L3: Human Microbiome I Flashcards

1
Q

explain the ratio between microbial vs human CELLS in the human body

A
  • ~100 trillion microbial cells vs ~30 trillion human cells
  • microbial cells outnumber human cells by: 10:1/3:1/1:1
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2
Q

explain the ratio between microbial vs human GENES in the human body

A
  • microbial genes: ~2,000,000
  • human genes: ~23,000
  • microbial genetic repertoire (microbiome) is ~100x greater than humans
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3
Q

what do the numbers of microbial vs human ratio depend on

A
  • the location of the sample
  • ex: blood vs gut
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4
Q

where is the majority of the microbes in the human body

A

in the gut

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5
Q

how so you get a good representation of microbes in the digestive system

A
  • feces
  • take it and dry it, then weight it
  • will find: 75% water and the remaining 25% is 1/3 fiber, 1/3 dead bacteria, and 1/3 is live bacteria
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6
Q

what is the human genome project

A

researchers took people from all over the world, sequenced their genomes, and put the results in a tree

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7
Q

human genome project - what was the trend seen

A

every sample had bacterial DNA

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8
Q

what is the human microbiome project

A
  • researchers took healthy people to see what the baseline of a healthy microbiome is
  • had two main phases
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9
Q

human microbiome project - main phase 1

A
  • HMP1: 2007-2014
  • used 300 healthy individuals and still generated so much data
  • observed their microbiomes to see variation during a particular time frame
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10
Q

human microbiome project - main phase 2

A
  • HMP2: 2014-2016
  • chose 5 major parts of the body and observed thousands of people’s microbiomes
  • did longitudinal studies and used other omics
  • found some context for diseases
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11
Q

human microbiome project: main phase 2 - what were the major parts chosen

A
  • nasal
  • oral cavity
  • gastro-intestinal
  • urogenital
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12
Q

human microbiome project: main phase 2 - what are the disease context

A
  • pregnancy and preterm birth
  • inflammatory bowel disease
  • type 2 diabetes
  • but remember positive correlation =/= biological meaning
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13
Q

human microbiome project - what did it achieve

A
  • over 650 peer-reviewed publications
  • cited over 70,000 times
  • development of databases and catalogs
  • development of tools and methods
  • establishment of research centers
  • include microbiome research as one of the NIH Roadmap of Medical Research
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14
Q

human microbiome project - what questions did they solve

A
  1. what is the identity of the microbes that populate their host?
  2. what are these microbes doing?
  3. how is the host responding to them?
  4. what are the forces that maintain equilibrium among the populations?
  5. what are the unique characteristics of each individuals
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15
Q

the microbiome project - what is the core human microbiome

A
  • none
  • no universal or core species of microbes were found
  • every individual had a different set of microbes
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16
Q

the microbiome project - what are the variable human microbiome

A
  • host lifestyle
  • host genotype
  • host pathology
  • host environment
  • transient community members
  • host immune system
  • host physiology
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17
Q

explain the diversity of the human microbiome across habitats

A
  • oral cavity and gut microbes are more similar to each other and are more stable
  • hair, skin, and nostril are more variable and less stable
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18
Q

diversity of human microbiome - interpersonal vs intrapersonal differences

A
  • interpersonal: between two or more people
  • intrapersonal: between you and yourself
  • intrapersonal differences (over time) were smaller than interpersonal differences (on each day) within all habitats examined
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19
Q

diversity of human microbiome - habitat vs temporal differences and people variation

A

body habitat had more influence on microbial community composition than temporal differences and variation among people

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20
Q

carriage of microbial taxa vs function

A
  • carriage of microbial taxa varies
  • function remains stable
  • example of functional redundancy
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21
Q

carriage of microbial taxa vs function - define functional redundancy

A

even if you have very different species of microbes, they often play similar roles

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22
Q

carriage of microbial taxa vs function: functional redundancy - why is this important

