Dynamic Tension Between the Microbiome and the Macrobiome

Two largely separate research traditions have transformed our understanding of what shapes human cognition. The first, microbiota–gut–brain axis research, has established that the gut microbiome contributes causally to affective and cognitive processing through neuroactive metabolites, vagal signalling, and immune modulation. The second, cultural niche construction and extended cognition research, has shown that symbolic systems — language, institutions, and cumulative culture — scaffold the architecture of human thought. No framework has yet integrated these two lines of evidence within a common computational principle. Here we propose that human cognition can be understood as the product of dynamic tension between two signal streams: bottom-up interoceptive signals from the gut microbiome, and top-down predictive structures from the external symbolic environment, which we term the macrobiome. We formalise this tension through precision-weighted Bayesian integration, where the relative influence of each stream depends on its estimated reliability. The sleep–wake cycle provides a physiological mechanism for alternating precision allocation: wakefulness privileges macrobiome-driven exteroceptive predictions, while NREM sleep allows microbiome-driven interoceptive recalibration. The framework generates six pre-registered, falsifiable predictions and suggests a chronobiologically timed approach to psychiatric intervention — chrono-psychobiotics. Rather than offering a comprehensive theory of cognition, the framework provides an integrative principle, a set of testable hypotheses, and a vocabulary for bridging two fields that have until now developed in isolation.