41) Introduction to the Microbiology of the gut Flashcards

1
Q

What is normal flora?

A
  • 1000s of species of bacteria that live in our body
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2
Q

What is the microbiome?

A
  • The collection of bacteria, archea, fungi, protozoa and virus (also called the microbiota)
  • These microbiota colonize our body surfaces, their respective genomes and metabolic activities
  • It is highly variable between people, sites and disease states
  • Plays a major role in human health and disease
  • They are generally symbiotic and non-pathogenic
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3
Q

How are bacteria divided?

A
  • They are divided into groups known as phylotypes

- The gut is dominated by a few phyla: firmicutes, Bacteroidetes, actinobacteria and proteobacteria

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4
Q

What is the ratio of human cells to microbial cells?

A
  • It is a 1:1 ratio

- Humans are a composite of microbial and human cells

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5
Q

What does our genetic landscape contain?

A
  • A collection of the genes embedded in our genome along with the collective genome of our habitat associated microbial communities
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6
Q

What do our metabolic features imclude?

A
  • A combination of human and bacterial attributes
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7
Q

Where are normal flora found?

A
  • Found on all surfaces in our body
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8
Q

What are the different types of normal flora?

A
  • Resident flora: A set of microorganisms that we have for life
  • Transient flora: Temporarily reduced can be carried, changes or lost
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9
Q

How does the amount of microbiota change as we grown?

A
  • When the foetus is in the womb it is in a sterile environment
  • As the baby starts to develop it develops microbial flora from the mother
  • The baby starts with sterile meconium which develops into facultative anaerobes (bacteria that can grow anaerobically and aerobically)
  • The facultative anaerobes are replaced by strictly aerobic bacteria (for example: bifidobacteria which is a gram positive rod shaped bacteria that produces lactic acid used to metabolise breast milk)
  • As the baby starts to wean the bifidobacter are replaced by Bacteroides (gram negative) and other eubacteria found in adult guts
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10
Q

What is symbiosis?

A
  • Organisms that are living together
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11
Q

What are the types of symbiosis?

A
  • Commensalism: Existence with no effect on another organism
  • Mutualism: Their existence benefits another organism
  • Parasitism: Existence causes harm to another organism
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12
Q

Why type of symbiosis takes place in our flora?

A
  • The flora is said to be commensal
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13
Q

How does the number of microbiota change along the GI tract?

A
  • As we go from the stomach to the anus the number of organisms increases
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14
Q

What is the distribution of microbiota in the GI tract?

A
  • In the stomach due to highly acidic conditions it is extremely sterile apart from some lactobacilli found
  • However H.pylori are adapted to implant themselves in the walls of the stomach and neutralise stomach acids allowing them to survive (and cause ulcers)
  • In the duodenum conditions become more alkali allowing lactobacilli and streptococcus to grow
  • In the jejunum and terminal ileum we see facultative bacteria (e.g. E.coli) and are called enterobacteria (bacteria that live in the gut)
  • In the colon it is very anaerobic and so we find obligate anaerobes (forced to be anaerobic) , facultative bacteria anaerobes (can be anaerobic and aerobic)
  • There are also enterococci
  • These species are highly variable in different people
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15
Q

What is dysbiosis?

A
  • Alteration in the microbiome from the normal flora
  • This can be through generalised diversity changes or species differences
  • Is often associated with diseased states
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16
Q

How do we study microbiome?

A
  • Culturnomics: We can culture the bacteria/organisms by taking a sample and growing them on plates in labs
  • Genomics: Extracting DNA and doing a genetic screen. Scientists can either target rRNA using marker genes and PCR. Or they can sequence the entire sample
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17
Q

What are host defences?

A
  • Mechanisms by which we protect ourselves from pathogens whilst allowing normal flora to exist
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18
Q

What are the different host defences?

A
  • Structural: Seamless epithelial layers and tight junctions. There is rapid turnover of our mucosal and epithelial cells in order to have rapid repair in the gut
  • Mechanical: Peristalsis, chewing, fluid movement through the gut
  • Biochemical: Gastric acid, bile and mucous
  • Immunological: Secretory IgA, intra-epithelial lymphocytes
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19
Q

What are problems associated with the breakdown of host defences in the gut?

A
  • Spread of infection to the body
  • Damage of barriers
  • pH change
  • Overgrowth
  • AIDS
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20
Q

What are the benefits of gut flora?

