Overlapping illnesses


In his article ‘How what happens homes in on your gut’ (Gut Reaction Issue 65) Prof Read describes how illnesses tend to overlap. People with IBS are also 60% more likely to have migraine and depression (1) as well as fibromyalgia, chronic fatigue syndrome and functional dyspepsia which were mentioned. A link has also been demonstrated between IBS and overactive bladder (2). 

A common thread through these ‘unexplained illnesses’ is the role of serotonin, also known as 5-hydroxytryptamine or 5HT. Many parts of the body have receptors for this chemical and are affected by its level. This is illustrated by drugs designed to modify the effects of 5HT on particular organs. For example, some types of antidepressants prevent the removal and breakdown of 5HT so as to sustain its level. Triptan drugs imitate the effects of 5HT on blood vessels in the head to abort a migraine attack. Drugs stimulating 5HT receptors in the gut can increase its activity while those which block these receptors can reduce bowel movement in the treatment of types of IBS (3). 5HT receptors are also involved in gut secretions, abdominal distension and the sensation and perception of bowel function (4). 

5HT levels can be affected by genetics, inflammation and production / reuptake mechanisms. There is research supporting the concept that D-IBS is characterised by reduced 5HT uptake and therefore raised levels, while C-IBS may be related to low levels of release (5). Deranged metabolism of amines has been found with migraine (6) where the levels of serum 5HT swings from raised to lowered to normal which can cause alternating bowel function.

Experiments in mice have found gender differences in the effects of 5HT (7) which might relate to the preponderance of ‘overlapping’ illnesses in females and the gender differences in the effects of 5HT drugs for IBS. Raised levels of 5HT in mice gave increased anxiety, reduced aggression and exaggerated stress response (8) correlating perhaps with personalities traditionally linked to D-IBS in humans.

 Colons with diverticular disease had more 5HT production cells than unaffected areas of the same colons (9). Increase in production and levels of 5HT are also found in caeliac disease (10) Symptoms due to 5HT are found with Inflammatory Bowel Disease (IBD) when in remission (11). These diseases have distinct pathology. It is debatable whether they should be described as having ‘overlapping IBS’ just because they sometimes have similar symptoms. Perhaps IBS should stand for Inappropriate Bowel Serotonin.

Orthodox medicine puts illnesses into pigeon-holes according to the body system and specialists would need to work together (12) to accommodate the concept of holistic disease such as the variety of mind and body effects of 5HT aberrations. There are a limited number of ways for the bowel to show that it is not working properly and the diagnosis of IBS is based on symptoms (13) not causes. It is convenient to describe such symptoms with other diseases as ‘overlapping IBS’ Hopefully research will continue into the effects of 5HT to provide better treatment for all diseases which give such symptoms.

© Mary Griffiths 2007

Note This article appeared in Gut Reaction, the Journal of the IBS Network, Issue No 67, Autumn 2007. It was a response to an article in Issue No 65 by Prof. Nick Reid, who considered that stress and inflammation might interact to cause IBS through cytokine production.


1 Cole J A et al.  Migraine, fibromyalgia and depression among people with IBS: a prevalence study. BMC Gastroenterol 2006, 6, 26

2 Monga A K et al.  Is there an irritable bladder in the irritable bowel syndrome. Br J Obstet Gynecol 1997, 104, 1409 

3 Baker D E  Rationale for using serotogenic agents to treat irritable bowel syndrome. Am J Health-Syst Pharm 2005, 62,700 

4 Gershon M D et al. The serotonin signalling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 2007, 132, 397

5 Atkinson W et al.  Altered 5-hydroxytryptamine signalling in patients with constipation- and diarrhoea-predominate irritable bowel syndrome. Gastroenterology 2006, 130, 34

6 D’Andrea G et al.  Abnormal platelet trace amine profiles in migraine with and without aura. Cephalalgia 2006, 26, 968

7 Cornelissen L L et al. Female, but not mal,e serotonin reuptake transporter (5-HTT)  knockout mice exhibit bladder instability. Auton Neurosci 2005, 122, 107                                                        

8 Holmes A et al. Abnormal behaviour phenotypes of serotonin transporter knockout mice: parallels with human anxiety and depression. Biol Psychiatry 2003, 54, 953 

9 Banerjee S et al.  Increased presence of serotonin-producing cells in colons with diverticular disease may indicate involvement in the pathophysiology of the condition. Int J Colorectal Dis. 2006, Nov 4 (Epub ahead of print) 

10 Coleman N S.  Abnormalities of serotonin metabolism and their relationship to symptoms in untreated celiac disease. Clin Gastroenterol Hepatol 2006, 4, 874 

11 Ginsburg P M.  Managing functional disturbances in patients with inflammatory bowel disease. Curr Treat Options Gastroenterol. 2005, 8, 211

12 Francis C Y et al.  High prevalence of irritable bowel syndrome in patients attending urological outpatient departments. Dig Dis Sci 1997, 42, 404.

13 Mawe G M et al. Review article: Intestinal serotonin signalling in irritable bowel syndrome Aliment Pharmacol Ther. 2006, 23, 1067. 

(Summaries of most references can be found at http://www.ncbi.nlm.nih.gov  from the first author, journal, year, volume, first page.)

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