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Microbiome and Enteric Signatures in Sepsis-associated Hepatorenal Injury (MESH)

2026年7月28日 更新者：First Affiliated Hospital of Zhejiang University

The Impact of Gut Microbiota on Sepsis-Associated Acute Hepatorenal Injury: A Prospective, Multicenter, Observational Study

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.

調査の概要

状態

募集

条件

研究の種類

観察的

入学 (推定)

200

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究場所

  • 中国
    • Zhejiang
      • Hangzhou、Zhejiang、中国、310000
        • 募集
        • First Affiliated Hospital of Zhejiang University School of Medicine
        • コンタクト：

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

はい

サンプリング方法

非確率サンプル

調査対象母集団

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.

説明

Inclusion Criteria:

-

For Sepsis Patients:

  1. Age ≥ 18 years；
  2. 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).
  3. Diagnosed with sepsis within 24 hours prior to enrollment.
  4. Informed consent signed by the patient or a legally authorized representative.

For Healthy Volunteers:

  1. Age ≥ 18 years.
  2. No chronic underlying diseases (including liver, kidney, gastrointestinal, or immune-related disorders).
  3. No use of antibiotics or probiotics, and no history of acute infection within 1 month prior to enrollment (to ensure baseline consistency).
  4. Informed consent signed by the volunteer.

Exclusion Criteria:

  1. History of chronic liver disease (e.g., cirrhosis, chronic hepatitis B/C, autoimmune hepatitis, hepatic carcinoma).
  2. History of chronic kidney disease (e.g., glomerulonephritis, IgA nephropathy).
  3. History of inflammatory bowel disease (including ulcerative colitis and Crohn's disease) or previous major intestinal resection.
  4. Patients with malignant tumors currently receiving chemotherapy or radiotherapy.
  5. Expected survival time of less than 72 hours.
  6. Pregnant or lactating women.
  7. Concurrent participation in other interventional clinical trials.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

コホートと介入

グループ/コホート
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.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Association of Baseline Gut Microbial Alpha Diversity With Sepsis-Associated Acute Kidney Injury
時間枠：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.
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
時間枠：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.
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.

二次結果の測定

結果測定
メジャーの説明
時間枠
Association of Baseline Fecal Microbial Beta Diversity With Sepsis-Associated Liver Injury
時間枠：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 according to the prespecified SALI criteria. Baseline fecal microbial beta diversity will be assessed using Bray-Curtis dissimilarity (unitless), calculated from metagenomic sequencing data and bioinformatic taxonomic profiling of a stool sample collected on Day 0 or, if unavailable, within 24 hours after sepsis diagnosis. Differences in baseline fecal microbial community composition between the SALI group and the sepsis control group will be evaluated using permutational multivariate analysis of variance (PERMANOVA) and reported as the PERMANOVA R-squared value (R²; unitless).
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
時間枠：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 beta diversity will be assessed using Bray-Curtis dissimilarity (unitless), calculated from metagenomic sequencing data and bioinformatic taxonomic profiling of a stool sample collected on Day 0 or, if unavailable, within 24 hours after sepsis diagnosis. Differences in baseline fecal microbial community composition between the S-AKI group and the sepsis control group will be evaluated using permutational multivariate analysis of variance (PERMANOVA) and reported as the PERMANOVA R-squared value (R²; unitless).
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
時間枠：Days 0, 3-5, 7-10, and 14-20 after sepsis diagnosis.
Total plasma short-chain fatty acid concentration will be reported as a single aggregate value at each prespecified time point. It will be calculated as the sum of plasma acetate, propionate, and butyrate concentrations, all measured in μmol/L by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
Days 0, 3-5, 7-10, and 14-20 after sepsis diagnosis.
Plasma Indoxyl Sulfate Concentration
時間枠：Days 0, 3-5, 7-10, and 14-20 after sepsis diagnosis.
Plasma indoxyl sulfate concentration will be measured by UPLC-MS/MS and reported in μmol/L at each prespecified time point.
Days 0, 3-5, 7-10, and 14-20 after sepsis diagnosis.
Fecal Calprotectin Concentration
時間枠：Days 0, 3-5, 7-10, and 14-20 after sepsis diagnosis.
Fecal calprotectin concentration will be measured using a validated fecal calprotectin immunoassay and reported in μg/g of stool at each prespecified time point.
Days 0, 3-5, 7-10, and 14-20 after sepsis diagnosis.
28-Day All-Cause Mortality
時間枠：Day 28 after sepsis diagnosis.
All-cause mortality within 28 days after sepsis diagnosis, reported as the percentage (%) of enrolled participants who die. Vital status will be ascertained from medical records and follow-up contact.
Day 28 after sepsis diagnosis.
Longitudinal Change in Fecal Microbial Alpha Diversity Among Patients With Sepsis
時間枠：Day 0 through Days 14-20 after sepsis diagnosis, with assessments on Day 0, Days 3-5, Days 7-10, and Days 14-20.
Fecal microbial alpha diversity will be measured using the Shannon diversity index (unitless), calculated from metagenomic sequencing data and bioinformatic analysis of stool samples collected on Day 0, Days 3-5, Days 7-10, and Days 14-20 after sepsis diagnosis. Longitudinal changes in the Shannon diversity index among patients with sepsis will be evaluated using a linear mixed-effects model accounting for repeated measurements within participants. The outcome will be reported as the model-estimated mean Shannon diversity index (unitless) at each prespecified time point. Healthy volunteers will not be included in this longitudinal analysis because stool samples are collected only once at enrollment.
Day 0 through Days 14-20 after sepsis diagnosis, with assessments on Day 0, Days 3-5, Days 7-10, and Days 14-20.

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

First Affiliated Hospital of Zhejiang University

協力者

Ningbo Medical Center Lihuili Hospital
The Second Affiliated Hospital of Jiaxing University
Lin'an Traditional Chinese Medicine Hospital
Taizhou Enze Medical Center Group

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2026年2月15日

一次修了 (推定)

2028年2月14日

研究の完了 (推定)

2028年2月14日

試験登録日

最初に提出

2026年7月15日

QC基準を満たした最初の提出物

2026年7月28日

最初の投稿 (実際)

2026年7月29日

学習記録の更新

投稿された最後の更新 (実際)

2026年7月29日

QC基準を満たした最後の更新が送信されました

2026年7月28日

最終確認日

2026年2月1日

詳しくは

本研究に関する用語

追加の関連 MeSH 用語

その他の研究ID番号

  • IIT20260155B-R2

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いいえ

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いいえ

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