A
  • Colonisation resistance
  • Metabolic benefits
  • Normal development of immunity
  • Aids digestion:
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21
Q

How does gut flora provide colonisation resistance?

A

Many gut flora present which are able to block pathogens from colonising the gut

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22
Q

How does gut flora provide metabolic benefits?

A
  • Produces metabolites the body cannot (such as Vitamin K and Vitamin B12) as well as other organic acids.
  • It also allows for the enhanced utilisation of amino acids. Synthesises butyrate for colonocytes to maintain anaerobiosis (the anaerobic nature of the colon)
23
Q

How does the normal flora aid with the normal development of immunity?

A
  • Hosting normal gut flora leads to immunological tolerance.
    This means antigenic stimulations and immunological responses are only mounted to pathogens and not to food
24
Q

How does gut flora aid digestion?

A
  • Allows fermentation of sugar and provide some energy that wouldn’t be possible if they were not present.
25
Q

How can people modify normal gut flora?

A
  • Probiotics

- Prebiotics

26
Q

What are probiotics?

A
  • Organisms that can produce certain metabolites (e.g. lactic acid and other organic acids) and maintain the environment in a healthy way
  • They allow us to extract more energy fibres that we wouldn’t be able to extract/ ferment ourselves
  • This increases the diversity of polysaccharides available for metabolism
27
Q

What are prebiotics?

A
  • Nutrients that alter the gut ecosystem and modify the host normal flora in the gut
  • They provide the correct nutrients for the growth of probiotics and so promotes the growth of probiotics
28
Q

What is microbial antagonism?

A
  • There is a complex interaction between the normal flora and the host gut
  • When infected with a pathogen, it will express virulence factors that leads to disease
  • The gut flora will limit the growth of competitors and pathogens
29
Q

How does microbial antagonism limit pathogen growth?

A
  • The normal flora releases bacteriocins which reduce the number of epithelial receptors
  • Normal flora also keep pH low to prevent the overgrowth of pathogens
  • They also control the oxidative potential of the gut (especially the anaerobic environment of the colon)
  • Microbial flora also occupy all niches in high numbers and the products of their metabolism prevents pathogen overgrowth
30
Q

What are the problems associated with loss of flora?

A
  • A loss in flora can lead to a primary infection or pathogen overgrowth
  • This can be caused by ciprofloxacin which is an antibiotic which decreases the diversity of the flora
  • This causes antibiotic associated colitis which is associated with the growth of Clostridium difficile
  • Clostridium difficile release cytotoxins causing ulcerations and severe diarrhoea
  • Outbreaks are common in hospital but is treatable with antibiotics however it is resistant to some antibiotics
31
Q

What is the effect of the microbiome in the gut?

A
  • The microbiome ellicit a stimuli which causes a response
32
Q

How is intestinal physiology affected by microbiome?

A
  • There is energy balance regulation and when compromised can lead to obesity
  • It modulates digestion and absorption
  • It increases energy harvesting
  • They contribute to the host’s metabolism and energy homeostasis
33
Q

What influences Microbiome?

A
  • Diet
  • Antibiotics
  • Surgery
  • Genes
34
Q

What is diarrhoea?

A
  • Watery or liquid stool with an increase in stool weight

- There is also an increase in frequency with an reoccuring sense of urgency

35
Q

What can excessive diarrhoea lead to?

A
  • It can lead to severe dehydration as there is excess fluid and electrolyte loss leading to hypovolaemia, hypokalaemia and organ failure
  • It can also lead to long term morbidity and reduced growth
36
Q

What is gastroenteritis?

A
  • An acute syndrome characterised by GI symptoms in any combination of nausea, vomiting, diarrhoea and abdominal discomfort
  • It is thought to be caused by an infection
37
Q

What is dysentery?

A
  • Inflammatory disorder of the GI tract (usually the large intestine) often associated with the presence of blood and pus in the faeces along with pain, fever and abdominal cramps
38
Q

Why is dysentery different from diarrhoea?

A
  • Dysentery involves diarrhoea along with an inflammatory process with blood and pus
  • The organisms that cause diarrhoea are invasive and can cause localised inflammatory responses
  • These inflammatory responses take place in the gut leading to tissue damage causing blood and pus to be found in the faeces
39
Q

What is enterocolitis?

