MICR5831 L10: Healthy Microbiome and Dysbiosis 8/13/25 NEEDS SAQ

Name the 7 most common bacterial phyla and describe their prevalence in different environmental settings (slide 3)

SAQ

How does the gut microbiome differ from the microbiome in other parts of the human body? (slide 4)

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What affects the composition of the human microbiome? (slide 5)

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Describe the changes in the microbiome abundance and composition throughout the digestive tract (slide 6)

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Where are the microbiota in the gut? (slide 7)

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How is the human gut colonised and describe each stage (slide 8)

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Explain how age affects the human microbiome (slide 9)

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What are the roles of the microbiota in the gut? (slide 10)

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Describe six positive roles of the microbiota in the gut (slide 11)

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Using two examples, describe how the microbiota of the gut inhibit bacterial pathogens (slide 12)

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Describe how antibiotics can be a driver of dysbiosis of the human microbiome (slide 14)

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Compare the development of a healthy gut microbiome to that found in people with chronic inflammation of the gut. (slide 15 and 16)

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Compare the development of a healthy gut microbiome to that found in people with host metabolic disorders.(slide 15 and slide 17)

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Compare the development of a healthy gut microbiome to that found in people with host allergies and autoimmune diseases. (slide 15 and slide 18)

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Describe the experimental evidence for Proteobacteria as a signal for gut dysbiosis. (slide 19)

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How does the microbiome drive our energy intake? (slide 20)

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How does the microbiome contribute to adiposity? (slide 21)

SAQ

What is this?

-Aggregate of all species in a particular environment

Microbiome

What is this?

-Individual bacterial species in the biome

Microbiota

How many of the 52 known phyla are represented in the human gut microbiome?

5-7 phyla

True or False: Large cohort studies suggest that composition of individual biomes is in response to environmental cues

True

True or False: The human microbiome is the same in all sites of the body

False

What is this?

-Best studied human microbiome

-Over 500 species identified so far (70 divisions)

-Equivalent to 1 kg mass and metabolically active as the liver

Human gut

What part of the human gut microbiome is this?

-10E14 (100 trillion+) organisms

-Most of our bacterial biomass

-Equivalent to 1 kg mass and metabolically active as the liver

Colon

True or False: 90% of the cells in our body are microbial

True

What factor that affects human microbiome composition is this?

-Air

-Fecal oral route

-Limited Community

Dispersal

What factor that affects human microbiome composition is this?

-pH (acidity)

-Temperature

-Oxygen

-Moisture

-Nutrient levels

-Disturbance regimes

Abiotic

What factor that affects human microbiome composition is this?

-Metabolism of other microbes

-Secretions from intestinal epithelium and other mucosal surfaces

-Bacteriophages

Biotic

What organisms can you find in this part of the digestive tract?

-Upper Gastrointestinal Tract (Stomach): 102 - 104 cells/ml

Lactobacilli, streptococci, Helicobacter pylori

What organisms can you find in this part of the digestive tract?

-Ileum: 105-108 cells /ml, upper bacteria plus

Faculative anaerobes: Enterobacteriaceae

Obligate anaerobes: Bacteroides, Clostridium, Fusobacterium, Veillonella

What organisms can you find in this part of the digestive tract?

-Colon: distal human colon

-Most biodense natural ecosystem known (1010-1014 cells/ml)

-Complex and diverse, too many species to name

-Comprise most of our bacterial biomass

What layer of the gut is this?

-Intestinal cells line this area

-Absorb nutrients, secrete antimicrobial peptides and immunoglobulin to control bacterial density

-Goblet cells secrete mucin

Lamina propia

What layer of the gut is this?

-Between Lamina Propia and inner mucus layer

Intestine with goblet cells

What layer of the gut is this?

-Traps antimicrobial peptides and immunoglobulins

-Prevents them being washed away during digestions

Inner Mucus Layer

What layer of the gut is this?

-Contains microbiota of the microbiome

-Organized into bacterial communities called biofilms

Outer Mucous Layer

How do bacterial pathogens enter the gut?

-Through the lumen from our food

-Motile species swim through mucin layers

-Reach gut surface, cause disease

What are the 4 phases of early gut colonization?

1) Sterile gut

2) Initial acquisition

3) Breastfeeding, bottlefeeding

4) Start of solids, adult flora

What is the 1st phase of early gut colonization?

