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肠道微生物群调节肺基因表达和代谢,以帮助SD大鼠适应低压缺氧。

Gut microbiota modulates lung gene expression and metabolism to aid SD rats in adapting to low-pressure hypoxia.

作者信息

Chen Zheng, Chai Shatuo, Ding Yuxia, Pang Kaiyue, Dong Tanqin, Dai Dongwen, Wang Jianmei, Wang Shuxiang, Liu Shujie

机构信息

Qinghai Academy of Animal Husbandry and Veterinary Sciences in Qinghai University, Xining, China.

College of Animal Science and Technology, China Agricultural University, Beijing, China.

出版信息

Microbiol Spectr. 2025 Jun 3;13(6):e0004525. doi: 10.1128/spectrum.00045-25. Epub 2025 May 6.

DOI:10.1128/spectrum.00045-25
PMID:40326772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12131785/
Abstract

UNLABELLED

Hypoxia has long posed a serious threat to the health of both animals and humans, causing respiratory acidosis, metabolic disorders, systemic inflammation, oxidative stress damage, and other issues, thereby endangering life and limiting development in high-altitude areas. Gut microbiota plays a crucial role in life activities and hypoxia adaptation. We transplanted the gut microbiota from small mammals, plateau zokors (), from the Qinghai-Tibetan plateau (3,500 m) to Sprague-Dawley (SD) rats housed in a hypobaric chamber (equivalent to 6,000 m altitude) for 30 days. The results showed that microbiota transplantation significantly reshaped the gut microbiota structure of the rats, notably increasing the abundance of short-chain fatty acid-producing bacteria Lachnospiraceae and Prevotellaceae, alleviating hypoxia and acidosis, reducing pulmonary hypertension and right ventricular hypertrophy, increasing the production of anti-inflammatory substances like indole-3-lactic acid, and reducing the generation of pro-inflammatory substances, such as histamine and uric acid. It also decreased the expression of inflammatory genes like lgE, TNFα, and IFN-γ in the lung. Fecal microbiota transplantation from plateau-specific species to low-altitude SD rats effectively altered metabolism, changed gene expression, decreased pulmonary artery pressure, and enhanced plateau adaptability. This study demonstrates the potential effectiveness of treating hypoxic pulmonary hypertension through microbiota transplantation and offers insights into improving hypoxia adaptation.

IMPORTANCE

We report the beneficial effects of FMT on respiratory capacity, lung metabolism, and lung gene expression in SD rats under hypoxic conditions. We revealed the inhibitory effects of gut microbiota on lung mast cells and histamine expression under hypoxic conditions. The study demonstrated the potential effectiveness of treating HPH through FMT and offers insights into improving hypoxia adaptation.

摘要

未标记

长期以来,缺氧一直对动物和人类的健康构成严重威胁,导致呼吸性酸中毒、代谢紊乱、全身炎症、氧化应激损伤等问题,从而危及生命并限制高海拔地区的发展。肠道微生物群在生命活动和缺氧适应中起着至关重要的作用。我们将来自青藏高原(3500米)的小型哺乳动物高原鼢鼠的肠道微生物群移植到置于低压舱(相当于海拔6000米)的Sprague-Dawley(SD)大鼠体内30天。结果表明,微生物群移植显著重塑了大鼠的肠道微生物群结构,显著增加了产生短链脂肪酸的菌科毛螺菌科和普雷沃氏菌科的丰度,减轻了缺氧和酸中毒,降低了肺动脉高压和右心室肥大,增加了吲哚-3-乳酸等抗炎物质的产生,并减少了组胺和尿酸等促炎物质的产生。它还降低了肺中lgE、TNFα和IFN-γ等炎症基因的表达。将来自高原特有物种的粪便微生物群移植到低海拔SD大鼠体内有效地改变了代谢,改变了基因表达,降低了肺动脉压,并增强了高原适应性。这项研究证明了通过微生物群移植治疗低氧性肺动脉高压的潜在有效性,并为改善缺氧适应提供了见解。

重要性

我们报告了粪便微生物群移植对缺氧条件下SD大鼠呼吸能力、肺代谢和肺基因表达的有益影响。我们揭示了缺氧条件下肠道微生物群对肺肥大细胞和组胺表达的抑制作用。该研究证明了通过粪便微生物群移植治疗低氧性肺动脉高压的潜在有效性,并为改善缺氧适应提供了见解。

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本文引用的文献

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Curr Issues Mol Biol. 2024 Nov 10;46(11):12733-12745. doi: 10.3390/cimb46110756.
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Rewiring of Uric Acid Metabolism in the Intestine Promotes High-Altitude Hypoxia Adaptation in Humans.肠道中尿酸代谢的重编程促进了人类对高海拔缺氧的适应。
Mol Biol Evol. 2024 Nov 1;41(11). doi: 10.1093/molbev/msae233.
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Dietary fibers boost gut microbiota-produced B vitamin pool and alter host immune landscape.
膳食纤维可促进肠道微生物群产生的 B 族维生素库,并改变宿主免疫图谱。
Microbiome. 2024 Sep 23;12(1):179. doi: 10.1186/s40168-024-01898-7.
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Bacteroides uniformis degrades β-glucan to promote Lactobacillus johnsonii improving indole-3-lactic acid levels in alleviating colitis.均匀拟杆菌将β-葡聚糖降解,促进约氏乳杆菌增加色氨酸-3-乳酸水平,从而缓解结肠炎。
Microbiome. 2024 Sep 19;12(1):177. doi: 10.1186/s40168-024-01896-9.
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Gut microbiota contributes to high-altitude hypoxia acclimatization of human populations.肠道微生物群有助于人类适应高海拔缺氧环境。
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Gut Microbiota-Derived Tryptophan Metabolites Alleviate Allergic Asthma Inflammation in Ovalbumin-Induced Mice.肠道微生物群衍生的色氨酸代谢产物减轻卵清蛋白诱导小鼠的过敏性哮喘炎症
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Exopolysaccharides and Surface-Layer Proteins Expressed by Biofilm-State Y42 Play Crucial Role in Preventing Intestinal Barrier and Immunity Dysfunction of Balb/C Mice Infected by ATCC 19115.生物膜态 Y42 表达的胞外多聚糖和表面层蛋白在预防 ATCC 19115 感染的 Balb/C 小鼠肠道屏障和免疫功能障碍方面发挥关键作用。
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