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Kefir peptides mitigate bleomycin-induced pulmonary fibrosis in mice through modulating oxidative stress, inflammation and gut microbiota - 27/04/24

Doi : 10.1016/j.biopha.2024.116431 
Ying-Wei Lan a, b, 1 , Ying-Cheng Chen a, c, 1 , Chih-Ching Yen a, d , Hsiao-Ling Chen e, f, Min-Che Tung g, Hueng-Chuen Fan g, Chuan-Mu Chen a, h,
a Department of Life Sciences, College of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan 
b Phoenix Children's Health Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix 85004, USA 
c Department of Basic Medical Sciences, Veterinary Medicines, Purdue University, West Lafayette, Indiana 47906, USA 
d Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan 
e Department of Biomedical Science, Da-Yeh University, Changhua 515, Taiwan 
f Phermpep Co., Ltd., China Chemical & Pharmaceutical Group (CCPG), Taichung 42881, Taiwan 
g Department of Surgery, and Tungs’ Taichung Metro Harbor Hospital, Taichung 435, Taiwan 
h The iEGG and Animal Biotechnology Research Center, National Chung Hsing University, Taichung 402, Taiwan 

Corresponding author at: Department of Life Sciences, College of Life Sciences, National Chung Hsing University, Kuo Kuang Rd, Taichung 402, Taiwan.Department of Life Sciences, College of Life Sciences, National Chung Hsing UniversityKuo Kuang RdTaichung402Taiwan

Abstract

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive and life-threatening lung disease with high mortality rates. The limited availability of effective drugs for IPF treatment, coupled with concerns regarding adverse effects and restricted responsiveness, underscores the need for alternative approaches. Kefir peptides (KPs) have demonstrated antioxidative, anti-inflammatory, and antifibrotic properties, along with the capability to modulate gut microbiota. This study aims to investigate the impact of KPs on bleomycin-induced pulmonary fibrosis.

Methods

Mice were treated with KPs for four days, followed by intratracheal injection of bleomycin for 21 days. Comprehensive assessments included pulmonary functional tests, micro-computed tomography (µ-CT), in vivo image analysis using MMPsense750, evaluation of inflammation- and fibrosis-related gene expression in lung tissue, and histopathological examinations. Furthermore, a detailed investigation of the gut microbiota community was performed using full-length 16 S rRNA sequencing in control mice, bleomycin-induced fibrotic mice, and KPs-pretreated fibrotic mice.

Results

In KPs-pretreated bleomycin-induced lung fibrotic mice, notable outcomes included the absence of significant bodyweight loss, enhanced pulmonary functions, restored lung tissue architecture, and diminished thickening of inter-alveolar septa, as elucidated by morphological and histopathological analyses. Concurrently, a reduction in the expression levels of oxidative biomarkers, inflammatory factors, and fibrotic indicators was observed. Moreover, 16 S rRNA sequencing demonstrated that KPs pretreatment induced alterations in the relative abundances of gut microbiota, notably affecting Barnesiella_intestinihominis, Kineothrix_alysoides, and Clostridium_viride.

Conclusions

Kefir peptides exerted preventive effects, protecting mice against bleomycin-induced lung oxidative stress, inflammation, and fibrosis. These effects are likely linked to modifications in the gut microbiota community. The findings highlight the therapeutic potential of KPs in mitigating pulmonary fibrosis and advocate for additional exploration in clinical settings.

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Highlights

Idiopathic pulmonary fibrosis (IPF), a severe lung condition with high mortality, poses a significant health threat.
A murine model effectively mimics IPF symptoms three weeks post intratracheal bleomycin administration.
Kefir peptides (KPs) alleviate bleomycin-induced lung injury, improving respiratory function and reducing fibrosis.
KPs offer multifaceted defense, combating oxidative stress, inflammation, and profibrotic factors in pulmonary fibrosis.
KPs induce structural changes in the gut microbiota of bleomycin-induced pulmonary fibrotic mice.

Le texte complet de cet article est disponible en PDF.

Keywords : Kefir peptides (KPs), Idiopathic pulmonary fibrosis (IPF), Inflammation, Bleomycin, Gut microbiota community


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