Dietary fiber to mitigate antibiotic-induced microbiome dysbiosis: a multi-omics approach

为了提高目前可用的抗生素的使用，我们需要了解它们如何影响宿主内的致病细菌和有益细菌。确定减少抗生素对核心微生物组影响的方法可能有助于减少多种微生物组相关疾病，如艰难梭菌相关性腹泻和炎症性肠病。微生物代谢被认为是抗生素敏感性的关键调节因素，我们认为通过饮食神经改变微生物体内的代谢环境可能会降低有益类群的抗生素敏感性。我们的初步数据表明，与典型的西方低纤维饮食相比，高植物性纤维饮食在抗生素侮辱期间对小鼠微生物群的结构提供了显著的保护。我们假设，植物来源的特定形式的多糖可以影响细菌的新陈代谢，从而调节共生细菌对抗生素的敏感性。反过来，在抗生素治疗期间，这种调节可能会对微生物群多样性提供保护。然而，目前还没有足够的知识来预测这些常见的饮食成分和补充剂将如何影响微生物组的结构、功能和反应。为了克服这一局限，我们将采取结合元基因组学、后转录组学和代谢组学的多组学方法来描述植物来源的多糖对微生物组的结构、功能和代谢状态的影响，并将这些因素与抗生素诱导的微生物组破坏和弹性联系起来。我们将在以下两个目标下进行这项工作：目标1.描述富含纤维的饮食对抗生素治疗期间小鼠微生物组的功能、结构和代谢反应的影响。目的2.系统测定短期和长期补充纯化纤维对抗生素治疗过程中小鼠微生物组稳态及其代谢反应的影响。通过识别减少抗生素诱导的微生物失调的益生素佐剂，了解纤维对抗生素破坏微生物组的影响可能具有重大的翻译潜力。在基础科学层面上，我们的代谢和代谢分析将使我们能够描绘微生物组代谢的变化如何影响抗生素的作用。这一知识可以指导未来靶向治疗的发展，进一步减少抗生素治疗的非靶向影响。

To enhance the use of currently available antibiotics, we need to understand how they impact both pathogenic and beneficial bacteria within the host. Identifying methodologies that reduce the impacts of antibiotics on the core microbiome may help to reduce multiple microbiome-related diseases, such as Clostridium difficile- associated diarrhea and inflammatory bowel disease. Microbial metabolism is known to be a key modulator of antibiotic susceptibility and we propose that changing the metabolic environment in the microbiome via dietary innervation may reduce the antibiotic susceptibility of beneficial taxa. Our preliminary data indicate that a diet high in plant-derived fiber provides significant protection to the structure of the murine microbiome during antibiotic insult compared to a typical Western low fiber diet. We hypothesize that specific forms of plant-derived polysaccharides can impact bacterial metabolism and thereby modulate antibiotic susceptibility in commensal bacteria. In turn, this modulation may provide protection to microbiome diversity during antibiotic therapy. At this time, however, there is insufficient knowledge to predict how these common dietary components and supplements will impact the structure, function, and response of the microbiome. To overcome this limitation, we will take a multi-omic approach combining metagenomics, metatranscriptomics and metabolomics to profile the impacts of plant-derived polysaccharides on the structure, function, and metabolic state of the microbiome and to relate those factors to antibiotic-induced microbiome disruption and resilience. We will conduct this work in the following two aims: Aim 1. Profile the impacts of a fiber-rich diet on the function, structure, and metabolic response of the murine microbiome during antibiotic therapy. Aim 2. Systematically determine the impacts of short-term and long-term purified fiber supplementation on murine microbiome homeostasis and its metabolic response during antibiotic therapy. Understanding the impacts of fiber on antibiotic disruption of the microbiome could have significant translational potential by identifying prebiotic adjuvants that reduce antibiotic-induced dysbiosis. On a basic science level, our metatranscriptomic and metabolomic analysis will allow us to profile how changes in microbiome metabolism can impact antibiotic action. This knowledge can direct future development of targeted therapies that further reduce the off-target impacts of antibiotic treatment.