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Background <p>Autophagy-related processes are crucial for maintaining cellular homeostasis in eukaryotic organisms. While alterations of these processes have been strongly linked to specific human disorders, including inflammatory bowel disease, neurodegenerative diseases, and metabolic syndromes, long-term autophagy stimulation appears to be safe and to extend lifespan in model organisms. Several studies indicate that gut microbiota or derived metabolites can modulate host autophagy at the gut mucosa level but also in peripheral organs. Here, we investigated in vitro and in vivo the potential of bacterial species commonly used in food fermentation (ferments) or for their health benefits (probiotics) to modulate host autophagy.</p> Methods <p>We screened 11 bacterial strains (lactobacilli and bifidobacteria) in vitro for autophagy induction in human epithelial cells. The most effective strain identified in vitro was then tested in vivo through long-term dietary supplementation in mice to confirm its pro-autophagic effects in the gut and a distant organ, the retina.</p> Results <p>In vitro screening of the 11 bacterial strains revealed a strain-dependent ability of bacteria to stimulate autophagy in human epithelial cells. The <i>Lactobacillus helveticus</i> strain VEL12193, isolated from cheese, emerged as the strongest autophagy inducer. Long-term dietary supplementation of mice with <i>L. helveticus</i> VEL12193 confirmed the pro-autophagic potential of this strain, as evidenced by autophagy stimulation in the gut mucosa but also at distance, in the retina. Finally, we identified membrane vesicles (MVs) from <i>L. helveticus</i> as a component involved in bacteria-induced autophagy in epithelial and immune cells, with lactate and specific lipid species potentially contributing to this effect.</p> Conclusion <p>In this study, we present evidence that intervention with ferments/probiotics stimulates autophagy in multiple cell types and organs, and we show in vitro that MVs mediate this effect. Additionally, we identify <i>L. helveticus</i> VEL12193 as a promising candidate for the development of healthy-aging strategies.</p>

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The food grade bacterium Lactobacillus helveticus VEL12193 promotes autophagy by releasing membrane vesicles

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月6日

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  • Marie-Agnès Bringer,
  • Simon Manceau,
  • Jana Al Azzaz,
  • Bénédicte Buteau,
  • Lil Proukhnitzky,
  • Amaury Aumeunier,
  • Luis G. Bermúdez-Humarán,
  • Florian Chain,
  • Catherine Daniel,
  • Elise Jacquin,
  • Zandile Mlamla,
  • Jean-Paul Pais de Barros,
  • Julia Novion Ducassou,
  • Yohann Couté,
  • Guilhem Faure,
  • Niyazi Acar,
  • Aurélie Rieu,
  • Pierre Lapaquette

摘要

Background

Autophagy-related processes are crucial for maintaining cellular homeostasis in eukaryotic organisms. While alterations of these processes have been strongly linked to specific human disorders, including inflammatory bowel disease, neurodegenerative diseases, and metabolic syndromes, long-term autophagy stimulation appears to be safe and to extend lifespan in model organisms. Several studies indicate that gut microbiota or derived metabolites can modulate host autophagy at the gut mucosa level but also in peripheral organs. Here, we investigated in vitro and in vivo the potential of bacterial species commonly used in food fermentation (ferments) or for their health benefits (probiotics) to modulate host autophagy.

Methods

We screened 11 bacterial strains (lactobacilli and bifidobacteria) in vitro for autophagy induction in human epithelial cells. The most effective strain identified in vitro was then tested in vivo through long-term dietary supplementation in mice to confirm its pro-autophagic effects in the gut and a distant organ, the retina.

Results

In vitro screening of the 11 bacterial strains revealed a strain-dependent ability of bacteria to stimulate autophagy in human epithelial cells. The Lactobacillus helveticus strain VEL12193, isolated from cheese, emerged as the strongest autophagy inducer. Long-term dietary supplementation of mice with L. helveticus VEL12193 confirmed the pro-autophagic potential of this strain, as evidenced by autophagy stimulation in the gut mucosa but also at distance, in the retina. Finally, we identified membrane vesicles (MVs) from L. helveticus as a component involved in bacteria-induced autophagy in epithelial and immune cells, with lactate and specific lipid species potentially contributing to this effect.

Conclusion

In this study, we present evidence that intervention with ferments/probiotics stimulates autophagy in multiple cell types and organs, and we show in vitro that MVs mediate this effect. Additionally, we identify L. helveticus VEL12193 as a promising candidate for the development of healthy-aging strategies.