Hua Feng, Cui Enhai, Lv Lu, Wang Bin, Li Liqin, Lu Huadong, Chen Na, Chen Wenyan
Department of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, China.
Traditional Chinese Medicine Key Laboratory Cultivation Base of Zhejiang Province for the Development and Clinical Transformation of Immunomodulatory Drugs, Huzhou, China.
Front Microbiol. 2023 Sep 28;14:1243102. doi: 10.3389/fmicb.2023.1243102. eCollection 2023.
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.
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 ( = 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.
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, , and were decreased, while the relative abundances of , and were increased in the ABX-LPS-FMT group.
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.
急性肺损伤（ALI）是一种严重的呼吸道疾病，由炎症失调、氧化应激和肠道生态系统紊乱引发。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，我们之前的研究证实，人脐带间充质基质细胞（HUC-MSCs）可通过改善GM组成来减轻ALI。因此，我们旨在探讨经HUC-MSCs处理的小鼠的FMT对ALI的疗效及机制。
简而言之，收集经HUC-MSCs处理的小鼠的新鲜粪便用于FMT，并将小鼠随机分为NC、FMT、LPS、ABX-LPS和ABX-LPS-FMT组（每组n = 12）。随后，给小鼠施用抗生素混合物以耗尽GM，并给予脂多糖和FMT以诱导ALI并重建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细胞凋亡情况。此外，检测BALF、血清、肺和回肠组织中氧化应激和炎症相关参数水平。评估肺和回肠组织中凋亡相关、TLR4/NF-κB途径相关、Nrf2/HO-1途径相关及紧密连接蛋白的表达。此外，进行16S rRNA检测以评估GM的组成和分布。
我们的结果显示，FMT明显改善了肺和回肠的病理损伤，恢复了外周血的免疫系统，减少了肺细胞凋亡，并抑制了BALF、血清、肺和回肠组织中的炎症和氧化应激。此外，FMT还提高了ZO-1、claudin-1和occludin蛋白的表达，激活了Nrf2/HO-1途径，但阻碍了TLR4/NF-κB途径。值得注意的是，ABX-LPS-FMT组中拟杆菌属、[具体菌属1]和[具体菌属2]的相对丰度降低，而[具体菌属3]、[具体菌属4]和[具体菌属5]的相对丰度增加。
经HUC-MSCs处理的小鼠的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途径可能参与了FMT对ALI的改善作用，这为经HUC-MSCs处理的小鼠的FMT对ALI的功能和机制提供了新的见解。
