A phase 2 randomized, placebo-controlled trial of inulin for the prevention of gut pathogen colonization and infection in the intensive care unit

Objective Patients admitted to the intensive care unit (ICU) often have gut colonization with pathogenic bacteria and such colonization is associated with increased risk for death and infection. We conducted a trial to determine whether a prebiotic would improve the gut microbiome to decrease gut pathogen colonization and decrease downstream risk for infection among newly admitted medical ICU patients. Design Randomized, double-blind, placebo-controlled trial with two prebiotic dose arms. Setting Two medical ICUs at a single center. Patients Adults who were admitted to the medical ICU for sepsis and were receiving broad-spectrum antibiotics. Intervention Participants were randomized 1:1:1 to placebo, inulin 16 grams/day, or inulin 32 grams/day for seven days. Measurements and main results The trial primary outcome was a surrogate measure for gut colonization resistance, namely the within-individual change from ICU admission to Day 3 in the relative abundance of short chain fatty acid (SCFA)-producing bacteria based on rectal swabs. Ninety participants were analyzed, including 30 in each study group. There was no difference between study groups in the relative abundance of SCFA-producing bacteria from ICU admission to ICU Day 3 (placebo: 0.0% change, IQR -8·0% to +7·4% vs. combined inulin: 0·0% change, IQR -10·1% to +4·8%; p=0·91). At end-of-treatment on ICU Day 7, inulin did not affect SCFA-producer levels, microbiome diversity, or rates of gut colonization with pathogenic bacteria. After 30 days of clinical follow-up, inulin did not affect rates of death or clinical infection. Patients who died or developed culture-proven infections had lower relative abundance of SCFA-producing bacteria at ICU admission compared to those who did not (p=0.03). Conclusions Prebiotic fiber had minimal impact on the gut microbiome in the ICU and did not improve clinical outcomes. Microbiome restitution therapies may face significant challenges in the ICU. Trial registration : Clinicaltrials.gov: NCT03865706. Registered 10/14/19