An observational study in Refractory Enteral Feeding Intolerance, Gut Microbiota and Metabolic Profiles, sponsored by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Not yet recruiting at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-08.
Sponsored by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology · Observational
Some adults in the intensive care unit (ICU) cannot receive enough nutrition through a feeding tube because of persistent digestive problems, even after standard measures to improve feeding. This condition is called refractory enteral feeding intolerance. The community of microorganisms living in the gut, known as the gut microbiota, and the substances produced by these microorganisms and the body may be associated with feeding tolerance and recovery.
This prospective observational study will enroll approximately 180 adults with refractory enteral feeding intolerance at a single hospital. It aims to describe changes in their gut microbiota and metabolic profiles over time and identify combinations of microbial markers associated with improved feeding tolerance and adequate nutritional intake.
Stool samples or rectal swabs will be collected at enrollment, on days 3-5 and day 7, and, when feasible, near the end of the ICU stay. The samples will be used to examine the types of microorganisms present. Selected samples will also be analyzed for metabolic substances. Clinical information about nutrition, digestive symptoms, medications, illness severity, and treatments will be collected. Participants will be followed for up to 90 days to assess survival and unplanned hospital readmissions.
The study will examine whether microbial and metabolic patterns provide additional information about feeding improvement by day 7 beyond routine clinical assessments. Where suitable public datasets are available, findings will also be evaluated in other patient groups.
Participants will continue to receive usual medical care. The study does not assign treatments or change feeding decisions. Its findings may help guide future research on feeding intolerance, but participants are not expected to receive a direct medical benefit from taking part.
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology is the lead sponsor of 162 studies on the registry; 131 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Adults aged 18 years or older receiving care in the ICU at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, who have refractory enteral feeding intolerance (rEFI). Eligible patients remain unable to achieve an enteral energy intake of 20 kcal/kg/day despite 72 consecutive hours of feeding strategy adjustments and standard measures, including prokinetic medications. Patients will be enrolled consecutively if they meet all eligibility criteria, can provide a spontaneously passed stool sample or safely undergo rectal swab collection within the baseline sampling window, and provide written informed consent personally or through a legally authorized representative.
Exclusion Criteria:
Other: Naturally Occurring Exposures
Serial stool samples or rectal swabs will be collected at enrollment, on days 3-5 and day 7, and, when feasible, before ICU discharge or death. Gut microbiota composition will be assessed using 16S rRNA gene sequencing. A prespecified subset of samples will undergo untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. These assessments are performed for research purposes and will not guide treatment or feeding decisions. All participants will receive usual clinical care.
Area Under the ROC Curve of a Locked Baseline Microbial Biomarker Comprising at Least 15 Taxonomic Units for Feeding Intolerance Improvement by Day 7
The area under the receiver operating characteristic curve (AUC) will measure the ability of a locked composite microbial biomarker comprising at least 15 taxonomic units to distinguish participants with and without enteral feeding intolerance (EFI) improvement by day 7. The biomarker will be developed from baseline 16S rRNA gene sequencing data using participant-level nested cross-validation. All preprocessing, feature selection, and model tuning will occur within training folds. EFI improvement is defined as achieving an enteral energy intake of at least 20 kcal/kg/day with no reduction or discontinuation of feeding due to gastrointestinal intolerance for 24 consecutive hours. An AUC of 0.5 indicates chance-level discrimination, and an AUC of 1.0 indicates perfect discrimination.
Time frame: Baseline (within 48 hours of T0) and day 7
Change in Gut Microbiota α Diversity Index From Baseline to Day 7
Within-participant change in the α diversity index, calculated as the day 7 value minus the baseline value using 16S rRNA gene sequencing data.
Time frame: Baseline (within 48 hours of T0) and day 7
Bray-Curtis Dissimilarity Between Baseline and Day 7 Gut Microbiota Samples
Within-participant Bray-Curtis dissimilarity between baseline and day 7 microbial relative abundance profiles obtained by 16S rRNA gene sequencing. Values range from 0 to 1, with 0 indicating identical composition and higher values indicating greater differences in composition.
