Enteric dysbiosis is associated with sepsis in patients

Abstract

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.—Liu, Z., Li, N., Fang H., Chen, X., Guo, Y., Gong, S., Niu, M., Zhou, H., Jiang, Y., Chang, P., Chen, P. Enteric dysbiosis is associated with sepsis in patients. FASEB J. 33, 12299‐12310 (2019). http://www.fasebj.org

The gut microbiome’s role in the development, maintenance, and outcomes of sepsis

“…Animal studies have demonstrated conflicting results regarding specific inflammatory pathways, reflecting the complexity of the relationship between the gut microbiome and the immune system. For example, in a mouse model of Streptococcus pneumoniae sepsis, pre-treatment with oral antibiotics prior to sepsis onset was associated with lower levels of lung TNF-α, a pro-inflammatory cytokine [25], whereas others have shown the opposite effect of gut microbiome depletion on TNF-α [21,22,[37][38][39]. Despite differences in specific cytokine expression between studies, the overall effect of alteration of normal gut microbiome structure prior to sepsis onset appears to be a more robust inflammatory response to sepsis [21,22,25,[37][38][39][40][41].…”

“…Several prospective cohort studies have identified an association between decreased gut microbiome diversity in sepsis and higher relative abundance of potentially pathogenic bacteria including aerobic gram negatives [39,46,56,[59][60][61]. The earliest study to examine microbiome changes in critically ill patients showed that patients with systemic inflammatory response syndrome (SIRS) had lower abundance of obligate anaerobes, and their gut microbiomes were enriched with potential pathogens such as Staphylococcus and Pseudomonas [46].…”

Gut-liver crosstalk in sepsis-induced liver injury

“…Schnabl has shown that gut dysbiosis seems to participate in the disruption of intestinal epithelial tight junctions and imbalance in the proliferation and apoptosis of IECs [13]. Recent research has found that gut microbial dysbiosis leads to serious liver injury in mice after cecal ligation and puncture [47]. Several mechanisms may answer this phenotype.…”

Fecal microbiota transplantation reconstructs the gut microbiota of septic mice and protects the intestinal mucosal barrier

“…The syndrome can be induced by a wide variety of microbes and, by de nition, involves a maladaptive response to a pathogen [5]. The gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, by both driving and perpetuating multiple organ dysfunction [8,9].…”