Endocannabinoids–at the crossroads between the gut microbiota and host metabolism

Cani, Patrice D.; Plovier, Hubert; Van Hul, Matthias; Geurts, Lucie; Delzenne, Nathalie M.; Druart, Céline; Everard, Amandine

doi:10.1038/nrendo.2015.211

Cited by 367Cannabis and Cannabinoid ResearchGut microbiota and healthAdipokines, Inflammation, and Metabolic Diseases

Endocannabinoids–at the crossroads between the gut microbiota and host metabolism

Cani, Patrice D., Plovier, Hubert, Van Hul, Matthias, Geurts, Lucie, Delzenne, Nathalie M., Druart, Céline, Everard, Amandine·2016·Nature Reviews Endocrinology

DOI 10.1038/nrendo.2015.211

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Abstract

Various metabolic disorders are associated with changes in inflammatory tone. Among the latest advances in the metabolism field, the discovery that gut microorganisms have a major role in host metabolism has revealed the possibility of a plethora of associations between gut bacteria and numerous diseases. However, to date, few mechanisms have been clearly established. Accumulating evidence indicates that the endocannabinoid system and related bioactive lipids strongly contribute to several physiological processes and are a characteristic of obesity, type 2 diabetes mellitus and inflammation. In this Review, we briefly define the gut microbiota as well as the endocannabinoid system and associated bioactive lipids. We discuss existing literature regarding interactions between gut microorganisms and the endocannabinoid system, focusing specifically on the triad of adipose tissue, gut bacteria and the endocannabinoid system in the context of obesity and the development of fat mass. We highlight gut-barrier function by discussing the role of specific factors considered to be putative 'gate keepers' or 'gate openers', and their role in the gut microbiota-endocannabinoid system axis. Finally, we briefly discuss data related to the different pharmacological strategies currently used to target the endocannabinoid system, in the context of cardiometabolic disorders and intestinal inflammation.

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Janssen, F. J., Deng, H., Baggelaar, M. P., Allarà, M., van der Wel, T., den Dulk, H., Ligresti, A., van Esbroeck, A. C. M., McGuire, R., Marzo, V. D., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500681z · Cited by 33 · see citing works
A comprehensive patents review on cannabinoid 1 receptor antagonists as antiobesity agents
Sharma, M. K., Murumkar, P. R., Barmade, M. A., Giridhar, R., & Yadav, M. R. (2015) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2015.1064898 · Cited by 31 · see citing works
Acute Activation of Cannabinoid Receptors by Anandamide Reduces Gastrointestinal Motility and Improves Postprandial Glycemia in Mice
Troy-Fioramonti, S., Demizieux, L., Gresti, J., Muller, T., Vergès, B. L., & Degrace, P. (2014) · Diabetes · doi:10.2337/db14-0721 · Cited by 18 · see citing works
GASTROINTESTINAL ENDOCANNABINOID SYSTEM: MULTIFACETED ROLES IN THE HEALTHY AND INFLAMED INTESTINE
Smid, S. D. (2008) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2008.05016.x · Cited by 15 · see citing works

