Mukherjee Sromona D, Batagello Carlos, Adler Ava, Agudelo Jose, Zampini Anna, Suryavanshi Mangesh, Nguyen Andrew, Orr Terry, Dearing Denise, Monga Manoj, Miller Aaron W
Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, United States.
Division of Urology, Hospital das Clínicas, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Elife. 2025 May 1;14:RP104121. doi: 10.7554/eLife.104121.
Decades of research have made clear that host-associated microbiomes touch all facets of health. However, effective therapies that target the microbiome have been elusive given its inherent complexity. Here, we experimentally examined diet-microbe-host interactions through a complex systems framework, centered on dietary oxalate. Using multiple, independent molecular, rodent, and in vitro experimental models, we found that microbiome composition influenced multiple oxalate-microbe-host interfaces. Importantly, the administration of the oxalate-degrading specialist, was only effective against a poor oxalate-degrading microbiota background and gives critical new insights into why clinical intervention trials with this species exhibit variable outcomes. Data suggest that, while heterogeneity in the microbiome impacts multiple diet-host-microbe interfaces, metabolic redundancy among diverse microorganisms in specific diet-microbe axes is a critical variable that may impact the efficacy of bacteriotherapies, which can help guide patient and probiotic selection criteria in probiotic clinical trials.
数十年的研究已明确表明，与宿主相关的微生物群涉及健康的方方面面。然而，鉴于微生物群固有的复杂性，针对微生物群的有效疗法一直难以捉摸。在此，我们通过一个以膳食草酸盐为核心的复杂系统框架，对饮食-微生物-宿主相互作用进行了实验研究。利用多个独立的分子、啮齿动物和体外实验模型，我们发现微生物群组成影响了多个草酸盐-微生物-宿主界面。重要的是，施用草酸盐降解专家[具体名称未给出]仅在草酸盐降解能力较差的微生物群背景下有效，并为该物种的临床干预试验为何呈现出不同结果提供了重要的新见解。数据表明，虽然微生物群的异质性会影响多个饮食-宿主-微生物界面，但特定饮食-微生物轴中不同微生物之间的代谢冗余是一个关键变量，可能会影响细菌疗法的疗效，这有助于指导益生菌临床试验中的患者和益生菌选择标准。
