Probiotic Propionibacterium freudenreichii requires SlpB protein to mitigate mucositis induced by chemotherapy

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Propionibacterium freudenreichii is a probiotic bacterium with known immunomodulatory effects.
• Surface protein SlpB is involved in P. freudenreichii's anti-inflammatory properties and epithelial cell adhesion.
• Mucositis, characterized by inflammation and mucosal injury, is a severe side effect of 5-fluorouracil (5-FU) chemotherapy.

Purpose of the Study:

• To investigate the impact of slpB gene mutation on the immunomodulatory capabilities of P. freudenreichii.
• To evaluate the role of SlpB in P. freudenreichii's ability to mitigate 5-FU-induced mucositis in a mouse model.

Main Methods:

• In vitro assays using LPS-stimulated HT-29 cells to measure cytokine expression (IL-8, TNF-α).
• In vivo study using a 5-FU-induced mucositis mouse model.
• Assessment of weight loss, inflammation, histopathological scores, and gene/cytokine markers (Claudin-1, IL-17a, IL-12, IL-1β).

Main Results:

• P. freudenreichii wild type (WT) significantly reduced IL-8 and TNF-α in vitro, while the ΔslpB mutant did not.
• WT strain prevented weight loss, reduced inflammation, and improved histopathological scores in the mucositis model.
• WT regulated key markers like Claudin-1, IL-17a, IL-12, and IL-1β, whereas the mutant showed opposite effects on Claudin-1 and IL-12.

Conclusions:

• The SlpB surface protein is essential for P. freudenreichii's anti-inflammatory effects and its protective role against mucositis.
• Targeting SlpB in probiotic bacteria offers a potential strategy for developing treatments to reduce chemotherapy-induced side effects.
• GRAS (Generally Recognized As Safe) bacteria with immunomodulatory surface proteins hold promise for novel therapeutic applications.