Preclinical disease and preventive strategies in IBD: perspectives, challenges and opportunities

IBDs, encompassing Crohn's disease (CD) and UC, are chronic, relapsing and remitting, inflammatory diseases of the GI tract. IBD is emerging as a globally important disease with epidemiological studies showing that there is a significant increase in IBD’s incidence in most regions of the world.1 In high-incidence areas such as North America, disease already affects around 0.6% of the population.1 As low/middle-income countries continue to become more industrialised, an increasing incidence is also expected to occur in areas of the globe where IBD was previously considered rare.2 ,3 Furthermore, as trends in life expectancy increase globally, the emergence of chronic health conditions, including IBD, will represent a growing proportion of individual and society health impact. The recent acknowledgement that IBD is a progressive disease has changed the focus of therapeutic strategies. It is now widely accepted that treating effectively at earlier stages of disease, before bowel damage occurs, is likely to produce better outcomes, resulting in reduced rates of hospitalisation and surgery.4 Unfortunately, despite ongoing efforts to change therapeutic paradigms, combining early diagnosis with best available effective therapies, drug-free remission or absence of progression of bowel wall damage remains a challenge in many patients.5 ,6 Once the diagnosis of IBD is made, bowel damage has already occurred in a significant number of patients, and the immune dysregulation, dysbiosis and tissue injury associated with full-blown disease is set, and in many cases, irreversible.6 At present, all therapeutic interventions in IBD target well-established disease, and even the most potent agents are not able to prevent or reverse chronic damage often present at diagnosis. In order to truly change the natural history and long-term consequences of IBD, an effective intervention should ideally occur at an earlier phase, targeting the primary biological processes that drive disease …