AUTHOR=Zhang Beiyuan , Chen Xiancheng , He Chenhang , Su Ting , Cao Ke , Li Xiaoyao , Duan Jianfeng , Chen Ming , Zhu Zhanghua , Yu Wenkui 

TITLE=Acute gastrointestinal injury and altered gut microbiota are related to sepsis-induced cholestasis in patients with intra-abdominal infection: a retrospective and prospective observational study

JOURNAL=Frontiers in Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1144786

DOI=10.3389/fmed.2023.1144786

ISSN=2296-858X

ABSTRACT=<sec id="sec1"><title>Background</title><p>Sepsis-associated liver dysfunction (SALD) has high incidence and mortality in patients with intra-abdominal infection (IAI). The associations between acute gastrointestinal injury (AGI), gut microbiota, and SALD were evaluated in patients with IAI.</p></sec><sec id="sec2"><title>Methods</title><p>A retrospective study was conducted to assess the relationship between AGI and SALD in patients with IAI. Patients were divided into non-SALD and sepsis-induced cholestasis (<italic>SIC</italic>) groups, which is a subtype of SALD. <italic>SIC</italic> was defined as total bilirubin &gt;2 mg/dL. AGI incidences between the two groups were compared using Chi-square test. Subsequently, a prospective study was conducted to investigate the gut microbiota differences between patients without SALD and those with <italic>SIC</italic>. Fecal samples were collected on days 1, 3, and 7 after admission to analyze changes in gut microbiota using 16S ribosomal ribonucleic acid sequencing.</p></sec><sec id="sec3"><title>Results</title><p>One hundred thirty-four patients with IAI were included retrospectively, with 77 SALD and 57 non-SALD cases. Among patients with SALD, 71 were diagnosed with <italic>SIC</italic>. Patients with <italic>SIC</italic> had a higher incidence of AGI compared to those without SALD (28.07% vs. 56.34%, <italic>p</italic> &lt; 0.05), and a severity-dependent relationship was found between AGI grade and <italic>SIC</italic> occurrence. Subsequently, 20 patients with IAI were recruited prospectively, with 10 patients each assigned to the non-SALD and <italic>SIC</italic> groups. Patients with <italic>SIC</italic> had a more severe gut microbiota disorder on day 7 than those without SALD, including lower microbiota diversities, decreased abundance of <italic>Firmicutes</italic> and <italic>Bacteroidetes,</italic> and increased abundance of <italic>Proteobacteria</italic> and <italic>Actinobacteria</italic> at the phylum level. Furthermore, <italic>Burkholderia − Caballeronia − Paraburkholderia</italic> and <italic>Delftia,</italic> the two most abundant genera, were significantly higher in the <italic>SIC</italic> group than in the non-SALD group. Functional prediction analysis showed that the top three KEGG pathways were ribosome, pyrimidine metabolism, and the two-component system. During the first week, the abundance of <italic>Proteobacteria</italic> decreased significantly, whereas <italic>Cyanobacteria</italic> increased in the non-SALD group; however, the phyla taxa did not change significantly in the <italic>SIC</italic> group.</p></sec><sec id="sec4"><title>Conclusion</title><p>There exists a severity-dependent relationship between AGI grade and <italic>SIC</italic> occurrence in adult patients with IAI. A severe gut microbiota disorder was discovered in <italic>SIC</italic> during the first week of the intensive care unit stay.</p></sec>