Fermented Lacticaseibacillus Paracasei Cultures Ameliorate Colitis by Modulating Microbiota-Derived Tryptophan...

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Inflammatory bowel disease (IBD) involves gut microbiota-immune dysregulation.
• Probiotic products offer potential therapeutic strategies for IBD.
• The efficacy of high-density fermented probiotics against IBD requires further investigation.

Purpose of the Study:

• To evaluate the therapeutic effects of high-density solid-state fermented Lacticaseibacillus paracasei (PYW) on dextran sulfate sodium (DSS)-induced colitis.
• To compare the efficacy of live PYW with its inactivated postbiotic (SPYW).
• To elucidate the mechanisms underlying PYW's anti-colitic effects.

Main Methods:

• Induction of colitis in a mouse model using DSS.
• Administration of live PYW and inactivated SPYW.
• Analysis of gut microbiota structure, tryptophan metabolism, and immune mediator expression.
• Investigation of the aryl hydrocarbon receptor (AhR) signaling pathway.
• Assessment of the role of microbiota via antibiotic depletion and fecal microbiota transplantation (FMT).

Main Results:

• PYW demonstrated superior efficacy compared to SPYW in alleviating DSS-induced colitis.
• A viable bacterial load of ≥ 5 × 10^10 CFU g^-1 was essential for PYW's therapeutic effect.
• PYW restored gut microbiota structure and enriched indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA).
• These metabolites activated the AhR pathway, suppressed pro-inflammatory mediators, and strengthened mucosal barriers.
• Antibiotic depletion abolished PYW's benefits, while FMT and ILA/IAA supplementation replicated them.

Conclusions:

• PYW alleviates colitis through a microbiota-dependent mechanism involving ILA/IAA enrichment and AhR pathway activation.
• Live bacterial presence is indispensable for the therapeutic efficacy of PYW.
• PYW holds potential as a probiotic therapeutic for IBD by targeting the microbiota-metabolism-immunity axis.