A
  • if you don’t have functional redundancy and take antibiotics, you may lose a specific function
  • if you do have functional redundancy, it does not matter what species is targeted as long as there’s another one from the same functional group
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23
Q

explain the carriage of specific microbes

A
  • there are different species within a microbiome but there is variation between species
  • when comparing bacteria and functional role, certain strains do not have certain enzymes or proteins
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24
Q

define the gut microbiome

A

microbial communities that reside in the digestive tracts of animals

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25
Q

gut microbiome - explain the compartments

A
  • stomach
  • traverse colon
  • distal colon
  • proximal colon
  • small intestine
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26
Q

gut microbiome - what is the differentiation of the compartments shaped by

A
  • pH
  • as pH increases, number of cells/g increases
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27
Q

gut microbiome - what are the dominant bacterial groups

A
  • Firmicutes
  • Bacteroidetes
  • Actinobacteria
  • Proteobacteria
  • Tenericutes
  • Fusobacteria
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28
Q

gut microbiome: dominant bacterial groups - which are most prominent

A

Firmicutes and Bacteroidetes

29
Q

gut microbiome - explain the overall diversity

A
  • defined and unique
  • Firmicutes and Bacteroidetes are always competing for the top spot and needs to be in balance (Firmicutes/Bacteroidetes ratio)
30
Q

gut microbiome: overall diversity - explain
the Firmicutes/Bacteroidetes ratio

A
  • a measure of the balance of the 2 largest phyla in the human gut microbiome
  • the ratio is often used as a biomarker for a number of conditions
31
Q

gut microbiome diversity: the Firmicutes/Bacteroidetes ratio - what happens when its high

A
  • Firmicutes levels are high and Bacteroidetes levels are low
  • indicator for obesity
32
Q

gut microbiome diversity: the Firmicutes/Bacteroidetes ratio - what happens when its low

A
  • Firmicutes levels are low and Bacteroidetes levels are high
  • indicator for IBD
33
Q

gut microbiome diversity: the Firmicutes/Bacteroidetes ratio - is it a good indicator for gut health

A
  • no
  • bc some studies showed opposite results
34
Q

gut microbiome diversity: explain alpha diversity and its relation to the Firmicutes/Bacteroidetes ratio

A
  • alpha diversity is associated with the Firmicutes/Bacteroidetes ratio
  • more Firmicutes = more diversity
  • more diversity = healthier individuals
35
Q

what are the factors shaping the gut microbiome

A
  • diet
  • pharmaceuticals
  • geography (connected to diet)
  • lifecycle stages (connected with diet)
  • birthing process
  • infant feeding method
  • stress (exercise, metabolic, psychological)
36
Q

factors shaping gut microbiome - diet

A
  • you can predict what type of diet based on an organisms microbial composition
  • and place them within a food web
37
Q

factors shaping gut microbiome: diet - dietary groups

A
  • research shows a 1:1 relationship between dietary groups and bacterial species
  • food diversity increases microbial diversity
  • microbiome responses to similar foods are personalized between individuals
38
Q

factors shaping gut microbiome: diet - fiber-rich diet

A

mature mucus layer and intact barrier function

39
Q

factors shaping gut microbiome: diet - why are there mucus eating microbes even when fiber is present

A
  • it is beneficial since too much mucus is bad for the cells
  • but these microbes must be kept in low density
40
Q

factors shaping gut microbiome: diet - fiber-free diet

A
  • microbiota eroded mucus layer and barrier is dysfunctional
  • bacteria goes into bloodstream
41
Q

factors shaping gut microbiome: diet - why do the microbes eat the mucus layer when there is no fiber

A
  • the mucus layer is full of sugars and microbes will eat it
  • in a fiber rich diet, the microbes will eat the fiber instead since its their preferred substance
42
Q

factors shaping gut microbiome: diet - what happens when there is no fiber intake

A

after a few days, microbiome composition will change and the bad microbes will proliferate

43
Q

factors shaping gut microbiome - lifestyle stages

A

each stage has a different microbial composition and diversity based on the food’s they eat

