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首页> 美国卫生研究院文献>Frontiers in Physiology >Hypoxia and Inactivity Related Physiological Changes (Constipation Inflammation) Are Not Reflected at the Level of Gut Metabolites and Butyrate Producing Microbial Community: The PlanHab Study
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Hypoxia and Inactivity Related Physiological Changes (Constipation Inflammation) Are Not Reflected at the Level of Gut Metabolites and Butyrate Producing Microbial Community: The PlanHab Study

机译：缺氧和与运动不相关的生理变化（便秘炎症）在肠道代谢产物和产生丁酸的微生物群落水平上未得到反映：PlanHab研究

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We explored the assembly of intestinal microbiota in healthy male participants during the run-in (5 day) and experimental phases [21-day normoxic bed rest (NBR), hypoxic bedrest (HBR)], and hypoxic ambulation (HAmb) in a strictly controlled laboratory environment, balanced fluid, and dietary intakes, controlled circadian rhythm, microbial ambiental burden, and 24/7 medical surveillance. The fraction of inspired O2 (FiO2) and partial pressure of inspired O2 (PiO2) were 0.209 and 133.1 ± 0.3 mmHg for NBR and 0.141 ± 0.004 and 90.0 ± 0.4 mmHg for both hypoxic variants (HBR and HAmb; ~4,000 m simulated altitude), respectively. A number of parameters linked to intestinal transit spanning Bristol Stool Scale, defecation rates, zonulin, α1-antitrypsin, eosinophil derived neurotoxin, bile acids, reducing sugars, short chain fatty acids, total soluble organic carbon, water content, diet composition, and food intake were measured (167 variables). The abundance, structure, and diversity of butyrate producing microbial community were assessed using the two primary bacterial butyrate synthesis pathways, butyryl-CoA: acetate CoA-transferase (but) and butyrate kinase (buk) genes. Inactivity negatively affected fecal consistency and in combination with hypoxia aggravated the state of gut inflammation (p < 0.05). In contrast, gut permeability, various metabolic markers, the structure, diversity, and abundance of butyrate producing microbial community were not significantly affected. Rearrangements in the butyrate producing microbial community structure were explained by experimental setup (13.4%), experimentally structured metabolites (12.8%), and gut metabolite-immunological markers (11.9%), with 61.9% remaining unexplained. Many of the measured parameters were found to be correlated and were hence omitted from further analyses. The observed progressive increase in two immunological intestinal markers suggested that the transition from healthy physiological state toward the developed symptoms of low magnitude obesity-related syndromes was primarily driven by the onset of inactivity (lack of exercise in NBR) that were exacerbated by systemic hypoxia (HBR) and significantly alleviated by exercise, despite hypoxia (HAmb). Butyrate producing community in colon exhibited apparent resilience toward short-term modifications in host exercise or hypoxia. Progressive constipation (decreased intestinal motility) and increased local inflammation marker suggest that changes in microbial colonization and metabolism were taking place at the location of small intestine.
机译：我们在磨合期（5天）和实验阶段[21天正常氧卧床休息（NBR），低氧卧床休息（HBR）]和低氧移动（HAmb）中探索了健康男性参与者的肠道菌群组装情况控制实验室环境，平衡液体和饮食摄入量，控制昼夜节律，微生物环境负担和24/7医疗监测。对于NBR，两种氧气含量低的变量（HBR和HAmb;〜4000 m模拟高度）的吸入氧气分数（FiO2）和吸入氧气分压（PiO2）分别为0.209和133.1±0.3 mmHg，分别为0.141±0.004和90.0±0.4 mmHg ， 分别。与肠运输有关的许多参数跨越了布里斯托尔粪便量表，排便率，zonulin，α1-抗胰蛋白酶，嗜酸性粒细胞衍生的神经毒素，胆汁酸，还原糖，短链脂肪酸，总可溶性有机碳，水含量，饮食组成和食物测量摄入量（167个变量）。使用两种主要的细菌丁酸酯合成途径，丁酰辅酶A：乙酸酯辅酶A转移酶（but）和丁酸酯激酶（buk）基因，评估了产生丁酸酯的微生物群落的丰度，结构和多样性。缺乏运动会对粪便的稠度产生负面影响，并且与缺氧相结合会加重肠道炎症状态（p <0.05）。相反，肠通透性，各种代谢标记，结构，多样性和产生丁酸的微生物群落的丰度没有受到显着影响。产生丁酸盐的微生物群落结构的重排由实验设置（13.4％），实验结构化的代谢物（12.8％）和肠道代谢物-免疫学标记物（11.9％）解释，尚有61.9％的原因无法解释。发现许多测量参数是相关的，因此在进一步的分析中被省略。观察到的两种免疫学肠道标记物的逐步增加表明，从健康的生理状态向低强度肥胖症相关综合征的已发展症状的转变主要是由于缺乏活动（NBR缺乏运动）的发作所致，而这种缺乏活动因全身性缺氧而加剧（ HBR），尽管有缺氧（HAmb），但通过运动可显着缓解。结肠中产生丁酸的群落对宿主运动或缺氧的短期变化表现出明显的适应力。进行性便秘（肠蠕动降低）和局部炎症标志物增加表明，微生物定植和新陈代谢的变化在小肠部位发生。

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