PDF(Pubmed)
Abstract：
UNASSIGNED: Acute lung injury (ALI) is a severe respiratory tract disorder facilitated by dysregulated inflammation, oxidative stress and intestinal ecosystem. Fecal microbiota transplantation (FMT) is a rapid method for gut microbiota (GM) reconstruction. Furthermore, our previous studies have confirmed that human umbilical cord mesenchymal stromal cells (HUC-MSCs) can alleviate ALI by improving GM composition. Therefore, we aimed to explore the efficacy and mechanism of FMT from HUC-MSCs-treated mice on ALI.
UNASSIGNED: In brief, fresh feces from HUC-MSCs-treated mice were collected for FMT, and the mice were randomly assigned into NC, FMT, LPS, ABX-LPS, and ABX-LPS-FMT groups (n = 12/group). Subsequently, the mice were administrated with antibiotic mixtures to deplete GM, and given lipopolysaccharide and FMT to induce ALI and rebuild GM. Next, the therapeutic effect was evaluated by bronchoalveolar lavage fluid (BALF) and histopathology. Immune cells in peripheral blood and apoptosis in lung tissues were measured. Furthermore, oxidative stress- and inflammation-related parameter levels were tested in BALF, serum, lung and ileal tissues. The expressions of apoptosis-associated, TLR4/NF-κB pathway-associated, Nrf2/HO-1 pathway related and tightly linked proteins in the lung and ileal tissues were assessed. Moreover, 16S rRNA was conducted to assess GM composition and distribution.
UNASSIGNED: Our results revealed that FMT obviously improved the pathological damage of lung and ileum, recovered the immune system of peripheral blood, decreased the cell apoptosis of lung, and inhibited inflammation and oxidative stress in BALF, serum, lung and ileum tissues. Moreover, FMT also elevated ZO-1, claudin-1, and occludin protein expressions, activating the Nrf2/HO-1 pathway but hindering the TLR4/NF-κB pathway. Of note, the relative abundances of Bacteroides, Christensenella, Coprococcus, and Roseburia were decreased, while the relative abundances of Xenorhabdus, Sutterella, and Acinetobacter were increased in the ABX-LPS-FMT group.
UNASSIGNED: FMT from HUC-MSCs-treated mice may alleviate ALI by inhibiting inflammation and reconstructing GM, additionally, we also found that the TLR4/NF-κB and Nrf2/HO-1 pathways may involve in the improvement of FMT on ALI, which offers novel insights for the functions and mechanisms of FMT from HUC-MSCs-treated mice on ALI.
UNASSIGNED: In brief, fresh feces from HUC-MSCs-treated mice were collected for FMT, and the mice were randomly assigned into NC, FMT, LPS, ABX-LPS, and ABX-LPS-FMT groups (n = 12/group). Subsequently, the mice were administrated with antibiotic mixtures to deplete GM, and given lipopolysaccharide and FMT to induce ALI and rebuild GM. Next, the therapeutic effect was evaluated by bronchoalveolar lavage fluid (BALF) and histopathology. Immune cells in peripheral blood and apoptosis in lung tissues were measured. Furthermore, oxidative stress- and inflammation-related parameter levels were tested in BALF, serum, lung and ileal tissues. The expressions of apoptosis-associated, TLR4/NF-κB pathway-associated, Nrf2/HO-1 pathway related and tightly linked proteins in the lung and ileal tissues were assessed. Moreover, 16S rRNA was conducted to assess GM composition and distribution.
UNASSIGNED: Our results revealed that FMT obviously improved the pathological damage of lung and ileum, recovered the immune system of peripheral blood, decreased the cell apoptosis of lung, and inhibited inflammation and oxidative stress in BALF, serum, lung and ileum tissues. Moreover, FMT also elevated ZO-1, claudin-1, and occludin protein expressions, activating the Nrf2/HO-1 pathway but hindering the TLR4/NF-κB pathway. Of note, the relative abundances of Bacteroides, Christensenella, Coprococcus, and Roseburia were decreased, while the relative abundances of Xenorhabdus, Sutterella, and Acinetobacter were increased in the ABX-LPS-FMT group.
