A novel Mediterranean diet-inspired supplement ameliorates cognitive, microbial, and metabolic deficits in a mouse model of low-grade inflammation

Pontifex, Matthew G. ORCID: https://orcid.org/0000-0003-2174-2313, Connell, Emily, Le Gall, Gwenaelle ORCID: https://orcid.org/0000-0002-1379-2196, Lang, Leonie, Pourtau, Line, Gaudout, David, Angeloni, Cristina, Zallocco, Lorenzo, Ronci, Maurizio, Giusti, Laura, Müller, Michael ORCID: https://orcid.org/0000-0002-5930-9905 and Vauzour, David ORCID: https://orcid.org/0000-0001-5952-8756 (2024) A novel Mediterranean diet-inspired supplement ameliorates cognitive, microbial, and metabolic deficits in a mouse model of low-grade inflammation. Gut Microbes, 16 (1). ISSN 1949-0976

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Abstract

The Mediterranean diet (MD) and its bioactive constituents have been advocated for their neuroprotective properties along with their capacity to affect gut microbiota speciation and metabolism. Mediated through the gut brain axis, this modulation of the microbiota may partly contribute to the neuroprotective properties of the MD. To explore this potential interaction, we evaluated the neuroprotective properties of a novel bioactive blend (Neurosyn240) resembling the Mediterranean diet in a rodent model of chronic low-grade inflammation. Behavioral tests of cognition, brain proteomic analysis, 16S rRNA sequencing, and 1H NMR metabolomic analyses were employed to develop an understanding of the gut-brain axis interactions involved. Recognition memory, as assessed by the novel object recognition task (NOR), decreased in response to LPS insult and was restored with Neurosyn240 supplementation. Although the open field task performance did not reach significance, it correlated with NOR performance indicating an element of anxiety related to this cognitive change. Behavioral changes associated with Neurosyn240 were accompanied by a shift in the microbiota composition which included the restoration of the Firmicutes: Bacteroidota ratio and an increase in Muribaculum, Rikenellaceae Alloprevotella, and most notably Akkermansia which significantly correlated with NOR performance. Akkermansia also correlated with the metabolites 5-aminovalerate, threonine, valine, uridine monophosphate, and adenosine monophosphate, which in turn significantly correlated with NOR performance. The proteomic profile within the brain was dramatically influenced by both interventions, with KEGG analysis highlighting oxidative phosphorylation and neurodegenerative disease-related pathways to be modulated. Intriguingly, a subset of these proteomic changes simultaneously correlated with Akkermansia abundance and predominantly related to oxidative phosphorylation, perhaps alluding to a protective gut-brain axis interaction. Collectively, our results suggest that the bioactive blend Neurosyn240 conferred cognitive and microbiota resilience in response to the deleterious effects of low-grade inflammation.

Item Type: Article
Additional Information: Supplementary material: Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2363011 Funding information: This project was funded by Activ’Inside [grant R209836] who received support for the Silver Brain Food project, a program co-financed by the “Future Investment Program” (Programme d’Investissements d’Avenir PIA3) and managed by the Investment General Secretariat and operated by Bpifrance.
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Medicine and Health Sciences > School of Health Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
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 > Norwich Institute for Healthy Aging
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User: LivePure Connector
Date Deposited: 05 Jun 2024 11:30
Last Modified: 06 Jun 2024 15:27
URI: https://ueaeprints.uea.ac.uk/id/eprint/95391
DOI: 10.1080/19490976.2024.2363011

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