ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1659142
This article is part of the Research TopicMechanisms of Fermented Foods and Interactions with the Gut MicrobiomeView all 7 articles
Lactiplantibacillus sp. LP03 Alleviates Pulmonary Fibrosis by Modulating Gut Microbiota and Elevating Host Palmitoylethanolamide to Suppress TGF-β1/Smad2/3-Mediated EMT
Provisionally accepted
- 1The First Hospital of Jilin University, Changchun, China
- 2Zibo First Hospital, Zibo, China
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Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited treatment options. Growing evidence indicates that gut microbiota dysbiosis plays a role in pulmonary disorders, highlighting the therapeutic potential of probiotics. In this study, we isolated three Lactobacillus strains—Lactiplantibacillus sp. LP03 (LP03), Levilactobacillus brevis LB06, and Loigolactobacillus coryniformis LC02 from Chinese sauerkraut juice and assessed for their antifibrotic effects in a bleomycin (BLM)-induced mouse model of pulmonary fibrosis. Among them, LP03 demonstrated the most significant therapeutic effects, including reductions in mortality, systemic inflammation, lung coefficient, interstitial thickening, and collagen deposition, as well as inhibition of BLM-induced epithelial-to-mesenchymal transition (EMT). LP03 treatment also restored gut microbial balance, notably increasing the abundance of beneficial genera such as Ligilactobacillus and Akkermansia. Serum metabolomic profiling revealed enhanced lipid metabolism, particularly in glycerophospholipid and fatty acid pathways, along with elevated levels of palmitoylethanolamide (PEA), a bioactive lipid with known anti-inflammatory and antifibrotic effects. Oral supplementation with PEA independently alleviated pulmonary fibrosis, and further mechanistic studies demonstrated that PEA mitigates fibrosis by inhibiting EMT via the TGF-β1/Smad2/3 signaling pathway in both in vivo and in vitro models. These findings indicate that LP03 holds promise as a probiotic-based therapeutic strategy for fibrotic lung diseases through gut microbiota modulation and PEA-mediated regulation of fibrotic signaling pathways.
Keywords: Lactiplantibacillus, Gut Microbiota, palmitoylethanolamide, TGF-β1/Smad2/3 signaling pathway, EMT, Idiopathic Pulmonary Fibrosis
Received: 03 Jul 2025; Accepted: 29 Aug 2025.
Copyright: © 2025 Zhou, Duan, Fan, Zhao, Wang, Wang and Hua. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shucheng Hua, The First Hospital of Jilin University, Changchun, China
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