Low FODMAP diet and probiotics in irritable bowel syndrome: a 2x2 factorial design, randomised, placebo-controlled trial

Background and aims: Feeding studies demonstrate the clinical potential of restriction of fermentable carbohydrates (low FODMAP diet, LFD) in irritable bowel syndrome (IBS). However, a placebo-controlled dietary advice study has not been conducted and the diet leads to a potentially detrimental shift in microbiota composition.Methods: A 2x2 factorial trial was undertaken in the tertiary care setting. Patients aged 18-65 years with Rome III IBS were recruited. Patients were randomised 1:1 for four weeks to a diet (sham diet vs LFD) and supplement (placebo vs probiotic), resulting in four different groups. The sham diet was equivalent in dietary restriction compared with LFD. The probiotic was multistrain (VSL#3). Patients were masked to the interventions. The primary endpoints were adequate relief of symptoms and stool Bifidobacteria abundance at four weeks. Results: 104 patients were randomised. 27 were allocated to sham diet/placebo, 26 to sham diet/probiotic, 24 to LFD/placebo and 27 to LFD/probiotic. There was no interaction between the interventions. In the intention-to-treat analysis, adequate symptom relief was higher for LFD (57%) versus sham (38%), although did not reach statistical significance (p=0.051), whereas in the per protocol analysis the higher proportion for LFD (61%) versus sham (39%) was statistically significant (p=0.043). Bifidobacteria were lower after LFD versus sham (8.8 vs 9.2 16S rRNA genes/g, p=0.008) and higher after probiotic versus placebo (p=0.019). There was no effect of LFD on microbiota diversity.Conclusions: This is the first placebo-controlled study of LFD advice in IBS, reporting adequate symptom relief that approached significance together with significantly reduced symptom scores compared with placebo. Probiotic co-administration ameliorated the diet-induced decline in Bifidobacteria abundance.