The Impact of Gut Microbiota on Sepsis-Associated Acute Hepatorenal Injury: A Prospective, Multicenter, Observational Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Association of Baseline Gut Microbial Alpha Diversity With Sepsis-Associated Acute Kidney Injury
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Association of Baseline Gut Microbial Alpha Diversity With Sepsis-Associated Acute Kidney Injury
时间窗: 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.
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.
Association of Baseline Gut Microbial Alpha Diversity With Sepsis-Associated Liver Injury
时间窗: 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.
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.
次要结局
- 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.)
- 28-Day All-Cause Mortality(Day 28 after sepsis diagnosis.)
- Longitudinal Change in Fecal Microbial Alpha Diversity Among Patients With Sepsis(Day 0 through Days 14-20 after sepsis diagnosis, with assessments on Day 0, Days 3-5, Days 7-10, and Days 14-20.)