1. In silico and functional analyses of immunomodulatory peptides encrypted in the human gut metaproteome
- Author
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Ministerio de Economía y Competitividad (España), Asociación Española Contra el Cáncer, Principado de Asturias, Xunta de Galicia, Hidalgo-Cantabrana, Claudio [0000-0002-7248-4564], Moro-García, Marco A. [0000-0001-9601-5757], Blanco-Míguez, Aitor [0000-0001-7386-5572], Fdez-Riverola, Florentino [0000-0002-3943-8013], Margolles Barros, Abelardo [0000-0003-2278-1816], Sánchez García, Borja [0000-0003-1408-8018], Cambeiro-Pérez, Noelia, Hidalgo-Cantabrana, Claudio, Moro-García, Marco A., Blanco-Míguez, Aitor, Fdez-Riverola, Florentino, Riestra, Sabina, Lourenço, Anália, Alonso-Arias, Rebeca, Margolles Barros, Abelardo, Martínez-Carballo, Elena, Sánchez García, Borja, Ministerio de Economía y Competitividad (España), Asociación Española Contra el Cáncer, Principado de Asturias, Xunta de Galicia, Hidalgo-Cantabrana, Claudio [0000-0002-7248-4564], Moro-García, Marco A. [0000-0001-9601-5757], Blanco-Míguez, Aitor [0000-0001-7386-5572], Fdez-Riverola, Florentino [0000-0002-3943-8013], Margolles Barros, Abelardo [0000-0003-2278-1816], Sánchez García, Borja [0000-0003-1408-8018], Cambeiro-Pérez, Noelia, Hidalgo-Cantabrana, Claudio, Moro-García, Marco A., Blanco-Míguez, Aitor, Fdez-Riverola, Florentino, Riestra, Sabina, Lourenço, Anália, Alonso-Arias, Rebeca, Margolles Barros, Abelardo, Martínez-Carballo, Elena, and Sánchez García, Borja
- Abstract
This work supports the massive presence of potential immunomodulatory peptides in the human gut metaproteome. These peptides were identified through the MAHMI database as potentially anti-inflammatory, and sixteen of them synthesized for characterize their mechanism of action. From them, peptide HM14 was encrypted in an extracellular protein produced by Bifidobacterium longum, a common member of the human microbiota, and displayed the highest anti-inflammatory capability. Molecular mechanism of action of HM14 pointed to a specific interaction between this immunomodulatory peptide and antigen presenting cells, which resulted in a higher formation of iTreg cells. Moreover, HM14 was effective in decreasing pro-inflammatory parameters in PBMCs isolated from a cohort of Crohn’s patients. Finally, non-targeted metabolomics confirmed the ability of HM14 to modulate the metabolic activity of PBMCs to fulfil its energy and biosynthetic requirements. Overall, our combined in silico/multiomics approach supports the human gut metaproteome as a source for immunomodulatory peptides.
- Published
- 2020