Beyond the 'second brain': the gut microbiota as a constitutive co-constructor of embodied cognitive network.

Cognition, emotion, and behavior arise from ongoing bidirectional communication between a host and its symbiotic gut microbes, not from brain-isolated processes alone. The gut microbiota acts as an embedded signaling system, producing cognitively active metabolites like short-chain fatty acids and neuroactive substances that shape interoceptive states and neural function through neural, immune, and metabolic pathways. Evidence from germ-free animal models, fecal microbiota transplantation, human multi-omics, and clinical interventions indicates that microbiota-derived processes are constitutively relevant to embodied cognitive architectures organized by interoceptive prediction, affective appraisal, and vagal-metabolic signaling. This framework moves beyond a linear gut-brain axis to a multispecies model, offering a biological foundation for the mind and enabling precision mental health interventions like psychobiotics.

Study at a glance

Abstract

Traditional cognitive science has historically confined the mind within the cranium. While the "second brain" metaphor underscores the autonomy of the enteric nervous system, it remains entrenched in a neurocentric paradigm. Here, we propose a transformative framework: the gut microbiota may function as a constitutively relevant contributor to specific embodied cognitive architectures. We contend that cognition, emotion, and behavior are not fully understandable in brain-isolated terms. Instead, these processes emerge from a sustained, bidirectional dialogue between the host and its symbiotic microbial ecosystem. Integrating 4E cognition theory, we systematically delineate how gut microbiota functions as an embedded signaling system-producing cognitively active metabolites, such as short-chain fatty acids and neuroactive substances-to shape interoceptive states and neural function via neural, immune, and metabolic/endocrine interfaces. We establish a rigorous evidential chain, categorized as "deprivation, replacement, observation, and intervention," synthesizing germ-free animal models, fecal microbiota transplantation, human multi-omics, and clinical interventions. These data-drawn from animal models that establish causal necessity and sufficiency, human cohort studies that reveal systematic ecological associations, and proof-of-concept intervention trials that demonstrate clinical plasticity-converge to support the view that microbiota-derived processes may be constitutively relevant to the realization of specific embodied cognitive architectures, especially those organized through interoceptive prediction, affective appraisal, and vagal-metabolic signaling, rather than functioning as merely transient or incidental regulators. The multi-level nature of this evidence base, spanning causal mechanisms in controlled settings to ecological validity in human populations, provides a robust foundation for reframing the gut microbiota as a symbiotic co-constructor of the embodied mind. Ultimately, we move beyond the linear "gut-brain axis" model to outline a multispecies framework for understanding the embodied architectures within which interoceptive, affective, and related cognitive processes unfold. This paradigm shift offers a novel biological foundation for the mind and enables precision interventions for mental health, such as psychobiotics and targeted ecological remodeling. Looking forward, we envision a unified "microbiota-mind" model that integrates computational modeling and ethical frameworks. This endeavor challenges the traditional concept of a "self" bounded by the skin, providing a roadmap for the future of precision psychiatry and cognitive science.