Succinate exacerbates mastitis in mice via extracellular vesicles derived from the gut microbiota: a potential new mechanism for mastitis

Abstract Background A high grain diet causes an ecological imbalance in the gut microbiota and serves as an important endogenous trigger of mastitis in dairy cows, but the underlying mechanisms are unclear. Our previous study revealed that subacute rumen acidosis (SARA)-associated mastitis has disti...

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Main Authors: Min Qiu, Cong Ye, Xiaotong Zhao, Chenyu Zou, Ruibo Tang, Jiaxin Xie, Yiheng Liu, Yubo Hu, Xiaoyu Hu, Naisheng Zhang, Yunhe Fu, Jun Wang, Caijun Zhao
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-024-02997-1
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author Min Qiu
Cong Ye
Xiaotong Zhao
Chenyu Zou
Ruibo Tang
Jiaxin Xie
Yiheng Liu
Yubo Hu
Xiaoyu Hu
Naisheng Zhang
Yunhe Fu
Jun Wang
Caijun Zhao
author_facet Min Qiu
Cong Ye
Xiaotong Zhao
Chenyu Zou
Ruibo Tang
Jiaxin Xie
Yiheng Liu
Yubo Hu
Xiaoyu Hu
Naisheng Zhang
Yunhe Fu
Jun Wang
Caijun Zhao
author_sort Min Qiu
collection DOAJ
description Abstract Background A high grain diet causes an ecological imbalance in the gut microbiota and serves as an important endogenous trigger of mastitis in dairy cows, but the underlying mechanisms are unclear. Our previous study revealed that subacute rumen acidosis (SARA)-associated mastitis has distinct metabolic profiles in the rumen, especially a significant increase in succinate, but the role of succinate in the pathogenesis of mastitis remains unclear. Results Succinate treatment exacerbates low-grade endotoxemia-induced mastitis in mice. Specifically, succinate increased the production of gut microbiota-extracellular vehicles (mEVs) containing lipopolysaccharides, which can diffuse across the damaged intestinal barrier into the mammary glands. Administration of mEVs promotes mammary inflammation via activation of the TLR4/NF-κB pathway. Conclusions Our findings suggest that succinate promotes mastitis through the proliferation of enteric pathogens and mEVs production, suggesting a potential strategy for mastitis intervention on the basis of intestinal metabolic regulation and pathogen inhibition. The role of mEVs in interspecific communication has also been elucidated. Graphical Abstract
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institution Kabale University
issn 1477-3155
language English
publishDate 2024-11-01
publisher BMC
record_format Article
series Journal of Nanobiotechnology
spelling doaj-art-7272af7f2e6349b7a92c70528980960f2024-11-17T12:47:00ZengBMCJournal of Nanobiotechnology1477-31552024-11-0122111810.1186/s12951-024-02997-1Succinate exacerbates mastitis in mice via extracellular vesicles derived from the gut microbiota: a potential new mechanism for mastitisMin Qiu0Cong Ye1Xiaotong Zhao2Chenyu Zou3Ruibo Tang4Jiaxin Xie5Yiheng Liu6Yubo Hu7Xiaoyu Hu8Naisheng Zhang9Yunhe Fu10Jun Wang11Caijun Zhao12Department of Gynecology, China-Japan Union Hospital of Jilin UniversityDepartment of Gynecology, China-Japan Union Hospital of Jilin UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin UniversityDepartment of Anesthesiology, China-Japan Union Hospital of Jilin UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin UniversityCollege of Animal Science and Technology, Jilin Agricultural UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin UniversityAbstract Background A high grain diet causes an ecological imbalance in the gut microbiota and serves as an important endogenous trigger of mastitis in dairy cows, but the underlying mechanisms are unclear. Our previous study revealed that subacute rumen acidosis (SARA)-associated mastitis has distinct metabolic profiles in the rumen, especially a significant increase in succinate, but the role of succinate in the pathogenesis of mastitis remains unclear. Results Succinate treatment exacerbates low-grade endotoxemia-induced mastitis in mice. Specifically, succinate increased the production of gut microbiota-extracellular vehicles (mEVs) containing lipopolysaccharides, which can diffuse across the damaged intestinal barrier into the mammary glands. Administration of mEVs promotes mammary inflammation via activation of the TLR4/NF-κB pathway. Conclusions Our findings suggest that succinate promotes mastitis through the proliferation of enteric pathogens and mEVs production, suggesting a potential strategy for mastitis intervention on the basis of intestinal metabolic regulation and pathogen inhibition. The role of mEVs in interspecific communication has also been elucidated. Graphical Abstracthttps://doi.org/10.1186/s12951-024-02997-1SuccinateMastitisExtracellular vesiclesTLR4/NF-κB
spellingShingle Min Qiu
Cong Ye
Xiaotong Zhao
Chenyu Zou
Ruibo Tang
Jiaxin Xie
Yiheng Liu
Yubo Hu
Xiaoyu Hu
Naisheng Zhang
Yunhe Fu
Jun Wang
Caijun Zhao
Succinate exacerbates mastitis in mice via extracellular vesicles derived from the gut microbiota: a potential new mechanism for mastitis
Journal of Nanobiotechnology
Succinate
Mastitis
Extracellular vesicles
TLR4/NF-κB
title Succinate exacerbates mastitis in mice via extracellular vesicles derived from the gut microbiota: a potential new mechanism for mastitis
title_full Succinate exacerbates mastitis in mice via extracellular vesicles derived from the gut microbiota: a potential new mechanism for mastitis
title_fullStr Succinate exacerbates mastitis in mice via extracellular vesicles derived from the gut microbiota: a potential new mechanism for mastitis
title_full_unstemmed Succinate exacerbates mastitis in mice via extracellular vesicles derived from the gut microbiota: a potential new mechanism for mastitis
title_short Succinate exacerbates mastitis in mice via extracellular vesicles derived from the gut microbiota: a potential new mechanism for mastitis
title_sort succinate exacerbates mastitis in mice via extracellular vesicles derived from the gut microbiota a potential new mechanism for mastitis
topic Succinate
Mastitis
Extracellular vesicles
TLR4/NF-κB
url https://doi.org/10.1186/s12951-024-02997-1
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