PMID- 37840733 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231020 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 14 DP - 2023 TI - Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulation. PG - 1243102 LID - 10.3389/fmicb.2023.1243102 [doi] LID - 1243102 AB - INTRODUCTION: 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. METHODS: 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-kappaB 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. RESULTS: 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-kappaB 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. CONCLUSION: FMT from HUC-MSCs-treated mice may alleviate ALI by inhibiting inflammation and reconstructing GM, additionally, we also found that the TLR4/NF-kappaB 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. CI - Copyright (c) 2023 Hua, Cui, Lv, Wang, Li, Lu, Chen and Chen. FAU - Hua, Feng AU - Hua F AD - Department of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, China. FAU - Cui, Enhai AU - Cui E AD - Department of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, China. FAU - Lv, Lu AU - Lv L AD - Department of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, China. FAU - Wang, Bin AU - Wang B AD - Department of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, China. FAU - Li, Liqin AU - Li L AD - Traditional Chinese Medicine Key Laboratory Cultivation Base of Zhejiang Province for the Development and Clinical Transformation of Immunomodulatory Drugs, Huzhou, China. FAU - Lu, Huadong AU - Lu H AD - Department of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, China. FAU - Chen, Na AU - Chen N AD - Department of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, China. FAU - Chen, Wenyan AU - Chen W AD - Department of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, China. LA - eng PT - Journal Article DEP - 20230928 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC10569429 OTO - NOTNLM OT - acute lung injury OT - fecal microbiota transplantation OT - gut microbiota OT - human umbilical cord mesenchymal stromal cells OT - inflammation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/10/16 06:48 MHDA- 2023/10/16 06:49 PMCR- 2023/09/28 CRDT- 2023/10/16 04:20 PHST- 2023/06/20 00:00 [received] PHST- 2023/08/29 00:00 [accepted] PHST- 2023/10/16 06:49 [medline] PHST- 2023/10/16 06:48 [pubmed] PHST- 2023/10/16 04:20 [entrez] PHST- 2023/09/28 00:00 [pmc-release] AID - 10.3389/fmicb.2023.1243102 [doi] PST - epublish SO - Front Microbiol. 2023 Sep 28;14:1243102. doi: 10.3389/fmicb.2023.1243102. eCollection 2023.