FN2230: Integrated Human Nutrition - Lecture 7

Question 1

Dysbiosis

Answer 1

A disturbance or imbalance in a biological system
Ex. Changes in the types and numbers of bacteria in the gut which may lead to developing different diseases, such as IBD

Question 2

Microbiome

Answer 2

A collection of different microbes and their functions or genes found in an environmental habitat.

Different parts of the body have different microbiomes

Question 3

Microbiota

Answer 3

The types of organisms that are present in an environmental habitat, whether they are bacteria, viruses (virome), or eukaryotes (protozoa or fungi)

Question 4

Probiotics

Answer 4

a selectively fermented ingredient that results in specific changes in the composition and/or activity of the GI microbiota thus conferring benefits upon host health

Question 5

Prebiotics

Answer 5

Usually non-digestible carbohydrates, oligosaccharides or short polysaccharides.
“Food” for probiotics

not all fibres are prebiotics but all prebiotics are fibres

Non-digestible CHO act as food for gut flora
- fructooligosaccharides , insulin, pectin, B-glucans, resistant starch

Increase bacteria numbers: including lactobacillus and bifidobacteria

control growth of pathogenic C perfringens

Question 6

Gut health is driven by three main factors:

Answer 6

1. Changes in stomach acid (declines as we age)
2. Changes in gut immunity
   (inflammation in the gut lining)
3. Changes in our gut flora (some microbes create more SCFA - which is good)

Question 7

Gut Microbiome

Answer 7

• Contains 100 times more genes than the human host
• Host-specific
• Contains heritable components

Question 8

What influences our gut microbiome?

Answer 8

Genetics
Factors related to the host
Environmental factors

Question 9

Describe the symbiotic relationship of the host-microbiota

Answer 9

Host: provides shelter and nutrients
Microbiota: supports nutrient metabolism, regulation of immune function, protection from pathogens

Question 10

How does the gut microbiome play a role in human health?

Answer 10

Can influence metabolic, immune and defense systems in the human intestine

Question 11

Colonization of the microbiome

Answer 11

Starts in gestation:
- the environment is not sterile, depends on the placental microbiome profile

Fetal meconium (baby’s first poop) biome:
- shows the general biome in the fetus’ gut, bacterial species in meconium shared with organisms found in amniotic fluid

Journey through caginal canal exposed infant to material microbiota
- differs from babies born via C-section

Question 12

How does prematurity impact the microbiome?

Answer 12

• Reduced microbial diversity & increased colonization of pathogenic bacteria
• Pre-term microbiota is less stable: associated with delayed transition to adult colonization patterns, immature gut epithelial gut barrier

Question 13

Compare how breastfeeding and formula feeding affects colonization

Answer 13

Breastmilk
- Oligosaccharides & glycoconjugates (inhibit binding pathogenic bacteria)
- lactoferrin & secretory IgA (promotes gut maturity)
- Antibodies & other factors (important mediators in inflammatory response)
- Live bacteria
- Non-digestible CHO (prebiotic)

Formula
- Different CHO, nutrients & bacteria (different colonization & immunomodulatory effects, no antibodies, antimicrobial proteins or secretory IgA)
- These changes may alter ability to store and utilize nutrients efficiently (potentially a contributing factor to obesity crisis??)

Question 14

Physical parts of the mucosal immune system

Answer 14

1. Intestinal epithelial barrier
2. Lamina propria
3. Gut-associated Lymphoid tissue (GALT)
   - Organized lymphoid tissue
   - Isolated lymphoid follicles
   - Mesenteric lymph nodes

Question 15

Describe the intestinal epithelial barrier

Answer 15

• Bodies largest mucosal surface (single layer of intestinal epithelial cells that are organized into crypts and villi)
• Main physical and biochemical barrier between lumen and lamina propria)

Question 16

What is the main function of the intestinal epithelial barrier?

