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
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
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
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
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
6
Q
What do our metabolic features imclude?
A
- A combination of human and bacterial attributes
7
Q
Where are normal flora found?
A
- Found on all surfaces in our body
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
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
10
Q
What is symbiosis?
A
- Organisms that are living together
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
12
Q
Why type of symbiosis takes place in our flora?
A
- The flora is said to be commensal
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
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
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
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
17
Q
What are host defences?
A
- Mechanisms by which we protect ourselves from pathogens whilst allowing normal flora to exist
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
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
20
Q
What are the benefits of gut flora?
A
- Colonisation resistance
- Metabolic benefits
- Normal development of immunity
- Aids digestion:
21
Q
How does gut flora provide colonisation resistance?
A
Many gut flora present which are able to block pathogens from colonising the gut
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
