Introduction to the Microbiology of the Gut Flashcards
Normal Flora
What is resident flora?
what is transient flora? Give an example of this
describe chnage in baby faecal
how does the flora we have change with regards to oxygen?
name the organism needed for breastmilk. what happens when we wean off breast milk?
Normal flora describes the flora of microorganisms that normally live within our intestines.We have microorganisms on all our surfaces, this includes the gut.
Resident flora is flora that are there for life
Transient flora are organisms that colonise us but can temporarily be reduced, carried or changed according to various factors including the environment we live in.
- An example of a change in transient flora, is baby -> adult, where there is a change from Bifidobacterium which likes breast milk. Other changes could be stress, hormones, age etc.
- We see this in baby faecal transitions. The first time a baby defecates (sterile meconium) it is sterile, we then see a change in the stools as the baby acquires microbial flora.
In the beginning we may start with facultative anaerobes (organisms that live anaerobically but can live in presence of oxygen also).
There then ends up being a strictly anaerobic gut (survive in oxygen free environments) that live in the colon.
Bifidobacterium is an example of a strict/obligate anaerobe. They metabolise breast milk sugars that gives itself energy and produces nutrients for the baby.
• As we wean off the breast milk, the microorganisms change, we quite adult-like gut microbiota.
Biological relationship of gut flora
what is extensive co-evolution in terms of flora being commensal?
3 different tyoes of symbiosis
bacteri distribution along the GI tract and why it is like this?
what kind of environment is the colon? what microbes will we find there?
what happens if you have IBD? what other examples are there?
Importantly, no one species of gut flora is a commensal, but together the flora may be regarded as commensal (no harm to the host). This is a product of extensive co-evolution.
Symbiosis includes: commensalism, parasitism, mutualism.
Bacteria are distributed throughout the GI tract. There are very few in the stomach due to the high acidity.
As we move through the duodenum and ileum and get to the terminal ileum we see much more bacteria here and a more complex mixture.
The colon, which is an anaerobic environment, contains facultative and obligate anaerobes. There are a very large number of bacteria here and a very complex mixture. e.g. bacterioides, clostridia, E. coli
In someone with inflammatory bowel disease the distribution of bacteria in the gut is very different.
Microbiome alterations are associated with disease states,
e.g. Crohn’s disease, Inflammatory bowel disease, IBS, C.difficle etc.
Properties of intestinal physiology affected by microbiome
how may antibiotics affect the gut?
What happens if you change the microbiome of the gut?
what does the microbiome modulate?
what is the microbiome influenced by?
What else does the microbiome contribute to beyond nutritional processing?
Changing the microbiome of the gut will substantially change the physiology of the gut e.g. the hormones it releases.
Exposure to antibiotics can affect the microbiome leading to a change in gut physiology.
Energy balance regulation and pathophysiology of obesity
Modulates digestion and absorption -> energy harvesting
Microbiome influenced by diet, antibiotics, surgery and genes
Microbiome contributes to host metabolism and energy homeostasis
beyond nutritional processing e.g. endocrine function and inflammatory signals
Host Defences and Normal Flora
If we have so many microbes living in the gut how are we not overwhelmed by them?
4 main categories for defence structures in our gut (and how they work)
how can these defence mechanisms go wrong?
There must be a balance in place whereby we can control our gut flora.
To appreciate this, we have to look at the defence mechanisms of our gut:
Structural:
• A seamless epithelium surface, with tight junctions, there is rapid turnover/sloughing
Mechanical:
• Peristalsis moves things from one end to the other, chewing, fluid movement
Biochemical
• Secretion of gastric acid, bile, mucus
Immunological:
• Secretory IgA (main protector (Ig) at mucosal surfaces), intra-epithelial lymphocytes
However, there can be problems when there is damage to barriers, pH changes, Overgrowth, AIDs etc.
Benefits of gut flora
How does it make it hard for pathogens to start to increase in number?
What can they make for us?
how does it help prevent an immune attack every time something enters the gut?
why is being germ free bad?
How does it aid in digestion?
- Colonisation resistance: If your gut is full of commensal organisms, it is hard for pathogens to get in and start to divide and cause diseases. Because the ecological niches have been taken up by our commensals
- Metabolites of benefit to host: Some bacteria produce metabolites that are useful to us that we ourselves cannot make, e.g. Vitamin K, B12, organic acids
- Normal development of immunity: Important in normal immunological development, in tolerating certain organisms and antigens at birth. We don’t want immune attack all the time for everything that enters the gut, so normal flora is important in this tolerance balance allowing us to live with these organisms.
- Germ free: Being germ free could be bad, problems with flora leading to things like asthma and eczema
- Aids digestions: About 10% of our energy is released from our colon, a lot of sugars we cannot digest until the microbial flora ferment the sugars into a form we can digest.
Probiotics and Prebiotics
What are probiotics?
what are prebiotes?
use of probiotics in medicine
Probiotics are organisms we think will contribute to a healthy biome, the best probiotic organisms produce lactic acid and organic acids e.g. lactobacillus
~10% absorbable energy from dietry fibre;
increased diversity of polysaccharides for metabolism
Pre-biotics encourage good microbes/probiotes to grow e.g. breast milk
Use of Probiotics in Medicine 1. Control diarrhoea in infants 2. Relieve constipation 3. Improve digestion of lactose • Restore normal gut flora (mix of microbes) after antibiotics • Control Candida (yeast) growth • Improve immune system • Treat inflammatory bowel disorders e.g. - ulcerative colitis • Reduce incidence of colon cancer • Reduce cholesterol in blood • Increase mineral absorption
Microbial Antagonism
what is this? how is it useful to us? How does it do this?
