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.
Age ≥18 years.
Receiving care in the ICU at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Meeting the protocol-defined criteria for refractory enteral feeding intolerance (rEFI): inability 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.
A spontaneously passed stool sample can be obtained, or a rectal swab can be safely collected, within the permitted baseline sampling window.
Pregnancy or reasonable grounds for the investigator to suspect pregnancy. Active inflammatory bowel disease, major gastrointestinal surgery, or any other condition within the past 3 months that significantly alters intestinal anatomy and affects interpretation of the study findings.
Receipt of fecal microbiota transplantation before ICU admission.
Active gastrointestinal bleeding, severe coagulopathy, anorectal surgery or lesions, or other conditions that make rectal swab collection unsafe, together with an inability to obtain a spontaneously passed stool sample within the specified sampling window.
Expected death within 24 hours, with informed consent and baseline procedures unable to be completed without interfering with emergency care.
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.
Case-only
Prospective
Naturally Occurring Exposures
Other interventionSerial 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.
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.
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.
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.
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.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
