Trust your gut: the neuro-gastroenteric mechanics of prediction and expectation.

Living organisms constantly make probabilistic predictions about what they expect to see in their external environment, and actively solicit information from the environment to inform their predictions. This process is foundational for many frameworks including Active Inference and Predictive Processing. It relies on organisms having prior expectations, entailed by an internal generative model of the environment. Posterior expectations are updated based on the selected data, driven by prediction error minimization. However, failures to contextualize the precision or confidence placed in predictions, can give rise to perceptual abnormalities that are at the basis of various psychiatric conditions. Different factors can influence this process. Notably, disruptions in the gut microbiome have been implicated in some psychotic disorders. Gut microbial dysregulation has also been associated with alterations in neurotransmitter synthesis, metabolism, and turnover, which may affect processes involved in the encoding of precision of prediction errors. On the basis of this gut-brain connection, this Hypothesis and Theory article hypothesizes that the gut microbiome plays a role as a modulator of predictive processing, influencing how predictions are formed and expectations updated. Specifically, this article explores the importance of "mental model" embodiment, and considers the role of hippocampal activity in predictive coding and its modulation by the gut microbiome. Finally, it offers a novel perspective on the use of cortico-hippocampal-gastroenteric frameworks for inferring personalized dietary interventions in nutritional psychiatry.