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Abstract <p>This study evaluated the anti-acne potential of extracellular proteins derived from <i>Lactobacillus gasseri</i> (LG-EPs) by integrating physicochemical characterization, antibacterial assessment, cellular assays, and an in vivo sebaceous gland model. LG-EPs were obtained by ammonium sulfate precipitation and characterized using gel permeation chromatography/light scattering (GPC/LS) and liquid chromatography–tandem mass spectrometry (LC–MS/MS). The molecular weight of LG-EPs was mainly distributed between 1.0 × 10⁴ and 2.0 × 10⁴ g/mol, and peptide analysis identified four peptides with antimicrobial potential and twelve peptides with antioxidant potential. LG-EPs exhibited direct antibacterial activity against acne-associated bacteria, with MIC and MBC values of 600&#xa0;µg/mL against <i>Cutibacterium acnes</i> and MIC and MBC values of 700&#xa0;µg/mL and 1&#xa0;mg/mL, respectively, against <i>Staphylococcus aureus</i>. Growth-curve and biofilm adhesion assays further showed that LG-EPs inhibited bacterial proliferation and adhesion. In LPS-stimulated HaCaT cells, LG-EPs reduced the secretion of pro-inflammatory cytokines, including IL-6, IL-8, IL-1β, and TNF-α, while increasing the expression of barrier-related factors such as AQP3, FLG, and LOR. In a golden hamster model, topical LG-EP treatment decreased sebum production and downregulated the transcription of lipogenesis-related genes, including SREBP-1, FAS, and ACC1. These effects were associated with reduced transcript levels of PI3K, AKT, and mTOR, while the anti-sebum effect was accompanied by increased AMPK transcription. Overall, LG-EPs showed multi-target anti-acne potential through antibacterial, anti-inflammatory, barrier-protective, and sebum-suppressive effects.</p> Graphical abstract

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Lactobacillus gasseri extracellular proteins suppress acne inflammation and sebum secretion via the PI3K/AKT/mTOR pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月1日

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  • Zixin Song,
  • Qinxuan Yuan,
  • Yifan Fang,
  • Bianbian Zhai,
  • Jiman Geng,
  • Meng Li,
  • Changtao Wang,
  • Dongdong Wang

摘要

Abstract

This study evaluated the anti-acne potential of extracellular proteins derived from Lactobacillus gasseri (LG-EPs) by integrating physicochemical characterization, antibacterial assessment, cellular assays, and an in vivo sebaceous gland model. LG-EPs were obtained by ammonium sulfate precipitation and characterized using gel permeation chromatography/light scattering (GPC/LS) and liquid chromatography–tandem mass spectrometry (LC–MS/MS). The molecular weight of LG-EPs was mainly distributed between 1.0 × 10⁴ and 2.0 × 10⁴ g/mol, and peptide analysis identified four peptides with antimicrobial potential and twelve peptides with antioxidant potential. LG-EPs exhibited direct antibacterial activity against acne-associated bacteria, with MIC and MBC values of 600 µg/mL against Cutibacterium acnes and MIC and MBC values of 700 µg/mL and 1 mg/mL, respectively, against Staphylococcus aureus. Growth-curve and biofilm adhesion assays further showed that LG-EPs inhibited bacterial proliferation and adhesion. In LPS-stimulated HaCaT cells, LG-EPs reduced the secretion of pro-inflammatory cytokines, including IL-6, IL-8, IL-1β, and TNF-α, while increasing the expression of barrier-related factors such as AQP3, FLG, and LOR. In a golden hamster model, topical LG-EP treatment decreased sebum production and downregulated the transcription of lipogenesis-related genes, including SREBP-1, FAS, and ACC1. These effects were associated with reduced transcript levels of PI3K, AKT, and mTOR, while the anti-sebum effect was accompanied by increased AMPK transcription. Overall, LG-EPs showed multi-target anti-acne potential through antibacterial, anti-inflammatory, barrier-protective, and sebum-suppressive effects.

Graphical abstract