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BIOL1008 > Gut microbiome > Flashcards

Gut microbiome Flashcards

1
Q

What are the ways of exposure to microbes

A

Direct physical contact (by touching)

Airborne transmission (inhalation)

Oral transmission (ingestion)

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2
Q

Is exposure to microbes normal

A

Yes, it is normal and even inevitable. In fact, having microbes is key to being normal

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3
Q

What sorts of surfaces are exposed to microbes

A

Exterior surfaces (skin) and internal cavities (respiratory, urogenital and gastrointestinal tracts)

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4
Q

What are the 3 outcomes of the microbes that we are exposed to

A

1) Fail to colonise (microbes come in but are unable to grow)

2) Become short term residents (body might reject)

3) Become long term residents (works with body)

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5
Q

Where is microbes not alllwed in

A

Presence of microbes in tissues isn’t normal

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6
Q

Describe what is preventing microbes from exiting the gut

A

There is a tight gut barrier formed by mucin layers over tightly joined epithelial cells. This prevents the microbes from getting to the tissues

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7
Q

What are the different possible classifications of interactions between organisms

A

Amensal, parasites, commensals, mutualists

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8
Q

What does parasitism involve

A

It is where one partner benefits (increased growth output for parasite), whereas the other partner is harmed (reduced growth output for the host)

The host is normally better without the parasite

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9
Q

What does commensalism involve

A

It is where one partner benefits (increased growth for commensal), whereas the other partner remains neutral (no change in growth for host)

Host is same with/without commensal

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10
Q

What does mutualism involve

A

It is where one partner benefits (increased growth for mutualist), whereas the other partner also benefits (increased growth for host)

Host needs microbe for optimal fitness

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11
Q

What does amensal mean

A

Amensalism is a sort of biological interaction between two organisms or species in which one is neither helped nor harmed, and the other is destroyed or inhibited

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12
Q

Through what kinds of experiments are we able to determine the importance of bacterial presence

A

Through experiments with mice, we can see that bacterial presence is important for normal function of the individual.

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13
Q

What are the drawbacks that occur in the absence of microbes

A

Gut functions are different - decreased digestive capacity

Immune functions are different - essentially no adaptive immunity

Metabolic regulation is different - altered neuro-endocrine signaling pathways (metabolic homeostasis is affected)

Cognitive functions and mood is different - underdevelopment of entire nervous system (mood and behaviour change)

Less development of a capillary network

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14
Q

When does the gut begin to develop

A

Develops around same time as postnatal development finishes

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15
Q

Is there a link between microbiome environment and immunity

A

Not being exposed to sufficient microbes in the environment would lead to a deviation from immune homeostasis –> immune releated diseases such as:

ASthma, type 1 diabetes, atopic disease, crohns and colitis

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16
Q

What is the DOHAD theory

A

Developmental origins of health and disease theory (DOHAD) hypothesises that environmental exposures during early life can permanently influence health and vulnerability to disease in later life

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17
Q

Are there microbes at other points in the body

A

There are different number of microbes at different body sites, however the gut microbiome is the most influential.

Stomach is continually exposed to microbes, but few actually grow there

The distal small intestine is a site of stable occupation by microbes

Large intestine (colon) has distinct conditions for microbial growth and far higher microbe cell density than ileum (small intestine)

However, most other internal organs are sites where presence of microbes isnt tolerated

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18
Q

What are the important parts to the gut

A

Duodenum
Jejunum
Ileum
Colon/large intestine

This is the order in which food will pass through

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19
Q

What is the duodenum

A

The first part of the small intestine. It connects to the stomach. The duodenum helps to further digest food coming from the stomach. It absorbs nutrients (vitamins, minerals, carbohydrates, fats, proteins) and water from food so they can be used by the body.

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20
Q

What is the jejunum

A

The middle part of the small intestine. It is between the duodenum (first part of the small intestine) and the ileum (last part of the small intestine). The jejunum helps to further digest food coming from the stomach.

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21
Q

What is the ileum

A

The last part of the small intestine. It connects to the cecum (first part of the large intestine). The ileum helps to further digest food coming from the stomach and other parts of the small intestine.

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22
Q

What is the colon/large intestine

A

The longest part of the large intestine (a tube-like organ connected to the small intestine at one end and the anus at the other). The colon removes water and some nutrients and electrolytes from partially digested food.

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23
Q

Where is bacterial numbers the highest from the above parts of the gut

A

Colon
Ileum
Jejunum
Duodenum

This is in decreasing order of how many bacterias

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24
Q

Justify the distribution of the number of bacteria in the gut micriobiome

A

The stomach is continually expsed to microbes but due to acidic environment, very few actually grow there.

