Nitrogen fixation in the human gut by sulphate-reducing bacteria

硫酸盐还原菌在人体肠道中的固氮作用

• 批准号: BB/Z514445/1
• 负责人: Lizbeth Sayavedra Camacho
• 金额: $ 53.54万
• 依托单位: Quadram Institute
• 依托单位国家: 英国
• 项目类别: Fellowship
• 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=BB%2FZ514445%2F1
• 关键词: Nitrogen; fixation; human; gut; sulphate

My recent research has resulted in the exciting discovery of a sulphate-reducing bacterium (SRB) from the human gut, Desulfovibrio diazotrophicus, which fixes nitrogen in vitro. While nitrogen-fixing bacteria have been found in the gut microbiomes of some animals, such as termites and ruminants, little is known about the process of nitrogen fixation in humans. Demonstrating that nitrogen fixation occurs in the human gut microbiome would represent a significant scientific finding and expand our understanding of the nitrogen cycle and microbial interactions within the human body. This research, therefore, has implications for human health and nutrition as well as the role of the microbiome.The composition and activity of bacterial populations in the gut are influenced by the host's diet, particularly the availability of nutrients. Investigating bacterial populations in response to different nitrogen levels and availability in the diet provides an opportunity to explore whether nitrogen fixation is influenced by our food intake. This research aims to determine whether diazotrophic (N-fixing) bacteria have a competitive advantage in the human gut when low-protein diets are consumed.My metagenomics analyses found that while SRB are frequently present in human gut microbiomes, not all species have the potential to fix nitrogen. Some SRB species could contribute to the bioavailable nitrogen in protein-deficient diets; however, blooms of SRB have been linked with colonic diseases, gut inflammation, and ulcerative colitis. The by-product of SRB respiration, H2S, is toxic in high concentrations but can also be anti-inflammatory. Therefore, this project will provide a better understanding of SRB ecology and metabolism in the gut, which is crucial to understanding whether they are beneficial or potentially harmful to health.I aim to investigate the impact of nitrogen fixation on D. diazotrophicus survival and metabolism, the effects nitrogen fixation has on the microbiota and the host, and how diet influences these interactions. The hypotheses are that sulphate-reducing bacteria can fix nitrogen under gastrointestinal conditions, and this process is influenced by the quantity and source of dietary protein, subsequently affecting H2S production. Additionally, it is hypothesized that fixed nitrogen is shared with the rest of the microbiota or utilized by the host. The specific objectives are:Investigate the rate of nitrogen fixation by D. diazotrophicus in the gut environment, if this nitrogen is shared, and assess the extent to which this process is influenced by dietary protein contentDetermine the influence of vegan diets on nitrogen fixation by D. diazotrophicus and identify key interactions within a complex microbiotaEvaluate the impact of D. diazotrophicus on the host's nitrogen pool and gut permeabilityImplicationsMy discovery of nitrogen-fixing SRB in the human gut has the potential to revolutionize our understanding of the complex interactions between human nutrition, the microbiome and health. Protein-deficient diets cause malnutrition and can be severe for vulnerable populations, as the elderly and pregnant women. The outcomes will inform new nutritional strategies that could address protein deficiency in vegan diets, the elderly and the malnourished.

我最近的研究导致了一个令人兴奋的发现硫酸盐还原菌（SRB）从人类肠道，脱硫弧菌重氮营养，固定氮在体外。虽然在一些动物的肠道微生物组中发现了固氮细菌，如白蚁和反刍动物，但对人类的固氮过程知之甚少。证明氮固定发生在人类肠道微生物组中将代表一个重要的科学发现，并扩大我们对人体内氮循环和微生物相互作用的理解。因此，这项研究对人类健康和营养以及微生物组的作用具有影响。肠道中细菌种群的组成和活性受到宿主饮食的影响，特别是营养物质的可用性。调查细菌种群对饮食中不同氮水平和可用性的反应提供了一个探索固氮是否受我们食物摄入影响的机会。这项研究旨在确定当低蛋白饮食被消耗时，重氮营养（固氮）细菌是否在人类肠道中具有竞争优势。我的宏基因组学分析发现，虽然SRB经常存在于人类肠道微生物组中，但并非所有物种都有固氮的潜力。一些SRB物种可能有助于蛋白质缺乏饮食中的生物可利用氮;然而，SRB的大量繁殖与结肠疾病，肠道炎症和溃疡性结肠炎有关。硫酸盐还原菌呼吸的副产物H2S在高浓度下是有毒的，但也可以是抗炎的。因此，本项目将提供一个更好的了解SRB的生态和代谢在肠道，这是至关重要的，以了解他们是否是有益的或潜在的有害健康。固氮菌的生存和代谢，固氮作用对微生物群和宿主的影响，以及饮食如何影响这些相互作用。假设是硫酸盐还原菌可以在胃肠道条件下固氮，这一过程受到膳食蛋白质的数量和来源的影响，随后影响H2S的产生。此外，假设固定氮与微生物群的其余部分共享或被宿主利用。具体目的是：研究D.在肠道环境中的固氮菌，如果这种氮是共享的，并评估在何种程度上，这一进程是由膳食蛋白质含量的影响确定素食饮食的影响固氮D。diazotrophicus和确定复杂微生物内的关键相互作用评估D.固氮菌对宿主氮库和肠道通透性的影响我在人类肠道中发现的固氮SRB有可能彻底改变我们对人类营养，微生物组和健康之间复杂相互作用的理解。缺乏蛋白质的饮食造成营养不良，对老年人和孕妇等弱势群体来说可能是严重的。研究结果将为新的营养战略提供信息，这些战略可以解决纯素饮食、老年人和营养不良者的蛋白质缺乏问题。