<i>Limosilactobacillus reuteri</i> ZY15 Alleviates Intestinal Inflammation and Barrier Dysfunction via AKT/mTOR/HIF-1α/RORγt/IL-17 Signaling and the Gut Microbiota in ETEC K88-Challenged <i>Mice</i>

<i>Limosilactobacillus reuteri</i>, a recognized probiotic, improves intestinal health in animals, but the mechanism remains unclear. This study investigates the mechanisms by which <i>L. reuteri</i> ZY15, isolated from healthy pig feces, mitigates intestinal barrier damage a...

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Main Authors: Xin Xu, Hongwei Zhang, Kun Meng, Hongying Cai, Weiwei Liu, Liye Song, Zihan Zhang, Qijun Zhu, Xiling Han, Yunsheng Han, Peilong Yang
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/14/1/58
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author Xin Xu
Hongwei Zhang
Kun Meng
Hongying Cai
Weiwei Liu
Liye Song
Zihan Zhang
Qijun Zhu
Xiling Han
Yunsheng Han
Peilong Yang
author_facet Xin Xu
Hongwei Zhang
Kun Meng
Hongying Cai
Weiwei Liu
Liye Song
Zihan Zhang
Qijun Zhu
Xiling Han
Yunsheng Han
Peilong Yang
author_sort Xin Xu
collection DOAJ
description <i>Limosilactobacillus reuteri</i>, a recognized probiotic, improves intestinal health in animals, but the mechanism remains unclear. This study investigates the mechanisms by which <i>L. reuteri</i> ZY15, isolated from healthy pig feces, mitigates intestinal barrier damage and inflammation caused by oxidative stress in Enterotoxigenic <i>Escherichia coli</i> (ETEC) K88-challenged mice. The results indicated that <i>L. reuteri</i> ZY15 increased antioxidant capacity by reducing serum reactive oxygen species (ROS) and superoxide dismutase (SOD) levels. <i>L. reuteri</i> ZY15 enhanced the intestinal barrier by upregulating mucin 1, mucin 2, <i>occludin</i>, <i>zonula occludens-1</i> (<i>ZO-1</i>), and <i>claudin-1</i> expressions in protein and mRNA levels. It significantly alleviated intestinal inflammation by reducing the proinflammatory cytokines <i>interleukin-1β</i> (<i>IL-1β</i>), <i>interferon-γ</i> (<i>IFN-γ</i>), tumor necrosis factor-α (TNF-α), and interleukin-17 (IL-17) mRNA and protein levels. Notably, <i>L. reuteri</i> ZY15 suppressed intestinal inflammation by inhibiting AKT/mTOR/HIF-1α/RORγt/IL-17 pathway activation. Additionally, it significantly altered the structure of gut microorganisms by enriching <i>Akkermansia</i> and <i>Clostridia_UCG.014</i>, and thereby re-establishing colonization resistance and alleviating ETEC K88-induced intestinal barrier damage and inflammation in mice. Taken together, our findings reveal the protective mechanism of <i>L. reuteri</i> ZY15 in mice challenged with ETEC K88 by regulating AKT/mTOR/HIF-1α/RORγt/IL-17 signaling and microbial imbalance. Leveraging these properties, live <i>L. reuteri</i> ZY15 offers a promising alternative treatment for <i>Escherichia coli</i>-induced diarrhea in weaned piglets.