Flagged first, then by citations

Sorted by citations

Gut microbiome and health: mechanistic insights
de Vos, W. M., Tilg, H., Van Hul, M., & Cani, P. D. (2022) · Gut · doi:10.1136/gutjnl-2021-326789 · Cited by 2,388 · see citing works
A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice
Plovier, H., Everard, A., Druart, C., Depommier, C., Van Hul, M., Geurts, L., Chilloux, J., Ottman, N., Duparc, T., Lichtenstein, L., et al. (2017) · Nature Medicine · doi:10.1038/nm.4236 · Cited by 2,204 · see citing works
Self-citation
Neurotransmitter modulation by the gut microbiota
Strandwitz, P. (2018) · Brain Research · doi:10.1016/j.brainres.2018.03.015 · Cited by 1,527 · see citing works
Next-Generation Beneficial Microbes: The Case of Akkermansia muciniphila
Cani, P. D., & de Vos, W. M. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01765 · Cited by 1,058 · see citing works
“We then discovered that live A. muciniphila increased the endogenous production of specific bioactive lipids that belongs to the endocannabinoid family and are known to have anti-inflammatory activities and regulating the endogenous production of gut peptides involved in glucose regulation and gut barrier, respectivel…”
Background
Cannabinoids and the expanded endocannabinoid system in neurological disorders
Cristino, L., Bisogno, T., & Di Marzo, V. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-019-0284-z · Cited by 970 · see citing works
The microbiota-gut-brain axis in obesity.
Torres-Fuentes, C., Schellekens, H., Dinan, T., & Cryan, J. (2017) · The Lancet Gastroenterology and Hepatology · doi:10.1016/s2468-1253(17)30147-4 · Cited by 506 · see citing works
Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice
Yoon, H. S., Cho, C. H., Yun, M. S., Jang, S. J., You, H. J., Kim, J.-H., Han, D., Cha, K. H., Moon, S. H., Lee, K., et al. (2021) · Nature Microbiology · doi:10.1038/s41564-021-00880-5 · Cited by 602 · see citing works
Microbial regulation of organismal energy homeostasis
Cani, P. D., Van Hul, M., Lefort, C., Depommier, C., Rastelli, M., & Everard, A. (2019) · Nature Metabolism · doi:10.1038/s42255-018-0017-4 · Cited by 569 · see citing works
Commensal bacteria make GPCR ligands that mimic human signalling molecules
Cohen, L. J., Esterhazy, D., Kim, S.-H., Lemetre, C., Aguilar, R. R., Gordon, E. A., Pickard, A. J., Cross, J. R., Emiliano, A. B., Han, S. M., et al. (2017) · Nature · doi:10.1038/nature23874 · Cited by 500 · see citing works
Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
Role of the gut microbiota in host appetite control: bacterial growth to animal feeding behaviour
Fetissov, S. O. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.150 · Cited by 403 · see citing works
Bioactive Lipids and Chronic Inflammation: Managing the Fire Within
Chiurchiù, V., Leuti, A., & Maccarrone, M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00038 · Cited by 427 · see citing works
Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer
Cani, P. D., & Jordan, B. F. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0025-6 · Cited by 383 · see citing works
Self-citation
Antibiotic-induced microbiota perturbation causes gut endocannabinoidome changes, hippocampal neuroglial reorganization and depression in mice
Guida, F., Turco, F., Iannotta, M., De Gregorio, D., Palumbo, I., Sarnelli, G., Furiano, A., Napolitano, F., Boccella, S., Luongo, L., et al. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.09.001 · Cited by 367 · see citing works
Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system
Chevalier, G., Siopi, E., Guenin‐Macé, L., Pascal, M., Laval, T., Rifflet, A., Boneca, I. G., Demangel, C., Colsch, B., Pruvost, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19931-2 · Cited by 324 · see citing works
The gut microbiota in obesity and weight management: microbes as friends or foe?
Hul, M. V., & Cani, P. D. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00794-0 · Cited by 335 · see citing works
The Gut Microbiome Influences Host Endocrine Functions
