1. In silico and functional analyses of immunomodulatory peptides encrypted in the human gut metaproteome
- Author
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Marco A. Moro-García, Sabino Riestra, Florentino Fdez-Riverola, Aitor Blanco-Míguez, Noelia Cambeiro-Pérez, Claudio Hidalgo-Cantabrana, Borja Sánchez, Elena Martínez-Carballo, Rebeca Alonso-Arias, Abelardo Margolles, Anália Lourenço, Universidade do Minho, Ministerio de Economía y Competitividad (España), Asociación Española Contra el Cáncer, Principado de Asturias, Xunta de Galicia, Hidalgo-Cantabrana, Claudio, Moro-García, Marco A., Blanco-Míguez, Aitor, Fdez-Riverola, Florentino, Margolles Barros, Abelardo, Sánchez García, Borja, 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], and Sánchez García, Borja [0000-0003-1408-8018]
- Subjects
0301 basic medicine ,Bifidobacterium longum ,In silico ,Medicine (miscellaneous) ,Peptide ,2304.18 Polipéptidos y Proteínas ,03 medical and health sciences ,0404 agricultural biotechnology ,Metabolomics ,medicine ,TX341-641 ,Antigen-presenting cell ,chemistry.chemical_classification ,030109 nutrition & dietetics ,Nutrition and Dietetics ,Innate immune system ,Science & Technology ,biology ,Nutrition. Foods and food supply ,Human microbiome ,04 agricultural and veterinary sciences ,biology.organism_classification ,040401 food science ,Extracellular proteins ,3. Good health ,Treg ,Biochemistry ,Mechanism of action ,chemistry ,medicine.symptom ,2414 Microbiología ,Anti-inflammatory ,Tolerance ,Food Science - Abstract
Supplementary data to this article can be found online at https:// doi.org/10.1016/j.jff.2020.103969., 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 Crohns 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., Our work is supported by the Spanish “Programa Estatal de Investigación. Desarrollo e Innovación Orientada a los Retos de la Sociedad” (grants AGL2013-44761-P and AGL2016-78311-R); the Asociación Española Contra el Cancer (“Obtención de péptidos bioactivos contra el Cáncer Colo-Rectal a partir de secuencias genéticas de microbiomas intestinales”, Grant PS-2016), by the Asturias Regional Plan I + D + i for research groups (FYCYT-IDI/2018/000236) and by the Autonomic “Investigadores Emerxentes do Sistema Universitario de Galicia” (Grant EM2014/046). This work was partially supported by the Consellería de Educación. Universidades e Formación Profesional (Xunta de Galicia) under the scope of the strategic funding of ED431C2018/55-GRC Competitive Reference Group. Finally, the authors wish to thank Jaume Morales and Rubén García form Agilent Technologies for technical support., info:eu-repo/semantics/publishedVersion
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- 2020