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

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.

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Publication Details

Journal
Frontiers in Neuroscience
Published
2026-06-03
DOI
https://doi.org/10.3389/fnins.2026.1808839
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
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article

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

Yanling Yuan, X Liu, Wenjie Zhu, Yue Gou et al.
Frontiers in Neuroscience
Gut microbiota and health
article

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

Yanling Yuan, X Liu, Wenjie Zhu, Yue Gou, Yu Wang, Qinglian Xie
article en

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.

Frontiers in NeuroscienceVol. 20
Sichuan University (CN), West China Hospital of Sichuan University (CN), Integrated Chinese Medicine (China) (CN), Zhongshan Hospital of Xiamen University (CN), National Institute of Mental Health (JP)
Openalex Percentile: Top 10%
Gut microbiota and health
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