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When Your Gut Feeling May Not Be Right

By Elizabeth Wilkins

Image credit: Pixabay

There is no denying the increases in gut disorders over the past few decades. Inflammatory bowel disease (IBD) most commonly refers to Crohn’s disease and ulcerative colitis. These increasingly prevalent features of our modern lives are both debilitating and costly. Secondary to this, it is somewhat unnerving; what exactly is driving significant growths in incidence? In this short article I will discuss an important new driver of IBD and also a surprising potential therapy.

Both forms of IBD are characterised by inflammation of the gut lining, accompanied by abnormal immune responses towards the bacterial flora of the gut. Crohn’s disease most commonly occurs in the ileum, the last part of the small intestine, and the colon (the large intestine). Inflammation can be patchy or penetrate deeper into the gut wall. Ulcerative colitis is limited to the colon and affects the innermost lining of the gut, the mucosa and submucosa, causing ulceration and inflammation. Both diseases are frequently diagnosed before the age of 30, and consequently lead to a huge disease burden in terms of disability-affected life years (DALY’s).

As with many pathologies of the developed world, the drivers of IBD are multifactorial. Proposed key players include prolonged antibiotic use, genetic susceptibility, enteric pathogens (bacteria etc. that live in the intestines), disruption to the gut microenvironment, sedentary lifestyle, and increasing sanitation. The extent and diversity of this list, which is not exhaustive, makes the study of IBD complex and difficult.

Epidemiology

IBD correlates with increasing industrialisation, with the highest incidences found in Europe, Northern America and New Zealand. [1] In a meta-analysis of over 200 incidence studies, 75% showed a significant increase in incidence over time for Crohn’s disease, and 60% for ulcerative colitis. [2] Interestingly, both diseases show a marked increase in populations originating from a developing country, which subsequently emigrate to a developed nation. This effect is not seen in first generation immigrants, but is clear in their children. [3, 4]

Food Additives as an Emerging Culprit

An intriguing component in the study of IBD is the effect of diet. It is well documented that the disease has a genetic component, but the role of environmental factors has only recently come under scrutiny. Food additives, especially emulsifiers and thickening agents, have been newly implicated in the development of IBD. To investigate their role, immunologists have fed mice several emulsifiers in widespread use in the United States. [5] They found that all animals have higher rates of metabolic disorders, such as glucose intolerance, when certain emulsifiers are added to their diets. In mice which are genetically predisposed to IBD, the incidence and severity of the disease is significantly increased when mice are fed many of the food additives tested.

This is not an entirely new phenomenon. Biofilms of normal gut bacteria are often observed in IBD patients. It has been shown that a polysaccharide called Maltodextrin, often found in corn-starch, can drive the formation of these biofilms. [6] Maltodextrin also promotes adherence of E. coli strains implicated in Crohn’s disease to the gut lining. We know that humans and other mammals have co-evolved with their gut microbiomes [7]. Perhaps the suddenness of the switch from a traditional diet to a heavily processed, westernised one may have simply been too fast for our gut bacteria to keep up with.

Cannabis- a Controversial Tool to Tackle a Growing Problem?

Cannabis may be seen by governments as a growing problem in itself, but could the anti-inflammatory properties of cannabis be harnessed to reduce the symptoms of IBD? [8] Cannabis has been in use for nearly 3000 years, and studies into its mechanism of action indicate the drug targets receptors known as Cannabinoid (CB) receptors. Aside from the psychoactive properties of cannabis, activation of CB1 and CB2 receptors in the gastro-intestinal tract is linked to gut mobility and inflammation, respectively. Studies in mice have shown reduced gut inflammation following the administration of cannabinoids. Patients have also reported increased appetite, reduced abdominal pain and an anti-diarrhoeal effect with cannabis use. [9] Synthetic compounds have also been made which mimic cannabis by acting as CB1/2 agonists, i.e. they activate the receptors in the same way that cannabis does, but have fewer psychoactive effects. There is little clinical data available for the efficacy of these in treating IBD, although they have been used successfully to counteract nausea and anorexia in chemotherapy patients.

Image credit: Wikimedia Commons

Overall the therapeutic use of cannabis seems like an important avenue for investigation, and the UK government has granted permission for the cultivation of cannabis to conduct large clinical trials. However, the status of cannabis as a class B drug, combined with the high cost of synthetic alternatives, means that patients cannot currently receive this treatment on the NHS.


References

  1. C. N. Bernstein and F. Shanahan, Gut, 2008, 57, 1185-1191.
  2. N. A. Molodecky et al., Gastroenterology, 2012, 142, 46-54.
  3. C. S. Probert et al., Gut, 1992; 33, 687–693.
  4. V. Pinsk et al., Am. J. Gastroenterol., 2007, 102, 1077–1083.
  5. B. Chassaing et al., Nature, 2015, 519, 92-96.
  6. K. P. Nickerson and C. McDonald, PLoS One, 2012, 12, e52132.
  7. B. D. Muegge, Science, 2011, 332, 970-974.
  8. M. D. Gerich, Am. J. Gastroenterol., 2015, 110, 208–214.
  9. J. Ravikoff Allegretti et al., Inflamm. Bowel Dis., 2013, 19, 2809–2814.

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