We assessed circulating concentrations of cytokines, PINP and betaCTX, as well as GC sensitivity in peripheral blood mononuclear cells. IL-6 was the only cytokine increased in active IBD, 2.35 (2.63) versus 1.64 (1.21) versus 1.31 (2.79) pg/microl active IBD, inactive IBD, and controls, respectively (median [interquartile range]) (P = 0.03, ANOVA). IL-6 was positively related to magnitude of GC sensitivity (beta = 0.02, 95% CI 0.008-0.04, P = 0.005). Following treatment with GC in active IBD, PINP decreased (P < 0.001), whereas betaCTX showed no significant change (P = 0.2). Subsequently, multiple regression analyses revealed that plasma IL-6 concentrations were inversely related to the extent of PINP suppression following GC (beta = 3.3, 95% CI 0.2-6.4, P = 0.04, adjusted for baseline PINP and duration of GC treatment), while no association was observed with GC sensitivity. In conclusion, IL-6 is elevated in active IBD and may protect against GC-induced suppression of bone formation via a mechanism which appears to be independent of systemic GC sensitivity.
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Affiliation(s)
- Muhammed Kriel
- Clinical Science at South Bristol, University of Bristol, Bristol, UK.
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Cox AJ, Pyne DB, Gleson M, Callister R. Resting plasma and salivary IL-6 concentrations are not correlated in distance runners. Eur J Appl Physiol 2008; 103:477-9. [PMID: 18351377 DOI: 10.1007/s00421-008-0722-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/10/2008] [Indexed: 10/22/2022]
Abstract
Measurement of IL-6 has been widely undertaken to examine inflammatory and immune responses to exercise. Use of salivary IL-6 offers an alternative to the invasive collection procedures required for IL-6 measurement in plasma samples. Rarely, however, has the degree of association between plasma and salivary IL-6 been reported. The aim of the current study was to investigate the relationship between resting salivary and plasma IL-6 concentrations in 45 trained distance runners (36 males, 9 females; age: 35.1 +/- 8.0 y, mean +/- SD). Plasma and saliva samples were collected from athletes under resting conditions. Plasma IL-6 concentrations were determined using a Bioplex suspension array system and commercially available reagents. Salivary IL-6 concentrations were determined using a commercially available high-sensitivity ELISA kit. At rest, the mean (+/- SD) plasma IL-6 concentration was 3.43 +/- 3.75 pg mL(-1) compared to a mean salivary IL-6 concentration of 1.80 +/- 4.25 pg mL(-1). IL-6 concentrations in plasma and saliva samples were not correlated (r = -0.031, p = 0.85). At rest, salivary IL-6 concentrations do not reflect plasma IL-6 concentrations. The potential for salivary IL-6 to act as a surrogate marker for plasma IL-6 responses when examining inflammatory and immune responses to exercise, therefore, appears unlikely.
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Affiliation(s)
- Amanda J Cox
- Department of Physiology, Australian Institute of Sport, PO Box 176, Canberra, Belconnen, ACT 2616, Australia.
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Minetto MA, Gazzoni M, Lanfranco F, Baldi M, Saba L, Pedrola R, Komi PV, Rainoldi A. Influence of the sample collection method on salivary interleukin–6 levels in resting and post-exercise conditions. Eur J Appl Physiol 2007; 101:249-56. [PMID: 17569075 DOI: 10.1007/s00421-007-0484-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/30/2007] [Indexed: 12/20/2022]
Abstract
Previous studies demonstrated that no significant relationships exist between salivary and serum IL-6 in resting conditions and following exercise and that appropriate saliva collection procedures allow to avoid analytical drawbacks. This investigation aimed to: (a) compare the effects of two methods of saliva collection on IL-6 assay; (b) search for correlation between salivary and serum IL-6 in resting and post-exercise conditions; (c) evaluate the IL-6 response to isometric contractions. Seventeen sedentary subjects and fifteen athletes underwent one blood and two salivary draws: saliva was collected chewing on cotton salivettes and using a plastic straw (SA method and ST method, respectively). Afterwards, the athletes only completed a fatiguing isometric exercise of the knee extensors and blood and saliva were sampled after the exercise. In the entire group (n=32), ST method produced higher IL-6 levels than SA method and serum sampling. The exercise elicited significant responses of lactate, serum IL-6, salivary IL-6 (by ST method): salivary IL-6 values using the ST collection method were higher at each sampling point than with the SA method. The correlation analyses applied to both resting levels in the entire group and absolute changes above baseline in the athlete group showed that: (1) no significant relationships exist between serum and salivary IL-6 levels; (2) the greater the salivary IL-6 measurement, the higher the resultant inaccuracy of the SA method; (3) significant correlations exist between isometric force and mechanical fatigue during exercise and peaks of lactate and serum IL-6. These data provided demonstration of a cotton-interference effect for the results of salivary IL-6 assay and confirmed the lack of significant correlation between salivary and serum IL-6 in resting and post-exercise conditions.
