Impact of Fiber-Based Enteral Nutrition on the Gut Microbiome of ICU Patients Receiving Broad-Spectrum Antibiotics: A Randomized Pilot Trial

Abstract

Objectives: Dietary fiber increases the abundance of bacteria that metabolize fiber into short-chain fatty acids and confers resistance against gut colonization with multidrug-resistant bacteria. This pilot trial estimated the effect of fiber on gut short-chain fatty acid-producing bacteria in the ICU.

Design: Randomized, controlled, open label trial.

Setting: Medical ICU.

Patients: Twenty ICU adults receiving broad-spectrum IV antibiotics for sepsis.

Intervention: 1:1 randomization to enteral nutrition with mixed soy- and oat-derived fiber (14.3 g fiber/L) versus calorie- and micronutrient-identical enteral nutrition with 0 g/L fiber.

Measurements: Rectal swabs and whole stools were collected at baseline and on study Days 3, 7, 14, and 30. The primary outcome was within-individual change in the cumulative relative abundance of short-chain fatty acid-producing taxa from baseline to Day 3 based on 16S sequencing of rectal swabs. The secondary outcome was Day 3 cumulative short-chain fatty acid levels based on mass spectrometry of whole stools. Analyses were all intent to treat.

Main results: By Day 3, the fiber group received a median of 32.1 g fiber cumulatively (interquartile range, 17.6-54.6) versus 0 g fiber (interquartile range, 0-4.0) in the no fiber group. The median within-individual change in short-chain fatty acid producer relative abundance from baseline to Day 3 was +61% (interquartile range -51 to +1,688) in the fiber group versus -46% (interquartile range, -78 to +13) in the no fiber group (p = 0.28). Whole stool short-chain fatty acid levels on Day 3 were a median of 707 μg short-chain fatty acids/g stool (interquartile range, 190-7,265) in the fiber group versus 118 μg short-chain fatty acids/g stool (interquartile range, 22-1,195) in the no fiber group (p = 0.16).

Conclusions: Enteral fiber was associated with nonsignificant trends toward increased relative abundance of short-chain fatty acid-producing bacteria and increased short-chain fatty acid levels among ICU patients receiving broad-spectrum IV antibiotics. Larger studies should be undertaken and our results can be used for effect size estimates.

Keywords: Clinical Trial; colonization; ICU; antimicrobial resistance; fiber; microbiome; nutrition; prebiotics; probiotics; sepsis; short-chain fatty acids.