<i>Limosilactobacillus fermentum</i> MG4244 Protects Against Metabolic and Inflammatory Stress in <i>Caenorhabditis elegans</i>

In this study, we investigated the effects of MG4244 on intestinal permeability, oxidative stress, and lipid accumulation in <i>Caenorhabditis elegans</i> with metabolic inflammation induced by <i>Pseudomonas aeruginosa</i> (PA) and a high-glucose diet (HGD). The worms infect...

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Main Authors: Yebin Kim, Opeyemi O. Deji-Oloruntoba, Yunji Choe, Jiyeon Lee, Jeongyong Park, Byoungkook Kim, Sooim Choi, Miran Jang
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Foods
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Online Access:https://www.mdpi.com/2304-8158/14/11/1995
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author Yebin Kim
Opeyemi O. Deji-Oloruntoba
Yunji Choe
Jiyeon Lee
Jeongyong Park
Byoungkook Kim
Sooim Choi
Miran Jang
author_facet Yebin Kim
Opeyemi O. Deji-Oloruntoba
Yunji Choe
Jiyeon Lee
Jeongyong Park
Byoungkook Kim
Sooim Choi
Miran Jang
author_sort Yebin Kim
collection DOAJ
description In this study, we investigated the effects of MG4244 on intestinal permeability, oxidative stress, and lipid accumulation in <i>Caenorhabditis elegans</i> with metabolic inflammation induced by <i>Pseudomonas aeruginosa</i> (PA) and a high-glucose diet (HGD). The worms infected with PA exhibited increased intestinal permeability and reactive oxygen species (ROS) production, which were improved upon MG4244 treatment. Also, MG4244 inhibited lipid and ROS accumulation induced by an HGD. In addition, MG4244-treated worms showed extended lifespans under various conditions. To elucidate the mechanism of the MG4244 effects, we conducted further investigation using mutant strains with knockdown of genes associated with the AMP-activated protein kinase (AMPK) and mitogen-activated protein kinase (MAPK) pathways. The results demonstrated that the MG4244 effect on lipid metabolism was primarily mediated through the AMPK signaling pathway. Furthermore, MG4244 enhanced pathogen resistance by MAPK signaling pathways, mitigating stress responses, and maintaining intestinal integrity. In further studies, combined treatment with PA and an HGD significantly increased intestinal permeability, lipid, and ROS levels, confirming their negative synergistic effects. However, MG4244 under PA and HGD co-treatment conditions effectively mitigated these health disruptions, suggesting a protective role of MG4244. This study provides an in vivo platform using <i>C. elegans</i> to evaluate probiotic efficacy related to the intestinal environment. Also, our results highlight the therapeutic potential of MG4244 in improving resilience to metabolic inflammation through gut-targeted mechanisms.
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spelling doaj-art-8f585e19ef234f4293cd27b9a218038e2025-08-20T02:33:08ZengMDPI AGFoods2304-81582025-06-011411199510.3390/foods14111995<i>Limosilactobacillus fermentum</i> MG4244 Protects Against Metabolic and Inflammatory Stress in <i>Caenorhabditis elegans</i>Yebin Kim0Opeyemi O. Deji-Oloruntoba1Yunji Choe2Jiyeon Lee3Jeongyong Park4Byoungkook Kim5Sooim Choi6Miran Jang7Department of Institute of Digital Anti-Aging Healthcare, Inje University, Gimhae 50834, Republic of KoreaBiohealth Convergence Unit, Food and Drug Biotechnology, Inje University, Gimhae 50834, Republic of KoreaDepartment of Food Technology and Nutrition, Inje University, Gimhae 50834, Republic of KoreaMEDIOGEN, Co., Ltd., Biovalley 1-ro, Jecheon 27159, Republic of KoreaMEDIOGEN, Co., Ltd., Biovalley 1-ro, Jecheon 27159, Republic of KoreaMEDIOGEN, Co., Ltd., Biovalley 1-ro, Jecheon 27159, Republic of KoreaMEDIOGEN, Co., Ltd., Biovalley 1-ro, Jecheon 27159, Republic of KoreaDepartment of Institute of Digital Anti-Aging Healthcare, Inje University, Gimhae 50834, Republic of KoreaIn this study, we investigated the effects of MG4244 on intestinal permeability, oxidative stress, and lipid accumulation in <i>Caenorhabditis elegans</i> with metabolic inflammation induced by <i>Pseudomonas aeruginosa</i> (PA) and a high-glucose diet (HGD). The worms infected with PA exhibited increased intestinal permeability and reactive oxygen species (ROS) production, which were improved upon MG4244 treatment. Also, MG4244 inhibited lipid and ROS accumulation induced by an HGD. In addition, MG4244-treated worms showed extended lifespans under various conditions. To elucidate the mechanism of the MG4244 effects, we conducted further investigation using mutant strains with knockdown of genes associated with the AMP-activated protein kinase (AMPK) and mitogen-activated protein kinase (MAPK) pathways. The results demonstrated that the MG4244 effect on lipid metabolism was primarily mediated through the AMPK signaling pathway. Furthermore, MG4244 enhanced pathogen resistance by MAPK signaling pathways, mitigating stress responses, and maintaining intestinal integrity. In further studies, combined treatment with PA and an HGD significantly increased intestinal permeability, lipid, and ROS levels, confirming their negative synergistic effects. However, MG4244 under PA and HGD co-treatment conditions effectively mitigated these health disruptions, suggesting a protective role of MG4244. This study provides an in vivo platform using <i>C. elegans</i> to evaluate probiotic efficacy related to the intestinal environment. Also, our results highlight the therapeutic potential of MG4244 in improving resilience to metabolic inflammation through gut-targeted mechanisms.https://www.mdpi.com/2304-8158/14/11/1995MG4244intestinal permeabilityreactive oxygen specieslipid accumulationAMPKMAPK
spellingShingle Yebin Kim
Opeyemi O. Deji-Oloruntoba
Yunji Choe
Jiyeon Lee
Jeongyong Park
Byoungkook Kim
Sooim Choi
Miran Jang
<i>Limosilactobacillus fermentum</i> MG4244 Protects Against Metabolic and Inflammatory Stress in <i>Caenorhabditis elegans</i>
Foods
MG4244
intestinal permeability
reactive oxygen species
lipid accumulation
AMPK
MAPK
title <i>Limosilactobacillus fermentum</i> MG4244 Protects Against Metabolic and Inflammatory Stress in <i>Caenorhabditis elegans</i>
title_full <i>Limosilactobacillus fermentum</i> MG4244 Protects Against Metabolic and Inflammatory Stress in <i>Caenorhabditis elegans</i>
title_fullStr <i>Limosilactobacillus fermentum</i> MG4244 Protects Against Metabolic and Inflammatory Stress in <i>Caenorhabditis elegans</i>
title_full_unstemmed <i>Limosilactobacillus fermentum</i> MG4244 Protects Against Metabolic and Inflammatory Stress in <i>Caenorhabditis elegans</i>
title_short <i>Limosilactobacillus fermentum</i> MG4244 Protects Against Metabolic and Inflammatory Stress in <i>Caenorhabditis elegans</i>
title_sort i limosilactobacillus fermentum i mg4244 protects against metabolic and inflammatory stress in i caenorhabditis elegans i
topic MG4244
intestinal permeability
reactive oxygen species
lipid accumulation
AMPK
MAPK
url https://www.mdpi.com/2304-8158/14/11/1995
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