Week 7: Microbiome Flashcards

1
Q

Microbiota

A

Community of microorganisms (eg. fungi, bacteria, viruses)

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2
Q

Microbiome

A

Collection of all microbial genes
Can exist in mouth, skin, digestive system, urogenital

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3
Q

What makes a healthy microbiome?

A

DIVERSE

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4
Q

What bacteria make up 90% of microbiome?

A

Bacteroidetes
Firmicutes

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5
Q

What bacteria make up 10% of microbiome?

A

Actinobacteria
Proteobacteria

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6
Q

Bacteroidetes

A

Beneficial effects on human health, anti-inflammatory
Help prevent or mitigate disease such as cancer, diarrhea and IBS

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7
Q

Firmicutes

A

Carbohydrate metabolism
Reduction in depressive symptoms

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8
Q

Actinobacteria

A

Gut homeostasis, functions in gut barrier, immune system and metabolism
ex. bifidobacteria

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9
Q

Proteobacteria

A

Microbial signature of disease
Associated with onset of CV events and IBS

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10
Q

Bacteroidetes and firmicutes ratio

A

High firmicute:bacteroidete ratio is associated with several pathological conditions such as obesity

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11
Q

Bifidobacterium

A

+
Reduced abundance in obesity

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12
Q

Lactobacillus

A

+
Attenuates IBD

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13
Q

Alistipes

A

-
Associated w disease

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14
Q

Roseburia

A

+
Reduced abundance in IBD

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15
Q

Eubacterium

A

+
Reduced abundance in IBD

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16
Q

Faecalibacterium

A

+
Reduced abundance in obesity and IBD

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17
Q

Enterobacteria

A

-
Increased abundance in IBD

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18
Q

Framework to study causality of gut microbial components

A
  1. Control vs disease population
  2. Perform metagenomic profiling to create a microbiome correlational network
  3. Perform faeces transplant
  4. if phenotype change is observed, there is an association btwn that disease and the microbiome
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19
Q

Microbiome correlational network

A

Identifies a relationship btwn microbes and can help identify microbial markers associated with diff health conditions

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20
Q

Faeces transplant

A

Transplant of microbiome from humans to germ-free rat

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21
Q

Germ-free

A

No microbiome

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22
Q

Microbiota-changing interventions

A
  1. Nutrition
  2. Exercise
  3. Faecal microbiota transplantation
  4. Prebiotics
  5. Probiotics
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23
Q

Function of gut microbiome

A
  1. Antimicrobial protection
  2. Immunomodulation
  3. Gut-brain axis
  4. Gut mucosal barrier
  5. Nutrient metabolism
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24
Q

Antimicrobial protection

A

Gut microbiota can induce the synthesis of antimicrobial proteins and local immunoglobins

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25
Q

Immunomodulation

A

Gut microbiota work w innate and adaptive immune systems to modify immune response

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26
Q

Gut-brain axis

A

Bidirectional communications btwn the central and enteric nervous systems; integrates neural, hormonal and immunological signalling

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27
Q

Gut-brain axis neurological circuit

A

Cross talk allows gut sensory visceral signals that travel with the vagus nerve to influence the CNS which modifies behaviours and moods and brain can also modulate gut physiology

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28
Q

Enteric nervous system

A

Complex network of neurons responsible for intrinsic innervation of gut functions

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29
Q

Gut mucosal barrier

A

Gut microbiota maintains structure and function of GI tract

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30
Q

Nutrient metabolism

A

Metabolized non-digestible carbs, can produce a variety of vitamins and can synthesize all essential and non-essential amino acids

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31
Q

Example 1 of gut brain axis

A

Physiological stress and gut microbiota

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32
Q

Examples 2 of gut brain axis

A

Hunger regulation

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33
Q

Homeostatic hunger regulation

A

Hormones stimulating hunger or fullness; hypothalamus

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34
Q

Hormones involved in hunger regulation

A

Ghrelin, leptin, insulin

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35
Q

Reward/hedonic hunger regulation

A

Desire or cravings; dopamine system

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36
Q

Cognition and hunger regulation

A

Integration of hedonic and homeostatic food intake regulation; prefrontal cortex

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37
Q

Homeostatic system feedback mechanisms

A

Metabolic feedback (appetite hormones that go to hypothalamus)
Visceral feedback (Vagus nerve- goes to brainstem)

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38
Q

Hedonic system areas

A
  1. Conscious cortical areas
  2. Unconscious subcortical areas
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39
Q

What type of feedback received by the conscious cortical area of the hedonic system?