Answer 16

Nutrient absorption
- adjacent epithelial cells form tight junctions
- acts as a defense against antigens, toxins, pathogens and enteric (intestinal) bacteria
- regulates paracellular movements of ions, solutes and water across the intestinal epithelial barrier

Question 17

Intestinal epithelial cell family

Answer 17

Enterocytes, endocrine cells, M cells, goblet cells and paneth cells (not present in the colon)

Question 18

Inflammatory Bowel Disease symptoms

Answer 18

dysfunction of the intestinal barrier, chronic inflammation

Question 19

Crohn’s disease

Answer 19

abnormal intestinal structure, leaky small intestine, high degree inflammation

Question 20

Obesity

Answer 20

impairment of intestinal barrier function, alteration in microbiome

Question 21

NAFLD

Answer 21

abnormal morphologies of crypts and villi in duodenal mucosa

Question 22

Celiac disease

Answer 22

dysfunction of the intestinal barrier (increase gliadin permeability and related immune response)

Question 23

Type 1 Diabetes Mellitus

Answer 23

Gut microbiota dysbiosis, increased intestinal permeability, heightened immune activation

Question 24

Describe the mucous barrier (intestinal epithelial barrier)

Answer 24

From specialized secretory cells
- goblets cells (mucins)
- paneth cells (antimicrobial proteins)

forms first line of defense against microbial invasion

intraepithelial lymphocytes
- maintain and protect mucosal barrier against invading pathogens

Question 25

Difference between the mucous barrier of the small intestine and the large intestine

Answer 25

Small intestine: thinner permeable mucous layer - allow for nutrient absorption Large intestine: two-layered mucous barriers with inner dense mucous barrier devoid of bacteria - larger amount of residing bacteria

Question 26

Describe the lamina propria

Answer 26

- Loosely packed connective tissue below the epithelium - Contains the majority of intestinal immune cells (lymphocytes, peyer's patches, innate immune cell populations include dendritic cells, macrophages, mast cells, eosinophils and lymphoid cells) - mesenteric lymph nodes - contains blood supply, lymphatic drainage system and nervous supply for mucosa

Question 27

How does antigen exposure occur and how does the GALT respond?

Answer 27

Can occur through penetration of mucosal barrier - barrier is not totally impermeable to macromolecules - this can be accelerated by inflammation or mucosal damage The adaptive immune response is orchestrated in GALT - cell-mediated cytotoxic reactions (neutrophils, macrophages, eosinophils, natural killer cells, mast cells) - antibody-dependent cell cytotoxicity (involving presentation and activation of immune cells, subpopulations of T cells have specialized functions)

Question 28

How does the microbiome affect gut homeostasis?

Answer 28

Gut microbiota - provides protection against pathogenic bacteria - required for normal immune system maturation (GALT) - Lactobacillus and Bifidobacterium induce tolerogenic dendritic cells and TREGs - Microbial by-products and metabolites also enhance immune function (SCFA modulates immune response by modulating gene expression, differentiation and chemotaxis in enterocytes)

Question 29

Fibre and gut health

Answer 29

Once in the colon, the bacteria colonies can metabolize several forms of fibre which can benefit microbiota by promoting diversity and numbers Cellulose is only partly degraded (human amylase cannot hydrolyze the covalent bonds found in this) SCFA produced by some forms of fibre are potential energy sources for colonic mucosal cells or can be absorbed into the hepatic portal vein

Question 30

Factors that influence digestion efficiency

Answer 30

Form and size of food particles Composition of the meal Transit time - influences the diversity and size of microbiota - transit time influenced by: exercise, caffeine and alcohol, diet, genetics, psychological status)

Question 31

Metabolites of gut microbiota

Answer 31

CHO - vitamins K and b-group - hydrogen - methane - alcohols - SCFA (acetate, butyrate, propionate) PRO - phenolic compounds - amines - ammonia - branched-chain fatty acids Fat - diacylglycerols - converts primary bile acids to secondary bile acids

