Module 6: Section 1B

Question 1

Enteric nervous system (ENS)

Answer 1

• ENS is composed of two thin layers of more than 100 million nerve cells lining the gastrointestinal tract from the esophagus to the rectum
• Called “second brain” or “brain in gut”
• Connected to the brain via vagus nerve that is made up of 80%-90% of afferent nerves

Question 2

Major roles of the ENS

Answer 2

• Controlling digestion, including swallowing
• Release of enzymes that break down food
• Control of blood flow to facilitate nutrient absorption
• Elimination

Question 3

The Gut-Brain Axis

Answer 3

• The gut and brain communicate bidirectionally to coordinate their functions in healthy conditions or when disrupted in disease
• Intestinal neuronal networks sense signals and communicate with the CNS through messaging pathways, while gut events also act through the enteric endocrine, immune, and metabolic systems
• GI tract microbes influence the quantity and types of signals reaching the CNS

Question 4

Peripheral serotonin - gut microbe that affects the brain

Answer 4

• Cells in the gut produce large quantities of serotonin
• May have an effect on signalling in the brain

Question 5

Immune system - gut microbe that affects the brain

Answer 5

Intestinal microbiome can prompt immune cells to produce cytokines that influence neurophysiology

Question 6

Bacterial molecules - gut microbe that affects the brain

Answer 6

• Microbes produce metabolites such as butyrate
• These can alter the activity of the cells in the blood brain barrier

Question 7

Microbiome impact on the gut-brain axis

Answer 7

• The intestines must keep bacteria contained in the lumen while allowing uptake of metabolites, microbial products, and water
• This balance is highly controlled, and if bacteria cross into underlying tissue, inflammation can occur and lead to dysbiosis

Question 8

Irritable bowel syndrome and the gut microbiome

Answer 8

• Stress-related functional brain-gut-microbiota axis disorder
• Associated with altered gut microbiota profile and increased intestinal permeability
• Person with IBS has increased levels of anxiety and depression symptoms

Question 9

Study by Jeffery et al. on the microbiome diversity in IBS subjects

Answer 9

• Microbial diversity decreased in patients with IBS
• Depression strongly correlated with a high Firmicutes and lower Bacterodietes

Question 10

Examples of autoimmune diseases

Answer 10

• Multiple sclerosis
• Type 1 diabetes
• Inflammatory bowel diseases (like Crohn’s, systemic lupus erythematosus and celiac disease)

Question 11

Role of intestinal barrier in autoimmune diseases

Answer 11

• Disruption of the barrier function in the GI tract could be responsible for the development of an autoimmune disease
• Could occur through the disruption of the tight junctions between the epithelial cells lining the GI tract
• This allows the infiltration of microbes from the lumen into the underlying tissue, resulting in chronic inflammation

Question 12

Molecular mimicry - potential factor leading to autoimmune disease

Answer 12

• Molecular mimicry between food ingredients and tight junction proteins
• Ex: antibodies against tight junction proteins would further degrade the intestinal barrier

Question 13

Changes in immunogenicity - potential factor leading to autoimmune diseases

Answer 13

Food additives could change the immunogenicity of a nutrient, leading to the production of antibodies that are cross-reactive with tight junction proteins

Question 14

Changes in microbiota composition - potential factor leading to autoimmune disease

Answer 14

• Food composition changes the intestinal microbiota
• Ex: Abnormal microbiota composition in the GI tract increases barrier permeability that amplifies the level of autoimmunity because of the pro-inflammatory environment

Question 15

Autoimmune disease - Food Additives & the Intestinal Barrier

Answer 15

• Modern processed foods contain many additives to improve flavour and shelf-life
• Increasing additive consumption in North America may negatively impact tight junction function in the GI tract
• Although additives can be deemed “safe” short-term, long-term testing is rarely done, so chronic exposure may have detrimental effects

Question 16

Obesity

Answer 16

• Obesity is caused by low physical activity and over-nutrition, along with some genetic factors
• Obesity is associated with inflammation, insulin resistance, and cardiovascular disease
• A high coincidence of obesity and asthma in the last 20 years may be explained by gut microbiota’s modulatory effects

Question 17

Adipose tissue - Connection to asthma and obesity

Answer 17

• Adipose tissue releases cytokines and adipokines that drive inflammation
• Two key molecules:
  
  • Leptin: pro-inflammatory
  • Adiponectin: anti-inflammatory
• In obese asthma patients: high leptin + low adiponectin results in systemic inflammation

Question 18

Dysbiosis of gut microflora - Connection to asthma and obesity

Answer 18

• Dysbiosis of the gut microflora results in a breakdown in intestinal barrier function
• Inflammation is increased due to leakage of microbial products (like LPS) into underlying tissues
• The increased inflammation increases the probability of generation of antibodies to self-antigens, contributing to asthma

Question 19

SCFA - Connection to asthma and obesity

Answer 19

• Low fibre and high fat diet alters SCFA production
• SCFAs influence functions like appetite suppression, gluconeogenesis, fat metabolism and modulation of serotonin synthesis

Question 20

Gut Microbes Influence Obesity

Answer 20

• Experiments transferring gut microbes from humans into germ-free mice showed that microbes from obese people cause weight gain, while microbes from underweight people cause weight loss
• Meaning microbiome composition can directly affect metabolism and obesity

Question 21

The gut microbiome and autism

Answer 21

• ASD is a neurodevelopment condition that is diagnosed from the presence and severity of specific behaviours and deficits in language and social interaction
• Altered GI motility and increased intestinal permeability are usually found along with ASD

Question 22

ASD Mouse Model & Microbiota Findings

Answer 22

• ASD-like behavior can be induced in mice using viral-mimicking dsRNA during pregnancy, causing ASD behaviors & GI dysfunction in offspring
• Giving these ASD mice Bacteroides fragilis improved gut barrier function and reduced ASD-like behaviors

Question 23

Probiotic treatment of mice with autism features

Answer 23

1. Alters composition of gut microbiota
2. Improves epithelial barrier integrity
3. Reduces leakage of GI metabolites
4. Restores serum metabolites

Question 24

Reestablishing Barrier Function

Answer 24

• Impaired gut barrier function contributes to dysbiosis-related disease, so restoring epithelial integrity is important
• Introducing beneficial bacteria can reduce inflammation and improve barrier function (basis of probiotics)