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

IF 5 2区 生物学 Q1 MICROBIOLOGY mSystems Pub Date : 2024-10-22 Epub Date: 2024-09-05 DOI:10.1128/msystems.00788-24
Luyao Liu, Lin Ma, Huan Liu, Fan Zhao, Pu Li, Junhua Zhang, Xin Lü, Xin Zhao, Yanglei Yi
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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 importance of innovative treatment approaches for this disease by targeting the gut microbiota.IMPORTANCEDeveloping effective treatment strategies for systemic inflammatory response syndrome (SIRS) is crucial due to its severe and often life-threatening nature. While traditional treatments like dexamethasone have shown efficacy, they also come with significant side effects and limitations. This study makes significant strides by demonstrating that the Xuanfei Baidu (XFBD) formula can substantially reduce mortality rates and inflammation in SIRS mice through effective modulation of the gut microbiota. By quantitatively assessing the impact of 51 compounds derived from XFBD on the gut microbiome, we developed a potent gut microbiome remodeling compound cocktail. This cocktail outperformed individual compounds and other mixtures in efficacy against SIRS. These findings highlight the potential of XFBD as a therapeutic solution for SIRS and underscore the critical role of innovative strategies targeting the gut microbiota in addressing this severe inflammatory condition.

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有针对性地发现肠道微生物组重塑化合物,用于治疗全身炎症反应综合征。
全身炎症反应综合征(SIRS)是一种严重的炎症反应,可导致器官功能障碍和死亡。调节肠道微生物组是控制 SIRS 的一种很有前景的治疗方法。本研究评估了玄参方治疗 SIRS 的潜力。结果显示,服用玄参白术散能有效降低SIRS小鼠的死亡率和炎症反应。通过 16S rRNA 测序和粪便微生物群移植(FMT),我们证实了 XFBD 的治疗效果部分归功于肠道微生物群的调节。我们进行了体外实验,以准确评估从 XFBD 中分离出的 51 种化合物对肠道微生物群重塑的影响。这些化合物在诱导与健康对照组非常相似的微生物结构方面表现出不同的能力。通过量化这些化合物对微生物结构的影响并对其调控模式进行聚类,我们设计出了多种肠道微生物组重塑化合物(GMRC)鸡尾酒。由杜仲甙、龙胆甙、丁香酸、没食子酸、对羟基苯甲醛、对羟基苯甲酸和异橙皮甙组成的 GMRC 鸡尾酒 C 在治疗 SIRS 方面的疗效优于单一化合物或其他鸡尾酒。最后,体外实验表明,GMRC 鸡尾酒 C 能有效地重新平衡 SIRS 患者体内的细菌组成。这项研究强调了 XFBD 在 SIRS 中的治疗潜力,并突出了通过靶向肠道微生物群来创新治疗这种疾病的方法的重要性。重要意义由于全身炎症反应综合征(SIRS)病情严重且常常危及生命,因此开发有效的治疗策略至关重要。虽然地塞米松等传统疗法已显示出疗效,但它们也有很大的副作用和局限性。这项研究取得了重大进展,证明了宣飞百度(XFBD)配方可以通过有效调节肠道微生物群来大幅降低 SIRS 小鼠的死亡率和炎症反应。通过定量评估从玄参中提取的 51 种化合物对肠道微生物群的影响,我们开发出了一种强效的肠道微生物群重塑复合鸡尾酒。这种鸡尾酒对 SIRS 的疗效优于单个化合物和其他混合物。这些发现凸显了 XFBD 作为 SIRS 治疗方案的潜力,并强调了针对肠道微生物群的创新策略在解决这一严重炎症问题中的关键作用。
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来源期刊
mSystems
mSystems Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
10.50
自引率
3.10%
发文量
308
审稿时长
13 weeks
期刊介绍: mSystems™ will publish preeminent work that stems from applying technologies for high-throughput analyses to achieve insights into the metabolic and regulatory systems at the scale of both the single cell and microbial communities. The scope of mSystems™ encompasses all important biological and biochemical findings drawn from analyses of large data sets, as well as new computational approaches for deriving these insights. mSystems™ will welcome submissions from researchers who focus on the microbiome, genomics, metagenomics, transcriptomics, metabolomics, proteomics, glycomics, bioinformatics, and computational microbiology. mSystems™ will provide streamlined decisions, while carrying on ASM''s tradition of rigorous peer review.
期刊最新文献
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