The North American Nurses Health Study (2 cohorts initiated in 1976 and 1989 with 121.7k and 116.7k subjects respectively) is a very powerful tool to uncover disease aetiologies with minimal bias (especially recall bias). This has been applied successfully to Crohn’s disease and UC. In this study, where there is a massive 3.4 million person years of follow-up, a total of 284 incident cases of Crohn’s disease and 363 incident cases of UC have been reported and verified.
Recently, study group have reported that long-term intake of dietary fibre, particularly from fruit, is protective for Crohn’s disease (they saw no effect with UC) (Ananthakrishnan AN et al Gastroenterology 2013 Nov;145(5):970-7).
The present study, published last week in the British Medical Journal (Khalili H et al, BMJ 2013 Nov 14; 347:f6633), examines the effect of physical activity on the development of IBD. At roughly 4 yearly intervals subjects were asked to document the average time per week in the preceding year that they participated in physical activity (ranging from running to moving the lawn) plus their usual outdoor walking pace. From this, a metabolic equivalent task (MET) was calculated.
They report an inverse association with physical activity level and the development of Crohn’s disease. In other words, those individuals who exercised more were less likely to develop Crohn’s disease. When they controlled for age, smoking status, the use of NSAIDs, oral contraceptives, HRT and a history of appendicectomy the differences persisted. One could argue that patients exercise less as they feel unwell prior to developing Crohn’s disease. However, the beneficial effects of exercise appeared to be robust over time, apparently discounting this possible confounder. No association between physical inactivity and UC was seen in this study.
The biggest potential confounder here is not mentioned anyway in the ms. Individuals who exercise more are much more likely to eat a healthy diet, including increased dietary fibers. The same group have reported from the same study that this type of diet reduces the risk of Crohn’s disease so it is very surprising that it has not been considered.
If the effect of physical activity is real then it is potentially most interesting. Autophagy has been shown in one recent Nature paper to be induced (in skeletal muscle in mice) by exercise (He C et al Nature 2012;481:511-5). We have established through large gene discovery experiments that defective autophagy is part of the reason why some individuals develop Crohn’s disease (Jostins et al Nature 2012;491:119-24). It is very tempting to bring these two observations together as the present authors have done; however, presently they provide no data to support this hypothesis.
Identifying environmental factors that are associated with the development of Crohn’s disease and which are potentially modifiable has great translational potential. High-risk individuals (first-degree relatives of family members) may be advised a) not to smoke b) to eat more non-digestible plant fibres and c) to increase physical activity / exercise levels. This would be an important development as presently it is argued that identifying high-risk individuals is worthless as we can do nothing to prevent the onset of disease. These lifestyle modifiers looks strikingly similar to the advise that might be given to a person at high risk of heart disease and type II diabetes mellitus (further food for thought as there are similarities both in the gut microbiota and in germ-line genetic variation in individuals with obesity, diabetes mellitus and inflammatory bowel disease).
However, this is still potentially of limited benefit as even in this highest risk group the incidence of Crohn’s disease remains very low. What about if these findings also translates to disease course in Crohn’s disease? This is potentially of much greater interest as it would be directly applicable to all patients with disease and allow patient directed intervention. As a physician, one of the commonest questions in the clinic after making a diagnosis of Crohn’s disease is “what should I eat” “what should I avoid” “any other lifestyle advice”. I would strongly encourage a cigarette smoker to quit (unfortunately people with Crohn’s disease find this as difficult, if not more so, that people without). I will frequently use an exclusive elemental diet (with a polymeric feed) to induce remission in ileal Crohn’s instead of corticosteroids. Patients with obstructive symptoms should follow a low residue diet. But, beyond this I can offer little evidence-based advice on diet and other lifestyle factors.
We therefore need to urgently pursue observational studies on cohorts of patients with established Crohn’s disease both at diagnosis and following successful induction of deep remission. We can then monitor their smoking status, dietary habits and now their exercise habits (using the above measures but also now with app based technology, such as a fit-band) and see how they correlate with time to remission / time to flare. It will be important to do this on a large sample of patients to allow for multiple potential confounders. If we can demonstrate an effect, interventional studies could then be carried out prior to translation. We will do this in Scotland as part of our research collaborative. We have a homogenous, stable population that is well characterised and gives us the perfect place to address these important questions. The integrated ehealth solution we are presently developing will give us the infrastructure to do this whilst driving forwards standards of clinical care across the country.