Akademik Veri Yönetim Sistemi
European Academy of Allergy and Clinical Immunology Congress, Aarau, İsviçre, 13 - 16 Haziran 2025, cilt.80, sa.1661, ss.818-819, (Özet Bildiri)
Background:
Gut microbiota metabolites have important roles in gut epithelial homeostasis. In addition, they have prominent roles in skin and respiratory epithelial homeostasis (gut–lung and gut–skin axis).
Method:
We aimed to investigate the inflammatory modulatory effect of indole-3-propionic acid (IPA) on mucosal and skin epithelial tissues using organ-on-a-chip, ex vivo tissue, and organoid models.
Results:
We showed that IPA improves gut epithelial barrier development speed and integrity, as demonstrated in gut-on-a-chip 3D cultures. Surface application of 0.25, 1, and 4 mM doses of IPA significantly increased gut epithelial barrier integrity. IPA increased the expression of claudin-1 at both transcriptomic and proteomic levels. It exhibited anti-inflammatory activity, demonstrated by decreased chemokines (CXCL-5, CXCL-10, CXCL-11, CCL-20, CCL-23, CCL-25, CSF-1, and MCP-1) and epithelial alarmin IL-1α levels in the culture medium detected by proteomics.
In addition, IPA rescued epithelial barrier impairment caused by a proinflammatory cytokine combination (TNF-α, IFN-γ, and IL-1β) in the gut-on-a-chip system. Next, we assessed its effects on respiratory and skin epithelial barrier sites. Systemic circulation–relevant doses of IPA (0.25, 1, and 4 μM) rescued respiratory epithelial barrier impairment caused by TNF-α in airway spheroids, as assessed by paracellular flux assay. In addition, TNF-induced proinflammatory cytokine release was downregulated by IPA.
Next, we assessed its effects on skin epithelial barrier integrity using an ex vivo skin tissue model. Treatment with IPA alone rescued surfactant cocoyl methyl glucamide–induced skin epithelial barrier damage within 24 h. In addition, IPA reversed inflammation caused by cocoyl methyl glucamide, demonstrated by decreased IL-18, CSF-1, PRDX-3, and PD-L1 protein levels. We demonstrated its inhibitory effect on the NF-κB signaling pathway in monocyte and colon reporter assays.
Conclusion:
In conclusion, our data highlight IPA, a gut microbiome metabolite, as a promising agent for preventing, rescuing, and treating gut, respiratory, and skin epithelial barrier impairment and inflammation.