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NCT07735182

Overview

NCT ID: NCT07735182
Lead Sponsor: First Affiliated Hospital of Zhejiang UniversityOTHER
Official Title: The Impact of Gut Microbiota on Sepsis-Associated Acute Hepatorenal Injury: A Prospective, Multicenter, Observational Study
Brief Summary: Sepsis is a major cause of morbidity and mortality in intensive care units. Sepsis-associated liver injury (SALI) and sepsis-associated acute kidney injury (S-AKI) are common complications associated with adverse clinical outcomes. Altered gut microbial diversity, microbial metabolites, intestinal barrier dysfunction, and systemic inflammation may contribute to hepato-renal injury during sepsis; however, prospective longitudinal evidence in patients with SALI and S-AKI remains limited.

This prospective, multicenter, longitudinal observational cohort study will enroll adult patients with sepsis across five medical centers and healthy adult volunteers as a baseline reference cohort. For patients with sepsis, stool and blood samples will be collected on Day 0, Days 3-5, Days 7-10, and Days 14-20 after sepsis diagnosis. Healthy volunteers will provide a single baseline stool and blood sample at enrollment. Fecal microbial alpha diversity and community structure will be assessed by metagenomic sequencing and bioinformatic analysis. Plasma metabolites, including total short-chain fatty acids, indoxyl sulfate, and additional targeted plasma metabolites, will be measured by ultra-high-performance liquid chromatography-tandem mass spectrometry. Intestinal barrier and clinical biomarkers will also be assessed.

The primary objectives are to evaluate the associations between baseline fecal microbial alpha diversity, measured by the Shannon diversity index, and SALI and S-AKI occurring within 7 days after sepsis diagnosis. Secondary objectives include evaluating the associations of baseline fecal microbial beta diversity with SALI and with S-AKI occurring within 7 days after sepsis diagnosis, characterizing longitudinal changes in fecal microbial alpha diversity, measuring plasma metabolite and intestinal biomarker concentrations at prespecified time points, and assessing 28-day all-cause mortality. Exploratory multi-omics analyses will evaluate Proteobacteria and additional microbial taxa, microbial functional genes, metabolites, and host biomarkers. This study aims to identify candidate biomarkers and biological pathways relevant to hepato-renal injury in sepsis.

Status and Timeline

Status: Recruiting
Last Update Posted: Jul 29, 2026Actual
Start Date: Feb 15, 2026Actual
Primary Completion Date: Feb 14, 2028Estimated
Completion Date

Participation Criteria

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers?: Yes
Eligibility Criteria: Inclusion Criteria:

-

For Sepsis Patients:

Age ≥ 18 years；

Admitted to the Intensive Care Unit (ICU) and meets the Sepsis-3 diagnostic criteria (an acute change in total Sequential Organ Failure Assessment [SOFA] score ≥ 2 points consequent to the infection).

Diagnosed with sepsis within 24 hours prior to enrollment.

Informed consent signed by the patient or a legally authorized representative.

For Healthy Volunteers:

Age ≥ 18 years.

No chronic underlying diseases (including liver, kidney, gastrointestinal, or immune-related disorders).

No use of antibiotics or probiotics, and no history of acute infection within 1 month prior to enrollment (to ensure baseline consistency).

Informed consent signed by the volunteer.

Exclusion Criteria:

History of chronic liver disease (e.g., cirrhosis, chronic hepatitis B/C, autoimmune hepatitis, hepatic carcinoma).

History of chronic kidney disease (e.g., glomerulonephritis, IgA nephropathy).

History of inflammatory bowel disease (including ulcerative colitis and Crohn's disease) or previous major intestinal resection.

Patients with malignant tumors currently receiving chemotherapy or radiotherapy.

Expected survival time of less than 72 hours.

Pregnant or lactating women.

Concurrent participation in other interventional clinical trials.

Study Plan

Study Type: Observational
Phase: No data available
Enrollment: 200Estimated
Primary Purpose: No data available
Allocation: No data available
Interventional Model: No data available
Masking: No data available

Contacts and Locations

Central Contacts: Wenqiao Yu, PhDContact
yuwenqiao1980@zju.edu.cn+86-18868787588

Similar Studies

Participant Group/Arms

Sepsis Patients

Adult patients (age ≥ 18 years) admitted to the ICU who meet the Sepsis-3.0 diagnostic criteria within 24 hours after sepsis diagnosis. This cohort will be longitudinally monitored with biospecimen collection at four time points (Day 0, 3-5, 7-10, and 14-20). Based on clinical progression from Day 0 through Day 7 after sepsis diagnosis, participants will be further categorized into subgroups: Sepsis Control (neither SALI nor S-AKI from Day 0 through Day 7 after sepsis diagnosis), Sepsis-Associated Liver Injury (SALI), and Sepsis-Associated Acute Kidney Injury (S-AKI) for comparative analysis. Participants meeting criteria for both SALI and S-AKI will be included in both outcome-specific analyses.

Healthy Volunteers

Healthy adult volunteers (age ≥ 18 years) without chronic underlying diseases (e.g., liver, kidney, or gastrointestinal disorders) and no history of antibiotic or probiotic use within the past month. This cohort serves as a baseline control to establish the normal range for gut microbiota and metabolic profiles; biospecimens will be collected only once at the time of enrollment.