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publisher MDPI AG
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series Antioxidants
spelling doaj-art-585a203d0a8c4013921945670d92bd6d2025-01-24T13:19:20ZengMDPI AGAntioxidants2076-39212025-01-011415810.3390/antiox14010058<i>Limosilactobacillus reuteri</i> ZY15 Alleviates Intestinal Inflammation and Barrier Dysfunction via AKT/mTOR/HIF-1α/RORγt/IL-17 Signaling and the Gut Microbiota in ETEC K88-Challenged <i>Mice</i>Xin Xu0Hongwei Zhang1Kun Meng2Hongying Cai3Weiwei Liu4Liye Song5Zihan Zhang6Qijun Zhu7Xiling Han8Yunsheng Han9Peilong Yang10Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, ChinaChengde Academy of Agriculture and Forestry Sciences, Chengde 067000, ChinaKey Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, ChinaKey Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, ChinaKey Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, ChinaKey Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, ChinaKey Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, ChinaKey Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, ChinaKey Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, ChinaKey Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, ChinaKey Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China<i>Limosilactobacillus reuteri</i>, a recognized probiotic, improves intestinal health in animals, but the mechanism remains unclear. This study investigates the mechanisms by which <i>L. reuteri</i> ZY15, isolated from healthy pig feces, mitigates intestinal barrier damage and inflammation caused by oxidative stress in Enterotoxigenic <i>Escherichia coli</i> (ETEC) K88-challenged mice. The results indicated that <i>L. reuteri</i> ZY15 increased antioxidant capacity by reducing serum reactive oxygen species (ROS) and superoxide dismutase (SOD) levels. <i>L. reuteri</i> ZY15 enhanced the intestinal barrier by upregulating mucin 1, mucin 2, <i>occludin</i>, <i>zonula occludens-1</i> (<i>ZO-1</i>), and <i>claudin-1</i> expressions in protein and mRNA levels. It significantly alleviated intestinal inflammation by reducing the proinflammatory cytokines <i>interleukin-1β</i> (<i>IL-1β</i>), <i>interferon-γ</i> (<i>IFN-γ</i>), tumor necrosis factor-α (TNF-α), and interleukin-17 (IL-17) mRNA and protein levels. Notably, <i>L. reuteri</i> ZY15 suppressed intestinal inflammation by inhibiting AKT/mTOR/HIF-1α/RORγt/IL-17 pathway activation. Additionally, it significantly altered the structure of gut microorganisms by enriching <i>Akkermansia</i> and <i>Clostridia_UCG.014</i>, and thereby re-establishing colonization resistance and alleviating ETEC K88-induced intestinal barrier damage and inflammation in mice. Taken together, our findings reveal the protective mechanism of <i>L. reuteri</i> ZY15 in mice challenged with ETEC K88 by regulating AKT/mTOR/HIF-1α/RORγt/IL-17 signaling and microbial imbalance. Leveraging these properties, live <i>L. reuteri</i> ZY15 offers a promising alternative treatment for <i>Escherichia coli</i>-induced diarrhea in weaned piglets.https://www.mdpi.com/2076-3921/14/1/58<i>Limosilactobacillus reuteri</i>intestinal barrierinflammationgut microbiotaoxidative stressIL-17
spellingShingle Xin Xu
Hongwei Zhang
Kun Meng
Hongying Cai
Weiwei Liu
Liye Song
Zihan Zhang
Qijun Zhu
Xiling Han
Yunsheng Han
Peilong Yang
<i>Limosilactobacillus reuteri</i> ZY15 Alleviates Intestinal Inflammation and Barrier Dysfunction via AKT/mTOR/HIF-1α/RORγt/IL-17 Signaling and the Gut Microbiota in ETEC K88-Challenged <i>Mice</i>
Antioxidants
<i>Limosilactobacillus reuteri</i>
intestinal barrier
inflammation
gut microbiota
oxidative stress
IL-17
title <i>Limosilactobacillus reuteri</i> ZY15 Alleviates Intestinal Inflammation and Barrier Dysfunction via AKT/mTOR/HIF-1α/RORγt/IL-17 Signaling and the Gut Microbiota in ETEC K88-Challenged <i>Mice</i>
title_full <i>Limosilactobacillus reuteri</i> ZY15 Alleviates Intestinal Inflammation and Barrier Dysfunction via AKT/mTOR/HIF-1α/RORγt/IL-17 Signaling and the Gut Microbiota in ETEC K88-Challenged <i>Mice</i>
title_fullStr <i>Limosilactobacillus reuteri</i> ZY15 Alleviates Intestinal Inflammation and Barrier Dysfunction via AKT/mTOR/HIF-1α/RORγt/IL-17 Signaling and the Gut Microbiota in ETEC K88-Challenged <i>Mice</i>
title_full_unstemmed <i>Limosilactobacillus reuteri</i> ZY15 Alleviates Intestinal Inflammation and Barrier Dysfunction via AKT/mTOR/HIF-1α/RORγt/IL-17 Signaling and the Gut Microbiota in ETEC K88-Challenged <i>Mice</i>
title_short <i>Limosilactobacillus reuteri</i> ZY15 Alleviates Intestinal Inflammation and Barrier Dysfunction via AKT/mTOR/HIF-1α/RORγt/IL-17 Signaling and the Gut Microbiota in ETEC K88-Challenged <i>Mice</i>
title_sort i limosilactobacillus reuteri i zy15 alleviates intestinal inflammation and barrier dysfunction via akt mtor hif 1α rorγt il 17 signaling and the gut microbiota in etec k88 challenged i mice i
topic <i>Limosilactobacillus reuteri</i>
intestinal barrier
inflammation
gut microbiota
oxidative stress
IL-17
url https://www.mdpi.com/2076-3921/14/1/58
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