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
How can people modify normal gut flora?
- Probiotics
| - Prebiotics
26
What are probiotics?
- 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
What are prebiotics?
- 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
What is microbial antagonism?
- 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
How does microbial antagonism limit pathogen growth?
- 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
What are the problems associated with loss of flora?
- 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
What is the effect of the microbiome in the gut?
- The microbiome ellicit a stimuli which causes a response
32
How is intestinal physiology affected by microbiome?
- 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
What influences Microbiome?
- Diet
- Antibiotics
- Surgery
- Genes
34
What is diarrhoea?
- Watery or liquid stool with an increase in stool weight
| - There is also an increase in frequency with an reoccuring sense of urgency
35
What can excessive diarrhoea lead to?
- 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
What is gastroenteritis?
- 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
What is dysentery?
- 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
Why is dysentery different from diarrhoea?
- 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
What is enterocolitis?
- Non-specific inflammation involving the mucosa of the small and large intestines
40
What micro-organisms cause diarrhoea?
- Bacteria
- Viruses
- Parasites (including protozoal and worms)
41
How does transmission of diarrhoea and dysentery occur?
- Shedding in faeces causes transmission to new host
42
What is the distribution of different gut infections?
- They can vary from non-inflammatory to inflammatory to penetrating invasive fevers
43
What damage does infection of the GI tract cause?
- 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
What are the mechanisms by which diarrhoea occurs?
- 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
What are the different types of enterotoxins?
- 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
What is the difference between crypt and villi cells?
- 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
How do heat-stable toxins work?
- 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
How do heat-labile toxins work?
- 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
How does adherence of pathogens cause diarrhoea?
- 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
What are entero-invasive bacteria?
- 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
What are entero-haemorrhagic bacteria?
- 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
Why do different E.coli cause infections differently?
- This is due to the differences in their virulence factors
53
How do viruses cause mucosal injury?
- 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
