Microbiota in Health and Disease

Question 1

Microbiome vs. Microbiota

Answer 1

Microbiome: Totality of microbes, their genetic information, and the milieu in which they interact (ex. the gut microbiome, tongue microbiome)

Microbiota: The microbial organisms that make up a specified microbiome (not just bacteria, but often focused on them)

Question 2

What is a metagenome?

Answer 2

The genetic information of a complex population that is made up of the genomes of many individual organisms

Question 3

Can the relationship between us and the bacteria inhabiting our body be considered commensal? What are commensal bacteria?

Answer 3

Commensal bacteria: used to indicate normal/expected microbiota in different environments of the body

However, the relationship is often interdependent and mutualistic (both benefit)

HOWEVER, a “friendly” bacteria can become pathogenic when its growth becomes uncontrolled or occurs in the wrong anatomical place

Question 4

Phylotype

Answer 4

The microbial group defined by 16S rRNA sequence similarity

Phylum

Question 5

Dysbiosis

Answer 5

Disturbed homeostasis of the microbiota composition

Question 6

How does the microbial diversity of an infant change as they grow up?

Answer 6

Microbial diversity increases due in part to diet changes and complex environmental exposures

Question 7

What is the “hygiene hypothesis”?

Answer 7

The idea that being exposed to animals, microbes, etc. early in life “trains” the immune system to respond better and more appropriately to pathogens and allergens later

Question 8

What is a prebiotic?

Answer 8

Food ingredients resistant to digestion (ex. fiber) fermented by the gut microbiota, with a selective effect on the microbiota and consequent beneficial effect on the host’s health

Stimulate growth or activity of certain types of bacteria

Question 9

What is a probiotic?

Answer 9

Live microorganisms, when consumed in adequate amounts, confer a health benefit on the host.

Question 10

What is the role of metabolites in the microbiota? What does this mean for the overall health of the microbiota?

Answer 10

Create conversion reactions that can detoxify ingested toxins, but can also result in the production of compounds that can be deleterious

Thus, the specific composition of the gut microbiota can determine the balance between beneficial and harmful chemical conversion reactions in the gut lumen

Question 11

How does the concentration of gut microbiota change throughout the gut?

Answer 11

Its concentration increases distally down the gut

Lowest: Stomach

Highest: Colon

Question 12

How does the composition of bacteria change throughout the gut?

Answer 12

Upper gut: Gram-positive

Lower: Gram-negativve and anaerobes

Also differed between the lumen and outer mucin layer

Question 13

What are some ways gut microbiota can influence health and disease?

Answer 13

• Carbohydrate fermentation, including carbs that are indigestible by the GI system
• Digest proteins that reach the gut, including host-derived proteins such as epithelial cells
• Metabolism of bile acids that escape enterohepatic circulation; removal of amino acid side chain
• Conversion of bilirubin to products excreted in feces and urine
• Role in cholesterol metabolism
• Role in vitamin synthesis (Vit. K, B12, other B vitamins)
• Prevent colonization by pathogens by competing for nutrients and sites of attachment
• Produce bacteriocins which kill or antagonize non-endogenous species
• Play a role in development and maintenance of the protective mucous layer in the gut
• Important role in “training” the immune system
• 2 way communication w/ immune system
• Role in controlling inflammation or promoting (dysbiosis)

Question 14

What are gut bacteria implicated in?

Answer 14

• Depression
• Anxiety
• Autism
• Obesity
• IBS
  etc

Question 15

How is C. diff spread? What happens when it reaches the body?

Answer 15

Spread via fecal-oral route

Once ingested, spores germinate to their vegetative state in the small intestine –> travel to the colon, attach to the colonic epithelium, reproduce

Question 16

Describe the toxins released by c. diff. What damage do they do?

Answer 16

Injury to the colon is caused by the release of exotoxins by the bacteria –> they attach to the colonic mucosa

Toxin A: causes inflammation leading to intestinal fluid secretion and mucosal injury

Toxin B: 10x more potent than A, causes much more damage to the colonic mucosa

Cause cell necrosis, apoptosis, and disruption of cellular tight junctions

Question 17

How is the new hypervirulent strain different?

