The microbiota-gut-brain axis in hippocampus-dependent learning and memory: current state and future challenges


Author: Eloise J Kuijer1, Laura Steenbergen2

Affiliation: <sup>1</sup> Biomedical Sciences Research, Leiden University Medical Centre, Leiden, the Netherlands; Department of Life Sciences, University of Bath, United Kingdom.

<sup>2</sup> Clinical Psychology Unit, Leiden University & Leiden Institute for Brain and Cognition, Leiden, the Netherlands. Electronic address: L.Steenbergen@fsw.leidenuniv.nl.
Conference/Journal: Neurosci Biobehav Rev
Date published: 2023 Jun 26
Other:
  Special Notes: doi: 10.1016/j.neubiorev.2023.105296.   ,  Word Count: 197  
    A fundamental shift in neuroscience suggests bidirectional interaction of gut microbiota with the healthy and dysfunctional brain. This microbiota-gut-brain axis has mainly been investigated in stress-related psychopathology (e.g. depression, anxiety). The hippocampus, a key structure both the healthy brain and these psychopathologies, is implicated by work in rodents that suggests gut microbiota substantially impact hippocampal-dependent learning and memory. However, understanding microbiota-hippocampus mechanisms in health and disease, and translation to humans, is hampered by the absence of a coherent evaluative approach. We review the current knowledge regarding four main gut microbiota-hippocampus routes in rodents: through the vagus nerve; via the hypothalamus-pituitary-adrenal-axis; by metabolism of neuroactive substances; and through modulation of host inflammation. Next, we suggest an approach including testing (biomarkers of) the four routes as a function of the influence of gut microbiota (composition) on hippocampal-dependent (dys)functioning. We argue that such an approach is necessary to proceed from the current state of preclinical research to beneficial application in humans to optimise microbiota-based strategies to treat and enhance hippocampal-dependent memory (dys)functions.



Keywords: Dysbiosis; Gut microbiota; HPA-axis; Hippocampus; Inflammation; Learning; Memory; Metabolites; Microbiota-gut-brain axis; Neurogenesis; Prebiotic; Probiotic; Short chain fatty acid; Vagus nerve.



PMID: 37380040 DOI: 10.1016/j.neubiorev.2023.105296