Microbiome and Enteric Signatures in Sepsis-associated Hepatorenal Injury

NCT07735182 | Recruiting

• 1 other identifier: IIT20260155B-R2
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis; Acute Kidney Injury Due to Sepsis; Gastrointestinal Microbiome; Sepsis-Associated Liver Injury; Intensive Care Medicine

Outcome Measures

Primary Outcomes (2)

• Association of Baseline Gut Microbial Alpha Diversity With Sepsis-Associated Acute Kidney Injury

  Sepsis-associated acute kidney injury (S-AKI) occurring from Day 0 through Day 7 after sepsis diagnosis, assessed according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria using serum creatinine and urine output obtained from routine clinical laboratory testing and medical records. Baseline fecal microbial alpha diversity will be measured using the Shannon diversity index (unitless), calculated from metagenomic sequencing and bioinformatic analysis of a stool sample collected on Day 0 or, if unavailable, within 24 hours after sepsis diagnosis. The association between the Shannon diversity index and S-AKI will be estimated using multivariable logistic regression and reported as an adjusted odds ratio per 1-unit increase in the Shannon diversity index.

  Baseline stool sample collected on Day 0 or within 24 hours after sepsis diagnosis; S-AKI assessed from Day 0 through Day 7 after sepsis diagnosis.

• Association of Baseline Gut Microbial Alpha Diversity With Sepsis-Associated Liver Injury

  Sepsis-associated liver injury (SALI) occurring from Day 0 through Day 7 after sepsis diagnosis, assessed using routine clinical laboratory measurements. SALI is defined by at least one of the following: total bilirubin (TBIL) \>2 mg/dL and international normalized ratio (INR) \>1.5; alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN); alkaline phosphatase (ALP) ≥2 times ULN; or ALT ≥3 times ULN with TBIL ≥2 times ULN. Baseline fecal microbial alpha diversity will be measured using the Shannon diversity index (unitless), calculated from metagenomic sequencing and bioinformatic analysis of a stool sample collected on Day 0 or, if unavailable, within 24 hours after sepsis diagnosis. The association between the Shannon diversity index and SALI will be estimated using multivariable logistic regression and reported as an adjusted odds ratio per 1-unit increase in the Shannon diversity index.

  Baseline stool sample collected on Day 0 or within 24 hours after sepsis diagnosis; SALI assessed from Day 0 through Day 7 after sepsis diagnosis.

Secondary Outcomes (7)

• Association of Baseline Fecal Microbial Beta Diversity With Sepsis-Associated Liver Injury

  Baseline stool sample collected on Day 0 or within 24 hours after sepsis diagnosis; SALI assessed from Day 0 through Day 7 after sepsis diagnosis.

• Association of Baseline Fecal Microbial Beta Diversity With Sepsis-Associated Acute Kidney Injury

  Baseline stool sample collected on Day 0 or within 24 hours after sepsis diagnosis; S-AKI assessed from Day 0 through Day 7 after sepsis diagnosis.

• Total Plasma Short-Chain Fatty Acid Concentration

  Days 0, 3-5, 7-10, and 14-20 after sepsis diagnosis.

• Plasma Indoxyl Sulfate Concentration

  Days 0, 3-5, 7-10, and 14-20 after sepsis diagnosis.

• Fecal Calprotectin Concentration

  Days 0, 3-5, 7-10, and 14-20 after sepsis diagnosis.

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population comprises two distinct groups recruited from multiple clinical centers. The primary clinical cohort consists of critically ill adult patients (aged ≥ 18 years) admitted to the Intensive Care Unit (ICU) who are diagnosed with sepsis according to the Sepsis-3 criteria and enrolled within 24 hours after sepsis diagnosis. This cohort will be monitored to observe longitudinal changes in the gut microbiome and the occurrence of sepsis-associated liver injury (SALI) and sepsis-associated acute kidney injury (S-AKI) from Day 0 through Day 7 after sepsis diagnosis. The secondary control cohort consists of healthy adult volunteers recruited from the community. These volunteers have no history of chronic underlying diseases or recent antibiotic/probiotic use, and they serve to establish baseline healthy profiles for the gut microbiome and circulating metabolites.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• Taizhou Enze Medical Center Group: collaborator
• The Second Affiliated Hospital of Jiaxing University: collaborator
• Lin'an Traditional Chinese Medicine Hospital: collaborator
• Ningbo Medical Center Lihuili Hospital: collaborator

Study Sites (1)

First Affiliated hospital of zhejiang university school of medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

The study will collect and retain the following types of biospecimens from sepsis patients and healthy volunteers: Stool Samples, Plasma Samples, and Whole Blood (TriZol-lysed).

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Wenqiao Yu, PhD

CONTACT

+86-18868787588; yuwenqiao1980@zju.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2026
• First Posted: July 29, 2026
• Study Start: February 15, 2026
• Primary Completion (Estimated): February 14, 2028
• Study Completion (Estimated): February 14, 2028
• Last Updated: July 29, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)