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Microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and tryptophan-derived indoles, can modulate GLP-1 secretion, gutbrain communication, insulin sensitivity, and inflammatory tone ( This mini-review critically examines the mechanisms underlying GLP-1induced weight loss, the physiological limits of energy expenditure in humans, and the emerging evidence supporting postbiotics as complementary modulators within convergence-based strategies aimed at lean mass preservation and weight-loss sustainability