Other Pathways

OTHER MECHANISMS OF COMMUNICATION BETWEEN THE GUT AND BRAIN

Hypothalamus-pituitary-adrenal (HPA) axis

The HPA axis is a neuroendocrine unit in the brain composed of the hypothalamus, pituitary gland, and the adrenal glands. Exposure to a stressor or a threat, the limbic system, comprised of the amygdala, hippocampus, and prefrontal cortex, processes sensory stimuli directed from the sympathetic nervous system. This axis is involved in the stress circuitry and response, by releasing cortisol and other hormones to help our body deal with stress. Gut microbiota influence the programming of the HPA axis and stress reactivity at early stages of development and throughout the lifespan. Studies found the HPA axis is disregulated in GF and antibiotic treated mice. ¹⁵ A malfunction of the HPA axis has been associated with depressive episodes showing a link between HPA activity and the microbiome. ¹⁷

Immune activation

Alterations in gut microbiota provide cues to neuroimmune system functioning, where probiotics have direct effects on the immune system. A bidirectional pathway from the luminal surface of the intestine to the CNS allows for the immune system to transport bacterial information to the nervous system. Alterations in anti-inflammatory and pro-inflammatory cytokines can affect brain function, from gut microbiota and probiotics. Additionally, a study found chronic gut inflammation has psychological influence, whereby patients with IBD have shown increased anxiety and depression. ²⁰

Short-chain fatty acids (SCFAs)

Short-chain fatty acids are neuroactive bacterial metabolites that help regulate the crosstalk of the gut-brain-axis. SCFAs are made by in the gastrointestinal tract by dietary fiber. SCFAs can influence CNS function through G-protien coupled receptors via hormonal, immune, or neural pathways and could be used as intervention targets for microbiota-gut-brain interactions. ⁹ SCFAs have been found to interact with cognition and emotion through dietary intervention research, and show a possible target for gut-brain-interactions in humans.