Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC) are incurable gastrointestinal diseases of the gastrointestinal tract, characterized by severe abdominal cramps, bloody diarrhea, weight loss, fever, fatigue, body aches and pain. Extraintestinal manifestations of IBD also include inflammatory-mediated damage to the eyes, joints and skin, and can also involve other organs such as liver and biliary tract, kidneys, lungs and the vascular system (1). The incidence of IBD has gradually increased since the 1950’s, with the highest rates occurring in northern Europe and North America (2).
IBD is a complex, multi-factorial disease thought to occur in genetically susceptible individuals who suffer from a weakened intestinal barrier or a “leaky gut” and overactive immune responses against normal gut bacteria.
Current therapies for IBD include aminosalicylates, corticosteroids, immune modulators and biologics, which are directed at suppressing inflammation and preventing complications.
There are numerous adverse events of current IBD therapies. For instance, corticosteroid therapy can cause mood changes, undesirable weight gain and bloating, severe acne, opportunistic infections, and long-term use can increase the risk of developing diabetes, atherosclerosis, osteoporosis as well as growth delay in children (8). Biologics are the newest class of drugs used in treating IBD and include the anti-TNF-α agents, which have dramatically changed the course of IBD- including steroid sparing, less hospitalizations, fewer surgeries, and achieving deep remission and better quality of life (9). Despite the benefits of anti-TNF therapy, there are still limitations, including the lack of primary response in some patients and the loss of response to treatment in other patients. For instance, loss of response has been reported in 25%–40% of Crohn’s disease patients in randomized controlled trials, with an estimated annual loss of response rate of about 13% per patient-year (10). Approximately 70% of people with Crohn’s disease and 40% of those with ulcerative colitis will require surgery at least once during the course of disease (11). There is currently no cure for Crohn’s disease, whereas ulcerative colitis may be ‘cured’ by surgically removing the colon, however this is not an ideal or a desired result. These findings underscore the need for new IBD therapies that can complement and/or replace existing treatments. Specifically, therapies for IBD that target overactive Th1/Th17 mediated immune responses, without increasing the risk of infection are needed.
Many nutrients can affect immune responses, for instance the active forms of vitamin D and vitamin A (retinoic acid) can both directly regulate T-cell responses, by binding to their respective nuclear receptors expressed on lymphoid cells and acting as transcription factors to induce or suppress inflammation (Raverdear et al, 2014). Zinc is also necessary for the normal function of the immune system, and dysfunction is observed, even in mild zinc deficiency (Ibs & Rink, 2003). Interestingly, while acute zinc deficiency causes a decrease in innate and adaptive immunity, chronic zinc deficiency increases inflammation (Bonaventura et al, 2015).