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(Wh)olistic (E)ndocannabinoidome-Microbiome-Axis Modulation through (N)utrition (WHEN) to Curb Obesity and Related Disorders

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The discovery of the endocannabinoidome (eCBome) is evolving gradually with yet to be elucidated functional lipid mediators and receptors. The diet modulates these bioactive lipids and the gut microbiome, both working in an entwined alliance. Mounting evidence suggests that, in different ways and with a certain specialisation, lipid signalling mediators such as N-acylethanolamines (NAEs), 2-monoacylglycerols (2-MAGs), and N-acyl-amino acids (NAAs), along with endocannabinoids (eCBs), can modulate physiological mechanisms underpinning appetite, food intake, macronutrient metabolism, pain sensation, blood pressure, mood, cognition, and immunity. This knowledge has been primarily utilised in pharmacology and medicine to develop many drugs targeting the fine and specific molecular pathways orchestrating eCB and eCBome activity. Conversely, the contribution of dietary NAEs, 2-MAGs and eCBs to the biological functions of these molecules has been little studied. In this review, we discuss the importance of (Wh) olistic (E)ndocannabinoidome-Microbiome-Axis Modulation through (N) utrition (WHEN), in the management of obesity and related disorders.

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Integrative Oncology Approaches to Supporting Immune Checkpoint Inhibitor Treatment of Solid Tumours

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The goal of this review was to examine the role and practical applications of integrative oncology strategies in supporting immune checkpoint inhibitor (ICI) treatment of adult solid tumours.

Recent Findings Beyond tumour-intrinsic factors, several patient-associated factors afect ICI response, including germline genetics, systemic infammation, the gut microbiota, and diet. Current promising supportive interventions include a Mediterranean-style diet with over 20 g of fbre, regular exercise, use of live biotherapeutics, minimisation of PPI and antibiotic use, and ensuring vitamin D repletion, with many other integrative oncology approaches under study. Caution around medical cannabis use in patients on ICIs is advised due to previously documented adverse impact on overall survival, while VAE (Viscum album extract) therapy studies have not highlighted any safety concerns so far.

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Mutual Links between the Endocannabinoidome and the Gut Microbiome, with Special Reference to Companion Animals: A Nutritional Viewpoint

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Dysbiosis, which is an imbalance of gut microbial composition and function, can be caused by several external as well as internal factors, contributing to the onset of human and animal disorders, not limited to the gastrointestinal tract. Accordingly, the mechanisms leading to disease development involve a crucial interaction between the gut microbiota, their metabolic products, and the host. The expanded endocannabinoid system, also known as the “endocannabinoidome”, includes endocannabinoids (e.g., anandamide) and endocannabinoid-like mediators (e.g., palmitoylethanolamide), their receptors and metabolic enzymes. Dysregulation of this newly recognized endogenous system is also involved in several diseases. It is becoming increasingly apparent that a link between the endocannabinoidome and the gut microbiome exists. Here, we review some of the latest discoveries related to the functional link between these two complex systems and the disorders emerging from the malfunctioning of such a mutual interaction: for example, idiopathic inflammation, chronic enteropathies, metabolic disease and certain neuroinflammatory disorders. It is expected that in the near future new nutritional tools will emerge based on the expanding knowledge in this cutting-edge field.

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