F. prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice

Abstract Background Emerging evidence has shown that extracellular vesicles (EVs) derived from gut bacteria play a crucial role in microbiota-host interactions. Here, we aimed to evaluate the attenuating effect of EVs derived from a reduced commensal bacterium, F. prausnitzii (Fp-EVs), in inflammato...

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Main Authors: Lin Ye, Yizhong Wang, Fangfei Xiao, Xufei Wang, Xiaolu Li, Rong Cao, Jiayue Zhang, Ting Zhang
Format: Article
Language:English
Published: BMC 2023-11-01
Series:Microbial Cell Factories
Subjects:
Online Access:https://doi.org/10.1186/s12934-023-02243-7
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author Lin Ye
Yizhong Wang
Fangfei Xiao
Xufei Wang
Xiaolu Li
Rong Cao
Jiayue Zhang
Ting Zhang
author_facet Lin Ye
Yizhong Wang
Fangfei Xiao
Xufei Wang
Xiaolu Li
Rong Cao
Jiayue Zhang
Ting Zhang
author_sort Lin Ye
collection DOAJ
description Abstract Background Emerging evidence has shown that extracellular vesicles (EVs) derived from gut bacteria play a crucial role in microbiota-host interactions. Here, we aimed to evaluate the attenuating effect of EVs derived from a reduced commensal bacterium, F. prausnitzii (Fp-EVs), in inflammatory bowel disease (IBD) on dextran sulfate sodium (DSS)-induced colitis in mice. Results Fp-EVs isolated by ultracentrifugation and typically exhibited a double concave disc shape with an average diameter of 172 nm. Fp-EVs treatment reduced DSS-induced weight loss, disease activity index (DAI) score, colon length shortening, histological damage, neutrophil infiltration and increased intestinal epithelial apoptotic cells in DSS-induced colitis mice. Fp-EVs upregulated the protein expression of zona occludens (ZO)-1 and Occludin and increased the ratio of Tregs in the colon tissue of colitis mice. Furthermore, Fp-EVs downregulated the expression of the proinflammatory cytokines interleukin-1β (IL-1β), IL-2, IL-6, IL-12a, IL-17a, Interferon-γ (IFN-γ), tumor necrosis factor - α (TNF-α), granulocyte-macrophage colony stimulating factor (GM-CSF) and upregulated the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor β (TGF-β) in DSS-treated mice. Moreover, Fp-EV treatment markedly reduced the phosphorylation of these proteins Nuclear factor-κB (NF-κB) and Mitogen activated protein kinase (MAPK), and regulated the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1). Conclusion Our findings revealed that Fp-EVs attenuated DSS-induced colitis by modulating the intestinal mucosal barrier function and immunological profile. Our findings reveal that Fp-EVs attenuate DSS-induced colitis by modulating intestinal mucosal barrier function and the immunological profile.
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spelling doaj.art-6beabdb55e374b0886ae26ae1d2e74f62023-11-20T11:22:28ZengBMCMicrobial Cell Factories1475-28592023-11-0122111510.1186/s12934-023-02243-7F. prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in miceLin Ye0Yizhong Wang1Fangfei Xiao2Xufei Wang3Xiaolu Li4Rong Cao5Jiayue Zhang6Ting Zhang7Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong University School of NursingDepartment of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of MedicineAbstract Background Emerging evidence has shown that extracellular vesicles (EVs) derived from gut bacteria play a crucial role in microbiota-host interactions. Here, we aimed to evaluate the attenuating effect of EVs derived from a reduced commensal bacterium, F. prausnitzii (Fp-EVs), in inflammatory bowel disease (IBD) on dextran sulfate sodium (DSS)-induced colitis in mice. Results Fp-EVs isolated by ultracentrifugation and typically exhibited a double concave disc shape with an average diameter of 172 nm. Fp-EVs treatment reduced DSS-induced weight loss, disease activity index (DAI) score, colon length shortening, histological damage, neutrophil infiltration and increased intestinal epithelial apoptotic cells in DSS-induced colitis mice. Fp-EVs upregulated the protein expression of zona occludens (ZO)-1 and Occludin and increased the ratio of Tregs in the colon tissue of colitis mice. Furthermore, Fp-EVs downregulated the expression of the proinflammatory cytokines interleukin-1β (IL-1β), IL-2, IL-6, IL-12a, IL-17a, Interferon-γ (IFN-γ), tumor necrosis factor - α (TNF-α), granulocyte-macrophage colony stimulating factor (GM-CSF) and upregulated the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor β (TGF-β) in DSS-treated mice. Moreover, Fp-EV treatment markedly reduced the phosphorylation of these proteins Nuclear factor-κB (NF-κB) and Mitogen activated protein kinase (MAPK), and regulated the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1). Conclusion Our findings revealed that Fp-EVs attenuated DSS-induced colitis by modulating the intestinal mucosal barrier function and immunological profile. Our findings reveal that Fp-EVs attenuate DSS-induced colitis by modulating intestinal mucosal barrier function and the immunological profile.https://doi.org/10.1186/s12934-023-02243-7F. PrausnitziiExtracellular vesiclesColitisIBD
spellingShingle Lin Ye
Yizhong Wang
Fangfei Xiao
Xufei Wang
Xiaolu Li
Rong Cao
Jiayue Zhang
Ting Zhang
F. prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice
Microbial Cell Factories
F. Prausnitzii
Extracellular vesicles
Colitis
IBD
title F. prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice
title_full F. prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice
title_fullStr F. prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice
title_full_unstemmed F. prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice
title_short F. prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice
title_sort f prausnitzii derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice
topic F. Prausnitzii
Extracellular vesicles
Colitis
IBD
url https://doi.org/10.1186/s12934-023-02243-7
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