Targeted discovery of gut microbiome-remodeling compounds for the treatment of systemic inflammatory response syndrome

作者：Luyao Liu, Lin Ma, Huan Liu, Fan Zhao, Pu Li, Junhua Zhang, Xin Lü, Xin Zhao, Yanglei Yi · 发表于：mSystems · 年份：2024 · DOI：10.1128/msystems.00788-24 · 被引用次数：5 · 研究领域：Gut microbiota and health、Tryptophan and brain disorders、Ginseng Biological Effects and Applications

ABSTRACT Systemic inflammatory response syndrome (SIRS) is a severe inflammatory response that can lead to organ dysfunction and death. Modulating the gut microbiome is a promising therapeutic approach for managing SIRS. This study assesses the therapeutic potential of the Xuanfei Baidu (XFBD) formula in treating SIRS. The results showed that XFBD administration effectively reduced mortality rates and inflammation in SIRS mice. Using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we substantiated that the therapeutic effects of XFBD are partly attributed to gut microbiota modulation. We conducted in vitro experiments to accurately assess the gut microbiome remodeling effects of 51 compounds isolated from XFBD. These compounds exhibited varying abilities to induce a microbial structure that closely resembles that of the healthy control group. By quantifying their impact on microbial structure and clustering their regulatory patterns, we devised multiple gut microbiome remodeling compound (GMRC) cocktails. GMRC cocktail C, comprising aucubin, gentiopicroside, syringic acid, gallic acid, p-hydroxybenzaldehyde, para-hydroxybenzoic acid, and isoimperatorin, demonstrated superior efficacy in treating SIRS compared to a single compound or to other cocktails. Finally, in vitro experiments showcased that GMRC cocktail C effectively rebalanced bacteria composition in SIRS patients. This study underscores XFBD’s therapeutic potential in SIRS and highlights the importanc...