Fecal microbiota transplantation and short-chain fatty acids reduce sepsis mortality by remodeling antibiotic-induced gut microbiota disturbances

Xiran Lou; Jinfang Xue; Ruifei Shao; Yan Yang; Deyuan Ning; Chunyan Mo; Fuping Wang; Guobing Chen

doi:10.3389/fimmu.2022.1063543

Fecal microbiota transplantation and short-chain fatty acids reduce sepsis mortality by remodeling antibiotic-induced gut microbiota disturbances

Front Immunol. 2023 Jan 11:13:1063543. doi: 10.3389/fimmu.2022.1063543. eCollection 2022.

Authors

Xiran Lou¹, Jinfang Xue¹, Ruifei Shao¹, Yan Yang¹, Deyuan Ning¹, Chunyan Mo¹, Fuping Wang², Guobing Chen²

Affiliations

¹ Medical School, Kunming University of Science and Technology, Kunming, China.
² Department of Emergency Medicine, The First People's Hospital of Yunnan Province, Kunming, China.

Abstract

Objective: Sepsis is the leading cause of death in critically ill patients. The gastrointestinal tract has long been thought to play an important role in the pathophysiology of sepsis. Antibiotic therapy can reduce a patient's commensal bacterial population and raise their risk of developing subsequent illnesses, where gut microbiota dysbiosis may be a key factor.

Methods: In this study, we analyzed the 16S rRNA of fecal samples from both healthy people and patients with sepsis to determine if alterations in gut bacteria are associated with sepsis. Then, we developed a mouse model of sepsis using cecal ligation and puncture (CLP) in order to examine the effects of fecal microbiota transplantation (FMT) and short-chain fatty acids (SCFAs) on survival rate, systemic inflammatory response, gut microbiota, and mucosal barrier function.

Results: Sepsis patients' gut microbiota composition significantly differed from that of healthy people. At the phylum level, the amount of Proteobacteria in the intestinal flora of sepsis patients was much larger than that of the control group, whereas the number of Firmicutes was significantly lower. Mice with gut microbiota disorders (ANC group) were found to have an elevated risk of death, inflammation, and organ failure as compared to CLP mice. However, all of these could be reversed by FMT and SCFAs. FMT and SCFAs could regulate the abundance of bacteria such as Firmicutes, Proteobacteria, Escherichia Shigella, and Lactobacillus, restoring them to levels comparable to those of healthy mice. In addition, they increased the expression of the Occludin protein in the colon of mice with sepsis, downregulated the expression of the NLRP3 and GSDMD-N proteins, and reduced the release of the inflammatory factors IL-1β and IL-18 to inhibit cell pyroptosis, ultimately playing a protective role in sepsis.

Disccusion: FMT and SCFAs provide a microbe-related survival benefit in a mouse model of sepsis, suggesting that they may be a viable treatment for sepsis.

Keywords: antibiotic; fecal microbiota transplantation; gut microbiota; sepsis; short-chain fatty acids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / therapeutic use
Fatty Acids, Volatile
Fecal Microbiota Transplantation
Gastrointestinal Microbiome* / physiology
Mice
RNA, Ribosomal, 16S / genetics
Sepsis* / microbiology
Sepsis* / therapy

Substances

RNA, Ribosomal, 16S
Anti-Bacterial Agents
Fatty Acids, Volatile

Grants and funding

This study was supported by the National Natural Science Foundation of China (Project No. 82160366) and Yunnan Clinical Medical Center Open Project (No. 2021LCZXXF-HX03).