Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulation
IntroductionAcute 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 conf...
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Frontiers Media S.A.
2023-09-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1243102/full |
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author | Feng Hua Enhai Cui Lu Lv Bin Wang Liqin Li Huadong Lu Na Chen Wenyan Chen |
author_facet | Feng Hua Enhai Cui Lu Lv Bin Wang Liqin Li Huadong Lu Na Chen Wenyan Chen |
author_sort | Feng Hua |
collection | DOAJ |
description | IntroductionAcute 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.MethodsIn 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.ResultsOur 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.ConclusionFMT 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. |
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spelling | doaj.art-ea0e68eabc0b4a1598bea7e3264a4ae02023-09-29T05:42:55ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-09-011410.3389/fmicb.2023.12431021243102Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulationFeng Hua0Enhai Cui1Lu Lv2Bin Wang3Liqin Li4Huadong Lu5Na Chen6Wenyan Chen7Department of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, ChinaDepartment of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, ChinaDepartment of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, ChinaDepartment of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, ChinaTraditional Chinese Medicine Key Laboratory Cultivation Base of Zhejiang Province for the Development and Clinical Transformation of Immunomodulatory Drugs, Huzhou, ChinaDepartment of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, ChinaDepartment of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, ChinaDepartment of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, ChinaIntroductionAcute 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.MethodsIn 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.ResultsOur 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.ConclusionFMT 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.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1243102/fullfecal microbiota transplantationhuman umbilical cord mesenchymal stromal cellsacute lung injuryinflammationgut microbiota |
spellingShingle | Feng Hua Enhai Cui Lu Lv Bin Wang Liqin Li Huadong Lu Na Chen Wenyan Chen Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulation Frontiers in Microbiology fecal microbiota transplantation human umbilical cord mesenchymal stromal cells acute lung injury inflammation gut microbiota |
title | Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulation |
title_full | Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulation |
title_fullStr | Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulation |
title_full_unstemmed | Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulation |
title_short | Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulation |
title_sort | fecal microbiota transplantation from huc msc treated mice alleviates acute lung injury in mice through anti inflammation and gut microbiota modulation |
topic | fecal microbiota transplantation human umbilical cord mesenchymal stromal cells acute lung injury inflammation gut microbiota |
url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1243102/full |
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