BUSCADOR RECOLECTA

Digital.CSIC. Repositorio Institucional del CSIC

oai:digital.csic.es:10261/337759

Ellagitannins (ETs) and ellagic acid (EA) are dietary polyphenols poorly absorbed but extensively metabolized by the human gut microbiota to produce different urolithins (Uros). Depending on the individuals' microbial signatures, ETs metabolism can yield the Uro metabotypes A, B, or 0, potentially impacting human health after consuming ETs. Human evidence points to improved brain health after consuming ET-rich foods, mainly pomegranate juices and extracts containing punicalagin, punicalin, and different EA-derivatives. Although ETs and (or) EA are necessary to exert the effects, the precise mechanism, actual metabolites, or final drivers responsible for the observed effects have not been unraveled. The cause-and-effect evidence on Uro-A administration and the improvement of animal brain health is consistent but not addressed in humans. The Uro-A's in vivo anti-inflammatory, mitophagy, autophagy, and mitochondrial biogenesis activities suggest it as a possible final driver in neuroprotection. However, the precise Uro metabolic forms reaching the brain are unknown. In addition to the possible participation of direct effectors in brain tissues, the current evidence points out that improving blood flow, gut microbiota ecology, and gut barrier by ET-rich foods and (or) Uro-A could contribute to the neuroprotective effects. We show here the current human evidence on ETs and brain health, the possible link between the gut microbiota metabolism of ETs and their effects, including the preservation of the gut barrier integrity, and the possible role of Uros. Finally, we propose a roadmap to address what is missing on ETs, Uros, and neuroprotection, This work was supported by the Projects PID 2019-103914RB-I00 from the Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033, Spain) and 21647/PDC/21, 20880/PI/18 and 19900/GERM/15 (Fundación Séneca de la Región de Murcia, Spain). C.E.I.-A. holds a predoctoral grant from MICIN (grant number FPU18/03961, Spain). J.A.G.-B. was supported by a Standard European Marie Curie Fellowship from the European Commission (European Union's Horizon, 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 838991)., Peer reviewed