The present opinion article provides an overview of the key improvements in metabolic and cardiovascular health following Roux-en-Y Gastric Bypass (RYGB). Some clinically important long-term complications of RYGB are also briefly described to contextualise the potential value of finding selective non-surgical means of replicating only the beneficial aspects of RYGB. Three biological responses linked to changes in gastrointestinal tract structure and function post-RYGB, that are implicated in the clinical efficacy of RYGB and that have actual or potential applications as non-surgical mimetic based approaches are addressed. These are (1) exaggerated post-prandial gut hormone responses; (2) local increases in undiluted bile in the gut lumen and augmented circulating bile acid and FGF19 concentrations and (3) compositional changes in the gut microbiota.
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