Answer 17

Produces a third toxin, CTD that modifies the host cell cytoskeleton and causes cell collapse and death

Produces larger quantities of Toxins A and B

Associated with the emergence of newer class of antibiotics (fluoroquinolones)

Question 18

What usually precedes a C. diff infection? Describe what happens.

Answer 18

Antibiotic use

Spores either ingested or small amounts of C. diff may already be present in the bowel, but under control

Antibiotic disturbs the balance of microbiota in the gut, killing bacteria that would keep C. diff in check (reduced bacterial diversity)

Replication and spread of C. diff

Question 19

Does everyone who ingests C. diff spores get an infection?

Answer 19

No

People with undisturbed microbiota are far more likely to not become infected

Resident microbiota may compete with c diff and outright kill it using bacteriocins

Or c. diff will live in the colon but be kept in check by resident microbiota and only exist in small populations (THESE PEOPLE ARE CARRIERS –> can still spread it via their feces)

Question 20

S/Sx of C. diff

Answer 20

AT LEAST 3 watery, unformed bowel movements per day (diarrhea is the cardinal symptom)

Abdominal pain, cramping, colitis

Fever, nausea (rarely vomiting)

Confusion in older adults

Severe infection

Question 21

What is pseudomembranous colitis?

Answer 21

C. diff sign

Severe inflammation of the colonic mucosa

Occurs following toxin-induced ulcer formation on the mucosal surface of the intestine –> release of serum proteins, mucus, and inflammatory cells

Do not function as a normal mucosal layer

Question 22

How do drugs that allow bowel motility affect C. diff patients?

Answer 22

Increase toxicity

NEVER administer to a C. diff patient

Question 23

How is prebiotics resistant to digestion?

Answer 23

They resist gastric acidity, hydrolysis by mammalian enzymes, and absorption in the upper GI tract

Question 24

SCFA Benefits

Answer 24

• Main energy source of colonic epithelium
• Maintains barrier function of colonic epithelium
• Regulates cytokine production
• Protects DNA from damage; tumor suppression
• Anti-inflammatory effects, but also promotes robust immune response when needed
• Promotes glucose control, improved insulin sensitivity
• Inhibition of inappropriate lipogenesis
• Role in signaling pathway that generates gut hormones such as GLP-1

Question 25

Probiotic Major MOA

Answer 25

Enhancement and repair of the epithelial barrier

Increased adhesion to intestinal mucosa –> inhibition of pathogen adhesion

Production of anti-microbial substances

Promote digestion and uptake of dietary nutrients

Modulation of the immune system

Question 26

In what ways can the brain influence the intestinal microbiota?

Answer 26

Via stress-induced changes in the GI tract:
- Physiology
- Epithelial function
- Mucin production
- EE cell function
- Motility

Release of neurotransmitters

Question 27

In what ways does the microbiota influence the brain, behavior, and mood?

Answer 27

Activation of neural pathways to the brain

Activation of mucosal immune responses

Production of metabolites that directly affect the CNS

Question 28

What is a functional GI disorder?

Answer 28

Comprises of symptoms arising in the mid or lower GI tract that are not attributable to anatomic or biochemical defects

sx: abdominal pain, early satiety, nausea, bloating, distention, and sx of disordered defecation

ex. IBS, constipation, functional dyspepsia

Question 29

What are some limitation to probiotics?

Answer 29

Product regulation: no incentive to maintain standards, vague claims

Product information: practical and clinical

Product efficacy: is it good enough? does it need to be __?

Product composition: which strains of bacteria __?

Product risks: rare complications such as bacteremia, endocarditis, sepsis

Question 30

What is FMT?

Answer 30

Decal Microbiota Transplantation

The administration of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient’s microbial composition and confer a health benefit

Question 31

How does the microbiota of a recipient of FMT change?

Answer 31

2 weeks after FMT, the recipient’s gut microbiome bears remarkable resemblance to the donor’s gut microbiome

The change in the recipient’s microbiome was accompanied by a resolution of symptoms

Question 32

Is FMT 100% risk-free? Explain

Answer 32

No, a small number of recipients have died from FMT

• Donor stool not screened for a highly antibiotic-resistant strain of E. coli
• Adverse Effects: diarrhea and abdominal cramping