The role of the mucin-glycan foraging Ruminococcus gnavus in the communication between the gut and the brain

Coletto, Erika, Latousakis, Dimitrios, Pontifex, Matthew G. ORCID: https://orcid.org/0000-0003-2174-2313, Crost, Emmanuelle H., Vaux, Laura, Perez Santamarina, Estella, Goldson, Andrew, Brion, Arlaine, Hajihosseini, Mohammad K., Vauzour, David ORCID: https://orcid.org/0000-0001-5952-8756, Savva, George M. and Juge, Nathalie (2022) The role of the mucin-glycan foraging Ruminococcus gnavus in the communication between the gut and the brain. Gut Microbes, 14 (1). ISSN 1949-0976

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Abstract

Ruminococcus gnavus is a prevalent member of the human gut microbiota, which is over-represented in inflammatory bowel disease and neurological disorders. We previously showed that the ability of R. gnavus to forage on mucins is strain-dependent and associated with sialic acid metabolism. Here, we showed that mice monocolonized with R. gnavus ATCC 29149 (Rg-mice) display changes in major sialic acid derivatives in their cecum content, blood, and brain, which is accompanied by a significant decrease in the percentage of sialylated residues in intestinal mucins relative to germ-free (GF) mice. Changes in metabolites associated with brain function such as tryptamine, indolacetate, and trimethylamine N-oxide were also detected in the cecal content of Rg-mice when compared to GF mice. Next, we investigated the effect of R. gnavus monocolonization on hippocampus cell proliferation and behavior. We observed a significant decrease of PSA-NCAM immunoreactive granule cells in the dentate gyrus (DG) of Rg-mice as compared to GF mice and recruitment of phagocytic microglia in the vicinity. Behavioral assessments suggested an improvement of the spatial working memory in Rg-mice but no change in other cognitive functions. These results were also supported by a significant upregulation of genes involved in proliferation and neuroplasticity. Collectively, these data provide first insights into how R. gnavus metabolites may influence brain regulation and function through modulation of granule cell development and synaptic plasticity in the adult hippocampus. This work has implications for further understanding the mechanisms underpinning the role of R. gnavus in neurological disorders.

Item Type:	Article
Additional Information:	Acknowledgments: The authors gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC); this research was funded by the BBSRC Institute Strategic Programme Grant Gut Microbes and Health BB/R012490/1 and its constituent projects BBS/E/F/000PR10353 (Theme 1, Determinants of microbe-host responses in the gut across life), and EC held a BBSRC Norwich Research Park Doctoral Training Grant BB/M011216/1. GS, AG, and AB were supported by the BBSRC Core Capability Grant BB/CCG1860/1.
Uncontrolled Keywords:	gut-brain axis,ruminococcus gnavus,gut microbiota,human gut symbiont,neurogenesis,sialic acid,intestinal mucus,gnotobiotic mice,mucin glycosylation,metabolite,cognitive function,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Biological Sciences 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 Science > Research Groups > Cells and Tissues 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 Centres > Lifespan Health
Related URLs:	https://www.tandfonline.com/doi/full/10....
Depositing User:	LivePure Connector
Date Deposited:	24 May 2022 14:58
Last Modified:	30 Mar 2024 01:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/85086
DOI:	10.1080/19490976.2022.2073784

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