Host-microbial interactions in the gut oxygen equilibrium

： 肠道是人口密集的微生物群落的家园，其 成员对氧气有不同的敏感性，从需氧菌到兼性菌都有。 厌氧菌为专性厌氧菌。人们普遍认为，结肠环境是 厌氧。细菌群落的复杂性以及细菌群落的戏剧性变化 在病理状态下观察到的群落结构，如炎症性肠病 (IBD)，表明肠道内滞留的微生物可能对管腔的改变做出反应 氧气。不幸的是，目前关于水中氧(O2)含量的数据很少 由于缺乏适当的方法来量化氧气水平，导致了对结肠的污染。更多 关键的是，有证据阐明了结肠的基本机制(S) 环境维持在厌氧状态是缺乏的。在初步数据中，我们显示 结肠组织和腔内氧气水平都可以在活体内非 采用磷光猝灭法，利用无毒水- 可溶性氧敏感染料-这一技术进步导致了以下两种 观察：1)盲肠腔内氧分压(PO2)显著降低 2)吸入纯O2可导致脑组织中PO2含量迅速增加 盲肠组织血氧分压和腔内血氧分压逐渐升高。基于这些 发现，我们假设氧气维持动态平衡 由结肠组织释放的物质被肠道微生物区系消耗，从而维持 厌氧环境。为了支持这一概念，我们还提供了数据，表明 附着在人结肠粘膜上的微生物群富含需氧和兼性 相对于粪便的厌氧菌，其中专性厌氧菌占主导地位。我们进一步 假设肠道微生物群中被描述为“非生物”的成分 在IBD中观察到的，伴随着需氧变形杆菌和放线菌的大量繁殖，是一种 肠道微生物区系对较高的PO2水平和随后的氧化应激的反应。

: 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.