American Journal of Gastroenterology ISSN 0002-9270 C  2007 by Am. Coll. of Gastroenterology doi: 10.1111/j.1572-0241.2007.01072.x Published by Blackwell Publishing The Degree of Breath Methane Production in IBS Correlates With the Severity of Constipation Soumya Chatterjee, M.B.B.S., Sandy Park, B.A., Kimberly Low, B.A., Yuthana Kong, M.P.H., and Mark Pimentel, M.D., F.R.C.P.(C) Cedars-Sinai Medical Center, Burns and Allen Research Institute, Los Angeles, California BACKGROUND: Recent work has demonstrated that among irritable bowel syndrome (IBS) subjects, methane on lactulose breath test (LBT) is nearly universally associated with constipation predominance. This work has been based on subjective constipation outcomes. In this study, methane is compared to constipation in another population of IBS subjects with constipation being determined both subjectively and objectively. METHODS: A nested study was conducted in subjects enrolled in a double-blind randomized placebo-controlled study. After consent, subjects were asked to complete a stool diary for 7 days. This included logging of all bowel movements that week as well as documenting the stool consistency for each during the same period using the Bristol Stool Score. After 7 days, subjects were asked to rate their symptoms on a visual analogue scale (VAS) score (0–100 mm) for diarrhea and constipation. They then had an LBT to evaluate both methane and hydrogen profiles over 180 min. Subjects with methane were compared to those without methane for Bristol Stool Score, stool frequency, as well as VAS scores for diarrhea and constipation. The degree of constipation was then compared to the quantity of methane production on LBT based on area under the curve. RESULTS: Among 87 subjects, 20 (23.8%) produced methane. IBS subjects with methane had a mean constipation severity of 66.1 ± 36.7 compared to 36.2 ± 30.8 for nonmethane producers (P < 0.001). The opposite was noted for diarrhea (P < 0.01). On LBT, the quantity of methane seen on breath test was directly proportional to the degree of constipation reported (r = 0.60, P < 0.01). In addition, greater methane production correlated with a lower stool frequency (r =-0.70, P < 0.001) and Bristol Stool Score (r =-0.58, P < 0.01). CONCLUSION: Methane on LBT is associated with constipation both subjectively and objectively. The degree of methane production on breath test appears related to the degree of constipation. (Am J Gastroenterol 2007;102:837–841) INTRODUCTION Irritable bowel syndrome (IBS) is a gastrointestinal condition characterized by alterations in bowel function and bloating (1). Despite the fact that IBS is common, the cause has been unknown. Recently, studies of gut flora have provided some insights into at least a subset of IBS. One area of investiga- tion of gut flora and IBS is the association between abnormal breath testing and IBS suggesting bacterial overgrowth. Ini- tially, the association between bacterial overgrowth and IBS has been reported using indirect measures such as the lac- tulose breath test (LBT) (2–4). Recent studies using glucose breath testing (5, 6) have confirmed this association. Despite the limitations of culture, proximal small bowel cultures have also demonstrated bacterial overgrowth in 12% of those la- beled with the diagnosis of IBS (7–9). Since bacterial overgrowth has by convention been part of the differential diagnosis for diarrhea, it has been difficult to reconcile bacterial overgrowth as a contributing factor in the constipation subcategory of IBS. Approximately, one- third of IBS patients are constipation predominant (C-IBS) (10). Recent data are, however, demonstrating an association between C-IBS and the presence of methane on LBT. The two gases that are routinely measured during breath testing are hydrogen and methane. The only source for these gases in humans is via intestinal bacterial fermentation. It was once thought that these gases were relatively inert to the host aside from their physical distending properties. Yet, in a growing number of studies, it is now shown that methane gas may not be inert. In clinical studies of IBS, it is found that methane-producing IBS subjects are almost universally suf- fering with constipation predominant IBS (3, 11). Although the exact mechanism of how methane slows transit is yet unknown, further work reveals that methane may exaggerate small intestinal contractile responses (12). This then suggests that methane may be causing the symptoms of constipation. 837