Rastelli, M., Cani, P. D., & Knauf, C. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00280 · Cited by 315 · see citing works
Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders?
Chakaroun, R., Massier, L., & Kovacs, P. L. (2020) · Nutrients · doi:10.3390/nu12041082 · Cited by 297 · see citing works
“More importantly, there have been efforts to establish systematic approaches to decipher structure and function of the gut microbiome in health and disease with the Human Microbiome Project (HMP) [9] as well as the European MetaHit project [5], leading to a multitude of publications linking the gut microbiome with sev…”
Background
Dysbiosis of gut microbiota in promoting the development of colorectal cancer
Zou, S., Fang, L., & Lee, M. (2017) · Gastroenterology report · doi:10.1093/gastro/gox031 · Cited by 279 · see citing works
“Gut microbiota can promote the development and progression of CRC by different processes, including the induction of a chronic inflammatory state or immune response, altering stem cell dynamics, the biosynthesis of toxic and genotoxic metabolites, and affecting the host metabolism [20,21].”
Background
Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet
Kang, C., Wang, B., Kaliannan, K., Wang, X., Lang, H., Hui, S., Huang, L., Zhang, Y., Zhou, M., Chen, M., et al. (2017) · mBio · doi:10.1128/mbio.00470-17 · Cited by 273 · see citing works
“The endocannabinoid system, particularly the cannabinoid (CB) receptor in the intestine, links the gut microbiota with metabolic endotoxemia and CLGI (28).”
Study of the impact of long-duration space missions at the International Space Station on the astronaut microbiome
Voorhies, A. A., Ott, C. M., Mehta, S. K., Pierson, D. L., Crucian, B. E., Feiveson, A. H., Oubre, C. M., Torralba, M., Moncera, K. J., Zhang, Y., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-46303-8 · Cited by 266 · see citing works
Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?
Sircana, A., Framarin, L., Leone, N., Berrutti, M., Castellino, F., Parente, R., Michieli, F. D., Paschetta, E., & Musso, G. (2018) · Current Diabetes Reports · doi:10.1007/s11892-018-1057-6 · Cited by 223 · see citing works
Gut‐liver axis at the frontier of host‐microbial interactions
Brandl, K., Kumar, V., & Eckmann, L. (2017) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00361.2016 · Cited by 201 · see citing works
“AEA can diminish epithelial barrier functions in vitro and in vivo through the cannabinoid receptor 1 (CB1) (50), while 2-AG is thought to be barrier protective (1), indicating that the balance of different endocannabinoids is likely to determine their overall impact on intestinal barrier permeability and translocatio…”
Background
Contribution of macronutrients to obesity: implications for precision nutrition
San-Cristóbal, R., Navas‐Carretero, S., Martínez‐González, M. Á., Ordovás, J. M., & Martínez, J. A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0346-8 · Cited by 201 · see citing works
Gut microbiota in overweight and obesity: crosstalk with adipose tissue
Cani, P. D., & Hul, M. V. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00867-z · Cited by 212 · see citing works
“2-Arachidonoylglycerol was the second endogenous cannabinoid receptor ligand identified 176 .”
Causality of small and large intestinal microbiota in weight regulation and insulin resistance
Scheithauer, T. P. M., Dallinga-Thie, G. M., de Vos, W. M., Nieuwdorp, M., & van Raalte, D. H. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.06.002 · Cited by 188 · see citing works
“Chronic CD receptor stimulation induced glucose intolerance, stimulated metabolic inflammation, and altered lipid storage in skeletal muscle [116,123].”
Background
Gut Microbes and Health: A Focus on the Mechanisms Linking Microbes, Obesity, and Related Disorders
Rastelli, M., Knauf, C., & Cani, P. D. (2018) · Obesity · doi:10.1002/oby.22175 · Cited by 188 · see citing works
“Endocannabinoids (eCBs) are bioactive lipids that are synthesized in and exert their action on several organs involved in metabolism and appetite regulation (41).”
