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.

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.

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.

This prospective observational study is registered at ClinicalTrials.gov ((ID: NCT06124833, data first posted: 9 November 2023); (ID: NCT06076083, data first posted: 21 November 2023) and (ID: NCT06183697, data first posted: 27 December 2023)).

The magnitude and persistence of diseases and multimorbidity between females and males are different. This study comprehensively quantified sex differences in the onset and progression of 108 major physical and mental diseases to multimorbidity through adulthood in Chinese population.

Quantitative analysis of real-world linked electronic health records.

Linked health records from 160 health facilities across primary, secondary and tertiary healthcare, comprising routinely collected electronic health records from the whole urban residents of Yichang, China between 1 January 2016 and 31 December 2019.

684 455 urban residents aged 20 years and above with documented health records during the study period.

The cumulative incidence, relative risks (RR) and 95% CIs, period prevalence, median age at disease diagnosis and the prevalence of multimorbidity of 108 major physical and mental diseases were computed. All analyses were stratified by sex and age groups.

The analysis included 684 455 individuals (54.8% females, mean age: 46.9), among whom 46.3% had multimorbidity, with a higher prevalence in females (47.6%) than males (44.9%). The chronological disease map revealed stark differences between females and males, with notable lower risk of obstructive sleep apnoea-hypopnoea syndrome (OSAHS, RR: 0.03, 95% CI: 0.01 to 0.11) for young adults, oesophageal cancer (RR: 0.02, 95% CI: 0.0 to 0.17) for mid-age adults and remarkable higher risk of lupus (RR: 8.8, 95% CI: 2.7 to 29.0) for older adults of females. Males exhibited an incidence surge in hypertension, diabetes, coronary disease and chronic obstructive pulmonary disease a decade earlier than females, while females had a life-long higher prevalence in immune-mediated diseases and urinary disorders. For the new incident diseases, the manifestation of eating disorders, anaemia and urinary incontinence was recorded 20 years earlier in females; whereas, males were diagnosed with hyperuricaemia, OSAHS and schizophrenia at younger ages.

The significant variations in disease nature and trajectory between sexes underscore the urgent needs for tailored prevention strategies and appropriate health resources allocation. Sex differences in disease profile should be considered to delay disease and multimorbidity progression, ultimately promoting health equity.