Irritable Bowel Syndrome - Cause Discovered?

Irritable bowel syndrome (IBS) is a poorly understood cluster of gastrointestinal (GI) tract symptoms that typically includes varying degrees of abdominal bloating and crampy pain, diarrhea, constipation, and the frequent discharge of mucus-like stools from the rectum. At any one time, an estimated 10 to 20 percent of all Americans chronically experience one or more of these intestinal symptoms. In most patients with IBS, these symptoms begin in childhood. In the United States, and in most other Western countries, IBS is at least 3 times more common in women than in men although, interestingly, in Southeast Asia, men are 2 to 3 times more commonly afflicted with IBS.

Numerous theories about the cause(s) of IBS have been proposed, but none have been definitively proven to cause this common syndrome, thus far. Because the precise cause(s) of IBS has not yet been determined, there is no specific medical test available to diagnose this condition. Likewise, there is no specific treatment available for IBS, although fiber supplements and careful attention to dietary "triggers" are often helpful. Moreover, as IBS is frequently associated with chronic depression and/or anxiety, the use of some types of antidepressant medications has also been associated with an improvement in IBS symptoms.

Among the numerous proposed causes of IBS, an excess of a powerful hormone and neurotransmitter, serotonin, within the GI tract has been the focus of considerable research, lately. (Serotonin is also commonly known as 5-HT, which is an abbreviated form of serotonin's chemical name.)

Serotonin has been shown to have multiple functions within the human body. Decreased serotonin levels in the brain have been associated with both depression and anxiety, which explains why the most commonly used antidepressant medications, the selective serotonin reuptake inhibitors (SSRIs), are used to treat both chronic depression and anxiety. (Commonly prescribed SSRIs include Prozac, Paxil, Zoloft, Lexapro and Celexa, among others.) Because more than 95 percent of the body's serotonin is found in the GI tract, SSRI drugs also have a profound effect on GI tract function, in addition to their effects on brain serotonin levels. Indeed, previous observations that certain SSRI antidepressant medications worsen cramping and diarrhea in patients with diarrhea-predominant IBS have at least suggested that serotonin in the GI tract may play an important role in this common form of IBS.

Another serotonin-related disease that is associated with severe abdominal cramping and diarrhea is carcinoid syndrome. In this relatively rare condition, serotonin-secreting carcinoid tumors of the GI tract cause profuse, watery diarrhea in affected patients after these tumors spread to the liver.

Based upon these apparent clinical links between IBS and serotonin (and for diarrhea-predominant IBS, in particular), additional research into the metabolism of serotonin in the GI tract of IBS sufferers is sorely needed. Fortunately, a newly published research study, which appears in the current issue of the journal Gastroenterology, sheds further light on the potential link between serotonin and at least some forms of IBS.

In this novel clinical research study, 98 children with chronic GI tract symptoms were evaluated. Twelve of these children presented with chronic symptoms suggestive of IBS. Endoscopic GI tract biopsies were performed on these 12 children, and the results of these biopsies were compared with similar biopsies performed on other age-matched children who were undergoing endoscopy for reasons other than IBS symptoms.

When compared with the biopsy results on the "control" children without IBS symptoms, the children with IBS symptoms were found to have significantly elevated levels of serotonin (5-HT) in the mucosal cells lining their GI tract. At the same time, the children with IBS symptoms were also found to have lower levels of a protein that is responsible for removing serotonin from the GI tract (serotonin transporter protein, or SERT) when compared to the children without IBS symptoms. Therefore, these two findings, in children with chronic IBS symptoms, further and strongly suggest that an excess of serotonin in the gut may be associated with classic IBS symptoms.

In view of the varying degrees of diarrhea and constipation (and other IBS-associated symptoms) observed among individual patients considered to have IBS, it is highly likely that this syndrome has more than just one cause. However, the biopsy-proven excess of serotonin in the GI tracts of the 12 children in this study with chronic IBS symptoms is a powerful indication that the abnormal regulation and metabolism of GI tract serotonin likely plays an important (if not causative) role in many, if not most, cases of this chronic and very common GI affliction. The data from this powerful little clinical study also supports the continued development and clinical testing of serotonin/5-HT blocking (antagonist) agents in patients with diarrhea-predominant IBS.

For additional information on IBS, please see my previous column on this topic:

Irritable Bowel Syndrome (IBS), Diet & Fiber