Gut Microbiota Analysis in IAI Patients With Sepsis-associated Liver Dysfunction
Condition: Gut Microbiota; Intra-abdominal Infections; Acute Gastrointestinal Injury; Sepsis-associated Liver Dysfunction
MeSH terms: Sepsis; Toxemia; Intraabdominal Infections; Liver Diseases
Study type: Observational [Patient Registry]

Summary: 
      With the rapid development of intensive care medicine, the mortality of patients with sepsis
      has decreased over the past decade, but it is still the leading cause of death in intensive
      care unit (ICU). As an important immune and metabolic organ, the liver plays a crucial role
      in host defense against invading pathogens and endotoxins, as well as maintenance of
      metabolic and immunological homeostasis. Some studies indicate that sepsis-associated liver
      dysfunction (SALD) has a substantial impact on the severity and prognosis of sepsis.

      Intra-abdominal infections (IAI) are the second leading source of infection for sepsis after
      pneumonia in ICU, and are often related to high morbidity and mortality rates. Studies had
      found that the incidence of SALD in IAI patients was considerably higher than that of general
      population with sepsis. Moreover, the incidence of acute gastrointestinal injury (AGI) in IAI
      patients was also much higher than that in sepsis patients with other site infections, as
      well as the degree of AGI was more serious according to guidelines proposed by the European
      Society of Intensive Care Medicine (ESICM) in 2012. IAI can directly cause AGI, and a subset
      of patients usually progress to increased intra-abdominal pressure, which further aggravates
      AGI.

      The pathogenesis of SALD remains unclear so far, and its mechanism is complicated and
      elusive. Nevertheless, the unique anatomical structure of the liver make it has close
      association with the gut, growing evidence indicates that the gut microbiota and related
      metabolites are related to several liver disease. In case of sepsis, gut microbiota disorder
      and low microbial diversity can cause severe liver injury. An important mechanism for this
      phenotype is the gut-liver axis, which refers to gut microbial metabolites and nutrients are
      transported to the liver through the portal vein and hepatic artery to maintain the healthy
      metabolism of liver.

      Therefore, we initially conducted a retrospective study to investigate the relationship
      between the occurrence of AGI and SALD among IAI patients. Subsequently, a prospective study
      was performed to analyze and compare the diversity and composition of gut microbiota in IAI
      patients with or without SALD, respectively, and the dynamic changes in the gut microbiota
      during the first week after ICU admission were also investigated.
    

Detailed description: 
      A retrospective cohort study was conducted involving sepsis patients with IAI treated in ICU
      department of Nanjing Drum Tower Hospital between April 2020 to April 2020. Adult patients
      (≥18 years) with IAI who met the criteria for sepsis 3.0 were included. The exclusion
      criteria included: discharged or died within 48 hours after ICU admission; known serious
      chronic liver disease, such as decompensated cirrhosis and end-stage liver cancer;
      hospitalization due to primary hepatobiliary disease, such as trauma, hepatitis,
      cholelithiasis, etc; other causes of liver injury include: drugs, poisons, etc; and
      pregnancy.The following data were collected within 24 hours after ICU admission: demographic
      Information: age, sex and comorbidity; the score of disease severity: Acute Physiology and
      Chronic Health Evaluation (APACHE) II score; Sequential Organ Failure Assessment (SOFA)
      score; the primary site of abdominal infection: upper or lower gastrointestinal tract,
      pancreas and others; laboratory indicators: white blood cells (WBC), percentage of
      neutrophils (N%), C-reactive protein (CRP), procalcitonin (PCT), human leukocyte antigen
      (HLA)-DR. Date during hospitalization were also collected: complications: respiratory
      failure, septic shock, acute kidney injury (AKI) and AGI; pathogenic bacteria of ascites
      culture; bacteremia or not; total parenteral nutrition (TPN) was given or not. Prognostic
      indicators included ICU length of stay (LOS), hospital LOS, ICU mortality, in-hospital
      mortality, and 28-day mortality were also recorded.SALD was diagnosed when the level of serum
      alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1000IU/L, or total
      bilirubin (TBIL) level >3mg/dL during hospitalization. IAI was diagnosed according to the
      2005 International Sepsis Forum Consensus Conference. Briefly, the patient present with
      abdominal symptoms and signs, such as fever (≥38℃), tenderness, rebound pain, etc; elevated
      inflammatory indicators in peripheral blood and positive culture of intra-abdominal
      specimens. Sepsis 3.0 and septic shock were diagnosed according to Third International
      Consensus Definition for Sepsis and Septic Shock in 2016. AKI was diagnosed according to the
      Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines. AGI diagnosis
      and grading are based on the ESICM recommendations in 2012.To further clarify the
      relationship between gut microbiota and SALD, we conducted a prospective observational study
      between April 2020 to April 2020 in our center. Eligible patients must fulfill the same
      criteria as above. Other exclusion criteria also include: with expected ICU LOS < 1 week; had
      participated in any other clinical trial; underwent enterostomy surgery; had chronic
      inflammatory bowel disease. All eligible patients were given antibiotics therapy, actively
      control infection source by puncture drainage or surgery if necessary, as well as other
      supportive therapy to maintain organ function. Moreover, fecal samples were collected per
      patient on days 1,3 and 7 after ICU admission. Other data collection and the definition of
      related diseases are the same as the above.
    

Intervention name(s): Gut microbiota Analysis
Intervention type(s): Behavioral
Intervention description(s): fecal samples were collected per patient on days 1,3 and 7 after ICU admission. All eligible patients were given antibiotics therapy, actively control infection source by puncture drainage or surgery if necessary, as well as other supportive therapy to maintain organ function.
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        All patients diagnosed with intra-abdominal infection (IAI). IAI was diagnosed according to
        the 2005 International Sepsis Forum Consensus Conference. Briefly, the patient present with
        abdominal symptoms and signs, such as fever (≥38℃), tenderness, rebound pain, etc; elevated
        inflammatory indicators in peripheral blood and positive culture of intra-abdominal
        specimens.
      
Biospecimen description: 
      fecal samples were collected per patient on days 1,3 and 7 after ICU admission. All fecal
      samples were collected in sterile tubes and then stored at -80°C refrigerator.

      The gut microbiota analysis was performed by LC-Bio Technology Co., Ltd. (Hangzhou, China)