Sterile gut, no bacteria or pathogens

What is the 2nd phase of early gut colonization?

Initial acquisition: vagina, feces, hospital

What is the 3rd phase of early gut colonization?

Breast feeding or bottle-feeding

What species would you expect a breastfed gut flora to have?

Bifidobacteria (~90% of flora)

What species would you expect a bottle-fed gut flora to have?

Bacteroides and Clostridial species, more diversity

What is the 4th phase of early gut colonization?

Start of solids; move to adult flora

True or False: The key flora from bottle-feeding to adulthood is Bifidobacteria

True

True or False: 92% of adult flora are novel species, according to 16S rRNA studies done using PCR

True

Which stool tend to have the greatest concordance?

Twins

Which stool tend to have the least concordance?

Households

True or False: Stool collections can include eukaryotes, bacteria and archaea

True

What species make up most of a serial stool collection?

-Firmicutes (Gram P, motile)

-Bacteroidetes (Gram N)

What is the ratio of anaerobes to aerobes in stool collections?

1000:1

True or False: There are far fewer species in stool than in the environment

True

What does the gut microbiome remove for us?

Xenobiotics (foreign chemicals at unusual concentrations) and toxins in our diet

How does the gut microbiome prevent colonization by pathogens?

Normal flora compete for attachment sites or for essential nutrients

What does our gut microbiome synthesize or excrete?

-Synthesizes Vitamin K

-Excretes/reabsorbs Vitamin B12 in the gut

What are some substances produced by our gut microbiome that can inhibit/kill nonindigenous species?

-Bacteriocins

-Nonspecific fatty acids

-Peroxides

What tissue development is stimulated by the gut microbiome?

-Capillary density

-Intestines

-Lymphatic tissues

True or False: The infant gut is tolerized to low levels of diverse antigens, which prevents allergies

True

How does the gut microbiome develop a mature immune system?

-Antibodies are produced to protect against normal flora

-Crossreaction with related pathogens

-Prevents cancer, infection, and invasion

-Reduces inflammation

What is a microbiome mechanism to reduce inflammation?

1) Acetate secreted by microbiota as a metabolic byproduct of fermentation

2) Interacts with GRP43 receptors on immune cells

3) Blocks secretion of chemoattractants for inflammatory cells

4) Protects us from auto-immune responses against our own microbiome

5) Important for development of a healthy immune system without allergy

What is a microbiome mechanism to antagonize pathogens?

1) Bifidobacterium secret acetate

2) Inhibits enterohemorrhagic E. coli

3) Microbiota metabolize carbohydrate fibres

4) Butyrate (short chain fatty acid) is secreted

5) Butyrate induces antimicrobial peptide synthesis by host cells

6) Inhibits Shigella, Salmonella etc

What is this?

-Microbial imbalance inside the body

-Caused by antibiotics, diet, disease, injury, surgery or stress

Dysbiosis

How do Antibiotics cause Dysbiosis?

-Age 2 microbiome reaches stasis

-Key taxa are lost when antibiotics introduced

-Either fast, slow or incomplete recovery

What is this form of post-antibiotics microbiome stasis?

-Short term loss without long term effect

Fast recovery

What is this form of post-antibiotics microbiome stasis?

-If it occurs during immune development, it may have long term impact on host health

Slow recovery

What is this form of post-antibiotics microbiome stasis?

-Compositional changes are drastic

-Gut microbiome reaches a completely new form of stasis

-Unusual metabolic outcomes

Incomplete recovery

What is the infant gut like after birth?

Proteobacteria and Firmicutes dominate

What is the infant gut like after breast milk diet?

Actinobacteria gradually increases

What is the infant gut like after the first year of life?

-Bacteroides and Firmicutes dominate

-Decline in Proteobacteria/Actinobacteria

What happens to the infant gut at ages 2 and 3?

-Dramatic compositional changes (age 2)

-Identical to adult microbiome (age 3)

How do broad spectrum antibiotics/diet/drugs/stress drive the chronic gut inflammation found in Crohn's disease and IBS?

