Hexadecanamide alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting inflammatory responses and restoring blood-milk barrier integrity.

Subacute ruminal acidosis (SARA) has been demonstrated to promote the development of mastitis, one of the most serious diseases in dairy farming worldwide, but the underlying mechanism is unclear. Using untargeted metabolomics, we found hexadecanamide (HEX) was significantly reduced in rumen fluid a...

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Main Authors: Lijuan Bao, Hao Sun, Yihong Zhao, Lianjun Feng, Keyi Wu, Shan Shang, Jiawen Xu, Ruping Shan, Shiyu Duan, Min Qiu, Naisheng Zhang, Xiaoyu Hu, Caijun Zhao, Yunhe Fu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-11-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1011764
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author Lijuan Bao
Hao Sun
Yihong Zhao
Lianjun Feng
Keyi Wu
Shan Shang
Jiawen Xu
Ruping Shan
Shiyu Duan
Min Qiu
Naisheng Zhang
Xiaoyu Hu
Caijun Zhao
Yunhe Fu
author_facet Lijuan Bao
Hao Sun
Yihong Zhao
Lianjun Feng
Keyi Wu
Shan Shang
Jiawen Xu
Ruping Shan
Shiyu Duan
Min Qiu
Naisheng Zhang
Xiaoyu Hu
Caijun Zhao
Yunhe Fu
author_sort Lijuan Bao
collection DOAJ
description Subacute ruminal acidosis (SARA) has been demonstrated to promote the development of mastitis, one of the most serious diseases in dairy farming worldwide, but the underlying mechanism is unclear. Using untargeted metabolomics, we found hexadecanamide (HEX) was significantly reduced in rumen fluid and milk from cows with SARA-associated mastitis. Herein, we aimed to assess the protective role of HEX in Staphylococcus aureus (S. aureus)- and SARA-induced mastitis and the underlying mechanism. We showed that HEX ameliorated S. aureus-induced mastitis in mice, which was related to the suppression of mammary inflammatory responses and repair of the blood-milk barrier. In vitro, HEX depressed S. aureus-induced activation of the NF-κB pathway and improved barrier integrity in mouse mammary epithelial cells (MMECs). In detail, HEX activated PPARα, which upregulated SIRT1 and subsequently inhibited NF-κB activation and inflammatory responses. In addition, ruminal microbiota transplantation from SARA cows (S-RMT) caused mastitis and aggravated S. aureus-induced mastitis, while these changes were reversed by HEX. Our findings indicate that HEX effectively attenuates S. aureus- and SARA-induced mastitis by limiting inflammation and repairing barrier integrity, ultimately highlighting the important role of host or microbiota metabolism in the pathogenesis of mastitis and providing a potential strategy for mastitis prevention.
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spelling doaj.art-d1c092902d9744b0ad207319055fc7252023-12-12T05:32:22ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-11-011911e101176410.1371/journal.ppat.1011764Hexadecanamide alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting inflammatory responses and restoring blood-milk barrier integrity.Lijuan BaoHao SunYihong ZhaoLianjun FengKeyi WuShan ShangJiawen XuRuping ShanShiyu DuanMin QiuNaisheng ZhangXiaoyu HuCaijun ZhaoYunhe FuSubacute ruminal acidosis (SARA) has been demonstrated to promote the development of mastitis, one of the most serious diseases in dairy farming worldwide, but the underlying mechanism is unclear. Using untargeted metabolomics, we found hexadecanamide (HEX) was significantly reduced in rumen fluid and milk from cows with SARA-associated mastitis. Herein, we aimed to assess the protective role of HEX in Staphylococcus aureus (S. aureus)- and SARA-induced mastitis and the underlying mechanism. We showed that HEX ameliorated S. aureus-induced mastitis in mice, which was related to the suppression of mammary inflammatory responses and repair of the blood-milk barrier. In vitro, HEX depressed S. aureus-induced activation of the NF-κB pathway and improved barrier integrity in mouse mammary epithelial cells (MMECs). In detail, HEX activated PPARα, which upregulated SIRT1 and subsequently inhibited NF-κB activation and inflammatory responses. In addition, ruminal microbiota transplantation from SARA cows (S-RMT) caused mastitis and aggravated S. aureus-induced mastitis, while these changes were reversed by HEX. Our findings indicate that HEX effectively attenuates S. aureus- and SARA-induced mastitis by limiting inflammation and repairing barrier integrity, ultimately highlighting the important role of host or microbiota metabolism in the pathogenesis of mastitis and providing a potential strategy for mastitis prevention.https://doi.org/10.1371/journal.ppat.1011764
spellingShingle Lijuan Bao
Hao Sun
Yihong Zhao
Lianjun Feng
Keyi Wu
Shan Shang
Jiawen Xu
Ruping Shan
Shiyu Duan
Min Qiu
Naisheng Zhang
Xiaoyu Hu
Caijun Zhao
Yunhe Fu
Hexadecanamide alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting inflammatory responses and restoring blood-milk barrier integrity.
PLoS Pathogens
title Hexadecanamide alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting inflammatory responses and restoring blood-milk barrier integrity.
title_full Hexadecanamide alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting inflammatory responses and restoring blood-milk barrier integrity.
title_fullStr Hexadecanamide alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting inflammatory responses and restoring blood-milk barrier integrity.
title_full_unstemmed Hexadecanamide alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting inflammatory responses and restoring blood-milk barrier integrity.
title_short Hexadecanamide alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting inflammatory responses and restoring blood-milk barrier integrity.
title_sort hexadecanamide alleviates staphylococcus aureus induced mastitis in mice by inhibiting inflammatory responses and restoring blood milk barrier integrity
url https://doi.org/10.1371/journal.ppat.1011764
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