Unresolved conundrum of the role of physical activity in inflammatory bowel disease: What next?

Abstract

There is considerable controversy on the role of physical activity in irritable bowel disease (IBD) since published reports are conflicting. It is well known that there is known relapse with specific treatment in IBD. This, in addition to onset of extraintestinal symptoms creates a need to think of alternate approaches. In this context, the current article describes the need of a multi-institutional study with standard protocol of physical activity for documenting its effect on both the primary disease and the extra alimentary manifestations. This paper also points out the possibility of using adjuvant complementary medicine such as yoga, whose effects have been documented in other diseases like irritable bowel syndrome. A third approach could be to focus on the intestinal dysbiosis in IBD and concentrate on research on restoring the microbial flora to normal, to see whether the extra-intestinal symptoms are alleviated.

Key Words: Extra intestinal symptoms of inflammatory bowel diseases, Management, Physical activity in inflammatory bowel diseases, Complementary medicine in inflammatory bowel diseases, Yoga in inflammatory bowel diseases, Dysbiosis in inflammatory bowel diseases

Core Tip: A multi institutional study has been suggested and the parameters defined to finally develop strong evidence for the use of complemetary measures for management of extralimentary symptoms of inflammatory bowel diseases such as depression, anxiety, stress, fatigue, poor quality of life etc.

INTRODUCTION

Inflammatory bowel diseases (IBD) can be a life and life-style modifying medical problem. Two of the major subtypes, viz. Crohn’s Disease and Ulcerative Colitis have been estimated to affect over 6.8 million people worldwide[1] varying in incidence from a low of 1.2/100000 in some countries, to as high as 31.2 in Manitoba, Canada[2,3]. The incidence continues to rise on a global scale and is of serious public health concern. The causation lies in the imbalance between pro-inflammatory and anti-inflammatory signaling in the bowel induced by various factors and perhaps influenced by genetic susceptibility, in association with an initiating bacterial or viral agent[4]. In general, between 50% and 60% of patients initially respond to therapy in terms of improvement in symptoms or in reduction of levels of inflammation biomarkers. Of these patients, approximately, a fraction, 20% to 30%, go into remission, and of those in remission, at least half remain in remission over time[5]. A more recent review mentioned that a high proportion of patients experience a primary loss of response to biologic therapy and a further 40% experience a secondary loss of response[6]. It is obvious from the above figures that risk of relapse is significant and may require interventions other than the initial therapy.

In addition to the issue of relapse, even when controlled and in remission as far as intestinal symptoms go, patients with IBD have significant extra-intestinal symptoms such as depression, anxiety, poor quality of life (QoL) and fatigue[1]. In one study, the life time risk of a diagnosis of depression was 40% and the risk of developing anxiety as high as 30%[7]. Not only these extra-intestinal symptoms affect QoL, they also increase the relapse rates of intestinal symptoms and need visits to the healthcare facility adding to the cost. In countries with resource constraints where access to health care facilities can involve significant travel and expense, many patients would rather “grin and bear” the extra intestinal symptoms than seek relief or even confess to having them.

Of various approaches to managing these extra intestinal symptoms of IBD, three are noteworthy and worth mentioning. These are: (1) The role of physical activity; (2) the role of complementary medicine such as Yoga or Music therapy as a mind-body medicine intervention; and (3) the role of intestinal microbiota regulation. All these interventions would be relatively less expensive. The probable mechanism of action of these interventions is likely to be by modification of the balance between pro-inflammatory and anti-inflammatory signaling in the bowel and elsewhere in the body. One paper has suggested: (1) Reduction of visceral adiposity; (2) an increase in production and release of anti-inflammatory cytokines from skeletal muscle; and (3) a reduction in monocyte and macrophage Toll-like receptors with consequent reduction in pro-inflammatory cytokines as the cause for benefit with physical activity[8]. Recent work on effect of altered intestinal microbiota has given evidence of how such signaling can be modified.

