Enterocyte Injury and Acute Gastrointestinal Dysfunction in Critical Illness

Enterocyte Injury and Acute Gastrointestinal Dysfunction in Critical Illness: A Prospective Observational Study of Blood and Urinary Intestinal Fatty Acid-Binding Protein(Implications for Sepsis Heterogeneity）

Acute gastrointestinal injury (AGI) is a common but not fully understood organ dysfunction in critically ill patients. Current AGI grading systems rely primarily on clinical presentation and feeding tolerance, which are inherently subjective and may not accurately reflect the underlying biological severity of intestinal damage.

Intestinal fatty acid-binding protein (I-FABP) is a protein expressed almost exclusively in the cytoplasm of mature small intestinal epithelial cells. In cases of ischemia, inflammation, or mechanical injury, I-FABP is rapidly released into the bloodstream and subsequently excreted in the urine. These characteristics make I-FABP a highly specific biomarker for intestinal epithelial cell injury and intestinal ischemia.

A prospective study combining paired blood and urine I-FABP measurements, standardized AGI assessment, and careful consideration of surgical status was conducted to elucidate the role of intestinal epithelial cell injury in acute gastrointestinal dysfunction.

Study Overview

• Status: Not yet recruiting
• Conditions: Adult; Patients Admitted to the ICU; Expected Hospital Stay ≥48 Hours
• Intervention / Treatment: Other: Plasma and urine I-FABP measurement

Detailed Description

This study is a prospective observational cohort study conducted in an adult intensive care unit. Biological samples and clinical data will be prospectively collected according to a pre-defined protocol, without any intervention other than standard treatment.

Primary objective: To prospectively assess the association between serum and urinary I-FABP levels and the severity of acute gastrointestinal injury in critically ill patients.

Secondary objectives: To investigate the relationship between serum and urinary I-FABP levels and clinical outcomes (including severe AGI and mortality); to explore whether the intestinal epithelial cell injury patterns reflected by serum and urinary I-FABP are associated with different sepsis subphenotypes; and to evaluate the impact of gastrointestinal surgery on I-FABP levels and its modifying effect on the association between I-FABP and AGI severity.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Yanhua Li; Phone Number: 86-15804301738; Email: liyanhua@jlu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This prospective observational cohort will consecutively enroll adult critically ill patients (≥18 years) admitted to the ICU with an expected ICU stay of at least 48 hours. Paired plasma and urine samples will be collected within 24 hours of ICU admission (and repeated on ICU day 3) to measure intestinal fatty acid-binding protein (I-FABP). Gastrointestinal function will be assessed daily during ICU stay to grade acute gastrointestinal injury (AGI) according to the ESICM definition. Patients with pre-existing inflammatory bowel disease, short bowel syndrome, chronic intestinal failure requiring long-term parenteral nutrition, pregnancy, or those who refuse/withdraw consent will be excluded.

Description

Inclusion Criteria:

• 1、 Age ≥18 years.
• 2 、Admission to the ICU with an expected ICU stay ≥48 hours.
• 3 、Availability of paired plasma and urine samples within 24 hours of ICU admission.
• 4 、Feasible daily gastrointestinal function assessment to complete AGI grading (ESICM definition).

Exclusion Criteria:

• 1、 Pre-existing inflammatory bowel disease.
• 2 、Short bowel syndrome.
• 3、 Chronic intestinal failure requiring long-term parenteral nutrition.
• 4、 Pregnancy.
• 5 、Refusal or withdrawal of informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Critically ill adults admitted to the ICU; Consecutive adult critically ill patients (≥18 years) admitted to the ICU will be enrolled if ICU stay is expected to be ≥48 hours. Eligible participants must have paired plasma and urine samples obtainable within 24 hours of ICU admission and be able to undergo daily gastrointestinal function assessment for AGI grading. Exclusion criteria: pre-existing inflammatory bowel disease or short bowel syndrome; chronic intestinal failure requiring long-term parenteral nutrition; pregnancy; refusal or withdrawal of informed consent. Exposure of interest is plasma and urine intestinal fatty acid-binding protein (I-FABP) concentrations measured within 24 hours of ICU admission (continuous variables). Paired plasma and urine are collected within 24 hours and repeated on ICU day 3.

Other: Plasma and urine I-FABP measurement; Paired plasma and urine samples will be collected within 24 hours of ICU admission to quantify intestinal fatty acid-binding protein (I-FABP) concentrations (continuous measures) using a standardized laboratory assay. A second paired sampling will be performed on ICU day 3 to assess changes over time. No therapeutic intervention is assigned; this study is observational.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum AGI grade during ICU stay (ESICM 0-IV)	AGI severity will be assessed daily during ICU stay and graded as an ordinal outcome (0, I, II, III, IV) according to the ESICM Working Group definition. The primary outcome is the maximum (worst) AGI grade observed from ICU admission (Day 1) through ICU discharge or death, up to 28 days. Effect modification by gastrointestinal surgery will be explored using an interaction term.	From ICU admission (Day 1) through ICU discharge or death, assessed daily, up to 28 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe AGI during ICU stay (AGI grade III-IV)	AGI severity will be assessed daily during ICU stay and graded (0, I, II, III, IV) according to the ESICM Working Group definition. Severe AGI is defined as any occurrence of AGI grade III or IV during the assessment period and will be reported as a binary outcome (yes/no).	From ICU admission (Day 1) through ICU discharge or death, assessed daily, up to 28 days.
28-day all-cause mortality	Death from any cause within 28 days after ICU admission.	Up to 28 days after ICU admission.
ICU length of stay	ICU length of stay, defined as the number of days from ICU admission to ICU discharge or death.	From ICU admission(Day 1) through ICU discharge or death, up to 28 days.
Sepsis subphenotype characterized by an intestinal epithelial cell injury pattern	A biomarker-defined sepsis subphenotype characterized by an intestinal epithelial cell injury pattern will be identified according to a prespecified definition/algorithm based on I-FABP profiles (plasma and urine) measured within 24 hours of ICU admission and on ICU day 3 (categorical classification).	Within 24 hours of ICU admission and ICU day 3 (for classification), with outcomes assessed during ICU stay and/or up to day 28 as applicable.

Collaborators and Investigators

• Sponsor: The First Hospital of Jilin University
• Investigators: Study Chair: Hongxiang Li, The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 10, 2026
• First Submitted That Met QC Criteria: February 23, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Critical Illness; Intestinal Fatty Acid-Binding Protein; Acute Gastrointestinal Dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Critical Illness
• Other Study ID Numbers: I-FABP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared at this time due to privacy and regulatory considerations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No