Microbiota in Health and Disease Flashcards
Microbiome vs. Microbiota
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)
What is a metagenome?
The genetic information of a complex population that is made up of the genomes of many individual organisms
Can the relationship between us and the bacteria inhabiting our body be considered commensal? What are commensal bacteria?
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
Phylotype
The microbial group defined by 16S rRNA sequence similarity
Phylum
Dysbiosis
Disturbed homeostasis of the microbiota composition
How does the microbial diversity of an infant change as they grow up?
Microbial diversity increases due in part to diet changes and complex environmental exposures
What is the “hygiene hypothesis”?
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
What is a prebiotic?
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
What is a probiotic?
Live microorganisms, when consumed in adequate amounts, confer a health benefit on the host.
What is the role of metabolites in the microbiota? What does this mean for the overall health of the microbiota?
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
How does the concentration of gut microbiota change throughout the gut?
Its concentration increases distally down the gut
Lowest: Stomach
Highest: Colon
How does the composition of bacteria change throughout the gut?
Upper gut: Gram-positive
Lower: Gram-negativve and anaerobes
Also differed between the lumen and outer mucin layer
What are some ways gut microbiota can influence health and disease?
- 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)
What are gut bacteria implicated in?
- Depression
- Anxiety
- Autism
- Obesity
- IBS
etc
How is C. diff spread? What happens when it reaches the body?
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
Describe the toxins released by c. diff. What damage do they do?
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
How is the new hypervirulent strain different?
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)
What usually precedes a C. diff infection? Describe what happens.
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
Does everyone who ingests C. diff spores get an infection?
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)
S/Sx of C. diff
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
What is pseudomembranous colitis?
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
How do drugs that allow bowel motility affect C. diff patients?
Increase toxicity
NEVER administer to a C. diff patient
How is prebiotics resistant to digestion?
They resist gastric acidity, hydrolysis by mammalian enzymes, and absorption in the upper GI tract
SCFA Benefits
- 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
Probiotic Major MOA
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
In what ways can the brain influence the intestinal microbiota?
Via stress-induced changes in the GI tract:
- Physiology
- Epithelial function
- Mucin production
- EE cell function
- Motility
Release of neurotransmitters
In what ways does the microbiota influence the brain, behavior, and mood?
Activation of neural pathways to the brain
Activation of mucosal immune responses
Production of metabolites that directly affect the CNS
What is a functional GI disorder?
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
What are some limitation to probiotics?
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
What is FMT?
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
How does the microbiota of a recipient of FMT change?
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
Is FMT 100% risk-free? Explain
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
