4.7 Article

Enteric dysbiosis is associated with sepsis in patients

Journal

FASEB JOURNAL
Volume 33, Issue 11, Pages 12299-12310

Publisher

FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201900398RR

Keywords

gut microbiota; metabolomics; metaproteomics

Funding

  1. National Science Funds for Distinguished Young Scholars of the Guangdong Province [2016A030306043]
  2. Young Pearl Scholar of the Guangdong Province Award [81873926]
  3. National Natural Science Foundation of China (NSFC) [81873926]
  4. NSFCGuangdong Joint Fund of China [U1601225]
  5. Key Science and Technology Projects Program of Guangzhou City [201607020016]
  6. Clinical Research Startup Program of Southern Medical University by High-Level University Construction Funding of the Guangdong Provincial Department of Education [LC2019ZD014]

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Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to microbial infection. For decades, the potential role of gut microbiota in sepsis pathogenesis has been revealed. However, the systemic and functional link between gut microbiota and sepsis has remained unexplored. To address this gap in knowledge, we carried out systematic analyses on clinical stool samples from patients with sepsis, including 16S rDNA sequencing, metabolomics, and metaproteomics analyses. In addition, we performed fecal microbiota transplantation from human to mice to validate the roles of gut microbiota on sepsis progression. We found that the composition of gut microbiota was significantly disrupted in patients with sepsis compared with healthy individuals. Besides, the microbial functions were significantly altered in septic feces as identified by metabolomics and metaproteomics analyses. Interestingly, mice that received septic feces exhibited more severe hepatic inflammation and injury than mice that received healthy feces after cecal ligation and puncture. Finally, several strains of intestinal microbiota and microbial metabolites were corelated with serum total bilirubin levels in patients with sepsis. Taken together, our data indicated that sepsis development is associated with the disruption of gut microbiota at both compositional and functional levels, and such enteric dysbiosis could promote organ inflammation and injury during sepsis.

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