Host-microbial interactions in the gut oxygen equilibrium

肠道氧平衡中宿主-微生物的相互作用

• 批准号: 8779726
• 负责人: GARY D. WU
• 金额: $ 32万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-10 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8779726
• 关键词: Actinobacteria class; Address; Aerobic; Aerobic Bacteria; Anaerobic Bacteria; Animals; Bacteria; Biochemistry; Biometry; Breathing; Colitis; Colon; Communities; Data; Development; Disease Management; Dyes; Elemental Diets; Environment; Equilibrium; Evaluation; Feces; Gastroenterology; Genomics; Home environment; Human; Human Microbiome; Hyperbaric Oxygenation; Inflammatory Bowel Diseases; Intestinal Diseases; Intestines; Laboratory Animals; Lead; Longitudinal Studies; Measurement; Measures; Medicine; Metagenomics; Methods; Microbe; Microbiology; Modeling; Mucous Membrane; Mus; Oral; Oxidative Stress; Oxygen; Partial Pressure; Pathologic; Patients; Pattern; Phylogenetic Analysis; Population; Process; Productivity; Proteobacteria; Publications; Recombinant DNA; Relative (related person); Research; Research Personnel; Sampling; Shotguns; Signal Transduction; Stress; Structure; Surveys; Techniques; Therapeutic; Tissues; Water; base; gut microbiota; human disease; human subject; in vivo; innovation; member; microbial community; microbiome; microorganism interaction; nanoprobe; novel strategies; optical spectra; phosphorescence; response; temporal measurement; tissue oxygenation

: The intestinal tract is home to a densely populated microbial community whose members have varying sensitivities to oxygen, ranging from aerobes to facultative anaerobes to obligate anaerobes. It is widely thought that the colonic environment is anaerobic. The complexity of bacterial communities along with the dramatic alterations in community structure observed in pathologic states, such as inflammatory bowel disease (IBD), suggests that resident gut microbes may be responsive to alterations in luminal oxygen. Unfortunately, very little data currently exists on the oxygen (O2) content in the colon due to the lack of appropriate methods for quantifying oxygen levels. More critically, evidence elucidating the fundamental mechanism(s) by which the colonic environment is maintained in an anaerobic state is lacking. In Preliminary Data, we show that both colonic tissue and luminal oxygen levels can be measured in vivo non- invasively by the phosphorescence quenching method, making use of non-toxic water- soluble oxygen-sensitive dyes - a technical advance that has led to the following two observations: 1) Partial pressure of oxygen (pO2) in the cecal lumen is remarkably lower than pO2 in the adjacent tissue; 2) Inspiration of pure O2 leads to a rapid increase in the cecal tissue pO2 and a more gradual increase in the luminal pO2. Based on these findings, we hypothesize that a dynamic equilibrium is maintained whereby oxygen released by colonic tissue is consumed by the gut microbiota thus maintaining an anaerobic environment. In support of this notion, we also provide data showing that the microbiota adherent to the human colonic mucosa is enriched for aerobic and facultative anaerobes relative to the feces where obligate anaerobes predominate. We further hypothesize that the well-described "dysbiotic" composition of the gut microbiome observed in IBD, with the bloom of aerobic Proteobacteria and Actinobacteria, is a response of the gut microbiota to higher pO2 levels and subsequent oxidative stress.

: 肠道是一个密集的微生物群落的家园， 成员对氧气的敏感性各不相同，从需氧菌到兼性菌 厌氧菌到专性厌氧菌。人们普遍认为，结肠环境是 厌氧的细菌群落的复杂性沿着 在病理状态下观察到的群落结构，如炎症性肠病 (IBD)这表明，肠道微生物可能对管腔内的变化有反应， 氧气不幸的是，目前关于氧气（O2）含量的数据很少。 结肠由于缺乏适当的方法来量化氧气水平。更 关键的是，阐明结肠炎的基本机制的证据 缺乏维持在厌氧状态的环境。在初步数据中，我们显示 结肠组织和管腔氧水平都可以在体内测量， 通过磷光猝灭法侵入，利用无毒的水- 可溶性氧敏感染料-一项技术进步，导致了以下两个 观察结果：1）盲肠腔氧分压（pO 2）明显降低 2）吸入纯O2导致邻近组织中的pO 2迅速增加; 盲肠组织pO 2和管腔pO 2的逐渐增加。基于这些 研究结果，我们假设，一个动态平衡是维持， 由结肠组织释放的蛋白质被肠道微生物群消耗， 厌氧环境为了支持这一观点，我们还提供了数据显示， 粘附于人结肠粘膜的微生物群富含有氧和兼性微生物。 相对于粪便中专性厌氧菌占优势，我们进一步 假设肠道微生物组中被充分描述的“生态失调”成分 在IBD中观察到，随着好氧变形菌和放线菌的大量繁殖， 肠道微生物群对较高pO 2水平和随后的氧化应激的反应。