BACMETH: Bacterial methylation of the human gut microbiome in response to diet for improvement of cardiometabolic health

BACMETH：人类肠道微生物组的细菌甲基化响应饮食以改善心脏代谢健康

• 批准号: EP/Y023765/1
• 负责人: Jordana Bell
• 金额: $ 215.82万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY023765%2F1
• 关键词: BACMETH; Bacterial; methylation; human; gut

Obesity and metabolic disease are a global health challenge and major risk factors for cardiovascular disease. Diet is a key modifiable risk factor for cardiometabolic disease but is challenging to study partly because metabolic response to diet is highly personalised. Diet exerts a major influence on the community of microbes in the human gut, the gut microbiota, which in turn plays a key role in metabolic health and disease. Understanding the links between diet, gut microbiota, and cardiometabolic health is crucial to provide tools to tackle the obesity crisis and its clinical consequences.Although diet-induced changes to the human gut microbiota have been identified in metabolic health and disease, our understanding of the bacterial molecular processes mediating these effects remains limited. DNA methylation of bacteria in our gut could play a key mechanistic role. Bacterial methylation has been under-explored at genome-wide scale, but recent developments in sequencing show that methylation is wide-spread, plays important roles including in regulation of bacterial gene function, and may provide a valuable stable biomarker of gene regulation.This project will characterise human gut bacterial methylation as a novel tool to uncover molecular pathways mediating diet impacts on cardiometabolic health. The hypothesis is that diet induces changes in bacterial methylation, which have functional consequences on the intestinal environment and its microbial community, and affect human health. The workflow includes 1/ diet intervention trials, 2/ large well-characterised cohorts, and 3/ functional experiments. The project will assess if diet-induced bacterial methylation marks together with bacterial methylation signatures of cardiometabolic traits can explain the inter-individual variability in metabolic response to diet, and its downstream effect on health. These novel mechanistic insights and tools will help to promote and optimise cardiometabolic disease prevention.

肥胖和代谢性疾病是全球性的健康挑战，也是心血管疾病的主要危险因素。饮食是心脏代谢疾病的一个关键的可改变的风险因素，但部分研究具有挑战性，因为对饮食的代谢反应是高度个性化的。饮食对人体肠道中的微生物群落（肠道微生物群）产生重大影响，而肠道微生物群又在代谢健康和疾病中起着关键作用。了解饮食、肠道微生物群和心脏代谢健康之间的联系对于提供应对肥胖危机及其临床后果的工具至关重要。尽管饮食诱导的人类肠道微生物群变化已在代谢健康和疾病中得到确认，但我们对介导这些影响的细菌分子过程的理解仍然有限。我们肠道中细菌的DNA甲基化可能起着关键的机械作用。细菌甲基化在全基因组水平上的研究还不够深入，但最近的测序进展表明，甲基化广泛存在，在细菌基因功能的调控中发挥重要作用，并可能提供一种有价值的稳定的基因调控生物标志物。本项目将人类肠道细菌甲基化作为一种新的工具，揭示介导饮食对心脏代谢健康影响的分子途径。该假说认为，饮食诱导细菌甲基化的变化，这对肠道环境及其微生物群落产生功能性影响，并影响人类健康。工作流程包括1/饮食干预试验，2/大型充分表征的队列和3/功能实验。该项目将评估饮食诱导的细菌甲基化标记以及心脏代谢特征的细菌甲基化特征是否可以解释饮食代谢反应的个体间差异及其对健康的下游影响。这些新的机制见解和工具将有助于促进和优化心脏代谢疾病的预防。