1) Loss of keystone taxa for homeostasis

2) Low diversity of microbiome allows pathogen bloom

3) Inflammation impairs gut function, increases permeability to pathogens

5) Sup-epithelial tissues get infected, chronic inflammation

True or False: Antibiotics-related chronic gut inflammation is caused by impairment of proper host immune system development

False

True or False: Antibiotics-related chronic gut inflammation is caused by low microbiome diversity, inflammation, increased gut permeability and bacteria in sub-epithelial tissues

True

True or False: The immune system does not develop normally during a poor diet

False

How does antibiotics and a poor diet drive host metabolic disorders?

-Microbiome is restored, permanently impaired

-Different taxa, different metabolic capabilities

-More efficient at extracting energy from dietary intake

-Creates more metabolites for the host

-Obesity and diabetes due to being "overfed"

True or False: Antibiotics and diet-driven host metabolic disorders are caused by the microbiome producing more metabolites than usual and overfeeding the host

True

How do antibiotics drive host allergies and autoimmune diseases?

-Keystone taxa are removed a key point in immune development (very young)

-Immune system develops abnormally, no differentiation of B/T cells

-Immature immune system can't produce secretory IgA or antimicrobial peptides

-Cannot prevent penetration of the gut epithelium by commensal flora

-Gut microbiome is restored, functions normally

-Keystone taxa are present, immune response is impaired

-Abnormal inflammatory responses to stimuli

-Leads to allergies and autoimmune disease

True or False: Proteobacteria are predominant in the human gut microbiome but not normally in the environment

False

True or False: Proteobacteria are predominant in the environment but not normally in the human gut microbiome

True

True or False: As the diversity and stability of the microbiome decrease, Proteobacteria prevalence increases

True

What levels of Proteobacteria would you expect diet-induced obesity in mice to show?

High levels of Enterobacter

What would you expect happens to mice that have Enterobacter and are fed?

Mice with Enterobacter gain more weight than regular mice

True or False: Proteobacteria are dominant in microbiomes of both malnourished children and obese individuals, preventing healthy microbiome

True

How does the microbiome control our energy intake?

-Complex carbohydrates (dietary fiber) are metabolized by the colonic microbiota

-Oligosaccharides and monosaccharides are fermented to short-chain fatty acid end-products

-Acetate, propionate and butyrates (SCFA) are absorbed in the colon

-Butyrate provides energy for colonic epithelial cells

-Acetate and propionate reach the liver/peripheral organs

-Gluconeogenesis and lipogenesis occur

-SCFA inhibit enzyme HDAC

-Inhibit metabolic regulation with GPCRs, such as GPR41 or GPR43.

How does the microbiome contribute to adiposity?

-Alterations to the composition and metabolic capacity of gut microbiota in obesity

-Promote adiposity

-Influence satiety in the brain, release of PYY and GLP-1 in the gut, and lipid metabolism

-Microbial molecules also increase intestinal permeability

-Leads to systemic inflammation, insulin resistance

What do obese and lean individuals' gene counts and microbiome look like?

Obese: Low gene count and taxa diversity

Lean: High gene count, more diverse microbiome

True or False: Low gene count of the microbiota indicates that weight loss, insulin, resistance, and correction of inflammatory tone will have a reduced response

True

What is this?

-Probiotics

-Gram Positive lactic acid producers

-Live microorganisms, confer a health benefit to the host when ingested in adequate amounts

-Survive transit through stomach and duodenum

What are some some species of Probiotics?

-Bifidobacteria, Lactobacillus

-Non-pathogenic streptococci, Enterococci, E. coli, Saccharomyces boulardii (yeast)

What is this?

-Prebiotics

-Ingested substances that selectively stimulate desirable bacteria in the host intestinal tract

-Non-digestible oligosaccharides (NDOs)

-Usually target bifidobacteria and lactobacilli

What are some species of prebiotics?

-Lactulose, galacto-oligosaccharides, lactosucrose

-Usually target Bifidobacteria and Lactobacilli

What are some possible treatment options for obesity?

-Probiotics

-Prebiotics

-Stool transplants

-GLP1 receptor agonist

What is this?

-GLP-1 receptor agonist such as wegovy

-Regulates appetite

-Reverse microbiome dysbiosis when diet is low fat

What other chronic diseases are affected by microbiome changes?

-Irritable bowel syndrome

-Ulcerative colitis

-Crohn's disease

-Celiac disease

-Colorectal Cancer

-Type 2 diabetes

-Depression