Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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IPA and its precursors differently modulate the proliferation, differentiation, and integrity of intestinal epithelial cells

  • Shamila Ismael (Nutricao e Metabolismo, NOVA Medical School - Faculdade de Ciencias Medicas (NMS - FCM), Universidade NOVA de Lisboa) ;
  • Catarina Rodrigues (Nutricao e Metabolismo, NOVA Medical School - Faculdade de Ciencias Medicas (NMS - FCM), Universidade NOVA de Lisboa) ;
  • Gilberto Maia Santos (Nutricao e Metabolismo, NOVA Medical School - Faculdade de Ciencias Medicas (NMS - FCM), Universidade NOVA de Lisboa) ;
  • Ines Castela (Nutricao e Metabolismo, NOVA Medical School - Faculdade de Ciencias Medicas (NMS - FCM), Universidade NOVA de Lisboa) ;
  • Ines Barreiros-Mota (Nutricao e Metabolismo, NOVA Medical School - Faculdade de Ciencias Medicas (NMS - FCM), Universidade NOVA de Lisboa) ;
  • Maria Joao Almeida (Nutricao e Metabolismo, NOVA Medical School - Faculdade de Ciencias Medicas (NMS - FCM), Universidade NOVA de Lisboa) ;
  • Conceicao Calhau (Nutricao e Metabolismo, NOVA Medical School - Faculdade de Ciencias Medicas (NMS - FCM), Universidade NOVA de Lisboa) ;
  • Ana Faria (Nutricao e Metabolismo, NOVA Medical School - Faculdade de Ciencias Medicas (NMS - FCM), Universidade NOVA de Lisboa) ;
  • Joao Ricardo Araujo (Nutricao e Metabolismo, NOVA Medical School - Faculdade de Ciencias Medicas (NMS - FCM), Universidade NOVA de Lisboa)
  • Received : 2022.10.26
  • Accepted : 2023.03.02
  • Published : 2023.08.01
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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.

Keywords

Acknowledgement

This work was supported by ERDF through the operation POCI-01-0145-ERDF-007746 funded by the Programa Operacional Competitividade e Internacionalizacao - COMPETE2020 and by FCT - Fundacao para a Ciencia e a Tecnologia, IP national support through CINTESIS, R&D Unit (UIDB/4255/2020), CHRC (UIDP/04923/2020 and UIDB/04923/2020), through the project reference PTDC/BAA-AGR/7419/2020 and the 2020.06333.BD.

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