Food Intolerance Syndromes, Lung Infection, Microbial Colonization
Conditions
Brief summary
Multidrug-resistant organism (MDRO)-infection represents a substantial global health burden. In the intensive care unit (ICU), the concurrent administration of antibiotics, opioids, proton pump inhibitors (PPIs), vasoconstrictors, and parenteral nutrition-compounded by the intrinsic severity of critical illness-induces profound gut microbiota dysbiosis. Accumulating preclinical and clinical evidence indicates that such intestinal dysregulation may trigger distal immunomodulatory and microbial shifts in the lung via the gut-lung axis, thereby contributing to pulmonary microecological imbalance and impairing recovery trajectories. Although pulmonary microecology has garnered increasing scientific attention, the causal and temporal relationship between gut dysbiosis and the establishment or exacerbation of pulmonary microbial dysbiosis in MDRO-infecction remains inadequately characterized. As a result, it is currently unclear whether gut dysbiosis serves as a primary pathogenic driver, a disease-amplifying factor, or a secondary epiphenomenon in the context of MDRO-infecction-associated lung injury. Fecal microbiota transplantation (FMT) is a targeted microbiome-modulating intervention that involves the transfer of functionally diverse, minimally processed microbial communities from comprehensively screened healthy donors to restore ecological stability and functional redundancy in the recipient gut. Robust clinical data demonstrate that FMT effectively decolonizes the gastrointestinal tract of MDROs and reduces the incidence of secondary infections in immunocompetent, non-critically ill populations. Over the past decade, FMT has demonstrated reproducible efficacy in recurrent Clostridioides difficile infection and emerging promise in select extra-intestinal inflammatory conditions-highlighting its capacity as a mechanism-informed strategy for systemic host-microbe recalibration. Given the established role of the gut as a reservoir for enteric pathogens implicated in sepsis, hospital-acquired bloodstream infections, and ventilator-associated pneumonia (VAP), we propose a prospective, single-center, open-Label, randomized controlled trial (RCT) enrolling mechanically ventilated adults with MDRO-infeccted ventilated patients. The primary objective is to evaluate whether adjunctive FMT-delivered via nasojejunal tube-decrease 28-day mortality.
Interventions
OTHERFecal suspension
Prepare 300 ml of intestinal flora suspension from 100-150 g of feces. Subjects can eat and drink freely during preparation but must fast for at least 2 hours before FMT (water allowed). No food or water is permitted within 2 hours after FMT.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-70 years, inclusive, irrespective of sex or ethnic background; 2. Admission to the intensive care unit (ICU) within 24-48 hours; 3. Anticipated ICU length of stay of ≥7 days, as determined by the attending intensivist prior to enrollment; 4. Mechanically ventilated patients with MDRO infection; 5. Provision of written informed consent by the participant or legally authorized representative.
