The Postprandial Chronobiome in Interorgan Glucose Homeostasis

ABSTRACT Postprandial glucose homeostasis depends on the coordinated function of the liver, pancreatic islets, adipose tissue, and skeletal muscle, each with a cell‐autonomous clock that gates nutrient responsiveness across the day. The gut microbiome adds a time‐varying layer: microbial abundance and metabolite output show 24‐h variation shaped by feeding and host clocks. Human stable‐isotope studies estimate systemic availability at approximately 36% for acetate, 9% for propionate, and 2% for butyrate under the conditions tested, supporting preferential hepatic exposure and limited direct exposure of peripheral tissues. We define the postprandial chronobiome as a hypothesis‐driven framework in which microbial features are characterized by phase, amplitude, and meal‐related lag relative to host biological time, rather than by identity or abundance alone. The liver provides the strongest mechanistic platform; evidence for pancreatic islets, adipose tissue, and skeletal muscle is predominantly indirect or animal‐based, and causal dynamic interorgan coupling has not been demonstrated in humans. We examine disrupted temporal organization in obesity, type 2 diabetes (T2D), metabolic dysfunction‐associated steatotic liver disease (MASLD), and circadian disruption, treat microbial timing as a plausible rather than established mediator of meal‐timing effects, and outline phase‐aware experiments needed to test whether it adds value beyond energy intake, static microbiome composition, and host circadian state.