Fecal profiling of volatile organic compounds (VOCs) may provide a low cost, non-invasive tool to predict the responses of irritable bowel syndrome (IBS) patients to probiotics and diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), according to British researchers.
Modeling baseline fecal VOCs, and using key features of VOC profiles, correctly predicted response to a low-FODMAP diet in 100% of patients and in 89% of patients receiving a probiotic, reported Megan Rossi, PhD, RD of King’s College in London, and colleagues.
This approach can potentially shed light on the pathophysiology of IBS, and advance its clinical management with more precisely personalized nutrition regimens, they wrote in Clinical Gastroenterology and Hepatology.
Multiple randomized trials have indicated that the low-FODMAP diet is effective in 50%-80% of IBS patients. “However, predicting response is clinically important because the diet requires intensive dietary counselling and impacts on both the gut microbiota and nutrient intake, and, therefore, avoiding this intervention in the 20%-50% who are unlikely to respond would be an important clinical advance,” Rossi’s group noted.
New approaches are definitely needed, according to William D. Chey, MD, of the University of Michigan in Ann Arbor.
“Only about half [of patients] get better on the diet, which has associated shopping costs and inconvenience to the patient, plus input from a dietitian and an extended three-step period of time to work through its stages,” Chey told MedPage Today. “This often gets glossed over but it’s not a trivial thing.”
Chey, who was not involved in the study, further explained that little is known about the long-term nutritional and microbiotic downsides of this restrictive diet. “By excluding prebiotic carbohydrates, you are very likely to have effects on the microbiome, so it’s important to identify strategies that enrich the likelihood of response and maximize choosing the right treatment for the right patient,” he said.
Rossi’s group used data and samples from patients with IBS-diarrhea, IBS-mixed, and IBS-unsubtyped treated at two major London hospitals and participating in a previous clinical trial. A total of 95 patients (majority white), whose age ranged from early to late 30s, completed the study. Of these, 93 (63 women) provided sufficient fecal sample for analysis and were randomized for 4 weeks to a low-FODMAP diet (n=46) or a sham diet plus dietary advice (n=47).
In 2-by-2 factorial fashion, patients in both dietary groups also received either a multi-strain probiotic supplement (n=49) or a placebo supplement (n=44).
Gas chromatography assessed VOCs in fecal samples at baseline and at study completion. The clinical endpoint was the IBS Severity Scoring System (IBS-SSS), which records abdominal pain, distension, stool frequency and consistency, and interference with life over a 10-day period.
All 93 participants were deemed compliant with diet, and 86 were classified as compliant with supplementation. At the end of the study, those in the low-FODMAP arm had a significantly lower total FODMAP intake (20+8 g/day) compared with those on the sham diet (33+16 g/day, P<0.001).
In terms of response, more patients reacted clinically to the low-FODMAP diet (37/46, 80%) than the sham diet (21/47 45%, P<0 .001), with a mean change in IBS-SSS score of –130 and –49 (P<0.001), respectively.
There was no difference in clinical response between patients given the probiotic (31/49, 63%) versus placebo (27/44, 61%, P=0.850), with no synergistic or antagonistic effects observed with supplementation. In addition, there was no difference in the mean change in IBS-SSS score between recipients of probiotic (–88) and placebo (–90, P=0.921).
The researchers found that baseline VOC profiles contained 15 features that explained 25% of response variation to the low-FODMAP diet with a mean accuracy of 97% (95% CI 96%-99%), as well as 10 features that explained 30% of response variation to the probiotic, with a mean accuracy of 89% (95% CI 86%-92%). At end of treatment, nine observed compounds explained 31% of variation in response to low-FODMAP and 11 compounds explained 27% of variation with the probiotic.
As to how VOCs predict response, the authors pointed out that many of these compounds are created from indigestible food substrates in the colon through both microbial metabolic activity and diet. VOC patterns at baseline may reflect the pathophysiology of an individual’s IBS and eating a high-FODMAP standard diet may, in the presence of IBS-associated dysbiosis, generate fermentation products that cause symptoms. Once the normal diet has been replaced, there is less substrate for bacterial metabolism and gas production and associated symptoms are reduced.
Study limitations included the relatively small sample size, its exploratory nature and the lack of data to inform a power calculation. Also, since the device that assessed fecal VOCs identified patterns of VOCs, not individual VOCs, detailed investigation of the potential mechanisms of individual VOCs could not be done. Finally, the 2-by-2 factorial design may have clouded the results.
Chey noted that, in his experience, about half of patients improve on the low-FODMAP diet, a remarkably high rate of success for a dietary therapy. Also, some of his patients have been following a reduced-FODMAP diet since his institution began introduced it in 2008.
“And up to 85% can move to a less restrictive diet after the phase of determining sensitivities,” Chey said.