Host-microbial interactions in the gut oxygen equilibrium

肠道氧平衡中宿主-微生物的相互作用

基本信息

批准号：
8995209
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
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-12-10 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8995209
关键词：
Actinobacteria class Address Aerobic Aerobic Bacteria Anaerobic Bacteria Animals Bacteria Biochemistry Biometry Breathing Colitis Colon Communities Crohn&apos s disease 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 Mucous Membrane Mus Oral Oxidative Stress Oxygen Partial Pressure Pathologic Patients Pattern Phylogenetic Analysis Population Process Productivity Proteobacteria Publications Recombinant DNA Research Research Personnel Sampling Shotguns Signal Transduction Stress Structure Surveys Techniques Therapeutic Tissues Water base gut microbiome gut microbiota human disease human subject in vivo innovation member microbial community microbiome microbiota microorganism interaction mouse model nanoprobe novel strategies optical spectra phosphorescence response temporal measurement tissue oxygenation

项目摘要

: 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，其成员对氧气的敏感性不同，从需氧菌到兼性菌厌氧菌专性厌氧菌。人们普遍认为结肠环境是厌氧。细菌群落的复杂性以及微生物群落的巨大变化在病理状态下观察到的群落结构，例如炎症性肠病（IBD），表明常驻肠道微生物可能对管腔的变化做出反应氧。不幸的是，目前关于氧气 (O2) 含量的数据非常少。结肠由于缺乏量化氧气水平的适当方法。更多的至关重要的是，证据阐明了结肠癌的基本机制缺乏将环境维持在厌氧状态。在初步数据中，我们显示结肠组织和腔内氧水平都可以在体内测量采用侵入式磷光猝灭法，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种观察结果：1) 盲肠腔内的氧分压 (pO2) 明显较低高于邻近组织的 pO2； 2) 吸入纯 O2 导致血氧浓度迅速增加盲肠组织 pO2 和管腔 pO2 逐渐增加。基于这些研究结果表明，我们假设氧气可以维持动态平衡结肠组织释放的物质被肠道微生物群消耗，从而维持厌氧环境。为了支持这一观点，我们还提供了数据表明附着在人类结肠粘膜上的微生物群丰富，有氧和兼性厌氧菌相对于粪便，其中专性厌氧菌占主导地位。我们进一步假设肠道微生物组的良好描述的“生态失调”组成在 IBD 中观察到，随着需氧变形菌和放线菌的大量繁殖，肠道微生物群对较高 pO2 水平和随后的氧化应激的反应。