Diagnosis and natural history of preclinical and early inflammatory bowel disease

Inflammatory bowel disease is a chronic and progressive disorder of the gastrointestinal tract. A relevant proportion of patients develop complicated lesions, defined as strictures, fistulas and/or abscesses already at diagnosis, and this proportion increases over time. The preclinical phase defines the period of time from the appearance of the first immune disturbances until the development of overt disease, and it may be present months to years before the diagnosis. Multiple biomarkers (e.g., C-reactive protein, interleukin-6, fecal calprotectin) and cellular mechanisms (e.g., complement cascade, lysosomes, innate immunity, and glycosaminoglycan metabolism) are already altered during this period. Research in this area allows the description of the initial immune disturbances that may identify potential targets and lead to the development of new drug therapies. During this period, different interventions in high-risk individuals, including drugs or environmental factors, will open the possibility of innovative strategies focused on the reduction of complications, or even prevention trials for inflammatory bowel disease. Here, we review the most relevant findings regarding the characteristics, prevalence and biomarkers associated with preclinical disease, along with their possible use in our future clinical practice.