FP - Microbiome-Gut-Brain axis

Question 1

What is the microbiome-gut-brain axis? (2)

Answer 1

• A bidirectional communication network between the gut microbiota and the central nervous system (CNS).
• Influences brain function and gut health.

Question 2

How does the gut microbiome impact neuronal functions? (2)

Answer 2

• Affects neurodevelopment, synaptic signaling, and behavior.
• Dysbiosis is linked to neurological and psychiatric disorders.

Question 3

What are the physical features of the gastrointestinal (GI) tract? (5)

Answer 3

• ~5 meters long
• Epithelial surface area of ~32 m².
• Houses 70%–80% of the body’s immune cells.
• > 100 million neurons
• > 100,000 extrinsic nerve endings

Question 4

What are the main types of intestinal epithelial cells and their functions? (4)

Answer 4

• Enterocytes: Absorption, physical barrier.
• Goblet cells: Produce and secrete mucin.
• Enteroendocrine cells (EECs): Hormone production, neuroendocrine signaling.
• Paneth cells: Secrete antimicrobial peptides (AMPs).

During infections, all epithelial cells produce inflammatory cytokines.

Question 5

How are the gut and brain connected? (5)

Answer 5

• Nerves: Vagus nerve, sensory nerves, and enteric nervous system (ENS).
• Neuroendocrine system: Via enteroendocrine cells.
• HPA axis: Regulates stress responses.
• Metabolic pathways: Microbial metabolites like SCFAs.
• Immune system: Modulates inflammation and signaling.

Question 6

What is the hypothalamic-pituitary-adrenal (HPA) axis and its role in stress? (4)

Answer 6

• CRH Release: Hypothalamus releases corticotropin-releasing hormone (CRH).
• ACTH Release: CRH stimulates the pituitary to release adrenocorticotropic hormone (ACTH).
• Cortisol Release: ACTH triggers adrenal glands to release cortisol.
• Cortisol Effects: Enhances stress adaptation but can suppress immunity.

Question 7

How does the gut microbiome influence the HPA axis? (2)

Answer 7

• Germ-free mice show an exaggerated stress response due to sensitized HPA activity.
• Probiotics can normalize HPA activity and reduce stress effects.

Question 8

What are the effects of germ-free conditions on gut and brain? (3)

Answer 8

Gut:

• Fewer neurons in the enteric nervous system (ENS)
• Decreased neuronal excitability
• Reduced gastrointestinal motility

Brain:

• Dendritic morphological changes in amygdala and hippocampus
• Altered microglia connection networks and gene profile
• More permeable blood-brain barrier (BBB)

Germ-free mice:

• Altered stress hormone signaling
• Anxiety-like behaviors
• Deficits in social cognition
• Lower levels of neurotransmitter receptors (e.g., serotonin)

Question 9

How does the microbiota signal to the brain? (3)

Answer 9

Microbial dietary metabolism: Fermentation of dietary fibers produces SCFAs and bile acids that influence neuronal activity and behavior.

Neurotransmitter production: Gut bacteria synthesize neurotransmitters (e.g., serotonin, GABA, dopamine) or their precursors, which modulate brain function.

Tryptophan metabolism: Gut bacteria regulate tryptophan metabolism, producing serotonin or kynurenine; the latter may generate neurotoxic compounds linked to neurodegenerative diseases.

Question 10

How does direct signaling occur between the microbiota and the brain? (2)

Answer 10

Afferent nerves: Convey sensory information from the gut mucosa, muscle, and subserous layers to the CNS.
Efferent nerves: Transmit signals from the CNS to regulate gut motility and secretion.

Question 11

How does indirect signaling occur between the microbiota and the brain? (3)

Answer 11

Endocrine and metabolic pathways: Microbiota signal to the brain via:

SCFAs: Regulate neuroplasticity, epigenetics, gene expression, and the immune system.

BDNF: SCFAs stimulate BDNF production, promoting neuronal growth and survival.

Gut hormones: Modulate hormones like GLP-1, affecting appetite, satiety, and insulin secretion.

Question 12

How does the microbiota influence serotonin signaling to the brain? (5)

Answer 12

• Serotonin Production: Approximately 90% of serotonin is produced and secreted by enterochromaffin cells (ECs) in the gut.
• Microbiota Influence: The gut microbiota, particularly Clostridia, strongly influences EC function by producing bile acids and short-chain fatty acids (SCFAs).
• Increased Serotonin: Clostridia stimulate ECs to increase Tph1 expression and 5-HT biosynthesis.
• Serotonin Secretion: Increased serotonin is secreted both luminally and basolaterally.
• Serotonin Uptake: Circulating platelets take up increased serotonin, stimulate myenteric neurons and enhance gut motility.
• Tryptophan Metabolism: The microbiota shapes the metabolism of tryptophan, an essential amino acid required for serotonin synthesis and mood regulation in the brain.

Question 13

How does the microbiota influence GABA signaling to the brain? (3)

Answer 13

Microbiota influence: The gut microbiome can modulate GABA levels in the brain.

• GABA-producing bacteria: Bacteroides, Bifidobacterium, and Lactobacillus genera produce GABA.
• Indirect signaling: GABA and 5-HT may not cross the blood-brain barrier but can influence the brain via the vagus nerve or peripheral pathways.