The distal small intestine (mainly ileum) is a site of stable occupation by microbes. Lower numbers than colon

The large intestine (colon) has distinct conditions for microbial growth and far higher microbe cell density than ileum or jejunum and duodenum

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25
Q

What is the distribution of the microbial cells in our gut

A

98% are bacteria

Eukarya microbes such as fungi and protists are present in small numbers

There are typically some Archaea cells present

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26
Q

What are the types of bacteria which can live in our gut

A

Bacteroidetes

Firmicutes

Proteobacteria

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27
Q

What is the distribution of the different types of bacteria

A

Bacteroidetes (10-90% of all cells) - There are tens to hundreds of bacteroidete species

Firmicutes (10-90% of all cells) - There are hundreds of firmicute species

Proteobacteria (1-5% of all cells) - There are tens of proteobacteria species

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28
Q

What is the distribution of archaea cells

A

Methanobrevibacter (1-2% of all cells) - one or two species

29
Q

What is the function of bacteroidetes

A

Vastly show fermentative metabolism

Diverse growth substrates commonly polysaccharides

30
Q

What is the function of firmicutes

A

Vast majority show fermentative metabolism

Diverse growth substrates commonly polysaccharides

31
Q

What is the function of proteobacteria

A

REspiratory and fermentative metabolism

Growth substrates rarely polysaccharides, commonly small molecules (sugars, amino acids and fatty acids)

32
Q

What is a polysaccharide

A

A large carbohydrate molecule

33
Q

Common sites for permanent microbe residence

A

Skin, nose, mouth, throat, large intestine, etc.

34
Q

Are microbiomes important for our nutrition? If so, explain why

A

It influences both the quantity and quality of the food that we have.

For germ free mice, they have to eat more food to get the same amount of nutrition, and the diet fed to germ free animals requires vitamin supplementation and a simple carbohydrate profile

35
Q

What is the function of the stomach

A

It is basically an acid hydrolysis tank - where gastric cells secrete acid and enzymes, allowing for the breakdown of food

36
Q

What is the function of the small intestine

A

Tank for further hydrolysis. Cells of accessory organs secrete enzymes and bile. Intestinal epithelial cells absorb nutrients

37
Q

What are the characteristics of the material being passed into the colon?

A

They are indigestible (chemically inacessible to human enzymes such as fiber)

They are inaccessible (particle structure prevents enzyme access i.e. intact corn kernel)

they are in excess - exceeded digestion/absorption capacity of small intestine

38
Q

Are plant based foods good source of nutrients?

A

They are potentially rich sources of macronutrients only if we can digest the cell wall polysaccharides. This typically makesplant cell walls digestion resistant.

39
Q

What is the importance of microbes for digestion

A

Microbes have a far wider repertoire of carbohydrate degrading enzymes than humans. As a result, multiple microbe species cooperate to help solubilise fibers for digestion

40
Q

What is the consequence of the need for microbe species to help with solubilising fibers for digestion (especially from plants), on plant specialists and carnivore specialists

A

Plant specialists have a complex digestive tract with a specialised fermentation chamber, whilst meat specialists have a simple digestive tract (i.e. lack of microbes in the digestive tract for meat specialists)

41
Q

Explain what happens when bacteria help with degrading fiber

A

Bacterial enzymes help degrade fiber. This leads to the uptake of the released sugars into the bacteria. This then stimulates further bacterial enzyme secretion to help degrade more fiber. Some of the energy is used for growth and synthesis of the bacteria, whilst some is secreted

Additionally, bacteria often form terminal metabolites for excretion

42
Q

What are terminal metabolites

A

Gut metabolites are the intermediates or end products of bacterial metabolic processes.

Some of the important metabolites produced are short chain fatty acids (SCFAs) , also releases things such as CO2 and H2

43
Q

What are common microbial metabolites

A

Most common metabolism is fermentation. This involves changing simple carbs to other things such as:

Acetate, propionate, butyrate, mixed SCFAs, CO2 and H2

44
Q

Which metabolites are used as energy sources

A

Acetate, propionate, butyrate, mixed SCFA

45
Q

Which metabolites above are used as intestinal gases

A

Co2 and H2

46
Q

What happens when there is too much SCFA

A

Causes specialised respiratory metabolism like sulfate reduction

SCFA –> CO2 + H2S

H2S is a toxic molecule which can damage gut barrier. Thus, we only want relatively low levels of SCFA

47
Q

What is the net effect of microbial metabolites on our health a product of

A

Food intake/diet
Microbial activity
Types of microbes
Adaptive responses

48
Q

What are some other bioactive microbial metabolites

A

Amino acid production(human essential nutrients)
Vitamin production (human essential nutrients)

Bile acid derivatives –> DCA and LCA
Neurotransmitter production (serotonin GABA)

49
Q

How is the microbiome managed

A

Microbe cell numbers and activity controlled by nutrients. Microbe types and location controlled by other microbes and immune functions

I.e. split into “nutrient control” and “immune functions”

50
Q

How can “nutrient control” determine population size and activity in the gut

A

This “encourages functions we need”.