A

Reward feedback- senses such as smell

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40
Q

Nutrient metabolism: dietary fibre

A

Fibre is broken down in to short chain fatty acids and acts as an indigestible dietary substrate for bacteria in large intestine

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41
Q

Short chain fatty acids

A

Key bacterial fermentation products

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42
Q

Three main short chain fatty acids

A
  1. Butyrate
  2. Propionate
  3. Acetate
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43
Q

Role of short chain fatty acids

A

Line epithelium to protect gut and help form tight junctions btwn cells, preventing permeability

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44
Q

What happens to the tight junctions when the bacteroidete:firmicute ratio is altered

A

Reduces proteins that form the junctions and lipopolysaccharides can leak through - LEAKY GUT

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45
Q

Butyrate

A

Key energy source for human coloncytes
Maintains intestinal barrier

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46
Q

Propionate

A

Energy source for epithelial sources
Transferred to liver
Role in gluconeogenesis
Imp satiety signal

47
Q

Acetate

A

Growth of other bacteria
Cholesterol metabolism and lipogenesis
Role in appetite regulation

48
Q

What SCFA inhibit growth of pathogens in gut?

A

Acetate and butyrate

49
Q

Factors affecting gut microbiota

A
  1. Age
  2. Stress
  3. Diet
  4. Breastfeeding
  5. Mode of birth
  6. Medication
50
Q

Factors affecting microbiome in newborn

A
  1. Maternal diet
  2. Gestational diabetes
  3. Environmental exposures
  4. Gestational age
  5. Delivery mode
51
Q

Factors affecting microbiome as we age

A
  1. Meds
  2. Diet
  3. Exercise
  4. Infection/disease
  5. Pets
52
Q

What is the microbiome like when were adults?

A

More diverse bc were exposed to more
Stable

53
Q

Human milk microbiota (HMM)

A

The nutritional and bioactive molecules (microorganisms) present in human milk; second primary source of microbes for infants (30%)

54
Q

How is breastfeeding associated with microbiota composition?

A
  1. Breastfed babies have lower diversity compared to formula fed children
  2. Cessation of breastfeeding is associated w shift towards mature, adult-like microbiome
55
Q

Is HMM a prebiotic or probiotic?

A

Both

56
Q

Direct (probiotic) property of HMM

A

Alter gut microbiota through transmission of bacteria

57
Q

Indirect (prebiotic) property of HMM)

A

Contains oligosaccharides that promote growth of specific bacteria

58
Q

Function of breastfeeding

A

Shapes composition of gut and respiratory microbiota
Promotes intestinal immune homeostasis
Facilitates digestive processes

59
Q

Resilience

A

Following a challenge, the microbiota of a healthy individual is able to return to baseline

60
Q

Dysbiosis- breastfeeding

A

Occurs when microbiota does not return to baseline after a challenge, leads to negative health outcomes in infants

61
Q

How does a C-section affect the microbiome?

A

Leads to dysbiosis of newborn gut microbiome bc of lack of exposure to maternal vaginal and fecal bacteria that occurs in vaginal birth; decreased microbial diversity

62
Q

What is a C-section a risk factor for?

A

Allergic outcomes (asthma)

63
Q

Antibiotics

A

Eradicate bacteroidetes, firmicutes and actinobacteria leaving an open niche for colonization or proliferation of opportunistic bacteria (often associated w GI disease)

64
Q

Western diet vs low fat diet- body fat

A

Western diet resulted in increased body fat %

65
Q

Western diet vs low fat diet bacteroidete:firmicute ratio

A

More firmicutes than bacteroidetes
Associated w obesity

66
Q

Mediterranean diet

A

Low in animal fat and protein, high in plant fibres
Fermentation and formation of SCFA

67
Q

What does mediterranean diet lead to?

A
  1. Reduced blood glucose
  2. Increased energy expenditure
  3. Increased glucose-stimulated insulin secretion
68
Q

Western diet

A

High in animal fat, protein and sugar, low in plant fibres
Proteolysis and production of microbiota related to metabolic disease

69
Q

What does the western diet lead to?

A
  1. Increased blood glucose
  2. Decreased metabolic endotoxemia
  3. Decreased glucose-stimulated insulin secretion
70
Q

Western diet vs mediterranean- bacteria

A

Dysbiosis and reduced total bacteria
Decreased favourable bacteria and increased unfavourable bacteria

71
Q

Effect of western diet

A

Inflammation, CVD, IBD, obesity

72
Q

Effect mediterranean diet

A

Reduced risk

73
Q

Protein consumption and microbial diversity

A

Positively correlated

74
Q

Why are plant protein sources beneficial?

A

Increased bifidobacterium and bacteroidetes
Increased SCFA, reduced inflammation and increased gut barrier

75
Q

Effect of animal protein sources

A

Increased bifidobacterium and bacteroidetes
Reduced SCFA, increased CVD and IBD

76
Q

Study on fat and the microbiome

A

Three conditions
1. Lower fat diet- 20%
2. Moderate fat diet- 30%
3. High fat diet- 40%
- controlled for source of fat, fibre and protein intake

77
Q

Results of study on fat and microbiome

A

High fat diet
- high ratio of firmicutes:bacteroidetes
- decreased SCFA
- decreased faecalbacterium
- increased alistipes
- reduced microbiome diversity

78
Q

Saturated vs unsaturated fat

A

Saturated fat reduces microbial diversity and abundance
Unsaturated fat increased beneficial bacteria

79
Q

How does sugar affect the microbiome?

A

Increased proteobacteria -inflammatory
Decreased bacteroidetes- antiflammatory

80
Q

What does sugar promote?

