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The anti-inflammatory effect of bacterial short chain fatty acids is partially mediated by endocannabinoids

Vijay, Amrita; Kouraki, Afroditi; Gohir, Sameer; Turnbull, James; Kelly, Anthony; Chapman, Vicky; Barrett, David A.; Bulsiewicz, William J.; Valdes, Ana M

The anti-inflammatory effect of bacterial short chain fatty acids is partially mediated by endocannabinoids Thumbnail


Authors

Afroditi Kouraki

Sameer Gohir

James Turnbull

Anthony Kelly

David A. Barrett

William J. Bulsiewicz



Abstract

The endocannabinoid (EC) system has pleiotropic functions in the body. It plays a key role in energy homeostasis and the development of metabolic disorders being a mediator in the relationship between the gut microbiota and host metabolism. In the current study we explore the functional interactions between the endocannabinoid system and the gut microbiome in modulating inflammatory markers. Using data from a 6week exercise intervention (treatment n =38 control n =40) and a cross sectional validation cohort (n=35), we measured the associations of 2-arachidonoylglycerol (2-AG), anandamide (AEA), N-oleoylethanolamine (OEA) and N-palmitoylethanolamine (PEA) with gut microbiome composition, gut derived metabolites (SCFAs) and inflammatory markers both cross-sectionally and longitudinally. At baseline AEA and OEA were positively associated with alpha diversity (β(SE)=.32 (.06), P =.002;.44 (.04), P <.001) and with SCFA producing bacteria such as Bifidobacterium (2-AG β(SE)=.21 (.10), P <.01; PEA β(SE)=.23 (.08), P <.01), Coprococcus 3 and Faecalibacterium (PEA β(SE)=.29 (.11), P =.01;.25 (.09), P <.01) and negatively associated with Collinsella (AEA β(SE)=−.31 (.12), P =.004). Additionally, we found AEA to be positively associated with SCFA Butyrate (β(SE)=.34 (.15), P =.01). AEA, OEA and PEA all increased significantly with the exercise intervention but remained constant in the control group. Changes in AEA correlated with SCFA butyrate and increases in AEA and PEA correlated with decreases in TNF-ɑ and IL-6 statistically mediating one third of the effect of SCFAs on these cytokines. Our data show that the anti-inflammatory effects of SCFAs are partly mediated by the EC system suggesting that there may be other pathways involved in the modulation of the immune system via the gut microbiome.

Citation

Vijay, A., Kouraki, A., Gohir, S., Turnbull, J., Kelly, A., Chapman, V., …Valdes, A. M. (2021). The anti-inflammatory effect of bacterial short chain fatty acids is partially mediated by endocannabinoids. Gut Microbes, 13(1), Article 1997559. https://doi.org/10.1080/19490976.2021.1997559

Journal Article Type Article
Acceptance Date Oct 21, 2021
Online Publication Date Nov 17, 2021
Publication Date Nov 17, 2021
Deposit Date Nov 9, 2021
Publicly Available Date Nov 17, 2021
Journal Gut Microbes
Print ISSN 1949-0976
Electronic ISSN 1949-0984
Publisher Taylor and Francis
Peer Reviewed Peer Reviewed
Volume 13
Issue 1
Article Number 1997559
DOI https://doi.org/10.1080/19490976.2021.1997559
Keywords Infectious Diseases; Microbiology (medical); Gastroenterology; Microbiology
Public URL https://nottingham-repository.worktribe.com/output/6674942
Publisher URL https://www.tandfonline.com/doi/full/10.1080/19490976.2021.1997559