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

Background: Recent studies show that the increase in breath hydrogen (BH₂) and symptoms after ingestion of inulin are reduced by coadministering psyllium (PI).

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

Methods: A total of 17 healthy adults were randomly assigned to a single-blind, 3-arm, crossover trial. All consumed 20 g inulin (I) powder dissolved in 500 mL water and mixed with either 20 g maltodextrin (control) or 20 g PI consumed as a single dose or 20 g inulin given in divided doses (DDI), 62.5 mL every 45 min over 6 h. Twenty-four-hour BH₂, dietary FODMAP intake, stool microbiota, and gas production in vitro were measured. Responders were defined as those whose AUC_{0-24 h} BH₂ was reduced by PI, whereas nonresponders showed no reduction.

Results: Compared with control, PI did not reduce average BH₂ AUC_{0-24 h}, whereas DDI increased it, P < 0.0002. DDI and PI both significantly reduced BH₂ AUC_{0-6 h} compared with the control, P < 0.0001. However, subsequently, DDI significantly increased BH₂ from 6 to 12 h (P < 0.0001) and overnight (12-24 h) (P < 0.0001), whereas PI did so only overnight (P = 0.0002). Nonresponders showed greater release of arabinose during in vitro fermentation and higher abundance of 2 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_{0-24 h} (r = -0.42, P = 0.09) and correlated with microbiome community composition.

Conclusions: DDI, like PI, reduces early BH₂ production. PI acts by delaying transit to the colon but not reducing colonic fermentation over 24 h. Dietary FODMAP intake correlates with BH₂ response to inulin and the microbiome. This trial was registered at www.

Clinicaltrials: gov as NCT05619341.