A

Leaky gut which leads to low grade inflammation and metabolic disorders

81
Q

What is the microbiota gut-brain axis implicated in?

A

Obesity (metabolic health)
Mental processes (mental health)
Disease onset and prevention (immunological health)

82
Q

Dysbiosis

A

Imbalance in bacterial composition, changes in bacterial metabolic activities or changes in bacterial distribution in the gut

83
Q

What does gut dysbiosis lead to?

A
  1. Loss of beneficial bacteria
  2. Overgrowth of potentially pathogenic bacteria
  3. Loss of overall bacterial activity
84
Q

Main roles of intestinal barrier

A
  1. Absorption of water, electrolytes, essential dietary nutrients from intestinal lumen into circulation
  2. First line of defense against external pathogens
85
Q

Structure of intestinal barrier

A
  1. Outer mucus layer
  2. Inner mucus layer
86
Q

Outer mucus layer

A

Contains microbiota, antimicrobial proteins and secretary immunoglobin A molecules

87
Q

Inner mucus layer

A

Physical barrier that covers epithelial cells

88
Q

How does the intestinal barrier affect the microbiome?

A

Mucus barrier provides a habitat and nutrients for microbiome
Breached barrier invokes inflammatory response that affects gut microbiota composition

89
Q

How does the microbiome affect the intestinal barrier?

A

Butyrate maintains intestinal barrier but those with IBD lack it, leading to lesions in tight junctions and impaired intestinal permeability
Microbiome helps repair injured mucosa
Gut microbiota modulates production and secretion of mucins and stratification of mucus layers

90
Q

LPS- lipopolysaccharide

A

Component of outer cell wall of gram-negative bacteria

91
Q

What is the main source of LPS?

A

Microbiota

92
Q

What in LPS involved in?

A

Macrophage activation which stimulates inflammation
Septic shock, sepsis and organ failure

93
Q

What does leaky gut/impaired gut barrier lead to?

A

LPS in circulatory system
Over-activation of gut immune system, inducing chronic systemic inflammation or an impaired immune response, promoting progressing of metabolic diseases

94
Q

High circulating levels of LPS

A

Metabolic endotoxemia; associated w obesity and related metabolic disorders

95
Q

Conditions associated with dysbiosis

A
  1. Pulmonary disorders
  2. Metabolic disorders
  3. Cognitive disorders
  4. Cardiovascular disorders
  5. Gastrointestinal disorders
96
Q

Inflammatory bowel syndrome (IBS)

A

GI disorder characterized by chronic recurrent abdominal discomfort and pain with changes in bowel habits

97
Q

SCFA producing bacteria and IBS

A

IBS patients have a lower abundance of butyrate producing bacteria (risk for leaky gut)

98
Q

Methanogens (archea)

A

Microbes responsible for removing excess hydrogen by converting it to methane

99
Q

What is methane production linked to?

A

Low transit time and anti-inflammatory effects in colon

100
Q

Methanogens and IBS

A

IBS patients have lower methanogens- reduced ability for hydrogen gas removal leading to excess gas in abdomen

101
Q

Small intestinal bacterial overgrowth

A

Leads to GI symptoms such as malabsorption through effects on GI motility, visceral sensation, immune activation and intestinal permeability

102
Q

What can small intestinal bacterial overgrowth lead to?

A

IBS
**bidirectional- IBS can also lead to small intestinal bacterial overgrowth

103
Q

Microbiome and T2D

A

Attempts to transfer gut microbiota from drug naive individuals with T2D to germ mice to preproduce T2D phenotype failed

104
Q

Microbiome and obesity study

A

Studies twins- one obese one lean
Performed faecal transplantation
Mice that received microbiota from obese doner gained weight

105
Q

How to enhance gut microbiome

A
  1. Eat a diverse range of food
  2. Eat fibre
  3. Eat fermentable food
106
Q

Why is fibre beneficial in diet?

A
  1. It is a prebiotic
  2. Promotes growth and activity of beneficial bacteria in GI tract by acting as a source of nutrition
  3. Increases microbiome diversity and SCFA-producing bacteria in gut
107
Q

Fermentation

A

Process whereby alcohols, carbon dioxide, and/or organic acids are produced by microorganisms from carbohydrates for energy production

108
Q

Benefits of fermented foods

A
  1. Provide nutrients that promote growth of gut microbes
  2. Microbes survive gastric transit and become a component of gut microbiome
  3. Enhance digestibility of carbs and proteins
  4. Produce antioxidants
  5. produce bioactive compounds
109
Q

Health benefits of fermented foods

A

Reduce BP, cholesterol and CVD
Improve metabolic syndromes and immune function
Anti-cancer effects
Weight management

110
Q

Bioactive compounds

A

Food derived compounds that exert physiological effect on body

111
Q

High fermented food diet benefits

A
  1. Increase microbiome diversity
  2. Reduce inflammatory signals and activity
112
Q

Problem with microbiome research

A

Diificult to establish causal rather than associative relationship btwn specific microbes and physiological or diseased state

113
Q
A