44
Q

factors shaping gut microbiome: lifestyle stages - neonatal

A
  • reduced diversity
  • high state of microbial flux
  • species of microbes are efficient at braking down milk (breast or formula)
45
Q

factors shaping gut microbiome: lifestyle stages - 2-3 years

A
  • introduction of food solids and exploration of new foods
  • formulation of adult-like microbial signature
46
Q

factors shaping gut microbiome: lifestyle stages - 6-12 years

A
  • greatest diversity in dietary intake
  • greatest microbial diversity
47
Q

factors shaping gut microbiome: lifestyle stages - adult

A
  • habitual diet based on lifestyle, availability, and palate
  • stable microbial composition
48
Q

factors shaping gut microbiome - stress

A
  • when cortisol levels are high, it is associated with certain types of enzymes
  • bacteria can directly or indirectly (via producing other molecules) interact with cortisol
49
Q

factors shaping gut microbiome - pharmaceuticals

A

some microbes that are beneficial may die and disappear completely when taking antibiotics

50
Q

gut microbiome and how it prevents disease

A
  • improves the integrity of the intestinal barrier function
  • supports a healthy immune response
  • builds healthy keystone gut bacteria
51
Q

list the integral functions of the gut microbiome

A
  1. interact with immune cells: cytokines
  2. trigger production of neuroactive molecules (ex: serotonin)
  3. production of neurotransmitters (ex: butyrate)
  4. gut bacteria can travel to the brain (via vagus nerve)
  5. affects the structure and function of the epithelial barrier
52
Q

integral functions of the gut microbiome - production of neurotransmitters (ex: butyrate)

A
  • butyrate is produced after metabolism of fiber
  • more fiber = more butyrate = less inflammation
53
Q

integral functions of the gut microbiome - affects the structure and function of the epithelial barrier

A
  • leaky gut syndrome happens if this function fails
  • no more mucus layer and molecules come into bloodstream, inflammation responses are then activated
54
Q

specific responses to diet - LPS and TMAO

A
  • LPS: Lipopolysaccharides
  • TMAO: Trimethylamine N-oxide.
  • both are molecules produced by bacteria that can produce impacts within the intestines
55
Q

specific responses to diet: LPS and TMAO - how can these impact the intestines

A
  • LPS: immunity
  • TMAO: Associated with adverse cardiovascular outcomes due to atherosclerosis and thrombosis
56
Q

how can the metabolism of fiber affect the hosts body?

A

it can impact:
1. Immune system
2. Brain health
3. Insulin resistance

57
Q

metabolism of fiber - what molecules are produced by bacteria after the metabolism of fiber

A

all are SCFAs (Short-Chain Fatty Acids):
- acetate
- propionate
- butyrate

58
Q

how can the gut microbiome response to fiber and polyphenols

A
  • western diet (animal based protein and fats) introduces bacteria that will produce LPS and TMAO
  • Mediterranean diet (plant based fats and protein) introduces bacteria that produce SCFAs
59
Q

how can the gut microbiome response to fiber and polyphenols - consequences of western diet to overall health

A
  • inflammation
  • endoxemia
  • dyslepidemia
  • hypertension
  • obesity
60
Q

how can the gut microbiome response to fiber and polyphenols - consequences of Mediterranean diet to overall health

A
  • anti-oxidant effect
  • anti-inflammatory effect
  • metabolic regulation
  • vasculoprotection
61
Q

gut microbiome - industrial vs nonindustrial diet

A
  • industrial: Opportunist bacteria are more common
  • nonindustrial: Commensal bacteria are more common
62
Q

gut microbiome - effect of migration

A
  • Higher risk of diseases: higher when migration happened in infancy/early childhood
  • Bc it is time where kid is forming microbiome
63
Q

gut microbiome - what is Lactobacillus

A
  • negatively correlated with disease (more Lactobacillus = less diseases)
  • Alleviates lactose intolerance
64
Q

gut microbiome - what is Bifidobacterium

A
  • Efficient fiber degraders
  • produce vitamin B
65
Q

gut microbiome - what is Akkermansia mucinophilia

A
  • A type of bacteria that restores mucus production in the gut
  • Accounts for 1–4% of the total fecal microbiota
66
Q

gut microbiome - what is Helicobacter pylori

A
  • Highly prevalent.
  • Causes ulcer disease and gastric cancer
67
Q

gut microbiome - what is Clostridium difficile

A
  • Most common in people who have recently taken antibiotics over a long period of time or high doses
  • Causes colitis
68
Q

gut microbiome - what is Prevotella spp.

A

Positively associated with several diseases