Background
The gut microbiota and its interactions with cardiovascular disease
Xu, H., Wang, X., Feng, W., Liu, Q., Zhou, S., Liu, Q., & Cai, L. (2020) · Microbial Biotechnology · doi:10.1111/1751-7915.13524 · Cited by 192 · see citing works
Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseases
Liu, M., Yang, J.-Y., Yan, Z.-H., Hu, S., Li, J.-Q., Xu, Z., & Jian, Y. (2022) · Clinical Nutrition · doi:10.1016/j.clnu.2022.08.029 · Cited by 171 · see citing works
Targeting the endocannabinoid system: future therapeutic strategies
Aizpurua-Olaizola, O., Elezgarai, I., Rico-Barrio, I., Zarandona, I., Etxebarria, N., & Usobiaga, A. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2016.08.005 · Cited by 209 · see citing works
Intestinal epithelial N-acylphosphatidylethanolamine phospholipase D links dietary fat to metabolic adaptations in obesity and steatosis
Everard, A., Plovier, H., Rastelli, M., Hul, M. V., d’Oplinter, A. D. W., Geurts, L., Druart, C., Robine, S., Delzenne, N. M., Muccioli, G. G., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08051-7 · Cited by 156 · see citing works
The role of Akkermansia muciniphila in obesity, diabetes and atherosclerosis
Hasani, A., Ebrahimzadeh, S., Hemmati, F., Khabbaz, A., Hasani, A., & Gholizadeh, P. (2021) · Journal of Medical Microbiology · doi:10.1099/jmm.0.001435 · Cited by 152 · see citing works
The therapeutic potential of second and third generation CB1R antagonists
Çınar, R., Iyer, M. R., & Kunos, G. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107477 · Cited by 151 · see citing works
“These changes could contribute to metabolic inflammation, infiltration of proinflammatory macrophages in adipose tissue and expanding fat mass (Cani et al., 2016).”
Background
Resveratrol attenuates high-fat diet-induced non-alcoholic steatohepatitis by maintaining gut barrier integrity and inhibiting gut inflammation through regulation of the endocannabinoid system
Chen, M., Hou, P., Zhou, M., Ren, Q., Wang, X., Huang, L., Hui, S., Yi, L., & Mi, M. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2019.05.020 · Cited by 148 · see citing works
The diet rapidly and differentially affects the gut microbiota and host lipid mediators in a healthy population
Bourdeau‐Julien, I., Castonguay-Paradis, S., Rochefort, G., Perron, J., Lamarche, B., Flamand, N., Marzo, V. D., Veilleux, A., & Raymond, F. (2023) · Microbiome · doi:10.1186/s40168-023-01469-2 · Cited by 148 · see citing works
Endocannabinoids in the Gut
DiPatrizio, N. V. (2016) · Cannabis and Cannabinoid Research · doi:10.1089/can.2016.0001 · Cited by 138 · see citing works
Lifestyle and Metabolic Syndrome: Contribution of the Endocannabinoidome
Marzo, V. D., & Silvestri, C. (2019) · Nutrients · doi:10.3390/nu11081956 · Cited by 135 · see citing works
“Thus, it appears that μB alterations in response to high-fat diets impacts upon the intestinal eCBome directly which, under obesity-inducing conditions, increases gut barrier permeability, subsequently resulting in increased circulating bacterially derived lipopolysaccharide (LPS) that subsequently modulates adipose t…”
Background
The Microbiota of the Extremely Preterm Infant
Underwood, M. A., & Sohn, K. (2017) · Clinics in Perinatology · doi:10.1016/j.clp.2017.01.005 · Cited by 123 · see citing works
“[1] [2] [3] The importance of the intestinal microbiota in extremely preterm infants is most clearly evident in considering the risks of developing necrotizing enterocolitis (NEC) and sepsis.”
The gut microbiome and mental health: advances in research and emerging priorities
Shoubridge, A. P., Choo, J. M., Martin, A. M., Keating, D. J., Wong, M., Licinio, J., & Rogers, G. B. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01479-w · Cited by 130 · see citing works
“Involved in numerous aspects of physiology [127, 128], the roles of the endocannabinoid system include modulation of CNS responses to stressors via a signalling system comprising of cannabinoid receptors, the mediator molecules N-arachidonoylethanolamine and 2-arachidonoylglycerol, and the enzymes involved in the synt…”
