6 - Microbiome Flashcards

1
Q

What is the microbiome?

A

The totality of microorganisms and their collective genetic material present in or on the human body of in another environment.

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2
Q

How does the number of microbial cells are there compared to human cells? What about genes?

A

The human microbiome outnumbers human celsl by 1.3 fold, microbial genetic content is 100-1000 fold greater than the human genome.

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3
Q

What is established by the colonizing microbiota in our body?

A

Distinct spatial organization at each body site.

Not just a big bag of bacteria, there is order to the colonization.

Speaks to bacteria lifestyle.

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4
Q

How do we determine which bacteria are present?

A

Molecular technology used to speciate bacteria based on the 16S sequence of the ribosome of microbes.

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5
Q

What approach is used for metagenomic analysis?

A

DNA from biological sample can be used to analyze 16S sequences of all bacteria present to determine the community structure and diversity.

Total genome can be sequenced and mapped to microbial genome database to determine community structure and can be annotated for genetic and metabolic profiling.

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6
Q

What are the regional differences in the microbiome? What are the differences from person to person?

A

Different regions of the body have distinct microbiomes.

Human gut contains majority of microbiota. Each individual has 400-500 species in the gut.

Different people have different species in their microbiome, but they have similar composite function.

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7
Q

In the absence of disease, each individual’s microbiota is _______ over time.

A

Stable.

Except with very young and very old age.

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8
Q

The ___ and ____ are both highly colonized with bacteria, while the ____, ____, and ____ are not highly colonized (not are not sterile).

A

Mouth and large intestine - highly colonized

Esophagus, stomach, and small intestine - less colonization

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9
Q

Moving from proximal to distal, there’s a movement from ______ to ______ colonization.

A

Aerobic to anaerobic.

This makes sense because we would assume the mouth has aerobic bacteria because it is exposed to air at all times.

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10
Q

How is the microbiome developed? How long is infant colonization unstable?

A

Commonly thought no microbiome in utero, but it’s now being questioned.

Infants colonized at birth; shaped by host and environmental factors starting with mode of birth and early feeding.

Unstable over the first 1-2 years of life.

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11
Q

What is the host-derived regulation of the microbiome?

A

Nutrients: mucus and surface cards

Non-immune factors: bile salts and digestive enzymes

Immune effectors: AMPs/defensins, IgA

Luminal microenvironment: O2, pHm ions

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12
Q

Exposure to what environmental factors regulates the composition of the microbiome?

A

Diet, antibiotics, exposure to environmental antimicrobials.

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13
Q

What happens to the microbiota of a previously germ-free zebra fish when mouse feces is put into it? What does this tell us? What is another reason we know this(think babies)?

A

The microbiome will start looking more like the composition of a zebra fish and not like the mouse.

Tells us that an organism (genetically) selects for the bacteria that live in its own environment.

Also know this because babies who are breastfed have 90% colonization with the type of bacteria that can digest breast milk whereas bottle fed babies don’t have that.

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14
Q

How does oxygen tension regulate microbiota composition; for example, what happens when someone receives hyperbaric oxygen treatment and their tissue oxygen tension increases?

A

Changes in oxygen tension were associated with an increase in abundance of facultative anaerobic bacteria.

Changes in composition were limited to mucosal associated bacteria.

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15
Q

What are bacteriocins? What is their function?

A

Plasmid-encoded antimicrobial peptides that can be circular or linear.

Encoded on pheromone responsive, conjugative plasmids.

Target and kill bacteria of the same species.

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16
Q

What do bacteria that make bacteriocin have to protect themselves against bacteriocin killing them? How does it spread the ability to make bacteriocin?

A

they produce an immunity peptide.

Alternatively, they can use a conjugation apparatus encoded by the bacteriocin plasmid to transfer the plasmid to bacteria that lack it.

17
Q

What regulates interspecies interactions in soil?

A

Specialized metabolites

18
Q

An abundance of biosynthetic gene clusters in the human microbiome encode for _____? What is an example?

A

Antibiotics.

Lactobacillus gasseri in the vagina can produce lactocillin.

19
Q

How do commensal bacteria differ from pathogenic bacteria?

A

Genome size: commensals have larger and more complex genomes.

Commensals can have carbohydrate-binding modules

Commensals can digest mucus because they have glycoside hydrolases, polysaccharide lyases, and carbohydrate esterases (pathogens can’t digest mucus)

Commensals can bind and use luminal nutrients to enhance their colonization to out-compete pathogens.

20
Q

What are the protective functions of the intestinal microbiota?

A

Compete with pathogens for available binding sites

Compete for nutrition

Produce toxins and antimicrobials

21
Q

What are the structural and developmental functions of the microbiota?

A

Maturation of epithelial architecture

Enhance barrier function

Immune development by inducing immune functoin

22
Q

What are the metabolic and nutritional functions of the intestinal microbiota?

A

Vitamin synthesis.

Production of SCFA’s for energy to the epithelium

Fermentation of non-digestible dietary components (fiber)

Metabolize dietary carcinogens.

Energy salvage.

23
Q

What are two approaches we use to study microbiota function?

A
  1. Axenic/germ-free mice.

2. Gnotobiotic systems (known)

24
Q

What do microbiome-host interactions drive the production of?

A

Immune system development via microbiota induced expression of antimicrobial peptides.

25
Q

What do microbiota induce to protect the intestines besides antimicrobials?

A

IgA, which helps to protect mucous membranes such as those within the GI tract.

Microbiota also induce specific T cell subsets.

26
Q

What parts of digestion are regulated by commensals?

A
  • mediation bile acid synthesis
  • lipid absorption
  • aa metabolism
  • vitamin synthesis
  • SCFA production
27
Q

Byproducts of commensal ________ regulate the immune system and shape mucosal immunity.

A

fermentation (metabolites)

28
Q

What are some diseases that are associated with intestinal dysbiosis (microbial imbalance)?

A
Inflammatory bowel disease (immune response to own bacteria) 
Atherosclerosis
Type 2 DB/Type 1 DB 
Obesity 
GI Cancers 
Infectious disease 
Obesity
29
Q

What is a possible mechanism of dysbiosis-disease associations?

A

It’s possible that the environment/host/microbiota are capable of causin dysbiosis, and dysbiosis causes disease.

30
Q

How does the adult diet shape the microbiota?

A

Decreased gut microbiome “richness” (decreased # of various bacteria and their genes) is associated with both disease states and the consumption of a westernized diet.

Increased consumption of an agragarian diet rich in fruits and veggie (high fiber) is associated with increased bacterial gene richness.

31
Q

Describe the mucus layer and barrier function of the intestines associated with a fiber rich, fiber free, and a regular diet with no commensals?

A

Fiber-rich: mature mucus layer; intact barrier function

Fiber-free: microbiota eroded mucus layer; barrier dysfunction

No commensals: immature barrier function

32
Q

What are the ways in which commensal microbiota prevent pathogen colonization?

A
  1. Bacteriocin production
  2. SCFA production
  3. Consumption of oxygen
  4. Competition for nutrients
  5. Competition for attachment sites
  6. Induction of epithelial antimicrobials
  7. Induction of mucus production and secretion
33
Q

What effect does C diff have on the microbiota of the intestine?

A

It causes dysbiosis of the gut microbiota and the C diff toxins induce inflammation and cell death.

Antibiotics needed to treat it, and those kill normal gut flora.

Donor fecal transplant can restore stable, healthy gut microbiota.