(Poly)phenol-rich grape and blueberry extract prevents LPS-induced disruption of the blood-brain barrier through the modulation of the gut microbiota-derived uremic toxins

Connell, Emily, Le Gall, Gwénaëlle ORCID: https://orcid.org/0000-0002-1379-2196, McArthur, Simon, Lang, Leonie, Breeze, Bernadette ORCID: https://orcid.org/0000-0002-2563-8823, Pontifex, Matthew G. ORCID: https://orcid.org/0000-0003-2174-2313, Sami, Saber, Pourtau, Line, Gaudout, David, Müller, Michael ORCID: https://orcid.org/0000-0002-5930-9905 and Vauzour, David ORCID: https://orcid.org/0000-0001-5952-8756 (2024) (Poly)phenol-rich grape and blueberry extract prevents LPS-induced disruption of the blood-brain barrier through the modulation of the gut microbiota-derived uremic toxins. Neurochemistry International, 180. ISSN 0197-0186

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Abstract

The dynamic protective capacity of (poly)phenols, attributed to their potent antioxidant and anti-inflammatory properties, has been consistently reported. Due to their capacity to alter gut microbiome composition, further actions of (poly)phenols may be exerted through the modulation of the microbiota-gut-brain axis. However, the underlying mechanisms remain poorly defined. Here, we investigated the protective effect of a (poly)phenol-rich grape and blueberry extract (Memophenol™), on the microbiota-gut-brain axis in a model of chronic low-grade inflammation (0.5 mg/kg/wk lipopolysaccharide (LPS) for 8 weeks). Dietary supplementation of male C57BL/6J mice with Memophenol™ prevented LPS-induced increases in the microbe-derived uremia-associated molecules, indoxyl sulfate (IS) and trimethylamine N-oxide (TMAO). These changes coincided with shifts in gut microbiome composition, notably Romboutsia and Desulfovibrio abundance, respectively. In the brain, LPS exposure disrupted the marginal localisation of the endothelial tight junction ZO-1 and downregulated ZO-1 mRNA expression to an extent closely correlated with TMAO and IS levels; a process prevented by Memophenol™ intake. Hippocampal mRNA sequencing analysis revealed significant downregulation in regulatory pathways of neurodegeneration with Memophenol™ intake. These findings may indicate a novel protective role of the (poly)phenol-rich grape and blueberry extract on the endothelial tight junction component ZO-1, acting through modulation of gut microbial metabolism.

Item Type:	Article
Additional Information:	Data availability statement: The 16S rRNA gene sequence data have been deposited in the NCBI BioProject database (https://www.ncbi.nlm.nih.gov/bioproject/) under accession number PRJNA1127570.
Uncontrolled Keywords:	3* ,/dk/atira/pure/researchoutput/REFrank/3_
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Medicine and Health Sciences > School of Health Sciences
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Science > Research Groups > Norwich Epidemiology Centre Faculty of Medicine and Health Sciences > Research Groups > Norwich Epidemiology Centre Faculty of Medicine and Health Sciences > Research Groups > Mental Health Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User:	LivePure Connector
Date Deposited:	10 Oct 2024 11:30
Last Modified:	04 Dec 2024 01:42
URI:	https://ueaeprints.uea.ac.uk/id/eprint/96980
DOI:	10.1016/j.neuint.2024.105878

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