IPA and its precursors differently modulate the proliferation, differentiation, and integrity of intestinal epithelial cells
- Author:
Shámila ISMAEL
1
;
Catarina RODRIGUES
;
Gilberto Maia SANTOS
;
Inês CASTELA
;
Inês BARREIROS-MOTA
;
Maria João ALMEIDA
;
Conceição CALHAU
;
Ana FARIA
;
João Ricardo ARAÚJO
Author Information
- Publication Type:Original Research
- From:Nutrition Research and Practice 2023;17(4):616-630
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND/OBJECTIVES:Indole-3-propionic acid (IPA) is a tryptophan-derived microbial metabolite that has been associated with protective effects against inflammatory and metabolic diseases. However, there is a lack of knowledge regarding the effects of IPA under physiological conditions and at the intestinal level.MATERIALS/METHODS: Human intestinal epithelial Caco-2 cells were treated for 2, 24, and/ or 72 h with IPA or its precursors – indole, tryptophan, and propionate – at 1, 10, 100, 250, or 500 μM to assess cell viability, integrity, differentiation, and proliferation.
RESULTS:IPA induced cell proliferation and this effect was associated with a higher expression of extracellular signal-regulated kinase 2 (ERK2) and a lower expression of c-Jun. Although indole and propionate also induced cell proliferation, this involved ERK2 and c-Jun independent mechanisms. On the other hand, both tryptophan and propionate increased cell integrity and reduced the expression of claudin-1, whereas propionate decreased cell differentiation.
CONCLUSIONS:In conclusion, these findings suggested that IPA and its precursors distinctly contribute to the proliferation, differentiation, and barrier function properties of human intestinal epithelial cells. Moreover, the pro-proliferative effect of IPA in intestinal epithelial cells was not explained by its precursors and is rather related to its whole chemical structure.Maintaining IPA at physiological levels, e.g., through IPA-producing commensal bacteria, may be important to preserve the integrity of the intestinal barrier and play an integral role in maintaining metabolic homeostasis.
