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存在基因改变时的小鼠肠道微生物组的反应。

The Response of Murine Gut Microbiome in the Presence of Altered Gene of .

机构信息

State Key Laboratory for Conservation and Utilization of Bioresources in Yunnan, Yunnan Agricultural University, Kunming 650201, China.

出版信息

Int J Mol Sci. 2024 Aug 25;25(17):9222. doi: 10.3390/ijms25179222.

Abstract

The murine model is invaluable for studying intricate interactions among gut microbes; hosts; and diseases. However; the impact of genetic variations in the murine microbiome; especially in disease contexts such as () infection; still needs to be explored. ; an opportunistic global pathogen; is becoming increasingly prevalent in regions like Asia; especially China. This study explored the role of the gut microbiota during infection using mouse model; including wild-type and mutants of Kp138; KpC4; and KpE4 from human; maize; and ditch water; respectively. Under stress conditions; RpoS reconfigures global gene expression in bacteria; shifting the cells from active growth to survival mode. Our study examined notable differences in microbiome composition; finding that and (particularly in WKp138) were the most abundant genera in mice guts at the genus level in all wild-type treated mice. In contrast; were predominant in the healthy control mice. Furthermore; was the dominant genus in all mutants; mainly in ∆KpC4; and was absent in wild-type treated mice. Differential abundance analysis identified that these candidate taxa potentially influence disease progression and pathogen virulence. Functional prediction analysis showed that most bacterial groups were functionally involved in biosynthesis; precursor metabolites; degradation; energy generation; and metabolic cluster formation. These findings challenge the conventional understanding and highlight the need for nuanced interpretations in murine studies. Additionally; this study sheds light on microbiome-immune interactions in infection and proposes new potential therapeutic strategies.

摘要

该鼠模型对于研究肠道微生物之间复杂的相互作用、宿主和疾病非常有价值。然而,仍需要探索鼠微生物组中的遗传变异的影响,特别是在感染等疾病情况下。作为一种机会性病原体,在亚洲等地区,尤其是在中国,正变得越来越普遍。本研究使用鼠模型,包括来自人类、玉米和沟渠水的 Kp138、KpC4 和 KpE4 的野生型和突变体,探索了肠道微生物群在感染过程中的作用。在应激条件下,RpoS 重新配置细菌的全局基因表达,将细胞从活跃生长状态转移到生存模式。我们的研究检查了微生物组组成的显著差异,发现和(特别是在 WKp138 中)在所有野生型处理的鼠肠道中,在属水平上是最丰富的属。相比之下,在健康对照鼠中占优势。此外,在所有突变体中,都是主要属,主要在 ∆KpC4 中,在野生型处理的鼠中不存在。差异丰度分析表明,这些候选分类群可能影响疾病进展和病原体毒力。功能预测分析表明,大多数细菌群在生物合成、前体代谢物、降解、能量生成和代谢簇形成方面具有功能。这些发现挑战了传统的理解,并强调了在鼠研究中需要进行细微的解释。此外,本研究揭示了感染中的微生物组-免疫相互作用,并提出了新的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c73/11395600/55020357543d/ijms-25-09222-g001.jpg

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