Let us look at the current information on these three alternate adjuvant approaches for IBD. There are a number of detailed reviews on the role of physical activity on IBD[4,6,9,10]. Specific guidelines for exercise in patients with IBD are lacking, although one study suggested that patients with IBD should participate in moderate physical activity at least three times a week for 30 min per day[11]. The rationale for physical activity lies in the fact that previous studies have shown that intense physical activity, as opposed to moderate physical activity, has marked effects on gastrointestinal function and endothelial integrity and movement of antigens across the mucosa[12]. However, it is unlikely that intense physical activity is going to be feasible or acceptable for patients with IBD since it may precipitate intestinal symptoms, worsen already existing fatigue or may result in uncontrolled bowel moments. Hence research has to focus on moderate physical activity or light physical activity for those who are unable to perform moderate activity. Effect of compliance is also important. Published results have tended to be inconclusive. A review in 2010 concluded that there is both paucity of literature and heterogeneity of studies which makes definite conclusions difficult to draw as regards utility of physical activity, as an adjunct, in management of IBD[4]. A more recent review concluded that there is a moderate level of evidence supporting body composition changes in IBD patients as a result of exercise[6]. Another review concluded that physicians may consider discussing physical activity interventions in IBD on an individual basis for symptoms such as poor QoL, fatigue, depression or anxiety as there is some evidence, till guidelines are available after further studies[10]. Yet another review while concluding that moderate intensity physical activity for adults with IBD is beneficial for anxiety, stress, depression and poor QoL, it may be associated with many barriers to performing physical activity for adults with IBD and hence suggested a cautious approach[9].

The second approach which may benefit patients with IBD and alleviate anxiety, stress, depression and fatigue are complementary medical approaches using yoga or music as adjuvants. That there is a scientific basis for complementary management in addition to allopathy in several diseases including stress, anxiety, depression etc. has been established by research[13,14]. Recently the beneficial effects of adjuvant yoga therapy have also been proved in irritable bowel syndrome and non-ulcer dyspepsia etc. in our institute[15]. The beneficial effects of yoga in IBD have also been mentioned in published papers[16]. Larger studies are required to confirm this.

The association of intestinal dysbiosis and IBD is well known. A third approach, therefore, less studied till now, is to document the change in intestinal microbiota in patients with IBD before and after control with appropriate drugs and follow them to see whether those with relapse or with extra alimentary symptoms have undergone fresh alterations in the microbiota, either as a consequence or as a cause, for the symptoms. If proved, an approach for management may include measure to restore the microbiota to normality. This approach again is understudied.

CONCLUSIONS AND SUGGESTIONS FOR A WAY FORWARD

In summary, evidence which is available is scanty, the number of patients studied is small, the results are conflicting and the methodology of study is not standardized.

The way forward, therefore, is to plan large, prospective, multi-institutional studies with a large sample size of patients with IBD, who have relapsed after initial conrol, to try one or more or all, of the above three approaches, since the positive effects may be synergistic. The methodology has to be standardized as regards the exact physical activity prescribed, preferably of moderate or light intensity, such as walking or running, under supervision, to ensure compliance. Monitoring of compliance is necessary by supervision to establish performance, although one review mentions that there was no difference between supervised and unsupervised physical activity[9].

Obviously considering the subjects of study, moderate or mild physical activity alone may be suitable. The comorbidity level of symptoms such as stress, anxiety, depression, fatigue and QoL must be objectively quantified by appropriate scales, and the improvement with intervention studied longitudinally along with relapse rates and the effect of interventions in preventing relapse. The indications for which this intervention is being tried, such as depression, anxiety, stress, fatigue, QoL etc., must be documented so that future endeavors may be directed towards those symptoms which have shown a beneficial effect. What is required, therefore: (1) Is standardization of the interventions as regards identification of indications for management; (2) The process and details of intervention; (3) The outcomes with particular reference to relief of extra intestinal manifestations; (4) The effect on delaying or averting relapse with its consequences; (5) Measurement of QoL at various points of follow up, before and after intervention; (6) The outcome measures which need to be recorded such as effects on relapse rates, difficulty in compliance, improvements in intestinal symptoms, if any, and most importantly, the effect on extra intestinal symptoms such as depression, anxiety, stress, fatigue, poor QoL etc.; (7) Also, the effect of body mass index, visceral fat and sarcopenia, on the response or absence of response, of the symptoms to these interventions needs to be documented; and (8) Studies need to also focus on the mechanism by which these interventions work by measurement of levels of pro and anti-inflammatory biomarkers.

If strong data is generated which proves benefit consistently, then they can then be incorporated in guidelines and patients counselled appropriately.

CONCLUSION

Since we are unsure currently about the path to take in patients who experience these extra intestinal symptoms, we have to follow the advice of Henry Wordsworth Longfellow who said, “Do not go where the path may lead, go instead where there is no path, and leave a trail behind.”