Background
The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease
Hasenoehrl, C., Taschler, U., Storr, M., & Schicho, R. (2016) · Neurogastroenterology & Motility · doi:10.1111/nmo.12931 · Cited by 120 · see citing works
Type 2 Diabetes Mellitus Associated with Obesity (Diabesity). The Central Role of Gut Microbiota and Its Translational Applications
Ortega, M. A., Fraile‐Μartinez, O., Naya, I., García‐Honduvilla, N., Álvarez‐Mon, M., Buján, J., Asúnsolo, Á., & de la Torre, B. (2020) · Nutrients · doi:10.3390/nu12092749 · Cited by 117 · see citing works
Intestinal Sensing by Gut Microbiota: Targeting Gut Peptides
Covașă, M., Stephens, R. W., Toderean, R., & Cobuz, C. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00082 · Cited by 114 · see citing works
“Degradation of PYY(1-36) into PYY(3-36) is an important step for control of food intake.”
BackgroundInfluential
Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain
Guida, F., Boccella, S., Belardo, C., Iannotta, M., Piscitelli, F., Filippis, F. D., Paino, S., Ricciardi, F., Siniscalco, D., Marabese, I., et al. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.04.006 · Cited by 111 · see citing works
“In the gut, vitamin D deficiency produced significant decreases of 2AG levels in the colon, confirming the dual role of the endocannabinoid system in gut pathophysiology (Cani et al., 2016).”
Background
Impact of prebiotics on metabolic and behavioral alterations in a mouse model of metabolic syndrome
de Cossío, L. F., Fourrier, C., Sauvant, J., Everard, A., Capuron, L., Cani, P. D., Layé, S., & Castanon, N. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.12.022 · Cited by 108 · see citing works
Links between Dietary Protein Sources, the Gut Microbiota, and Obesity
Madsen, L., Myrmel, L. S., Fjære, E., Liaset, B., & Kristiansen, K. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.01047 · Cited by 110 · see citing works
“Further, changes in the composition of the gut microbiota during obesity induce gut-barrier dysfunction, which may lead to leakage from the gut of components from Gram-negative bacteria and metabolic endotoxemia triggering the onset of metabolic disorders associated with obesity (Cani et al., 2016).”
Background
The role of gut microbiota in non-alcoholic fatty liver disease: pathways of mechanisms
Jasirwan, C. O. M., Lesmana, C. R. A., Hasan, I., Sulaiman, A. S., & Gani, R. A. (2019) · Bioscience of Microbiota Food and Health · doi:10.12938/bmfh.18-032 · Cited by 112 · see citing works
“Specific bacteria, namely Akkermansia muciniphila, were suspected to improve the functionality of intestinal wall tight junctions by inducing production of several bioactive lipids known as “gatekeepers”, such as N-palmitoylethanolamine (PEA), 2-arachidonoylglycerol (2-AG), 2-oleoylglycerol (2-OG), 2-palmitoylglycerol…”
Background
Growth effects of N-acylethanolamines on gut bacteria reflect altered bacterial abundances in inflammatory bowel disease
Fornelos, N., Franzosa, E. A., Bishai, J. D., Annand, J. W., Oka, A., Lloyd‐Price, J., Arthur, T. D., Garner, A., Ávila-Pacheco, J., Haiser, H. J., et al. (2020) · Nature Microbiology · doi:10.1038/s41564-019-0655-7 · Cited by 105 · see citing works
Obesity Affects the Microbiota–Gut–Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators
Forte, N. R., Fernández-Rilo, A. C., Palomba, L., Marzo, V. D., & Cristino, L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051554 · Cited by 104 · see citing works
“It is composed of approximately 3‐ to 10‐fold the amount of cells forming the human body; more than 90% of gut bacteria belong to the three main phyla, namely, Actinobacteria, Bacteroidetes and Firmicutes, which encode for at least 150‐fold more singular genes than the human genome [1].”
Background
Endocannabinoid modulation of homeostatic and non-homeostatic feeding circuits
Lau, B. K., Cota, D., Cristino, L., & Borgland, S. L. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.05.033 · Cited by 102 · see citing works