What is bacteriocins?
what is antiobiotic associated colitis? what can it lead to?
Microbial antagonism is the idea that some organisms inhibit the growth of other organisms. It limits the growth of competitors and pathogens.
How? • Bacteriocins • Reduced numbers of available epithelial receptors • Keeps pH low • Controls oxidative potential (anaerobic growth) • Limits pathogen growth • Occupy all niches • High numbers • Waste products
- Bacteriocins
o Loss of Flora -> Bacterial or pathogen overgrowth - Certain antibiotics (e.g. ciprofloxacin) disrupt our microbiome more than others.
o This leads to antibiotic associated colitis (inflammation of colon caused by introduction of antibiotics).
o The antibiotics have reduced the no. of gut flora and changed it, this may lead to overgrowth of clostridium difficile = pseudomembranous colitis.
Intestinal Infections and Mechanisms of Diarrhoea
What is gastroenteritis?
What is diarrhoea? clinical consequences of this?
What is dysentery?
What is enterocolitis?
Gastroenteritis
An acute syndrome characterised by generalised gastrointestinal symptoms in any combination including: nausea, vomiting, diarrhoea and abdominal discomfort
Diarrhoea
Watery or liquid stools, usually with an increase in stool weight and an increase in daily stool frequency and a sense of urgency.
Clinical consequences of diarrhoea include:
o Severe dehydration, due to excessive fluid and electrolyte loss, hypovolemia, hypokalemia, organ failure
o Long term morbidity and reduced growth
Dysentery
Inflammatory disorder of GI tract, usually large intestine, it is often associated with blood and pus (as penetrated natural barriers). As well as pain, fever and abdominal cramps.
Enterocolitis
Inflammation involving mucosa of small and large intestine e.g. Crohn’s disease
Impact of Diarrhoeal Disease:
which age group dies the most?
what is a common reason for it? what are these? how do they pass on?
Produce many deaths a year (2 million)
Especially of under 5’s (undergo multiple episodes a year) -> massive global health burdens
The common reason is infectious
• Bacteria
• Virus
• Parasites (protozoal and worms)
These are shed in faeces and spread to new host (faecal-oral route)
Patterns of gut infections
4 common ways infections can occur
extra info at the bottom
Travellers’ diarrhoea = Normally e.coli
Food poisoning: Diarrhoea from eating food, either due to eating food containing toxins that make us ill or food that contain bacteria that then grow inside us and produce toxins
Immunocompromised hosts: AIDS, immunosuppressed, elderly, very young
Antibiotic related diarrhoea: Altered normal flora
Dyspepsia : ulcers Helicobacter pylori
Dysphagia : oesophagus and Candida
Chronic diarrhoea + or – malabsorption - poor fat adsorption
Acute or chronic diarrhoea + blood + Pus -> this is dysentery
Damage Resulting Infection of Gastrointestinal Tract
4 different effects
- Pharmacological action of bacterial toxins, that have local or distant effects to the site of infection e.g. Cholera
- Local inflammation in response to superficial microbial invasion e.g. shigella dysentery or campylobacter food poisoning
- Deep invasion to blood and lymphatics and dissemination of organism to other body sites e.g. typhoid fever
- Perforation/Ulceration of mucosal epithelium, peritonitis
Mechanisms of Diarrhoea
what are the three mechanims?
what are enterotoxins?
what are exotoxins and effect?
what are cytotoxins?
Bacterial toxins
• Enterotoxins are toxins that affect the gut
• Exotoxins affect fluid/electrolyte transport by increasing/decreasing cAMP
• Cytotoxins produce direct cell damage
• Entero-toxigenic
Adherence
Bacteria can adhere to the cells like villus and crypt, and damage the epithelium e.g. E. coli, enterpathogenic
Penetration and invasion into epithelium entero-invasive
function of villus and crypts
What happens if virus of bacteria penetrate villus? 2 effects of this happening? How is the gut restored?
The function of the villus is absorption from the gut, and the function of crypts is secretion into the GI tract.
Viruses (or bacteria) can penetrate the villi, resulting in villus atrophy (cell death).
There means there is no absorptive capacity in the gut, causing anti-absorptive diarrhoea.
Crypt hyperplasia follows this to replace the dead villus. When this occurs, there will also be a lot of secretion, and the combination of atrophy and high secretion culminates in anti-absorptive diarrhoea.
Eventually, the villus is restored and the mucosa will recover.
Heat-stable and heat-labile toxins
what produces these two?
heat stable?
heat labile?
how do the toxins work?
E. coli produces heat-stable and heat-labile toxins. When heat-stable toxins are heated, they are not destroyed. Heat-labile toxins can be inactivated by cooking.
The toxins work by affecting the electrolyte channels in epithelial cells lining the GI tract:
- Heat labile toxin simulates adenylate cyclase, causing cAMP to dysregulate the protein kinase, resulting in more open chloride channels
- Heat-stable toxin stimulates guanylate cyclase, causing cGMP to dysregulate protein kinase, resulting in more open chloride channels
More open chloride channels will lead to electrolyte imbalances and thus fluid imbalance.
E. coli – Friend or Foe?
How can e.coli act as a pathogen? (as in symptoms/diseases) and what does it produces
E. coli can act as a commensal gut organism (i.e. have no harmful effects) but it can also act as a pathogen producing:
- Diarrhoea
- Dysentery
- Haemolytic uremic syndrome (HUS)
- Septicaemia
- Pneumonia and meningitis
It can also produce virulence factors such as toxins, adhesins and invasins.
