Indole-3-acetic acid promotes differentiation while suppressing proliferation in human intestinal epithelial cells

Area of Science:

• Gastroenterology
• Cell Biology
• Microbiome Research

Background:

• Indole-3-acetic acid (IAA), a tryptophan-derived microbial metabolite, plays a role in intestinal homeostasis, immune regulation, and epithelial function.
• The precise molecular effects of IAA on intestinal epithelial cells are not fully understood.

Purpose of the Study:

• To investigate the concentration-dependent effects of IAA on intestinal epithelial biology.
• To analyze IAA's impact on cytotoxicity, epithelial repair, stemness, and differentiation in Caco-2 cells.

Main Methods:

• Caco-2 cell line was used to assess cell viability (MTT assay) and colony-forming capacity.
• Cytokine expression (IL-17, IL-1β, IL-6) was quantified using qPCR.
• Epithelial differentiation was evaluated by dome formation and analysis of markers (DPPIV, SI, KLF4, E-cadherin) via qPCR and immunofluorescence.

Main Results:

• IAA exhibited concentration-dependent effects, reducing Caco-2 cell viability and colony-forming potential.
• Higher IAA concentrations decreased the expression of inflammatory cytokines IL-17, IL-1β, and IL-6.
• IAA promoted dome formation and upregulated differentiation markers, indicating a shift towards a mature epithelial phenotype.

Conclusions:

• IAA directly modulates intestinal epithelial cell viability, inflammatory signaling, repair capacity, and differentiation.
• These findings suggest a role for IAA in regulating intestinal growth, repair, and differentiation, impacting gut homeostasis and disease pathophysiology.
• Further research is needed to explore the therapeutic implications of IAA, particularly in colorectal cancer.