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Connection Between Dysbiotic Oral Microbiota and Deregulation of Salivary Gland Epithelial Cells in Sjogren's Syndrome

22 Pages Posted: 18 Nov 2018

See all articles by Jehan Alam

Jehan Alam

Seoul National University - Department of Immunology and Molecular Microbiology; Baylor University - Department of Ophthalmology

Ahreum Lee

Seoul National University - Department of Immunology and Molecular Microbiology

Junho Lee

Seoul National University - Department of Immunology and Molecular Microbiology

Dong Il Kwon

Seoul National University - Department of Immunology and Molecular Microbiology; Pohang University of Science and Technology (POSTECH) - Division of Integrative Biosciences and Biotechnology (IBB)

Hee Kyung Park

Seoul National University - Oral Medicine and Oral Diagnosis

Jung-Hyun Park

Government of the United States of America - Experimental Immunology Branch

Sumin Jeon

Seoul National University - Department of Immunology and Molecular Microbiology

Keumjin Baek

Seoul National University - Department of Immunology and Molecular Microbiology

Jennifer Lee

Catholic University of Korea - Division of Rheumatology

Sung-Hwan Park

Catholic University of Korea - Division of Rheumatology

Youngnim Choi

Seoul National University - Department of Immunology and Molecular Microbiology

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Abstract

Background: Dysbiosis of the gut and oral microbiomes is a potential environmental factor in Sjogren's syndrome (SS), but its connection to the etiopathogenesis of SS remains unclear. This study aimed to characterize the oral microbiota in SS and to investigate its potential role in the pathogenesis of SS.  

Methods: Oral bacterial communities collected by whole mouthwash from 15 healthy individuals, 10 drug/radiation-induced sicca patients, and 25 primary SS patients were analyzed by pyrosequencing. Four SS-associated species and 2 control species were selected and used to challenge human submandibular gland tumor (HSG) cells. The expression of MHC I, MHC II, CD80, CD86, and IFNλ in HSG cells and the bacterial invasion into HSG cells were examined. Sections of labial salivary gland (LSG) biopsies from 8 non-SS subjects and 15 SS patients were subjected to in situ hybridization using universal and Prevotella melaninogenica-specific probes.

Findings: The SS oral microbiota was characterized by an increased bacterial load and Shannon diversity. Although a substantial portion of the changes observed in SS patients overlapped with those in drug/radiation-induced sicca patients, SS-specific changes were identified. Among the selected SS-associated bacterial species, P. melaninogenica uniquely upregulated the expression of MHC molecules, CD80, and IFN λ in HSG cells. Concomitantly, P. melaninogenica efficiently invaded HSG cells. Ductal cells and the areas of infiltration were heavily infected with bacteria in the LSGs with focal lymphocytic sialadenitis.

Interpretation: Dysbiotic oral microbiota is associated with deregulation of salivary gland epithelial cells and acquisition of IFN signatures through bacterial invasion into ductal cells.  

Funding Statement: This study was supported by a grant of the Korean Health Technology R&D Project (HI13C0016) from Ministry of Health & Welfare, Republic of Korea. Labial salivary gland biopsy specimens used in this manuscript are from the Sjögren’s International Collaborative Clinical Alliance [SICCA], funded under contract N01 DE-32636 by the National Institute of Dental and Craniofacial Research, with funding support from the National Eye Institute and Office for Research in Women’s Health. The funders had no role in study design, data collection, analysis, and interpretation, and writing of the report.

Declaration of Interests: The authors declare no conflicts of interest.

Ethics Approval Statement: All procedures involving human subjects and materials were performed in accordance with the Helsinki Declaration under approved protocols from the Institutional Review Boards at Seoul St. Mary’s Hospital (KC13ONMI0646) and at Seoul National University, School of Dentistry (S-D20140022, S-D20170004). Informed consent was obtained from all subjects.

Keywords: Sjogren’s Syndrome; Oral Microbiota; Epithelitis; IFN-lamda; Bacterial Infection

Suggested Citation

Alam, Jehan and Lee, Ahreum and Lee, Junho and Kwon, Dong Il and Park, Hee Kyung and Park, Jung-Hyun and Jeon, Sumin and Baek, Keumjin and Lee, Jennifer and Park, Sung-Hwan and Choi, Youngnim, Connection Between Dysbiotic Oral Microbiota and Deregulation of Salivary Gland Epithelial Cells in Sjogren's Syndrome (November 15, 2018). Available at SSRN: https://ssrn.com/abstract=3286118

Jehan Alam

Seoul National University - Department of Immunology and Molecular Microbiology

101 Daehak-ro, Jongno-gu
Seoul, 03080
Korea, Republic of (South Korea)

Baylor University - Department of Ophthalmology

Houston, TX 77030
United States

Ahreum Lee

Seoul National University - Department of Immunology and Molecular Microbiology ( email )

101 Daehak-ro, Jongno-gu
Seoul, 03080
Korea, Republic of (South Korea)

Junho Lee

Seoul National University - Department of Immunology and Molecular Microbiology ( email )

101 Daehak-ro, Jongno-gu
Seoul, 03080
Korea, Republic of (South Korea)

Dong Il Kwon

Seoul National University - Department of Immunology and Molecular Microbiology

101 Daehak-ro, Jongno-gu
Seoul, 03080
Korea, Republic of (South Korea)

Pohang University of Science and Technology (POSTECH) - Division of Integrative Biosciences and Biotechnology (IBB)

77 Cheongam-ro
Pohang, 37673
Korea, Republic of (South Korea)

Hee Kyung Park

Seoul National University - Oral Medicine and Oral Diagnosis ( email )

101 Daehak-ro, Jongno-gu
Seoul, 03080
Korea, Republic of (South Korea)

Jung-Hyun Park

Government of the United States of America - Experimental Immunology Branch

Bethesda, MD
United States

Sumin Jeon

Seoul National University - Department of Immunology and Molecular Microbiology

101 Daehak-ro, Jongno-gu
Seoul, 03080
Korea, Republic of (South Korea)

Keumjin Baek

Seoul National University - Department of Immunology and Molecular Microbiology ( email )

101 Daehak-ro, Jongno-gu
Seoul, 03080
Korea, Republic of (South Korea)

Jennifer Lee

Catholic University of Korea - Division of Rheumatology

Korea, Republic of (South Korea)

Sung-Hwan Park

Catholic University of Korea - Division of Rheumatology

Korea, Republic of (South Korea)

Youngnim Choi (Contact Author)

Seoul National University - Department of Immunology and Molecular Microbiology ( email )

101 Daehak-ro, Jongno-gu
Seoul, 03080
Korea, Republic of (South Korea)

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