Capsaicin and Gut Microbiota in Health and Disease
Roşca, A. E., Ieșanu, M. I., Zahiu, C. D. M., Voiculescu, S. E., Paslaru, A. C., & Zăgrean, A. (2020) · Molecules · doi:10.3390/molecules25235681 · Cited by 102 · see citing works
Linking Gut Microbiome and Lipid Metabolism: Moving beyond Associations
Lamichhane, S., Sen, P., Alves, M. A., Ribeiro, H. C., Raunioniemi, P., Hyötyläinen, T., & Orešič, M. (2021) · Metabolites · doi:10.3390/metabo11010055 · Cited by 97 · see citing works
Dietary fatty acid intake and gut microbiota determine circulating endocannabinoidome signaling beyond the effect of body fat
Castonguay-Paradis, S., Lacroix, S., Rochefort, G., Parent, L., Perron, J., Martin, C., Lamarche, B., Raymond, F., Flamand, N., Marzo, V. D., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-72861-3 · Cited by 97 · see citing works
Incretins in obesity and diabetes
Chia, C. W., & Egan, J. M. (2020) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14211 · Cited by 93 · see citing works
The endocannabinoidome as a substrate for noneuphoric phytocannabinoid action and gut microbiome dysfunction in neuropsychiatric disorders
Marzo, V. D. (2020) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2020.22.3/vdimarzo · Cited by 91 · see citing works
The gut microbiome, endocannabinoids and metabolic disorders
Iannotti, F. A., & Marzo, V. D. (2020) · Journal of Endocrinology · doi:10.1530/joe-20-0444 · Cited by 89 · see citing works
Mediterranean diet consumption affects the endocannabinoid system in overweight and obese subjects: possible links with gut microbiome, insulin resistance and inflammation
Tagliamonte, S., Laiola, M., Ferracane, R., Vitale, M., Gallo, M. A., Meslier, V., Pons, N., Ercolini, D., & Vitaglione, P. (2021) · European Journal of Nutrition · doi:10.1007/s00394-021-02538-8 · Cited by 88 · see citing works
The CB1 Receptor as the Cornerstone of Exostasis
Piazza, P. V., Cota, D., & Marsicano, G. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.002 · Cited by 89 · see citing works
SIRT3 Deficiency Promotes High‐Fat Diet‐Induced Nonalcoholic Fatty Liver Disease in Correlation with Impaired Intestinal Permeability through Gut Microbial Dysbiosis
Chen, M., Hui, S., Lang, H., Zhou, M., Zhang, Y., Kang, C., Zeng, X., Zhang, Q., Yi, L., & Mi, M. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201800612 · Cited by 85 · see citing works
Obesity and Asthma: Microbiome–Metabolome Interactions
Shore, S. A., & Cho, Y. (2016) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2016-0052ps · Cited by 86 · see citing works
“The production of metabolites that activate cannabinoid receptors (which impact eating) is also affected by gut bacteria (57).”
Background
Endocannabinoids in the gastrointestinal tract
Lee, Y., Jo, J., Chung, H. Y., Pothoulakis, C., & Im, E. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00294.2015 · Cited by 82 · see citing works
“In addition, endocannabinoid analogs that structurally resemble prototypic endocannabinoids either enhance the effects of endocannabinoids or exert their own activities (17).”
Background
Short-Chain Fatty Acids: A Soldier Fighting Against Inflammation and Protecting From Tumorigenesis in People With Diabetes
Yang, Q., Ouyang, J., Sun, F., & Yang, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.590685 · Cited by 83 · see citing works
“Other than SCFAs and bacterial toxins, microbiota might influence the intestinal barrier through other signal pathways, including bile acids metabolism and endocannabinoid system (34, 35).”
Background
Interactions of dietary fat with the gut microbiota: Evaluation of mechanisms and metabolic consequences
Mokkala, K., Houttu, N., Cansev, T., & Laitinen, K. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2019.05.003 · Cited by 82 · see citing works
Roles for the gut microbiota in regulating neuronal feeding circuits
Yu, K. B., & Hsiao, E. Y. (2021) · Journal of Clinical Investigation · doi:10.1172/jci143772 · Cited by 81 · see citing works
“In addition to taste, endocannabinoid signaling (38–40) may be another possible avenue for gut microbes to affect host food preference (41).”
