# Extracellular Vesicles from the Probiotic Yeast Pichia kudriavzevii: Proteomic Characterization and Modulation of Immune and Defense Responses in an Induced Inflammation Model of Intestinal Epithelial Cells

## TL;DR

This study explores extracellular vesicles from a probiotic yeast and their potential to modulate immune responses and reduce inflammation in intestinal cells.

## Contribution

The paper introduces a novel proteomic characterization of EVs from Pichia kudriavzevii and demonstrates their safety and immunomodulatory potential.

## Key findings

- EVs from Pichia kudriavzevii are 100-150 nm in size and contain 189 proteins with antimicrobial and immunomodulatory properties.
- The vesicles showed no cytotoxicity in Caco-2 cells or in vivo in Galleria mellonella larvae.
- The study supports the use of probiotic-derived EVs as a safe alternative to live probiotics.

## Abstract

Background/Objectives: Extracellular vesicles (EVs) derived from probiotics represent a new and exciting frontier in host-microbe therapeutics. These nanoscale carriers are not merely cellular byproducts but are sophisticated mediators of intercellular communication, capable of modulating immune responses, reducing inflammation, and inhibiting pathogens through a rich cargo of bioactive molecules. Methods: The EVs isolated from the culture supernatants of the yeast probiotic candidate Pichia kudriavzevii were characterized for their dimensions, protein composition, and targeting both the gut pathogen virulence and the host inflammatory response. Results: The vesicles had a size distribution from 100 to 150 nm, which is consistent with previous reports on fungal EVs. Proteomic analysis of the purified EVs identified a complex array of 189 proteins, hypothesized to be responsible for some of the antimicrobial and immunomodulatory properties observed. Safety was a key consideration, and the isolated EVs demonstrated no cytotoxicity in human Caco-2 cells and no in vivo toxicity in the Galleria mellonella larval model, confirming their potential for safe use. Conclusions: The field is moving towards a new era of “postbiotics,” where cell-free therapies offer a safer, more stable alternative to live probiotics.