RT Journal Article
T1 The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation
A1 Castelo, Janire
A1 Araujo-Aris, Sarai
A1 Barriales, Diego
A1 Tanner Pasco, Samuel
A1 Seoane, Iratxe
A1 Peña-Cearra, Ainize
A1 Palacios, Ainhoa
A1 Simó, Carolina
A1 García-Cañas, Virginia
A1 Khamwong, Muthita
A1 Martín-Ruiz, Itziar
A1 González-López, Monika
A1 Bárcena, Laura
A1 Martín Rodríguez, José Ezequiel
A1 Lavín, José Luis
A1 Gutiez, Naiara
A1 Marcos, Raquel
A1 Atondo, Estibaliz
A1 Flores Landeira, Juana María
A1 Rodríguez, Héctor
AB Phloroglucinol is a key byproduct of gut microbial metabolism that has been widely used as a treatment for irritable bowel syndrome. Here, we demonstrate that phloroglucinol tempers macrophage responses to pro-inflammatory pathogens and stimuli. In vivo, phloroglucinol administration decreases gut and extraintestinal inflammation in murine models of inflammatory bowel disease and systemic infection. The metabolite induces modest modifications in the microbiota. However, the presence of an active microbiota is required to preserve its anti-inflammatory activity. Remarkably, the protective effect of phloroglucinol lasts partially at least 6 months. Single-cell transcriptomic analysis of bone marrow progenitors demonstrates the capacity of the metabolite to induce long-lasting innate immune training in hematopoietic lineages, at least partially through the participation of the receptor and transcription factor, aryl hydrocarbon receptor (AhR). Phloroglucinol induces alterations in metabolic and epigenetic pathways that are most prevalent in upstream progenitors as hallmarks of central trained immunity. These data identify phloroglucinol as a dietary-derived compound capable of inducing central trained immunity and modulating the response of the host to inflammatory insults.
PB Taylor & Francis
SN 1949-0984
YR 2024
FD 2024-12-15
LK https://hdl.handle.net/20.500.14352/116719
UL https://hdl.handle.net/20.500.14352/116719
LA eng
NO Castelo, J., Araujo-Aris, S., Barriales, D., Tanner Pasco, S., Seoane, I., Peña-Cearra, A., … Rodríguez, H. (2024). The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation. Gut Microbes, 16(1). https://doi.org/10.1080/19490976.2024.2438829
NO Author contributions:Conceptualization: JA, HRMethodology: HP, FTGS, CW, JRK, NJB, PRB, JLS, EHInvestigation: JC, SAA, DB, STP, IS, APC, APa, CS, VGC, MK, IMR, MGL, LB, NG, RM, EA, AC, LPV, APl, ESF, Ape, MVSData analysis and interpretation: AFT, MCV, JMM, AMA, BdlR, RM, AM, PRM, MVS, MGA, LA, JA, HRHistopathological analysis: JMFMetagenomic and scRNAseq data analysis: JEMR, JLL, STP and JAProject administration: JA, HRSupervision: JA, HRWriting – original draft: JC, STP, JA, HRWriting – review & editing: all authors
NO Ministerio de Ciencia e Innovación (España)
NO European Commission
DS Docta Complutense
RD 6 abr 2025