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代谢反馈抑制影响人类肠道共生菌嗜热栖热放线菌的代谢物分泌。

Metabolic Feedback Inhibition Influences Metabolite Secretion by the Human Gut Symbiont Bacteroides thetaiotaomicron.

作者信息

Catlett Jennie L, Catazaro Jonathan, Cashman Mikaela, Carr Sean, Powers Robert, Cohen Myra B, Buan Nicole R

机构信息

Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.

Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.

出版信息

mSystems. 2020 Sep 1;5(5):e00252-20. doi: 10.1128/mSystems.00252-20.

DOI:10.1128/mSystems.00252-20
PMID:32873608
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7470985/
Abstract

Microbial metabolism and trophic interactions between microbes give rise to complex multispecies communities in microbe-host systems. () is a human gut symbiont thought to play an important role in maintaining host health. Untargeted nuclear magnetic resonance metabolomics revealed secretes specific organic acids and amino acids in defined minimal medium. Physiological concentrations of acetate and formate found in the human intestinal tract were shown to cause dose-dependent changes in secretion of metabolites known to play roles in host nutrition and pathogenesis. While secretion fluxes varied, biomass yield was unchanged, suggesting feedback inhibition does not affect metabolic bioenergetics but instead redirects carbon and energy to CO and H Flux balance analysis modeling showed increased flux through CO-producing reactions under glucose-limiting growth conditions. The metabolic dynamics observed for , a keystone symbiont organism, underscores the need for metabolic modeling to complement genomic predictions of microbial metabolism to infer mechanisms of microbe-microbe and microbe-host interactions. is a highly abundant taxon in the human gut, and () is a ubiquitous human symbiont that colonizes the host early in development and persists throughout its life span. The phenotypic plasticity of keystone organisms such as is important to understand in order to predict phenotype(s) and metabolic interactions under changing nutrient conditions such as those that occur in complex gut communities. Our study shows prioritizes energy conservation and suppresses secretion of "overflow metabolites" such as organic acids and amino acids when concentrations of acetate are high. Secreted metabolites, especially amino acids, can be a source of nutrients or signals for the host or other microbes in the community. Our study suggests that when metabolically stressed by acetate, stops sharing with its ecological partners.

摘要

微生物代谢以及微生物之间的营养相互作用在微生物-宿主系统中形成了复杂的多物种群落。()是一种人类肠道共生菌,被认为在维持宿主健康方面发挥着重要作用。非靶向核磁共振代谢组学研究表明,()在特定的限定基本培养基中分泌特定的有机酸和氨基酸。研究发现,人体肠道中生理浓度的乙酸盐和甲酸盐会导致已知在宿主营养和发病机制中起作用的代谢物分泌发生剂量依赖性变化。虽然分泌通量有所不同,但生物量产量保持不变,这表明反馈抑制并不影响代谢生物能学,而是将碳和能量重新导向一氧化碳和氢气。通量平衡分析模型显示,在葡萄糖限制生长条件下,通过产生一氧化碳的反应的通量增加。对关键共生生物体()观察到的代谢动态强调了需要进行代谢建模,以补充微生物代谢的基因组预测,从而推断微生物-微生物和微生物-宿主相互作用的机制。()是人类肠道中高度丰富的分类群,而()是一种普遍存在的人类共生菌,在发育早期定殖于宿主,并在其整个生命周期中持续存在。为了预测在复杂肠道群落中发生的变化营养条件下的表型和代谢相互作用,了解诸如()这样的关键生物体的表型可塑性很重要。我们的研究表明,当乙酸盐浓度较高时,()会优先进行能量守恒,并抑制“溢流代谢物”如有机酸和氨基酸的分泌。分泌的代谢物,尤其是氨基酸,可能是宿主或群落中其他微生物的营养或信号来源。我们的研究表明,当受到乙酸盐代谢应激时,()会停止与生态伙伴共享。

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