Gut-brain axis

Question 1

Germ-free vs colonised mice

Answer 1

Compared to colonised mice, GF mice showed exaggerated HPA stress reaction, impaired social behaviours, reduced anxiety-like behaviour and increased motor and rearing activity.
Anomalies are restored after colonisation.

Question 2

Autonomic control

Answer 2

Afferent signals arising from the lumen and transmitted through enteric, spinal and vagal pathways to the CNS.
Efferent signals from the CNS to the intestinal wall.

Question 3

Dysbiosis links

Answer 3

The microbiota contributes to brain development and neuroinflammatory and psychiatric disorders.
Dysbiosis is linked to autism, anxiety-depressive behaviours and neurodegeneration.

Question 4

Serotonin

Answer 4

> 90% of the body’s serotonin is synthesised by gut bacteria and released in the circulation

Question 5

Short-chain fatty acids

Answer 5

Produced by the microbiome, act within the GIT, vasculature and brain. Binding of these to GPCRs causes a cascade of intracellular events.
These can cross the BBB and influence neuroinflammation and neurogenesis.

Question 6

Impacts on the gut-brain axis

Answer 6

The composition of the gut microbiota can be influenced by diet, ageing, disease state, and antibiotic and probiotic use. Regular exercise protects the health of the gut microbiota.

Question 7

Microbiota metabolites

Answer 7

Metabolites can activate enteroendocrine cells to release gut hormones.
They can also be absorbed across the epithelial cell layer to enter the bloodstream or to activate the vagus nerve to communicate with the brain.

Question 8

c-Fos

Answer 8

c-Fos is a proto-oncogene
The brains of mice inoculated with Campylobacter jejuni (harmful) had an increase in c-Fos expression in every brain region → direct connection between the microbiome and brain function

Question 9

Alzheimer’s link

Answer 9

Lipopolysaccharides (LPS) are outer membrane components of gram-negative bacteria. Pro-inflammatory LPS levels were elevated in the brains of Alzheimer’s paients, particularly in the hippocampus.
Targeting harmful bacteria and introducing positive bacteria in the gut can help relieve cognitive dysfunction and neuroinflammation in AD.
High-fat diets exacerbate AD phenotypes, leading to increased amyloid deposition in the hippocampus and neuroinflammation due to penetration of short-chain fatty acids in the brain. This was not seen in WT mice: it is a combination of genetic and environmental factors.

Question 10

Faecal microbiota transplantation

Answer 10

Transplanting microbiota from young mice into old ones counteracts age-associated behavioural deficits. Expression of interleukins and microglia decreases. Ability to learn improves.

Question 11

Autism link

Answer 11

Bacteroides fragilis treatment ameliorates autism-related behavioural abnormalities in ‘maternal immune activation’ offspring, reversing anxious behaviour.
Lactobacillus reuteri has the capacity to upregulate plasma and brain levels of oxytocin, which increases social behaviour. It is associated with increased social behaviour in mouse models of ASD.

Question 12

Bacteria species and brain mediation

Answer 12

Lactobacillus rhamnosus produces GABA and regulates GABA receptors in the brain.
Bifidobacterium longum and Lactobacillus upregulate BDNF, augment neuronal plasticity in the ENS and reduces anxiety and depression-like behaviours in mice.
Lactobacillus reuteri has the capacity to upregulate plasma and brain levels of oxytocin, which increases social behaviour. It is associated with increased social behaviour in mouse models of ASD.
Bacteroides fragilis improves anxiety-like behaviour, repetitive behaviour and communication in mice.