Metabolic Feedback Inhibition Influences Metabolite Secretion by the Human Gut Symbiont Bacteroides thetaiotaomicron
Metabolic Feedback Inhibition Influences Metabolite Secretion by the Human Gut Symbiont Bacteroides thetaiotaomicron
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DOI：
10.1128/msystems.00252-20
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发表时间：
2020-09-01
期刊：
影响因子：
6.4
通讯作者：
Buan, Nicole R.
中科院分区：
文献类型：
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作者：
Catlett, Jennie L.;Catazaro, Jonathan;Buan, Nicole R.
微生物代谢和微生物之间的营养相互作用导致了微生物-宿主系统中复杂的多物种群落。多形拟杆菌（B. theta）是一种人类肠道共生体，被认为在维持宿主健康方面发挥重要作用。非靶向核磁共振代谢组学显示为B。Theta在确定的基本培养基中分泌特定的有机酸和氨基酸。在人体肠道中发现的乙酸盐和甲酸盐的生理浓度显示可引起已知在宿主营养和发病机制中发挥作用的代谢物分泌的剂量依赖性变化。虽然分泌通量变化，生物量产量不变，这表明反馈抑制不影响代谢生物能学，而是将碳和能量重定向到CO2和H-2。通量平衡分析模型表明，通过CO2产生的葡萄糖限制生长条件下的反应增加通量。观察到B的代谢动力学。拟杆菌是一种重要的共生生物，它强调了代谢模型的需要，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。theta）是一种普遍存在的人类共生体，在发育早期定殖宿主并在其整个生命周期中持续存在。关键生物如B的表型可塑性。为了预测在不断变化的营养条件下（例如在复杂的肠道群落中发生的营养条件下）的表型和代谢相互作用，理解θ是重要的。我们的研究表明B.当乙酸盐浓度高时，Theta优先考虑能量保存并抑制“溢出代谢物”如有机酸和氨基酸的分泌。分泌的代谢物，特别是氨基酸，可以是宿主或群落中其他微生物的营养物质或信号来源。我们的研究表明，当代谢应激乙酸，B。theta停止与它的生态伙伴分享
Microbial metabolism and trophic interactions between microbes give rise to complex multispecies communities in microbe-host systems. Bacteroides thetaiotaomicron (B. theta) is a human gut symbiont thought to play an important role in maintaining host health. Untargeted nuclear magnetic resonance metabolomics revealed B. theta 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 CO2 and H-2. Flux balance analysis modeling showed increased flux through CO2-producing reactions under glucose-limiting growth conditions. The metabolic dynamics observed for B. theta, 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.IMPORTANCE Bacteroides is a highly abundant taxon in the human gut, and Bacteroides thetaiotaomicron (B. theta) 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 B. theta 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 B. theta 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, B. theta stops sharing with its ecological partners.