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Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism
BACKGROUNDS AND PURPOSE: The theory of “entero-pulmonary axis” proves that pneumonia leads to gut microbiota disturbance and Treg/Th17 immune imbalance. This study is aimed to explore the potential mechanism of fecal microbiota transplantation (FMT) in the treatment of Pseudomonas aeruginosa pneumon...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243233/ https://www.ncbi.nlm.nih.gov/pubmed/35782123 http://dx.doi.org/10.3389/fcimb.2022.856633 |
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author | Wen, Long Shi, Lei Kong, Xiang-Long Li, Ke-Yu Li, Hui Jiang, Di-Xuan Zhang, Fan Zhou, Zhi-Guo |
author_facet | Wen, Long Shi, Lei Kong, Xiang-Long Li, Ke-Yu Li, Hui Jiang, Di-Xuan Zhang, Fan Zhou, Zhi-Guo |
author_sort | Wen, Long |
collection | PubMed |
description | BACKGROUNDS AND PURPOSE: The theory of “entero-pulmonary axis” proves that pneumonia leads to gut microbiota disturbance and Treg/Th17 immune imbalance. This study is aimed to explore the potential mechanism of fecal microbiota transplantation (FMT) in the treatment of Pseudomonas aeruginosa pneumonia, in order to provide new insights into the treatment of pneumonia. METHODS: Pseudomonas aeruginosa and C57/BL6 mice were used to construct the acute pneumonia mouse model, and FMT was treated. Histopathological changes in lung and spleen were observed by HE staining. The expression of CD25, Foxp3 and IL-17 was observed by immunofluorescence. The proportion of Treg and Th17 cells was analyzed by flow cytometry. Serum IL-6, LPS, and IFN-γ levels were detected by ELISA. The expression of TNF-α, IFN-γ, IL-6, IL-2, Foxp3, IL-17, IL-10, and TGFβ1 in lung tissue homogenate was detected by qRT-PCR. 16S rRNA sequencing and non-targeted metabolomics were used to analyze gut microbiota and metabolism. RESULTS: Pseudomonas aeruginosa caused the decrease of body weight, food and water intake, lung tissue, and spleen injury in mice with pneumonia. Meanwhile, it caused lung tissue and serum inflammation, and Treg/Th17 cell imbalance in mice with pneumonia. Pseudomonas aeruginosa reduced the diversity and number of gut microbiota in pneumonia mice, resulting in metabolic disorders, superpathway of quinolone and alkylquinolone biosynthesis. It also led to the decrease of 2-heptyl-3-hydroxy-4(1H)-quinolone biosynthesis, and the enrichment of Amino sugar and nucleotide sugar metabolism. FMT with or without antibiotic intervention restored gut microbiota abundance and diversity, suppressed inflammation and tissue damage, and promoted an immunological balance of Treg/Th17 cells in mice with pneumonia. In addition, FMT inhibited the aerobactin biosynthesis, 4-hydroxyphenylacetate degradation, superpathway of lipopolysaccharide biosynthesis and L-arabinose degradation IV function of microbiota, and improved amino sugar and nucleotide sugar metabolism. CONCLUSIONS: FMT restored the Treg/Th17 cells’ balance and improved inflammation and lung injury in mice with Pseudomonas aeruginosa pneumonia by regulating gut microbiota disturbance and metabolic disorder. |
format | Online Article Text |
id | pubmed-9243233 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92432332022-07-01 Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism Wen, Long Shi, Lei Kong, Xiang-Long Li, Ke-Yu Li, Hui Jiang, Di-Xuan Zhang, Fan Zhou, Zhi-Guo Front Cell Infect Microbiol Cellular and Infection Microbiology BACKGROUNDS AND PURPOSE: The theory of “entero-pulmonary axis” proves that pneumonia leads to gut microbiota disturbance and Treg/Th17 immune imbalance. This study is aimed to explore the potential mechanism of fecal microbiota transplantation (FMT) in the treatment of Pseudomonas aeruginosa pneumonia, in order to provide new insights into the treatment of pneumonia. METHODS: Pseudomonas aeruginosa and C57/BL6 mice were used to construct the acute pneumonia mouse model, and FMT was treated. Histopathological changes in lung and spleen were observed by HE staining. The expression of CD25, Foxp3 and IL-17 was observed by immunofluorescence. The proportion of Treg and Th17 cells was analyzed by flow cytometry. Serum IL-6, LPS, and IFN-γ levels were detected by ELISA. The expression of TNF-α, IFN-γ, IL-6, IL-2, Foxp3, IL-17, IL-10, and TGFβ1 in lung tissue homogenate was detected by qRT-PCR. 16S rRNA sequencing and non-targeted metabolomics were used to analyze gut microbiota and metabolism. RESULTS: Pseudomonas aeruginosa caused the decrease of body weight, food and water intake, lung tissue, and spleen injury in mice with pneumonia. Meanwhile, it caused lung tissue and serum inflammation, and Treg/Th17 cell imbalance in mice with pneumonia. Pseudomonas aeruginosa reduced the diversity and number of gut microbiota in pneumonia mice, resulting in metabolic disorders, superpathway of quinolone and alkylquinolone biosynthesis. It also led to the decrease of 2-heptyl-3-hydroxy-4(1H)-quinolone biosynthesis, and the enrichment of Amino sugar and nucleotide sugar metabolism. FMT with or without antibiotic intervention restored gut microbiota abundance and diversity, suppressed inflammation and tissue damage, and promoted an immunological balance of Treg/Th17 cells in mice with pneumonia. In addition, FMT inhibited the aerobactin biosynthesis, 4-hydroxyphenylacetate degradation, superpathway of lipopolysaccharide biosynthesis and L-arabinose degradation IV function of microbiota, and improved amino sugar and nucleotide sugar metabolism. CONCLUSIONS: FMT restored the Treg/Th17 cells’ balance and improved inflammation and lung injury in mice with Pseudomonas aeruginosa pneumonia by regulating gut microbiota disturbance and metabolic disorder. Frontiers Media S.A. 2022-06-16 /pmc/articles/PMC9243233/ /pubmed/35782123 http://dx.doi.org/10.3389/fcimb.2022.856633 Text en Copyright © 2022 Wen, Shi, Kong, Li, Li, Jiang, Zhang and Zhou https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular and Infection Microbiology Wen, Long Shi, Lei Kong, Xiang-Long Li, Ke-Yu Li, Hui Jiang, Di-Xuan Zhang, Fan Zhou, Zhi-Guo Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism |
title | Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism |
title_full | Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism |
title_fullStr | Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism |
title_full_unstemmed | Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism |
title_short | Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism |
title_sort | gut microbiota protected against pseudomonas aeruginosa pneumonia via restoring treg/th17 balance and metabolism |
topic | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243233/ https://www.ncbi.nlm.nih.gov/pubmed/35782123 http://dx.doi.org/10.3389/fcimb.2022.856633 |
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