The anti-inflammatory effect of bacterial short chain fatty acids is partially mediated by endocannabinoids
Open accessAbstract
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 6 week 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.
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In humans, changes in eCBs correlate with increased butyrate levels and decreased TNF, IL-6, and IL-10.
“Changes in eCBs correlated with increased butyrate levels, and decreased TNF, IL-6 and IL-10.”
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Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
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- Authors
- Vijay, A., Kouraki, A., Gohir, S., Turnbull, J., Kelly, A., Chapman, V., Barrett, D. A., Bulsiewicz, W. J., & Valdes, A. M.
- Affiliations
- University of Nottingham (GB)
- University of Nottingham
- University of South Carolina (US)
- Corresponding author
- Vijay, Amrita
- Venue
- Gut Microbes
- Publisher
- Informa UK Limited
- Published
- 2021-01-01
- Volume
- 13
- Issue
- 1
- Pages
- 1997559-1997559
- ISSN
- 1949-0976 (ISSN-L)
- 1949-0984
- PMC
- PMC8604388
- OpenAlex
- W3212121879
- Cited by
- 93
- References
- 58
- Citations by year
- 2026: 12 · 2025: 29 · 2024: 17 · 2023: 16 · 2022: 19
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Gut Microbes (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Funders
- Versus Arthritis (20777)
- Pfizer Global medical grant (WI243608)
- MRC grant (MR/V027883/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- endocannabinoid system, short-chain fatty acids, gut microbiota, anti-inflammatory activity, butyrate, anandamide, 2-arachidonoylglycerol, N-oleoylethanolamine, N-palmitoylethanolamine, exercise intervention, inflammatory cytokines, TNF-α, interleukin-6, Bifidobacterium, Faecalibacterium, Collinsella, gut-brain-immune axis
- MeSH terms
- Gastrointestinal Microbiome, Anti-Inflammatory Agents, Bacteria, Cross-Sectional Studies, Fatty Acids, Volatile, Female, Humans, Immune System, Longitudinal Studies, Male, Middle Aged, Cohort Studies, Interleukin-6, Endocannabinoids
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