Microbiota and Obesity: Where Are We Now?
Ballini, A., Scacco, S., Boccellino, M., Santacroce, L., & Arrigoni, R. (2020) · Biology · doi:10.3390/biology9120415 · Cited by 78 · see citing works
Gut microbiota: sculptors of the intestinal stem cell niche in health and inflammatory bowel disease
Markandey, M., Bajaj, A., Ilott, N. E., Kedia, S., Travis, S. P. L., Powrie, F. M., & Ahuja, V. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1990827 · Cited by 79 · see citing works
“These lipids act as epithelial gatekeepes and are known to act as ligands for GPR119, expressed on the surface of intestinal L-cells, where it promotes the release of GLP-2, eliciting anti-inflammatory effects.(94,95) Significantly reduced levels of circulating and tissue-associated GLP-2 have been reported in IBD, wh…”
Background
Targeting gut dysbiosis against inflammation and impaired autophagy in Duchenne muscular dystrophy
Kalkan, H., Pagano, E., Paris, D., Panza, E., Cuozzo, M., Moriello, C., Piscitelli, F., Abolghasemi, A., Gazzerro, E., Silvestri, C., et al. (2023) · EMBO Molecular Medicine · doi:10.15252/emmm.202216225 · Cited by 78 · see citing works
“Additionally, more recent evidence points to the endocannabinoid system as a key regulator in the communication between the gut microbiota and the host (Cani et al , 2016; de Vos et al , 2022).”
Background
Influence of Bactrian camel milk on the gut microbiota
Wang, Z., Zhang, W., Wang, B., Zhang, F., & Shao, Y. (2018) · Journal of Dairy Science · doi:10.3168/jds.2017-13860 · Cited by 78 · see citing works
Dissecting dietary melanoidins: formation mechanisms, gut interactions and functional properties
Shaheen, S., Shorbagi, M., Lorenzo, J. M., & Farag, M. A. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1937509 · Cited by 79 · see citing works
Diabesity and mood disorders: Multiple links through the microbiota-gut-brain axis
Farzi, A., Hassan, A. M., Zenz, G., & Holzer, P. D. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.11.003 · Cited by 77 · see citing works
Influence of Endogenous and Exogenous Estrogenic Endocrine on Intestinal Microbiota in Zebrafish
Liu, Y., Yao, Y., Li, H., Qiao, F., Wu, J., Du, Z., & Zhang, M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0163895 · Cited by 76 · see citing works
Role of the endocannabinoid system in the regulation of intestinal homeostasis
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Cannabinoid receptor type-1: breaking the dogmas
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Authors: Cani, P. D., Plovier, H., Van Hul, M., Geurts, L., Delzenne, N. M., Druart, C., & Everard, A.
Affiliations: Walloon Excellence in Lifesciences and Biotechnology (BE)
UCLouvain (BE)
Corresponding author: Cani, Patrice D.
ORCID: Cani, Patrice D.
Plovier, Hubert
Geurts, Lucie
Delzenne, Nathalie M.
Druart, Céline
Everard, Amandine
Venue: Nature Reviews Endocrinology
Publisher: Springer Science and Business Media LLC
Published: 2015-12-18
Volume: 12
Issue: 3
Pages: 133-143
ISSN: 1759-5029 (ISSN-L)
1759-5037
DOI: 10.1038/nrendo.2015.211
OpenAlex: W2206708469
Cited by: 367
References: 156
Citations by year: 2026: 23 · 2025: 30 · 2024: 27 · 2023: 37 · 2022: 51 · 2021: 55 · 2020: 45 · 2019: 25 · 2018: 30 · 2017: 24 · 2016: 20
FWCI: 3.09
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Endocrinology (publishedVersion)
PubMed (publishedVersion)
Digital Access to Libraries (submittedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords: endocannabinoid system, gut microbiota, host metabolism, intestinal permeability, intestinal barrier, bioactive lipids, obesity, adipose tissue, type 2 diabetes, cardiometabolic disease, intestinal inflammation, fat mass
MeSH terms: Gastrointestinal Microbiome, Animals, Humans, Gastrointestinal Tract, Receptors, Cannabinoid, Endocannabinoids

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Endocannabinoids–at the crossroads between the gut microbiota and host metabolism

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