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From Inclusion Complexes to Metabolic Signaling: The Emerging Role of γ-Cyclodextrin in Gut Microbiota and Metabolic
Pirscoveanu Denisa Floriana Vasilica1, Pluta Ion Dorin2, Dîrnu Rodica2
1Department of Neurology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
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γ-Cyclodextrin (γ-CD) is a cyclic oligosaccharide with high aqueous solubility, low toxicity, and a large internal cavity that enables inclusion complex formation with selected bioactive compounds. Beyond its established role as a pharmaceutical and food excipient, emerging evidence suggests that γ-CD may influence metabolic regulation through interactions with the gut microbiota, microbial fermentation products, and host metabolic signaling pathways. This review synthesizes current evidence on the effects of γ-CD on short-chain fatty acid production, lipid homeostasis, glycemic control, and obesity- and type 2 diabetes-related metabolic disturbances. Particular attention is given to the gut-metabolism axis, SCFA-mediated GPCR signaling, microbial taxa potentially involved in γ-CD fermentation, and the relative contribution of prebiotic-like effects versus lipid-binding mechanisms. Available data indicate that γ-CD may modulate microbial composition and metabolic outcomes, but most evidence derives from in vitro experiments, animal models, and limited human studies. Therefore, the clinical relevance of γ-CD remains insufficiently established. Future studies should include well-designed human trials, standardized doses, multi-omics analyses, and direct comparisons between native and modified cyclodextrins to clarify whether γ-CD can be translated into nutritional or therapeutic strategies for metabolic disorders.
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