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 in both the healthy brain and 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.
Keyphrases
- cerebral ischemia
- subarachnoid hemorrhage
- blood brain barrier
- resting state
- brain injury
- white matter
- healthcare
- functional connectivity
- public health
- cognitive impairment
- sleep quality
- prefrontal cortex
- depressive symptoms
- mass spectrometry
- risk assessment
- drinking water
- social media
- mesenchymal stem cells
- cell therapy
- working memory
- bone marrow
- single molecule
- peripheral nerve
- growth hormone
- anorexia nervosa