Mode of Action of Psyllium in Reducing Gas Production from Inulin and its Interaction with Colonic Microbiota: A 24 hours, Randomised, Placebo-Controlled Trial in Healthy Human Volunteers

Background: Recent studies show that the increase in breath hydrogen (BH₂) and symptoms after ingestion of inulin is reduced by co-administering psyllium.

Objectives: To determine if slowing delivery of inulin to the colon by administering it in divided doses would mimic the effect of psyllium. Primary endpoint was the BH₂ area under the curve AUC_0-24hours. Secondary endpoints included BH₂ AUC_{0-6h, 6-12h, and 12-24h}. Exploratory endpoints included the correlation of BH₂ AUC_0-24h with dietary FODMAPs intake and in vitro fermentation results.

Methods: 17 Healthy adults were randomised to a single-blind, 3-arm, crossover trial. All consumed 20g inulin (I) powder dissolved in 500mL water and mixed with either 20g maltodextrin (control) or 20g psyllium (PI) consumed as a single dose or 20g inulin given in divided doses (DDI), 62.5mL every 45 minutes over 6h. 24-h BH₂, dietary FODMAP intake, stool microbiota, and gas production in vitro were measured. Responders were defined as those whose AUC_0-24h BH₂ was reduced by psyllium, while non-responders showed no reduction.

Results: Compared to control, PI did not reduce average BH₂ AUC_0-24h while DDI increased it, p<0.0002. DDI and PI both significantly reduced BH₂ AUC_0-6h compared to the control, p<0.0001. However, subsequently, DDI significantly increased BH₂ from 6-12h (p<0.0001) and overnight (12-24h) (p<0.0001), while PI did so only overnight (p=0.0002). Non-responders showed greater release of arabinose during in-vitro fermentation and higher abundance of two species, Clostridium spp. AM22_11AC and Phocaeicola dorei, which also correlated with BH₂ production on PI. Dietary FODMAP intake tended to correlate inversely with BH₂ AUC_0-24h (r=-0.42, p=0.09) and correlated with microbiome community composition.

Conclusions: DDI, like psyllium, reduces early BH₂ production. Psyllium acts by delaying transit to the colon but not reducing colonic fermentation over 24h. Dietary FODMAP intake correlates with BH₂ response to inulin and the microbiome.

Clinical trial registry number: www.

Clinicaltrials: govID: NCT05619341Ethical approval for this study was obtained from the Research Ethics Committee at the Faculty of Medicine and Health Sciences, University of Nottingham (FMHS 17-622).

Statement of significance: This mechanistic study adds to recent evidence that psyllium reduces colonic gas and symptoms in the 6 hours after ingestion. The underlying mechanism includes slowing of delivery to the colon, but total fermentation over 24 hours is not altered. While some subjects do show a reduction, not all do, possibly due to the degradation of psyllium by the colonic microbiota. Habitual FODMAP intake correlates negatively with gas production, raising the possibility that dietary manipulation could alter colonic fermentation pathways to produce less gas.