What goes down may come up: regurgitative behaviors and their underlying gut-brain axes-insights from genetic models...

Most humans have experienced regurgitation and vomiting (emesis) at some point in their lives. These behaviors are also commonly observed throughout the rest of the animal kingdom, serving various functions such as feeding, courtship, defense against predators, and protection from accidental toxin ingestion. Studying these behaviors offers valuable insights into the underlying gut-brain axis and presents opportunities to identify new therapeutic targets. However, detailed mechanistic studies on the molecular, genetic, and neural circuit basis of regurgitative behaviors have been hampered until recently due to the lack of suitable genetic model organisms capable of regurgitation. This review introduces researchers to the mechanisms of regurgitative behaviors, particularly those related to the gut-brain axis. We summarize these behaviors across different taxa, review current knowledge of their underlying mechanisms with a focus on gut-brain connections, and discuss related pathologies. Finally, we present recent findings from Drosophila models of regurgitation and emesis, and outline key questions that still require attention.