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

为了加强现有抗生素的使用，我们需要了解它们如何影响宿主内的致病菌和有益细菌。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，如艰难梭菌相关腹泻和炎症性肠病。微生物代谢是抗生素敏感性的关键调节因子，我们提出通过饮食神经支配改变微生物组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，高植物纤维饮食在抗生素损伤期间对小鼠微生物群结构提供了显著的保护。我们假设特定形式的植物衍生多糖可以影响细菌代谢，从而调节共生细菌的抗生素敏感性。反过来，这种调节可能在抗生素治疗期间为微生物组多样性提供保护。然而，目前还没有足够的知识来预测这些常见的膳食成分和补充剂将如何影响微生物群的结构、功能和反应。为了克服这一限制，我们将采用多组学方法，结合宏基因组学、元转录组学和代谢组学来分析植物源性多糖对微生物组结构、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恢复能力联系起来。我们将围绕以下两个目标开展工作：目标一。描述富含纤维的饮食对抗生素治疗期间小鼠微生物群的功能、结构和代谢反应的影响。目标2。系统地确定短期和长期补充纯化纤维对抗生素治疗期间小鼠微生物组稳态及其代谢反应的影响。通过鉴定减少抗生素引起的生态失调的益生元佐剂，了解纤维对抗生素破坏微生物组的影响可能具有重要的翻译潜力。在基础科学层面上，我们的亚转录组学和代谢组学分析将使我们能够描述微生物组代谢的变化如何影响抗生素的作用。这些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脱靶影响。

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.