Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans.
Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans.
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DOI：
10.1128/mbio.01282-15
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发表时间：
2015-11-10
期刊：
影响因子：
6.4
通讯作者：
Martens EC
中科院分区：
文献类型：
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作者：
Pudlo NA;Urs K;Kumar SS;German JB;Mills DA;Martens EC
许多共生肠道细菌具有降解多种多糖的能力，从而为其宿主提供营养优势。就像适应其他复杂营养环境的微生物一样，肠道共生体对混合物中存在的底物赋予不同的代谢优先级。我们研究了多形拟杆菌的反应，这是一种常见的人类肠道细菌，可代谢十多种不同的多糖，包括分泌粘蛋白中丰富的 O 连接聚糖。粘蛋白聚糖与其他碳水化合物同时呈递的实验表明，在替代底物存在的情况下，这些宿主碳水化合物的降解始终受到抑制，即使是先前习惯于在纯粘蛋白聚糖中生长的 B. thetaiotaomicron 也是如此。使用含有系统变化的碳水化合物线索和基因突变体的培养基进行的实验表明，参与粘蛋白聚糖代谢的基因的转录抑制是由单糖施加的，并且在一个测试的例子中，是通过转录自主方式通过一个小的基因间区域介导的。与 B. thetaiotaomicron 相比，另外两种人类肠道细菌（马西拟杆菌和脆弱拟杆菌）中粘蛋白聚糖反应性基因簇的抑制表现出可变的、有时甚至是相反的反应，这表明这些共生体对粘蛋白聚糖的偏好不同，并且这些差异发生在控制个体基因簇的水平上。我们的结果表明，聚糖的传感和代谢分类是复杂的过程，因物种而异，强调了这样的观点，即这些现象可能是微生物群落动态的隐藏驱动因素，并可能决定哪些微生物在不断变化的营养环境中优先致力于不同的生态位。人类肠道微生物影响健康和疾病的许多方面，包括消化和发生炎症和结肠癌等疾病的倾向。复杂碳水化合物是肠道栖息地的主要组成部分，许多物种已经进化并完善了策略来竞争这些令人垂涎的营养物质。我们的研究结果表明，个体细菌对宿主饮食和粘膜分泌物中的碳水化合物表现出不同的偏好，并且其中一些优先策略是彼此相反的。因此，我们揭示了单个细菌（其中一些具有相似的代谢潜力）如何在复杂的肠道生态系统中分配到“首选生态位”的新方面，这对于理解和预测该群落的行为动态具有重要而直接的影响。
Many symbiotic gut bacteria possess the ability to degrade multiple polysaccharides, thereby providing nutritional advantages to their hosts. Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. Complex carbohydrates are a major component of the intestinal habitat, and numerous species have evolved and refined strategies to compete for these coveted nutrients. Our findings reveal that individual bacteria exhibit different preferences for carbohydrates emanating from host diet and mucosal secretions and that some of these prioritization strategies are opposite to one another. Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to “preferred niches” in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community.