Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2021; 27(19): 2376-2393
Published online May 21, 2021. doi: 10.3748/wjg.v27.i19.2376
Effects of sepsis and its treatment measures on intestinal flora structure in critical care patients
Xiao-Juan Yang, Dan Liu, Hong-Yan Ren, Xiao-Ya Zhang, Jun Zhang, Xiao-Jun Yang
Xiao-Juan Yang, Xiao-Ya Zhang, Jun Zhang, Xiao-Jun Yang, Department of Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Dan Liu, Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
Hong-Yan Ren, Shanghai Mobio Biomedical Technology Co., Shanghai 201318, China
Author contributions: Yang XJ was the guarantor and designed the study; Yang XJ participated in the acquisition, analysis, and interpretation of the data, and drafted the initial manuscript; Liu D, Zhang XY, Ren HY, and Zhang J revised the article critically for important intellectual content.
Supported by the National Key Research and Development Program of China, No. 2016YFD0400605.
Institutional review board statement: This study was approved by the Ethics Committee of the General Hospital of Ningxia Medical University (Ethical Approval No. 2016-258).
Informed consent statement: Informed consent was obtained from all patients or their immediate family members.
Conflict-of-interest statement: Yang XJ reports grants from Ministry of Science and Technology of the People's Republic of China, during the conduct of the study. Other authors have nothing to disclose.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Jun Yang, MM, Chief Doctor, Professor, Department of Critical Care Medicine, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan 750004, Ningxia Hui Autonomous Region, China. yxjicu@163.com
Received: January 16, 2021
Peer-review started: January 16, 2021
First decision: February 10, 2021
Revised: February 23, 2021
Accepted: April 22, 2021
Article in press: April 22, 2021
Published online: May 21, 2021

Sepsis is a common disease in intensive care units, with high morbidity and mortality. Intestinal microecology plays a vital part in the development and progression of this disease, possibly because sepsis and its treatment cause specific changes in the composition of the intestinal flora.


To investigate the characteristics of intestinal flora disturbance in sepsis patients treated with antibiotics.


In this prospective comparative study, we enrolled ten patients with sepsis (sepsis group), hospitalized in the Department of Critical Care Medicine of the General Hospital, Ningxia Medical University, China (a class IIIa general hospital) from February 2017 to June 2017; ten patients without sepsis hospitalized in the same period (non-sepsis group) and ten healthy individuals (control group) were also enrolled. Fecal samples collected from the three groups were subjected to 16S rRNA gene sequencing and the intestinal flora diversity, structure, and composition were determined. Additionally, the dynamics of the intestinal flora diversity, structure, and composition in sepsis patients were investigated via 16S rRNA gene sequencing of samples collected 0 d, 3 d, and 7 d after admittance to the intensive care unit. Correlations between the serum levels of procalcitonin, endotoxin, diamine oxidase, and D-lactic acid and the intestinal flora composition of sepsis patients were also investigated.


Compared with the healthy control group, sepsis and non-sepsis patients showed reduced intestinal flora α-diversity and a distinct flora structure, with Firmicutes as the dominant phylum, and significantly decreased proportions of Bacteroidetes, as well as Prevotella and Lachnospira, among other genera. Of note, the proportion of Enterococcus was significantly increased in the intestinal tract of sepsis patients. Interestingly, the α-diversity in the sepsis group decreased gradually, from days 1 to 7 of treatment. However, pairwise comparisons showed that both the diversity and structure of the intestinal flora were not significantly different considering the three different time points studied. Curiously, the serum levels of procalcitonin, endotoxin, diamine oxidase, and D-lactic acid in sepsis patients correlated with the prevalence of various bacterial genera. For example, the prevalence of Ruminococcus was positively correlated with serum procalcitonin, endotoxins, and diamine oxidase; similarly, the prevalence of Roseburia was positively correlated with serum procalcitonin, endotoxins, and D-lactic acid.


Sepsis patients in intensive care units show dysbiosis, lasting for at least 1 wk.

Keywords: Sepsis, Intestinal flora, 16S rRNA gene sequencing, Dynamic changes, Intestinal barrier index, Procalcitonin

Core Tip: As the largest reservoir of bacteria and endotoxins in the body, the intestinal tract is regarded as the “engine” of sepsis and multiple organ dysfunction. Through 16S rRNA gene sequencing, we observed that intestinal flora disturbance occurs in sepsis patients. Notably, here, we revealed for the first time the intestinal flora dynamic changes in sepsis patients during treatment. We found that the abundance of some intestinal bacteria in sepsis patients significantly correlated with infection- and intestinal barrier-related clinical indicators. These findings add to the understanding of the intestinal flora in sepsis, providing a basis for the reversal of dysbiosis.