The Gut-Brain Axis

Question 1

What implies the importance of the gut microbiata relative to overall health?

Answer 1

• The vast number of microoragnisms in the gut, 100 trillion , equivalent to human cells.
• The gut microbiome outnumbers the human genome by almost 9-10 folds.

Question 2

Which phyla compromise the majority of the gut microbiata?

Answer 2

Firmicutes and Bacteriodetes are the most abundant, 90% of the gut microbiata.

Question 3

When and how was interest reintroduced in the gut-brain axis?

Answer 3

In the early 2000s, a study by Backhead et al. (2004) highlighted how the gut microbiata composition alters the hosts phenotype.

Question 4

How does the gut communicate with the brain?

Answer 4

The gut brain crosstalk occurs on 4 main levels:
* The vagus nerve
* The Immune system
* Systemic circulation
* The endocrine system
by action of metabolites, NTs, hormones and inflammatory modulators.

Question 5

Elaborate on the harmful gut metabolites.

Answer 5

LPS and LCFAs are products of potentially pathogenic microbiata, which:
* Induce chronic inflammation in gut and CNS.
* Depress expression of BDNF and NMDA receptor.
* Increase BBB permeability.
* Induce cognitive decline.

Question 6

Is a healthy gut important for immune system of the CNS ?

Answer 6

YES, the symbiosis of the gut microbiata ensures the normal proliferation and maturity of microglia in brain.
(since GF mice had ramified immature microglia)

Question 7

Which cells in gut secrete hormones?

Answer 7

• Enteroendocrine Cells (EEC), secrete hormones in response to microbiata products.
• Some microoragnism have the potential to secrete hormones themselves, Lactobacillus secretes dopamine.

Question 8

Which areas in brain are affected by gut hormones?

Answer 8

Amygdala, hippocampus, hypothalamus, thalamus, brain stem nuclei, and cortical areas have receptors for gut hormones.

Question 9

Explain the relation between a leaky gut and a leaky brain.

Answer 9

In the case of gut dysbiosis, the increase in pathogenic microoragnisms induces chronic gut inflammation, causing leaky gut and allowing harmful metabolites to spread to the brain compromising BBB.

Question 10

Does stress impact gut microbiata ?

Answer 10

Dysregulated HPA axis (chronic stress) causes beneficial gut species to decrease and causes gut dysbiosis which in turn inflicts stress on the body and triggers a more dysregulated HPA axis.

Question 11

Why is the gut called the second brain?

Answer 11

Due to:
* The large number of neurons (100-500 million)
* Similair function, structure and chemical coding of the CNS.

Question 12

Which gut NT is a part of AD pathogensis?

Answer 12

GABA, as evidence showed decreased GABA levels in gut and brain of AD patients.

Question 13

What does the vagus nerve projec onto in brain?

Answer 13

VN projects on Nucleus Track Solitary (NTS) that projects to limbic system (amygdala) followed by cortical areas.

Question 14

What factors affect the composition of gut microbiata?

Answer 14

• Type of delivery (vaginal vs C section).
• Breastfeeding vs formula milk.
• Antibiotic use.
• DIET.
• Stress.

Question 15

What are the worst and best types of diets to adapt and why?

Answer 15

• Western diets rich in unhealthy fats and sugars favor pathogenic species in gut (Proteobacteria and Bacteriodetes).
• Mediterranean diets rich in DHAs favor probiotic species in gut (Firmicutes and Actinobacteria).

Question 16

What triggers the misfolding and amyloidogenic splicing of APP?

Answer 16

Neuroinflammation and inhibition of BDNF in hippocampus induced by the dysbiosis of the gut (Lactobacillus and Bifidobacterium decrease).

Question 17

What feature of AD occurs first?

Answer 17

• The increased Amyloid β accumulation in brain of AD patients. (coupled with Aβ clearance)
• Both are driven by neuroinflammation.

Question 18

Which metabolite of the gut has the potential to soothe different ailments?

Answer 18

SCFAs have been proven to decrease inflammation and reverse neurodegenration as well as other aspects of congnitive decline caused by gut dysbiosis.

Question 19

What are the gut hormones that control hunger and satiety ?

Answer 19

Ghrelin, Leptin and CCK.

Question 20

Is Ghrelin only responsible for inducing hunger and promoting obesity ?

Answer 20

NO, recent studies, Moon et al. (2009) found that ghrelin is involved in the proliferation of Dentate Gyrus and thus increase hippocampal neurogenesis.

Question 21

Where is most of the serotonin produced ?

Answer 21

90-95% of the serotonin in our body is secreted in the gut and mediated by SCFAs.

Question 22

what are the major genes found to increase risk of AD.

Answer 22

APoE and TREM2 genes.

Question 23

What aspects differ AD from dementia?

Answer 23

• Elevated APP mRNA and protein expression.
• Increased β and γ secretases.
• Amyloid β accumulation in brain of AD patients.

Question 24

Percentage of afferent to efferent vagus nerve fibers.

Answer 24

Afferent VS fibers (90%) outnumber the efferent ones (10%) significantly, emphasizing on the role of the gut on the brain.

Question 25

How do the probiotic gut species affect BBB?

Answer 25

In gut symbiosis, probiotic species take over, secreting good metabolites (SCFAs) which circulate and reach the brain and increase the expression of tight junction proteins (Occludin and Claudin) thus enhancing the BBB integrity.

Question 26

Name some anti-inflammatory cytokines.

Answer 26

IL-4, IL-10.

Question 27

Kindly follow the link provided to find a very helpful image that summarizes aspects of neurodegenration related to gut dysbiosis.

Answer 27

https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=7912578_nutrients-13-00361-g001.jpg