Time frame: Baseline (within 48 hours of T0) and day 7.
Number of Fecal Metabolite Features With Significant Changes From Baseline to Day 7
Number of quality-controlled metabolite features showing significant changes in normalized signal intensity between paired baseline and day 7 samples in the prespecified nested metabolomics subgroup. Features will be measured using untargeted liquid chromatography-mass spectrometry. Statistical significance will be defined as a false discovery rate-adjusted q-value below 0.05.
Time frame: Baseline (within 48 hours of T0) and day 7
Number of Predicted Microbial Functional Pathways With Significant Changes From Baseline to Day 7
Number of microbial functional pathways showing significant changes in predicted relative abundance between paired baseline and day 7 samples. Pathways will be inferred from 16S rRNA gene sequencing data using PICRUSt2. Statistical significance will be defined as a false discovery rate-adjusted q-value below 0.05. These measurements represent predicted functional potential rather than directly measured microbial activity.
Time frame: Baseline (within 48 hours of T0) and day 7
Change in Cross-Validated AUC After Adding the Baseline Microbial Biomarker to a Clinical Model for Day 7 Feeding Intolerance Improvement
Difference in cross-validated AUC between a prespecified clinical model with the baseline microbial biomarker added and the same model without the biomarker, for EFI improvement by day 7. The difference will be calculated as the combined-model AUC minus the clinical-model AUC using identical participant-level validation folds. Positive values indicate additional discrimination provided by the biomarker.
Time frame: Baseline (within 48 hours of T0) and day 7
Change in Cross-Validated AUC After Adding the Baseline Microbial Biomarker to a Clinical Model for Enteral Energy Target Achievement by Day 7
Difference in cross-validated AUC between a prespecified clinical model with the baseline microbial biomarker added and the same model without the biomarker, for achievement of an actual enteral energy intake of at least 20 kcal/kg/day by day 7. Parenteral energy intake is excluded. The difference will be calculated as the combined-model AUC minus the clinical-model AUC using identical participant-level validation folds.
Time frame: Within 7 days after enrollment
Adjusted Odds Ratio for 28-Day All-Cause Mortality per Standard Deviation Increase in the Baseline Microbial Biomarker Score
Adjusted odds ratio for death from any cause by day 28 per one standard deviation increase in the baseline microbial biomarker score. Logistic regression will adjust for prespecified clinical covariates. Results will be reported with 95% confidence intervals. Mortality will be established using hospital records and telephone follow-up when necessary.
Time frame: Within 28 days after enrollment
Adjusted Odds Ratio for 90-Day All-Cause Mortality per Standard Deviation Increase in the Baseline Microbial Biomarker Score
Adjusted odds ratio for death from any cause by day 90 per one standard deviation increase in the baseline microbial biomarker score. Logistic regression will adjust for prespecified clinical covariates. Results will be reported with 95% confidence intervals. Mortality will be established using hospital records and telephone follow-up when necessary.
Time frame: Within 90 days after enrollment
Percentage of Microbial Biomarker Components With Concordant Associations With Day 7 Feeding Improvement in Independent Cohorts
Percentage of evaluable components of the locked microbial biomarker showing the same direction of association with day 7 EFI improvement in the study cohort and eligible independent cohorts. The percentage will equal the number of concordant components divided by the total number of evaluable components, multiplied by 100. Results will be reported separately for each external cohort. If no cohort with comparable feeding outcomes is available, this outcome will be reported as not evaluable.
Time frame: Baseline and day 7
Number of Microbial Taxa Meeting High-Priority Criteria for Subsequent Experimental Validation
Number of candidate microbial taxa assigned to the highest priority tier using prespecified criteria covering feature-selection stability, associations with feeding outcomes, cross-cohort reproducibility, and consistency with functional and metabolic profiles. Classification thresholds will be established before ranking. Species-level identities will be reported only when supported by sequencing resolution.
Time frame: Baseline, days 3-5, and day 7
Plan to share: No
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Union Hospital, Tongji Medical College, Huazhong University of Science and Technology