Altered Gut Microbiota Taxonomic Compositions of Patients With Sepsis in a Pediatric Intensive Care Unit

Abstract

Background: The gut is thought to play an important role in the pathogenesis of sepsis. Changes in the gut microbiota are closely related to the occurrence and development of human diseases, but few studies have focused on taxonomic composition of gut microbiota in septic patients. Knowledge of changes in the gut microbiota is a key issue in intensive care. Clinicians must understand how an altered gut microbiota affects the susceptibility and prognosis of septic patients. Measurements and Main Results: In the single-center case control study, 20 septic patients and 20 healthy children were recruited. The taxonomic composition of gut microbiota was determined via 16S rRNA gene sequencing. Gut microbiota diversity in children with sepsis was significantly reduced compared with that in healthy children. The taxonomic composition of gut microbiota can effectively distinguish children with sepsis from healthy children. Thirteen taxa of gut microbiota were significantly increased in the guts of children with sepsis compared with those of healthy children. The increased abundances of Enterococcaceae, Enterococcus, and Enterococcus durans in gut of septic patients were significantly positively correlated with blood inflammation indicators CRP and WBC. The abundances of seven bacteria were significantly decreased in the guts of septic children compared with those of healthy children. The decreased abundance of Bifidobacteriales in gut of septic patients is significantly negatively correlated with blood inflammation index WBC. A machine-learning classifier was built for distinguishing sepsis and achieved the AUC value of 81.25%. It shows that the composition of gut microbiota has certain potential for diagnosis of sepsis. Conclusions: Gut microbiota alterations in septic patients exhibit proliferation of opportunistic pathogenic bacteria, the massive reduction of the commensal flora, and the significant decrease in the diversity of the gut microbiota. Dysbiosis may also account for some changes in the inflammation indexes.

Keywords: 16S rRNA gene; Enterococcus; gut microbiota; sepsis; short-chain fatty acids.

Figure 1

Gut microbiota taxa distinguished sepsis patients from healthy children. (A) NMDS of taxonomic composition of gut microbiota of HC vs. SE. (B) Gut microbiota Shannon diversity of HC vs. SE. (C) In sepsis, gut microbiota Shannon diversity was positively correlated with CRP; (D) In sepsis, the gut abundance of Bifidobacteriales was negatively correlated with WBC. *p < 0.05.

Figure 2

The increase in the abundance of Enterococcaceae bacteria in gut of patients with sepsis is positively correlated with the increase in blood indicators WBC and CRP. (A–C) the increased abundance of gut Enterococcaceae (A), Enterococcus (B), and Enterococcus durans (C) is positively correlated with WBC, respectively; (D–F) the increased abundance of gut Enterococcaceae (D), Enterococcus (E), and Enterococcus durans (F) is positively correlated with CRP, respectively.

Figure 3

Significantly enriched taxa in the guts of sepsis patients are potential makers for diagnosis of sepsis. (A) importance of significantly enriched taxa; (B) AUC of significantly enriched taxa used for sepsis diagnosis.