Capturing the Biologic Onset of Inflammatory Bowel Diseases: Impact on Translational and Clinical Science

Abstract

While much progress has been made in the last two decades in the treatment and the management of inflammatory bowel diseases (IBD)—both ulcerative colitis (UC) and Crohn’s Disease (CD)—as of today these conditions are still diagnosed only after they have become symptomatic. This is a major drawback since by then the inflammatory process has often already caused considerable damage and the disease might have become partially or totally unresponsive to medical therapy. Late diagnosis in IBD is due to the lack of accurate, non-invasive indicators that would allow disease identification during the pre-clinical stage—as it is often done in many other medical conditions. Here, we will discuss what is known about the biologic onset and pre-clinical CD with an emphasis on studies conducted in patients’ first degree relatives. We will then review the possible strategies to diagnose IBD very early in time including screening, available disease markers and imaging, and the possible clinical implications of treating these conditions at or close to their biologic onset. Later, we will review the potential impact of conducting translational research in IBD during the pre-clinical stage, especially focusing on the role of the microbiome in disease etiology and pathogenesis. Finally, we will highlight possible future developments in the field and how they can impact IBD management and our scientific knowledge of these conditions.

Gut microbiota in the early stage of Crohn’s disease has unique characteristics

“…The balance between beneficial gut commensals and pathogens is crucial to human health. The dysbiosis of gut microbiota contributes to gut inflammation and may be closely related to the onset and progression of CD [ 4 , 5 , 7 ]. However, our understanding of the relationship between gut microbiota and CD is still relatively poor as it is difficult to detect and diagnose CD in the biologic onset or early stage of disease (e.g., preclinical) [ 5 , 25 ].…”

“…Previous studies indicated that the changes in the abundance of Bacteroides in CD patients were controversial. The increased abundance of Bacteroides in the CD group compared with health participates was related to the maintenance of postoperative remission [ 4 , 29 ]. However, other studies provided that the abundance of Bacteroides in CD patients was reduced [ 27 , 30 ]; B. thetaiotaomicron , belonging to the Bacteroides was found to prevent weight loss, colonic histopathological changes and the production of inflammatory factors in a mouse enteritis model induced by dextran sodium sulfate (DSS) [ 31 ].…”

“…However, the course of CD is difficult to predict, as it varies from patient to patient. Also, the characteristics of this disease in early stage and the factors influencing the progression of the disease are poorly understood, significantly affecting the clinical decision-making [ 4 ]. Further investigations of the influencing factors may provide evidence for CD management, especially in the early treatment, and improves the outcomes of disease [ 4 , 5 ].…”

“…The pathogenesis of CD has not been thoroughly studied. Multiple factors, such as genetics, diet, dysbiosis of gut microbiota and overactivated immune response, are involved in the onset of CD [ 1 , 4 , 5 ]. Among these factors, gut microbiota dysbiosis has been identified as the key factor in the pathogenesis of CD and has been observed in CD patients [ 6 ].…”

“…However, whether the gut microbiota is a cause or a consequence remains unclear, and the relationship between the gut microbiota and the course of CD is still not clearly understood [ 7 , 10 , 21 ]. Perhaps the best way to capture these clues is to investigate the characteristics of gut microbiota changes during the biologic onset or early clinical stage of CD [ 4 ].…”