W3 T1 P3

• The gut-brain axis involves communication between the gut and the brain.
• It influences each other.

Studying the Gut-Brain Axis

• Two main experimental strategies exist for studying the gut-brain axis
• These involve either adding something or removing something.
• Germ-free animal models:
  • These models use genetically modified animals raised in sterile conditions and lack gut microbiota.
• Antibiotic studies:
  • Antibiotics wipe out the microbiota.
  • This can be harmful to the microbiota, but is useful in treating infections or conditions.
  • Antibiotics can cause effects to other biological mechanisms or behaviour.
• Bacterial infections can produce similar effects.
• Supplements, like probiotics, can allow for observation of their impact on the microbiota and the gut-brain axis.
• Fecal microbiota transplants involve transplanting microbiota from one individual to another.
  • Changes to host biology can then be monitored.

Animal Studies and Gut-Brain Axis

• Studies show that germ-free mice, mice given antibiotics, or mice with induced bacterial infections exhibit:
  • Increased stress response
  • Anxiety and depression-like behaviours
  • Deficits in social behaviour
• A 2013 study in molecular psychiatry reveals that microbiota is essential for the development of appropriate social behaviour in mice.
• These animals also exhibit cognitive deficits, particularly in memory and learning.
• Some studies combine multiple experimental strategies, such as adding probiotic treatments.
• The negative effects of infections or antibiotics can be reversed or prevented with probiotic treatments.

Pathways of Gut Microbiota Modulation

• The gut microbiota modulates the brain and behavior through direct and indirect pathways.
• The HPA axis produces the stress hormone cortisol.
  • Production of cortisol is over-activated in affective disorders.
  • Cortisol affects immune cells both locally in the gut and systemically.
  • It also alters gut permeability, barrier function, and gut microbiota composition.
• This cascade can also be triggered in the opposite direction starting from gut microbiota composition.
• Neurotransmitter production is directly dependent on bacteria, especially serotonin.
  • About 95% of the body's serotonin is produced and located in the gut.
  • Some serotonin goes via the vagus nerve to the brain.
  • Tryptophan is an essential amino acid for serotonin production.
  • Probiotics increase tryptophan levels.
• The gut microbiota and probiotics- agents alter circulating inflammatory cytokines, affecting brain function.
• Certain bacteria produce short-chain fatty acids (bacterial metabolites of dietary fiber).
  • These produce anti-inflammatory cytokines and promote a healthy state.
• Direct neuronal connections via the vagus nerve and the enteric nervous system relay the influence of the gut microbiota to the brain and vice versa.

Mechanisms Overview

• Animal studies have shown increased levels of tryptophan, increased levels of brain-derived neurotrophic factor.
• Probiotics pre-treatment or treatment after infection decreases HPA axis activation and reduces pro-inflammatory cytokines.

Healthy vs. Unhealthy Microbiota

• In an unhealthy microbiota:
  • There is an increase of inflammatory bacterial species.
  • This leads to intestinal barrier leaks and a compromised intestinal barrier.
  • This results in increased inflammation, circulating inflammatory cytokines, and stress hormones.
• In a healthy microbiota:
  • Homeostasis and a tight, healthy gut lining are seen.

The gut-brain axis involves communication between the gut and the brain. It influences each other. Experimental strategies for studying the gut-brain axis involve adding or removing something, like probiotics, fecal microbiota transplants. Antibiotic studies wipe out the microbiota.