• Heekuk Park, Elissa Lynch, Alice Tillman, Kristen Lewis, Zhezhen Jin, Anne-Catrin Uhlemann, Julian A Abrams, and Daniel E Freedberg.
• Division of Infectious Diseases & Microbiome Core Facility, Columbia University Irving Medical Center, 630 West 168th Street, PS 9-428, New York, NY, 10032, USA.
• Crit Care. 2025 Jan 13; 29 (1): 2121.

BackgroundPatients 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 with sepsis.MethodsThis was a randomized, double-blind, placebo-controlled trial of adults who were admitted to the medical ICU for sepsis and were receiving broad-spectrum antibiotics. Participants were randomized 1:1:1 to placebo, inulin 16 g/day, or inulin 32 g/day which were given for seven days. 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. Additional outcomes sought to evaluate the impact of inulin on the gut microbiome and downstream clinical effects.ResultsNinety participants were analyzed including 30 in each study group. There was no difference between study groups in the within-individual change 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, culture-proven 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).ConclusionsPrebiotic fiber had minimal impact on the gut microbiome in the ICU and did not improve clinical outcomes.Trial RegistrationClinicaltrials.gov: NCT03865706.© 2025. The Author(s).

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