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Affiliation(s)
- M A Minetto
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy.
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Abstract
Two major antibody classes operate in saliva: secretory IgA (SIgA) and IgG. The former is synthesized as dimeric IgA by plasma cells (PCs) in salivary glands and is exported by the polymeric Ig receptor (pIgR). Most IgG in saliva is derived from serum (mainly via gingival crevices), although some is locally produced. Gut-associated lymphoid tissue (GALT) and nasopharynx-associated lymphoid tissue (NALT) do not contribute equally to mucosal PCs throughout the body. Thus, enteric immunostimulation is an inadequate mode of stimulating salivary IgA antibodies, which are poorly associated with the intestinal SIgA response, for instance after enteric cholera vaccination. Nevertheless, the IgA response in submandibular/sublingual glands is better related to B cell induction in GALT than the parotid response. Such disparity is suggested by the elevated levels of IgA in submandibular secretions of AIDS patients, paralleling their highly upregulated intestinal IgA system. Moreover, in patients with active celiac disease, IgA antibodies to disease-precipitating gliadin are reliably represented in whole saliva but not in parotid secretion. Parotid SIgA may be more consistently linked to immune induction in palatine tonsils and adenoids (human NALT), as supported by the homing molecule profile of NALT-derived B cell blasts. Also several other variables influence the levels of antibodies in oral secretions. These include difficulties with reproducibility and standardization of immunoassays, the impact of flow rate, acute or chronic stress, protein loss during sample handling, and uncontrolled admixture of serum-derived IgG and monomeric IgA. Despite such problems, saliva remains an interesting biological fluid with great scientific and clinical potentials.
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Affiliation(s)
- Per Brandtzaeg
- Laboratory for Immunohistochemistry and Immunopathology, Department and Institute of Pathology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Norway.
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Ruffolo C, Scarpa M, Faggian D, Romanato G, De Pellegrin A, Filosa T, Prando D, Polese L, Scopelliti M, Pilon F, Ossi E, Frego M, D'Amico DF, Angriman I. Cytokine network in chronic perianal Crohn's disease and indeterminate colitis after colectomy. J Gastrointest Surg 2007; 11:16-21. [PMID: 17390181 DOI: 10.1007/s11605-006-0021-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Antitumor necrosis factor alpha (anti-TNF-alpha) therapy in perianal Crohn's disease (CD) is widely established but recent studies suggest that the underlying fistula tract and inflammation may persist. Treatment with a monoclonal antibody against interleukin (IL)-12 was reported to induce clinical responses and remissions in patients with active CD. The aim of our study was to analyze the cytokine network (TNF-alpha, IL-12, IL-1beta, and IL-6) in 12 patients with chronic perianal CD and a Crohn's disease activity index (CDAI) score <150 to exclude active intestinal disease, in 7 patients with indeterminate colitis (IC) after restorative proctocolectomy with perianal complications, in 7 patients with active intestinal CD without perianal manifestations, and in 19 healthy controls. Nonparametric Mann-Whitney U test and Spearman's rank correlation test were used. Serum TNF-alpha levels were significantly higher in patients with IC than perianal CD patients and healthy controls. Serum TNF-alpha levels significantly correlated with perianal CDAI score and with the presence of anal fistulas. Serum IL-12 levels correlated with the presence of anal strictures and were similar in all groups. Serum IL-6 levels were significantly higher in the presence of perianal fistulas and lower in the presence of anal strictures. Our study confirmed that TNF-alpha plays a major role in the perianal and intestinal CD. Furthermore, the significantly higher TNF-alpha serum levels in patients with IC suggest the use of anti-TNF-alpha in such patients. On the contrary, according to our results the efficacy of anti-IL-12 antibodies appears doubtful in chronic perianal CD or IC without anal strictures. The role of IL-6 as a systemic mediator for active chronic inflammation was confirmed and a possible role for its monoclonal antibody was suggested.
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Affiliation(s)
- Cesare Ruffolo
- Clinica Chirurgica, Department of Surgical and Gastroenterological Sciences, University of Padua, Padova, Italy.
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