A
  • Non-specific inflammation involving the mucosa of the small and large intestines
40
Q

What micro-organisms cause diarrhoea?

A
  • Bacteria
  • Viruses
  • Parasites (including protozoal and worms)
41
Q

How does transmission of diarrhoea and dysentery occur?

A
  • Shedding in faeces causes transmission to new host
42
Q

What is the distribution of different gut infections?

A
  • They can vary from non-inflammatory to inflammatory to penetrating invasive fevers
43
Q

What damage does infection of the GI tract cause?

A
  • Pharmacological action: Toxins released by bacteria damage defence mechanisms which can be local or distal to the site of the infection
  • Local inflammation: This can be in response to superficial microbial invasion
  • Deep invasion: When the pathogen invades into the blood or lymphatics and disseminates to other sites of the body and can give rise to enteric fevers
  • Perforation/ulceration: This can take place on mucosal epithelial layers causing peritonitis and intra-abdominal abscesses
44
Q

What are the mechanisms by which diarrhoea occurs?

A
  • Bacterial toxins: Bacteria can sometimes release enterotoxins (toxins that affect the gut) in the form of exotoxins and cytotoxins
  • Adhereance: Some bacteria can adhere directly to the surface of the epithelium and can damage the epithelial structure
  • Penetration and invasion: Some bacteria penetrate and invade cells. In doing so disrupt tissue architecture and function and can cause inflammation
45
Q

What are the different types of enterotoxins?

A
  • Exotoxins: released from the bacteria which causes changes in intracellular cAMP, affecting fluid and electrolyte transport in the host
  • Cytotoxins: toxins released from the bacteria that directly damage host cells
46
Q

What is the difference between crypt and villi cells?

A
  • Villi cells are the finger-like projections on the endothelial layer of the gut where absorption occurs
  • The crypt cells are the indentations between the villi in the endothelial layer of the gut where secretion occurs
47
Q

How do heat-stable toxins work?

A
  • These toxins bind to a receptor n the surface of an enterocyte (epithelial) cell
  • This activates guanylate cyclase to convert GTP to cGMP
  • cGMP activates protein kinase which phosphorylates membrane channels causing them to be active
  • This causes the transport of Cl- and water out of the cell
48
Q

How do heat-labile toxins work?

A
  • These toxins use their B sites to bind to the enterocyte (endothelial cell).
  • The active unit (A1 unit) penetrates the cell which stimulates Gs protein (which is a G-protein)
  • Gs stimulates adenylate cyclase which converts ATP to cAMP
  • cAMP activates protein kinase which phosphorylates membrane channels causing them to be active
  • This causes the transport of Cl- and water out of the cell
49
Q

How does adherence of pathogens cause diarrhoea?

A
  • Pathogens can adhere very tightly to enterocytes in the GI tract and in doing so destroys the brush wall of the microvilli
  • It causes an attaching and effacing lesion which prevents normal electrolyte transport necessary for a healthy gut
  • As a result we get microvilli elongation, effacing microvilli and pedestal formation
  • Hence the structure and function of the cell is compromised by the toxins released by the pathogen and its adherence
50
Q

What are entero-invasive bacteria?

A
  • Some pathogens are able to invade tissues and spread to nearby cells
  • They cause inflammatory responses and they can alter the epithlial structure of the gut which can alter their ability to achieve their function
  • This causes blood, pus and pain
  • These pathogens are called entero-invasive bacteria
51
Q

What are entero-haemorrhagic bacteria?

A
  • Some bacteria can bind to and damage epithelial cells of the gut
  • These bacteria can also produce potent toxins which can travel systemically (e.g. in the blood)
  • They travel to the kidneys and cause kidney damage through haemolytic uremic syndrome
  • They can also cause UTIs, Septicaemia, pneumonia and meningitis
52
Q

Why do different E.coli cause infections differently?

A
  • This is due to the differences in their virulence factors
53
Q

How do viruses cause mucosal injury?

A
  • First the virus invade individual cells and replicate in them
  • This causes the cells to die and causing the villi atrophy (denaturation)
  • In response to this crypt hyperplasia (enlargement of the crypt cells)
  • Since secretion happens at the crypt cells, hypersecretion occurs leading to hypersecretory anti absorption disease
  • This means there is increased secretion occurring and less absorption leading to malnutrition and diarrhoea