Physiological adaptations following Roux-en-Y gastric bypass and the identification of targets for bariatric mimetic pharmacotherapy

• RYGB induces afferent signals from the gut involved in metabolic control.
• Certain of these phenomena can be mimicked by pharmacotherapy.
• Bariatric mimetics may deliver the benefits of surgery without its complications.

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.