Enteral Nutrition and Colonization Resistance Through Microbiota Modulation in Critically Ill Patients

Official title

Enteral Nutrition to Enhance Colonization Resistance Through Gut Microbiota Modulation in Critically Ill Patients: A Randomized Controlled Pilot Trial

Overview

The goal of this clinical trial is to learn whether enteral nutrition enriched with fiber can influence gut microbiota and improve resistance to colonization with multidrug-resistant bacteria in critically ill patients. The study will also evaluate the safety and clinical outcomes associated with fiber-enriched enteral nutrition. The main questions it aims to answer are: * Does fiber-enriched enteral nutrition reduce the acquisition of colonization with multidrug-resistant bacteria during intensive care unit (ICU) hospitalization? * Does fiber-enriched enteral nutrition modify the composition and diversity of the intestinal microbiota? * Are there differences in clinical outcomes, including adverse events, between patients receiving fiber-enriched and non-fiber enteral nutrition? Researchers will compare patients receiving fiber-enriched enteral nutrition with patients receiving standard enteral nutrition without added fiber to determine whether fiber supplementation influences gut microbiota and colonization resistance. Participants will: * Receive enteral nutrition through a feeding tube according to their clinical needs. * Receive either a fiber-enriched enteral nutrition formula or a standard enteral nutrition formula. * Have stool samples collected during ICU hospitalization for analysis of intestinal microbiota and detection of multidrug-resistant bacteria. * Be monitored for clinical outcomes, infections, antibiotic exposure, and adverse events during their ICU stay and follow-up period.

Detailed description

Critically ill patients frequently experience alterations of the intestinal microbiota due to factors such as severe illness, antibiotic exposure, and the ICU environment. These changes may contribute to loss of colonization resistance and increased susceptibility to acquisition of multidrug-resistant bacteria, which are associated with increased morbidity and mortality in critically ill populations.

Enteral nutrition is commonly used in ICU patients who are unable to meet their nutritional requirements orally. Beyond its role in providing calories and nutrients, enteral nutrition may influence intestinal barrier function and microbiota composition. Fiber-containing enteral formulas include nondigestible carbohydrates that may act as substrates for microbial fermentation and may promote the growth of beneficial bacterial populations and the production of short-chain fatty acids.

Previous studies have suggested that fiber supplementation during enteral nutrition may influence gut microbiota composition and clinical outcomes; however, results remain inconsistent, particularly in critically ill patients receiving broad-spectrum antibiotics. The potential effect of fiber-enriched enteral nutrition on acquisition of multidrug-resistant bacterial colonization has not been adequately investigated.

This clinical trial aims to evaluate whether modulation of the intestinal microbiota through fiber-enriched enteral nutrition may influence colonization resistance in critically ill patients. The study will provide preliminary data regarding microbiota changes associated with enteral nutrition strategies and their potential relationship with multidrug-resistant bacterial colonization. These findings may support the design of future larger clinical trials evaluating nutritional interventions as a strategy to preserve microbiome function and reduce ICU-associated complications.

Interventions

• Dietary supplement Fibre-Enriched Enteral Nutrition
  Participants will receive enteral nutrition administered through an enteral feeding tube according to their clinical nutritional requirements. The intervention consists of an enteral nutrition formula enriched with dietary fiber, including fermentable fibers with potential prebiotic effects, intended to modulate intestinal microbiota composition and function. It will be administered according to the study protocol and clinical care requirements of critically ill patients. The intervention will b
• Dietary supplement Standard Enteral Nutrition
  Participants will receive enteral nutrition administered through an enteral feeding tube according to their clinical nutritional requirements. The comparator intervention consists of a standard enteral nutrition formula without added fiber. It will be administered according to the study protocol and clinical care requirements of critically ill patients. The type and amount of enteral nutrition administered will be documented throughout the study period.

Primary outcome measures

• Proportion of Participants With New Multidrug-Resistant Bacterial Colonization Between Days 5 and 7 [Time frame: ICU days 5-7 after admission]

Secondary outcome measures (7)

