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
Processing time: 116 Days and 19.3 Hours
ARTICLE HIGHLIGHTS
Research background

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 to the intestinal flora. However, there are few studies on the sepsis-related intestinal flora and its dynamic changes. An improved understanding of the status and degree of intestinal flora disturbances in sepsis patients is of great significance, to allow for the accurate evaluation of the disease condition and prognosis and to optimize the treatment measures.

Research motivation

Studies have shown a dose–response relationship between the degree of intestinal microecological disturbance and the incidence of subsequent severe sepsis. Critical illness leading to abnormal changes in the types, quantities, proportions, and locations of microorganisms in the intestinal flora may, thus, increase susceptibility to sepsis. Therefore, an improved understanding of the status and degree of intestinal flora disturbances in sepsis patients is of great clinical significance.

Research objectives

The main objective of this study was to investigate the characteristics of intestinal flora disturbance in sepsis patients treated with antibiotics.

Research methods

We enrolled ten patients with sepsis admitted to the intensive care unit (ICU), ten patients without sepsis admitted to the ICU in the same period, and ten healthy individuals (sepsis group, non-sepsis group, and control group, respectively). Using 16S rRNA gene sequencing technology, the fecal samples of the three groups were analyzed, and the intestinal flora diversity, structure, and composition were compared. The fecal samples of sepsis patients on days 1, 3, and 7 after ICU admittance were also analyzed, and the dynamics of the diversity, structure, and composition of the intestinal flora of sepsis patients were compared. Lastly, the serum levels of procalcitonin, endotoxin, diamine oxidase, and D-lactic acid were determined in sepsis patients on days 1, 3, and 7 after ICU admittance and correlated with the abundance of intestinal bacteria.

Research results

Sepsis patients showed a reduced intestinal flora α-diversity and a different flora structure, with Firmicutes as the dominant bacteria, and significantly decreased proportions of Bacteroidetes, as well as Prevotella, Lachnospira, and other genera. Enterococcus was significantly increased in the intestinal tract of sepsis patients. Additionally, from days 1 to 7 of treatment, the α-diversity of the intestinal flora in the sepsis group decreased gradually, although without statistical significance. Of note, some harmful bacteria such as Coprococcus disappeared, the abundance of beneficial bacteria such as Prevotella and Bifidobacterium decreased, while that of Enterococcus and other genera increased. Interestingly, the serum levels of procalcitonin, endotoxin, diamine oxidase, and D-lactic acid in sepsis patients correlated with the abundance of various intestinal bacterial genera.

Research conclusions

In this study, we report the characteristics of sepsis intestinal flora disturbance and reveal, for the first time, the dynamic characteristics of the intestinal flora in sepsis patients under antibiotic treatment. Altogether, our results suggest that sepsis patients in the ICU show intestinal microecological disorders, lasting for at least 1 wk. Importantly, we also show that the intestinal microecological disorder in sepsis patients is correlated with inflammation-related and intestinal barrier-related indexes. Of note, the sample size of this study was small, and thus, it is necessary to conduct larger and multicenter studies to support these findings.

Research perspectives

We plan to carry out animal studies to clarify the molecular mechanisms of intestinal flora disturbance in sepsis.