UNASSIGNED: FMT from HUC-MSCs-treated mice may alleviate ALI by inhibiting inflammation and reconstructing GM, additionally, we also found that the TLR4/NF-κB and Nrf2/HO-1 pathways may involve in the improvement of FMT on ALI, which offers novel insights for the functions and mechanisms of FMT from HUC-MSCs-treated mice on ALI.
摘要：
■急性肺损伤（ALI）是一种由炎症失调引起的严重呼吸道疾病，氧化应激和肠道生态系统。粪便微生物群移植（FMT）是一种快速重建肠道微生物群（GM）的方法。此外，我们之前的研究已经证实，人脐带间充质基质细胞（HUC-MSCs）可以通过改善GM组成来缓解ALI。因此,我们旨在探讨HUC-MSCs治疗小鼠FMT对ALI的疗效和机制。
■简而言之，收集HUC-MSCs处理小鼠的新鲜粪便用于FMT,将小鼠随机分配到NC中，FMT,LPS,ABX-LPS,和ABX-LPS-FMT组(n=12/组)。随后，给小鼠施用抗生素混合物以消耗转基因，并给予脂多糖和FMT诱导ALI和重建GM。接下来,通过支气管肺泡灌洗液(BALF)和组织病理学评估治疗效果.检测外周血中的免疫细胞和肺组织中的凋亡。此外，在BALF中测试氧化应激和炎症相关参数水平，血清,肺和回肠组织。细胞凋亡相关基因的表达，TLR4/NF-κB通路相关,评估了肺和回肠组织中Nrf2/HO-1途径相关和紧密连接的蛋白。此外，进行16SrRNA以评估GM组成和分布。
■我们的结果表明FMT明显改善了肺和回肠的病理损伤，恢复外周血的免疫系统，减少肺细胞凋亡，并抑制BALF中的炎症和氧化应激，血清,肺和回肠组织。此外，FMT还升高了ZO-1，claudin-1和occludin蛋白的表达，激活Nrf2/HO-1通路，但阻碍TLR4/NF-κB通路。值得注意的是，拟杆菌的相对丰度，Christensenella,球菌,罗斯布里亚减少了，而相对丰富的Xenorhabdus，Sutterilla,ABX-LPS-FMT组不动杆菌升高。
■来自HUC-MSCs治疗小鼠的FMT可能通过抑制炎症和重建GM来减轻ALI，此外，我们还发现TLR4/NF-κB和Nrf2/HO-1通路可能参与FMT对ALI的改善,这为HUC-MSCs治疗小鼠对ALI的FMT的功能和机制提供了新的见解。
■简而言之，收集HUC-MSCs处理小鼠的新鲜粪便用于FMT,将小鼠随机分配到NC中，FMT,LPS,ABX-LPS,和ABX-LPS-FMT组(n=12/组)。随后，给小鼠施用抗生素混合物以消耗转基因，并给予脂多糖和FMT诱导ALI和重建GM。接下来,通过支气管肺泡灌洗液(BALF)和组织病理学评估治疗效果.检测外周血中的免疫细胞和肺组织中的凋亡。此外，在BALF中测试氧化应激和炎症相关参数水平，血清,肺和回肠组织。细胞凋亡相关基因的表达，TLR4/NF-κB通路相关,评估了肺和回肠组织中Nrf2/HO-1途径相关和紧密连接的蛋白。此外，进行16SrRNA以评估GM组成和分布。
■我们的结果表明FMT明显改善了肺和回肠的病理损伤，恢复外周血的免疫系统，减少肺细胞凋亡，并抑制BALF中的炎症和氧化应激，血清,肺和回肠组织。此外，FMT还升高了ZO-1，claudin-1和occludin蛋白的表达，激活Nrf2/HO-1通路，但阻碍TLR4/NF-κB通路。值得注意的是，拟杆菌的相对丰度，Christensenella,球菌,罗斯布里亚减少了，而相对丰富的Xenorhabdus，Sutterilla,ABX-LPS-FMT组不动杆菌升高。
■来自HUC-MSCs治疗小鼠的FMT可能通过抑制炎症和重建GM来减轻ALI，此外，我们还发现TLR4/NF-κB和Nrf2/HO-1通路可能参与FMT对ALI的改善,这为HUC-MSCs治疗小鼠对ALI的FMT的功能和机制提供了新的见解。
