Title: Oral–gut microbiome axis in a Korean cohort with inflammatory bowel disease and ankylosing spondylitis (INTEGRATE): a prospective and observational study protocol

Journal: BMJ Group

Authors:  Hyun Sik Kim¹, Bo-Hyung Kim^2,3, Bora Nam⁴, Shin Ju Oh⁵, Soo-Kyung Park ^6,7, Sang Won Lee⁸, Jae-Yun Le ⁹, Sungsin Jo^4,10, Yeon-Ah Lee¹¹, June-Young Lee¹, Dong Il Park^12,7, Tae-Hwan Kim¹³, Chang Kyun Lee¹⁴

Affiliations

¹ Department of Biology, Kyung Hee University, Seoul, Korea

² Department of Clinical Pharmacology and Therapeutics, Kyung Hee University Hospital, Seoul, Korea

³ East-West Medical Research Institute, Kyung Hee University, Seoul, Korea

⁴ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

⁵ Department of Gastroenterology, Center for Crohn's and Colitis, Kyung Hee University College of Medicine, Seoul, Korea

⁶ Division of Gastroenterology, Department of Internal Medicine and Inflammatory Bowel Disease Center, Kangbuk Samsung Hospital, Seoul, Korea

⁷ Medical Research Institute, School of Medicine, Sungkyunkwan University, Seoul, Korea

⁸ Department of Clinical Pharmacology and Therapeutics, Hanyang University Seoul Hospital, Seoul, Korea

⁹ Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Korea

¹⁰ Department of Biology, Soonchunhyang University, Asan, Korea

¹¹ Division of Rheumatology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea

¹² Division of Gastroenterology, Department of Internal Medicine and Inflammatory Bowel Disease Center, Kangbuk Samsung Hospital, Seoul, Korea

¹³ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

¹⁴ Department of Gastroenterology, Center for Crohn's and Colitis, Kyung Hee University College of Medicine, Seoul, Korea

Abstract:

Introduction: The global burden of chronic immune-mediated inflammatory diseases (IMIDs) is increasing, and rising prevalence rates significantly affect socioeconomic factors and quality of life. Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), along with ankylosing spondylitis (AS), are prominent chronic IMIDs that share overlapping pathophysiological mechanisms. Recent research has highlighted the importance of the gut microbiota in the pathogenesis of these diseases, suggesting that shared microbial dysbiosis may contribute to their development. Comprehensive research focusing on the gut and oral microbial characteristics and environmental factors is essential to elucidate the fundamental pathophysiology and develop personalised management strategies for IBD and AS. In-depth analyses and insights based on multiomics approaches are required to achieve these objectives.

Methods and analysis: This protocol describes a nationwide prospective observational study of CD, UC and AS in a Korean population. Over 5 years, we aim to recruit at least 900 patients with IBD and 200 first-degree relatives (FDRs), 500 patients with AS and 200 of their FDRs, and 2244 healthy controls. We will systematically collect clinical data and biological samples, including saliva, stool, blood and tissue biopsies, for integrative multiomics analyses focusing primarily on the microbiome. Highly advanced full-length 16S ribosomal RNA gene sequencing and shotgun metagenomics will be used to characterise the microbial composition of saliva and stool samples. Quantitative microbiome profiling will be used to address the pathological, physiological and ecological differences between microbial groups that may be masked by their relative abundance. Metabolomic analyses will be conducted on saliva, stool and plasma samples to assess functional metabolic profiles. Culturomics will be used to isolate, identify and characterise the diversity of microbial species, including rare or previously unrecognised species, to provide a comprehensive understanding of the microbiota associated with these diseases.

Ethics and dissemination: Ethical approval was obtained from the Ethics Committee of Kyung Hee University Hospital, Hanyang University Hospital, Kangbuk Samsung Hospital, Yeungnam University Hospital, Kyungpook National University Hospital, Chonnam National University Hospital, Wonkwang University Hospital, Catholic University Daejeon St. Mary's Hospital, Soon Chun Hyang University Hospital Cheonan, Chung-Ang University Hospital, Inje University Haeundae Paik Hospital, Dankook University Hospital, Hanyang University Guri Hospital, Kyung Hee University Hospital at Gangdong, Chung-Ang University Gwangmyeong Hospital and Keimyung University Dongsan Hospital. Our research team will provide detailed information about the study, including an information sheet explaining its aims and procedures, prior to enrolment. Prospective participants will be informed that they have the right to withdraw from the study at any time, without penalty. Participants will be assured of the anonymity and confidentiality of any data they provide throughout the study, using participant numbers and the storage of sensitive data in locked cabinets. Participants will be enrolled in the study only after providing written informed consent to the research staff. The results of this study will be disseminated to healthcare and academic professionals through publications in peer-reviewed journals and presentations at international conferences.

Keywords: Inflammatory bowel disease; MICROBIOLOGY; Microbiota; PUBLIC HEALTH; Rheumatology.

DOI: 10.1136/bmjopen-2024-092075

​Published: 10 August 2025

붙임: Oral–gut microbiome axis in a Korean cohort with inflammatory bowel disease and ankylosing spondylitis (INTEGRATE) a prospective and observational study protocol.pdf