Psychological factors like anxiety, depression may be central drivers of IBS, rather than inflammation

In a separate study also released at the Annual Scientific Meeting of the American College of Gastroenterology today, researchers from the Alimentary Pharmabiotic Centre at University College Cork suggest that psychological factors such as anxiety and depression may be central drivers of inflammatory changes in IBS rather than inflammation originating in the gut itself.

Research Suggests Efficacy of Diagnostic Blood Test for Irritable Bowel Syndrome (IBS)

Anti- vinculin antibodies are elevated in IBS compared to non-IBS, according to the results of the study, "Anti-Vinculin Antibodies: Multicenter Validation of a Diagnostic Test for Irritable Bowel Syndrome," which assessed anti-vinculin antibodies as a predictor of IBS as compared to healthy subjects and IBD.

Vinculin is a cell migration and adherence protein found predominantly on nerves and epithelium. A series of studies leading up to this result suggests that acute gastroenteritis causes antibodies to be formed to vinculin and is associated with IBS development.

"This is the first test that discriminated IBS from IBD," said Dr. Pimentel, Director of the Gastrointestinal Motility Program and Laboratory at Cedars-Sinai Medical Center in Los Angeles, who coauthored the multicenter study with researchers from Beth Israel Deaconess Medical GAS in Boston.

In total 165 IBS, 30 IBD and 26 healthy control subjects were evaluated. Demographics were similar between groups. Overall, IBS had a significantly greater optical density for antibodies to vinculin compared to IBD and healthy subjects. The test had a high specificity for IBS.

"Anti-vinculin antibodies are elevated in IBS compared to non-IBS," said Dr. Pimentel. "This is the first diagnostic test for IBS based on serum and a pathophysiologic mechanism of IBS through acute gastroenteritis precipitating molecular mimicry and autoimmunity. This is a major breakthrough as the first test to potentially distinguish IBS from IBD and reduce the need for unnecessary testing in these conditions. Moreover, this test is based on a potential pathophysiologic mechanism of IBS development."

"The authors have identified a potentially novel clinical biomarker for IBS, possibly of the post-infectious type," said Douglas A. Drossman MD, President of the Rome Foundation and the Center for Education and Practice of Biopsychosocial Care, LLC. "However, we need to be careful not to over interpret the significance of the findings with regard to diagnostic or therapeutic specificity. IBS is a collection of symptoms with heterogeneous determinants. Perhaps with further confirmation, anti-vinculin antibodies may in the future identify one of possibly several meaningful physiological subsets that are more amenable to targeted treatments."

Anxiety, Depression May be Central Drivers of IBS rather than Gut Inflammation

Cytokines are a family of molecules that modulate the immune response; some promote inflammation (pro-inflammatory cytokines) and others reduce inflammation (anti-inflammatory cytokines). In the study, "Circulating Cytokines in IBS Subgroups," researchers from the Alimentary Pharmabiotic Centre at University College Cork aimed to determine whether circulating cytokine levels are associated with distinct IBS subgroups.

"The main finding, which confirms several prior studies from our group, is the elevated level of the cytokine interleukin-6 (IL-6), a pro-inflammatory cytokine, in the blood in those with IBS," said Eamonn M.M. Quigley, MD, FACG, lead author who is now head of Gastroenterology at Houston Methodist Hospital. "For the first time, we showed that this is a constant finding over time."

Dr. Quigley and his team looked at a whole range of demographic factors that could be related to IL-6 levels and, in particular, to the IBS subgroups that have been so widely studied before and defined according to dominant stool pattern: diarrhea-predominant (IBS-D), constipation-predominant (IBS-C), and alternating constipation-diarrhea (IBS-M).

According to the results, higher levels of plasma IL-6 are associated with the presence of psychological comorbidity in those with IBS. This suggests that disturbances in circulating cytokines may be centrally mediated rather than reflecting inflammation at the mucosal level.

"While these are relatively low levels and rather subtle changes, their relationship to anxiety and depression is interesting as these disorders, per se, have been linked to increased inflammatory tone," said Dr. Quigley. "The results also suggest that variability in the levels of these cytokines is linked to symptom severity as well as levels of anxiety and depression. When one sees elevated levels of inflammatory markers in any intestinal disorder the immediate assumption is that it originates from an inflammatory process in the intestine itself. But our results suggest that it may be central factors like anxiety and depression that are actually the drivers and it has been shown in other contexts that this, indeed, can happen."

With IBS sometimes challenging to treat and manage, the results of this study raise two issues, according to Dr. Quigley. "Can we use this as a test to differentiate those IBS subjects for whom central factors, like anxiety and depression, may be more important; and will centrally-directed therapies (antidepressants and anti-anxiety drugs) be more effective in this group?"

"The relationship between inflammatory cytokines with anxious and depressed mood is well recognized within psychiatry," commented Dr. Drossman, who is Adjunct Professor of Medicine and Psychiatry at the University of North Carolina. "Dr. Quigley's group has confirmed that in a cohort of patients with IBS this association of mood with cytokine activation exists more so than in healthy controls who were presumably psychologically healthy."