Exclusion criteria
1. Severe systemic infection during early resuscitation, accompanied by hemodynamic instability, profound tissue hypoperfusion, or life-threatening electrolyte and acid-base disturbances; 2. Clinician-assessed high risk of mortality within 5 days, or presence of formal treatment-limiting directives (e.g., do-not-intubate or do-not-resuscitate orders); 3. Active gastrointestinal bleeding or perforation consistent with severe intestinal barrier dysfunction; 4. Inability to tolerate enteral nutrition providing ≥50% of estimated caloric requirements due to structural intestinal pathology-including fibrotic bowel stenosis or high-output enterocutaneous fistula; 5. Planned abdominal surgery or history of abdominal surgery within 14 days prior to enrollment; 6. Confirmed diagnosis of fulminant colitis or toxic megacolon; 7. Neutropenia defined as absolute neutrophil count \< 1.5 × 10⁹/L; 8. Recent exposure to high-risk immunosuppressive or cytotoxic agents within the preceding 3 months, including but not limited to: rituximab (within 6 months), anthracyclines (e.g., doxorubicin), or systemic corticosteroids at ≥20 mg/day prednisone-equivalent dose for ≥4 consecutive weeks; 9. Pregnancy or lactation; 10. Participation in another interventional clinical trial within 3 months prior to enrollment or ongoing at the time of study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 28-day all-cause mortality rate | Within 28 days after inclusion | The mortality rate within 28 days after inclusion in the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dynamic changes in the total SOFA score | Within 24 hours before FMT intervention, and on days 1, 2, 3, 4, 5, 6 and 7 after FMT initiation | Change in total SOFA score from randomization (baseline) to 168 hours post-intervention |
| Changes in pulmonary microbiota diversity | Within 24 hours before FMT intervention, and at 72 hours after last FMT administration | Metagenomics profiling of BALF was conducted to compare the pulmonary microbiota between the two groups. Metagenomic sequencing will be performed to analyze the dynamic changes in α-diversity (Shannon index), β-diversity, and the relative abundance of specific microbial taxa, including the Firmicutes-to-Bacteroidetes ratio, and potential pathogens. |
| Changes in intestinal microbiota diversity | Within 24 hours before FMT intervention, and at 72 hours and 28 days after FMT initiation | Metagenomics profiling of rectal swabs was conducted to compare the gut microbiota between the two groups. Metagenomic sequencing will be performed to analyze the dynamic changes in α-diversity (Shannon index), β-diversity, and the relative abundance of specific microbial taxa, including the Firmicutes-to-Bacteroidetes ratio, and potential pathogens. |
| Alterations in serum metabolites | Within 24 hours before FMT intervention, and at 72 hours after FMT initiation | Serum samples were collected for metabolomics analysis to comprehensively examine the composition and changes of endogenous small molecule metabolites in the blood. |
| Change in the respiratory subscore of SOFA | Within 24 hours before FMT intervention, and on days 1, 2, 3, 4, 5, 6 and 7 after FMT initiation | Change in the respiratory subscore of SOFA from randomization (baseline) to 168 hours post-intervention |
| Correlation between gut microbiota and pulmonary microecology | Within 24 hours before FMT intervention, and at 72 hours after last FMT administration | The results obtained from metagenomic and metabolomic analyses of rectal swabs and BALF were used to explore the relationship between the two |
| Serum Citrulline | Within 24 hours before FMT intervention, and on days 1, 2, 3, 4, 5, 6 and 7 after FMT initiation | The determination of serum Citrulline is used as an indicator for evaluating intestinal barrier function. |
| Changes of APACHE II score | Within 24 hours before FMT intervention, and on days 1-7 after inclusion | The APACHE II scoring system serves as a critical tool for evaluating the clinical status and prognosis of ICU patients. This system comprises three components: the Acute Physiology Score (APS), the Age Score, and the Chronic Health Evaluation Score. The total score is derived by summing these three components. The theoretical maximum score is 71, with higher scores indicating more severe conditions. Notably, the APS encompasses 12 physiological parameters and introduces a formula for calculating the risk of death (R). By aggregating the R values of all patients and dividing by the total number of patients, the predicted mortality rate for the patient population can be estimated. |
| ICU mortality rate | From date of randomization until the date of discharge from the ICU or date of death from any cause during ICU stay, whichever came first, assessed up to 6 weeks | Mortality rate in ICU |
| In-hospital mortality rate | From date of randomization until the date of discharge from the hospital or date of death from any cause during hospitalization, whichever came first, assessed up to 6 weeks | Mortality rate during hospitalization |
| 90-day all-cause mortality rate | Within 90 days after inclusion | The mortality rate within 90 days after inclusion in the study |
| 90-day post-discharge readmission rate | Within 90 days after inclusion | The proportion of patients readmitted within 90 days after discharge among those enrolled in the study |
| Secondary pulmonary infection rate within 90 days of study enrollment | Within 90 days after inclusion | The incidence of secondary pulmonary infection within 90 days following study enrollment |
Countries
China
Outcome results
None listed