Body directs bacteria to use fiber - rapidly absorbs other nutrients

Body selects for fementative metabolism - excludes O2 and removes iron

Body supports growth on fiber - adds back nitrogen ‘fertilizer’ (uric acid, urea)

Body limits total bacterial biomass - poops often

Overall, bacteria is trained to ‘do the right thing’: stay in gut, grow on fiber, release SCFA

51
Q

How can “immune functions” determine population size and activity in the guts

A

It punishes activity we don’t need, and aims to contain bacterial activity within the gut:

The interstinal mucosal surface limits bacterial contact with epithelium

Immune defenses kill bacteria at epithelium

The lamina propria (adjoining intestinal tissue) is kept ‘sterile’

Bacteria near the wrong places or in the wrong places aren’t tolerated

52
Q

Why are metabolites from fermentation typically beneficial but metabolites from anaerobic respiration harmful

A
53
Q

How can an overgrowth of microbes cause pain or other intestinal problems

A
54
Q

What are some features of pathogens

A

Not normally present

Presence is associated with disease

Experimental infection is sufficient to cause disease

These are excluded from the body

55
Q

What are some features of commensals

A

Normally present

Absence leads to abnormal physiology (in experimental germ free animals)

may indirectly contribute to disease

56
Q

WHat are the 3 forms of defence against pathogens

A

Colonisation resistance

Barrier functions (mucin layer and epithelium provide a physical barrier)

Immune response functions

57
Q

What is colonisation resistance

A

Body’s natural ability to prevent and limit establishment and proliferation of potentially harmful microbes

In this, it involves resident microbes competing with incoming pathogens for space and nutrients –> prevents colonisation and growth of potential pathogens

58
Q

Describe the role of immune response functions

A

It can either down regulate immune responses to avoid collateral damage to cells

OR

upregulate immune responses to exclude microbes from our body

Ultimately seeking to minimise bad microbes etc.

59
Q

What is the balance required for immune functions

A

Too much down regulation –> increased susceptibility to infections and cancer due to weaker immune response or immunodeficiency

Too much up regulation of immune responses to exclude microbes from body –> allergies, autoimmunity and inflammatory bowel disorders are diseases due to inability to regulate immune response –> might lead to self harm (in terms of cells)

60
Q

How can pathogens cause damage to host

A

They colonise various body surfaces and can do the following:

Produce toxin or tissue destructive enzyme which attacks the host

Obstruction

Trigger immune response to initiate inflammation. However, failure to resolve immune response or altered immune tone can cause damage

61
Q

What are the potential pathogenic mechanisms

A

Direct pathogen activity

Indirect mechanisms

62
Q

What is direct pathogen activity as a pathogenic mechanisms

A

Release of toxins direct from the pathogen which causes harm

E.g. cholera toxin activity

63
Q

What are indirect mechanisms as a form of pathogenic mechanism

A

Response triggered by damage (damaged cells release cytokines –> inflammation, damage associated molecular pathways)

Inflammation triggered by microbe presence (specific antigens detected by antibody, microbe associated molecular patterns)

64
Q

What is dysbiosis

A

A term for diseases of a poorly functioning symbiosis

65
Q

What is immune tone

A

The immune tone is defined as an immunological state during which the readiness for immune response is potentiated.

66
Q

What can non infectious diseases be caused by?

A

Loss of resident microbe functions - most notably contributions to regulation of immune tone

intolerance of normal microbes - most notably chronic low grade intestinal inflammation

67
Q

Why do normal resident microbe species still trigger inflammation

A
  1. Disruption of the Epithelial Barrier

The epithelial barrier of the gut and other mucosal surfaces is crucial for maintaining a physical separation between commensal microbes and the immune system. If this barrier is compromised due to injury, infection, or inflammation, commensal microbes can translocate into deeper tissues where they are recognized as foreign by the immune system, triggering an inflammatory response.

  1. Immune Dysregulation

The immune system normally maintains tolerance towards commensal microbes through mechanisms involving regulatory T cells and anti-inflammatory cytokines. However, if there is dysregulation of the immune system, such as in autoimmune diseases or due to genetic predispositions, the immune system may respond inappropriately to commensal microbes, leading to inflammation.

  1. Microbiota Imbalance (Dysbiosis)

Dysbiosis refers to an imbalance in the composition of the microbiota, where potentially harmful bacteria may become more prevalent. This imbalance can lead to increased production of pro-inflammatory signals, loss of beneficial bacteria that help regulate inflammation, and increased permeability of the epithelial barrier.

68
Q

Explain the role of tolerance (resolution of inflammation) in normal physiological processes

A
69
Q

Explain the relationship between postnatal development of microbiome and immune functions to chronic disease risk as adults

A

BIOL1008 (17 decks)

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