Question 32

Micronutrients and Food Additives as Microbiota Modulators

Answer 32

Polyphenols - Modulate microbiota by increasing bifidobacterial & lactobacilli - Antimicrobial effects - Bioactive compounds (equol, enterodiol etc) Dietary Riboflavin - Improve redox state in gut Deficiencies - Vitamin A, C, E alters bacterial community structures Vitamin B6 - Selective bacterial physiology Magnesium - Influence physiology of bifidobacteria Artificial non-calorie sweeteners - functional consequence (impaired glucose homeostasis) Food emulsifying agents - detergent like properties - influence composition microbiota (linked to IBD)

Question 33

Carbohydrate fermentation

Answer 33

- Core activity of gut - Drives energy and carbon economy of the colon - competition for available CHO but also advantageous cooperation

Question 34

Describe the process of bacteria breakdown of CHO

Answer 34

Initial breakdown of complex plant-derived polysaccharides to less complex oligosaccharides Other bacteria specialize in oligosaccharide fermentation (eg. bifidobacterium) to produce SCFA and gases - fuel for colonic cells (about 10% of our energy requirements comes from colonic fermentiaont)

Question 35

What is the importance of carbohydrate fermentation

Answer 35

Initial breakdown of complex plant-derived polysaccharides to less complex oligosaccharides Other bacteria specialize in oligosaccharide fermentation (eg. bifidobacterium) to produce SCFA and gases - fuel for colonic cells (about 10% of our energy requirements comes from colonic fermentation) - butyrate and propionate can regulate intestinal physiology and immune function - also serve as carbon and energy substrate for other more specialized bacteria (reductive acetogens, sulfate-reducing bacteria, and methanogens) Cross-feeding

Question 36

Short-chain fatty Acids (SCFA) and functions

Answer 36

Products of carbohydrate breakdown in the absence of oxygen - primarily acetate, propionate and butyrate - 95% of SCFA generated in the colon are metabolized by the host body Improves Colonic function - colonic blood flow - fluid and electrolyte uptake - butyrate promotes tight junctions, cell proliferation and increased mucin production by goblet cells Improves immune function - anti-inflammatory effects - butyrate and propionate can induce differentiation of T cells Regulates intestinal hormone production and lipogenesis Acidic environment to inhibit cancer growth energy - colonic cells or to the liver - propionate is glucogenic - acetate and butyrate are lipogenic

Question 37

Describe the steps of the fermentation of carbohydrates

Answer 37

CHO is first degraded to pyruvate - then converted to succinate, lactate, acetyl-coA and other compounds Succinate can also be a direct product of CHO fermentation Acetate produced via direct conversion of acetyl-CoA for energy or acetogenesis Propionate has 3 potential pathways Butyryl CoA (precursor for butyrate) generated from either acetyl CoA or Succinate

Question 38

Describe the relationship between protein and gut microbiota

Answer 38

Non-digested proteins and peptides enter colon and subjected to bacterial metabolism - proteolysis higher in distal rather than proximal region - uses proteases - microbes can either deaminate to produce acid plus ammonia or decarboxylate to produce an amine plus CO2 (but high ammonia can be toxic) - next steps depend on class amino acid (most ends to pyruvate or acetyl coA, branch chain fatty acids can also be produced)

Question 39

_____________ increase with consumption of animal-based proteins

Answer 39

Bile-tolerant anaerobes

Question 40

What are the most common types of proteins

Answer 40

Primary sulfur-containing or aromatic AA - hydrogen sulfide - degradation of polycyclic aromatic hydrocarbons (carcinogenic compounds) - Trimethyl amine N-oxide (TMAO) - generated from dietary phospholipid phosphatidylcholine and L-carnitine => risk factor for cardiovascular disease and potentially some neurological disorders

Question 41

Describe the relationship between Fat and gut microbiota

Answer 41

Evidence that high fat intake rather than obesity has direct effect on microbiota - microorganisms in gut known to have lipases - modulates intestinal microbiota composition based on impact on bile acid secretion - modulation may also be linked to macronutrient shift