• Change in Gut Microbiota Diversity and Composition [Time frame: From ICU admission (Day 1) to ICU days 5-7]
• Proportion of Participants With MDRO Colonization at Day 14 and 28 [Time frame: Day 14 and 28 after ICU admission]
• Incidence of Nosocomial Infections [Time frame: From ICU admission (Day 1) to hospital discharge or Day 28, whichever occurs first]
• Duration of Mechanical Ventilation and Ventilator-Free Days [Time frame: Day 28 after ICU admission]
• Duration of ICU and Hospital Stay [Time frame: ICU stay: From ICU admission through ICU discharge, an average of 28 days; Hospital stay: From hospital admission through hospital discharge, an average of 90 days.]
• 28-Day Mortality and In-Hospital Mortality [Time frame: 28-Day Mortality: 28 days after ICU admission; In-Hospital Mortality: during the hospital stay, up to hospital discharge, up to 90 days.]
• Correlation Between Immunological and Inflammatory Profile Changes and MDRB Colonization or Microbiota Changes [Time frame: From ICU admission (Day 1) to Day 28 after ICU admission]

Eligibility criteria

Inclusion criteria

• Patients with medical (non-surgical) conditions admitted to the ICU.
• ICU admission within the previous 48 hours at the study site.
• Initiation of enteral nutrition within the first 48 hours after ICU admission.
• Written informed consent obtained for participation in the study.

Exclusion criteria

• Surgical ICU patients.
• Patients in whom enteral nutrition was not initiated within the first 48 hours after - ICU admission.
• Patients with galactosemia.
• Patients with major contraindications to enteral nutrition, including: intestinal obstruction, intestinal ischemia, intestinal perforation, severe hemodynamic instability, patients who refuse participation in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Romania · 1 center

• Emergency Military Clinical Hospital "Dr. Constantin Papilian" Cluj-Napoca — Cluj-Napoca

Publications

• Caparros T, Lopez J, Grau T. Early enteral nutrition in critically ill patients with a high-protein diet enriched with arginine, fiber, and antioxidants compared with a standard high-protein diet. The effect on nosocomial infections and outcome. JPEN J Parenter Enteral Nutr. 2001 Nov-Dec;25(6):299-308; discussion 308-9. doi: 10.1177/0148607101025006299. PMID 11688933
• Koch JL, Lew CCH, Kork F, Koch A, Stoppe C, Heyland DK, Dresen E, Lee ZY, Hill A. The efficacy of fiber-supplemented enteral nutrition in critically ill patients: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis. Crit Care. 2024 Nov 7;28(1):359. doi: 10.1186/s13054-024-05128-2. PMID 39511681
• Andersen S, Kennedy G, Banks M, Flanagan B, Henden A. Prebiotic fiber enteral supplementation after allogeneic transplantation: feasibility and impact on the microbiome. Blood Adv. 2025 Aug 26;9(16):4167-4179. doi: 10.1182/bloodadvances.2024015703. PMID 40489796
• O'Keefe SJ, Ou J, Delany JP, Curry S, Zoetendal E, Gaskins HR, Gunn S. Effect of fiber supplementation on the microbiota in critically ill patients. World J Gastrointest Pathophysiol. 2011 Dec 15;2(6):138-45. doi: 10.4291/wjgp.v2.i6.138. PMID 22180847
• Freedberg DE, Messina M, Lynch E, Tess M, Miracle E, Chong DH, Wahab R, Abrams JA, Wang HH, Munck C. Impact of Fiber-Based Enteral Nutrition on the Gut Microbiome of ICU Patients Receiving Broad-Spectrum Antibiotics: A Randomized Pilot Trial. Crit Care Explor. 2020 Jun 11;2(6):e0135. doi: 10.1097/CCE.0000000000000135. eCollection 2020 Jun. PMID 32695998
• Majid HA, Cole J, Emery PW, Whelan K. Additional oligofructose/inulin does not increase faecal bifidobacteria in critically ill patients receiving enteral nutrition: a randomised controlled trial. Clin Nutr. 2014 Dec;33(6):966-72. doi: 10.1016/j.clnu.2013.11.008. Epub 2013 Nov 16. PMID 24290345
• Serbanescu MA, Wright MC, Elebasy M, Shi P, Arnold JW, Haines KL, White JR, Surana NK, Wischmeyer PE. Impact of fiber-containing enteral nutrition on microbial community dynamics in critically ill trauma patients: a pilot-randomized trial. BMC Med. 2025 Dec 29;23(1):706. doi: 10.1186/s12916-025-04511-2. PMID 41462238
• Fu Y, Moscoso DI, Porter J, Krishnareddy S, Abrams JA, Seres D, Chong DH, Freedberg DE. Relationship Between Dietary Fiber Intake and Short-Chain Fatty Acid-Producing Bacteria During Critical Illness: A Prospective Cohort Study. JPEN J Parenter Enteral Nutr. 2020 Mar;44(3):463-471. doi: 10.1002/jpen.1682. Epub 2019 Aug 6. PMID 31385326

Identifiers

NCT: NCT07719673 · DEP227/25.06.2026

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