Abstract
BACKGROUND: Functional constipation is a common disorder of the gut-brain interaction characterized by infrequent bowel movements and hard stools, which substantially affects patients' quality of life. Supplementation with gut microbiome-targeted prebiotics is a promising non-pharmacological alternative to current treatments. METHODS: In a randomized, double-blind, placebo-controlled, cross-over trial, we investigated the effect of four-week daily 12 g chicory inulin intake in 39 individuals, with functional constipation according to Rome III criteria. We assessed stool frequency and consistency, constipation-related quality of life (PAC-QOL) and symptoms (PAC-SYM), and microbiota composition through 16S rRNA gene sequencing of fecal samples. RESULTS: After inulin intake, we observed larger changes in stool frequency, abdominal symptoms, and particularly social and emotional well-being related to quality of life, compared to placebo. Additionally, relative abundances of putative butyrate-producing Anaerostipes spp. and Coprococcus 1 spp. were higher. Further investigation, however, pointed to a carry-over whereby half of the participants receiving inulin in the first period had the largest improvements in all outcomes during inulin intake. Moreover, these same participants had higher baseline relative abundances of butyrate-producing Faecalibacterium spp. and Roseburia spp., and lower baseline relative abundances of Bifidobacterium spp. In turn, these participants' microbiota responded more strongly to inulin intake through a stronger increase in the relative abundance of Bifidobacterium spp. and Anaerostipes spp. To address this apparent carry-over induced bias, we analyzed the first period alone as a parallel trial which supported the observed positive effect of inulin, also affirming its established bifidogenic effect. CONCLUSIONS: Daily intake of 12 g inulin improves functional constipation by increasing stool frequency, positively affecting abdominal symptoms and well-being, and modulating the gut microbiota towards higher relative abundances of butyrate-producing genera. TRIAL REGISTRATION: Ethical approval was obtained from the Cork Research Ethics Committee of the Cork Teaching Hospitals (Reference ECM 4 (v) 01/09/15), and the trial design was retrospectively registered at ClinicalTrials.gov (NCT05447481; 07/2022).