<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> 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
Subjects:
<i>Limosilactobacillus reuteri</i>
intestinal barrier
inflammation
gut microbiota
oxidative stress
IL-17
Online Access:https://www.mdpi.com/2076-3921/14/1/58
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Summary:<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.
ISSN:2076-3921

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