The human microbiome Flashcards
Why will two people respond differently to the same drug
because of the genes of the microbes they carry
How many cells are in a human body (2)
- Approx 10^12 /kg
- 80kg = 80 trillion
How many bacteria cells are in the human body (human microbiome) (2)
- Approx 10:1 (bacteria: human cells)
- 1-2% of total body mass
What is the definition of microbiome
The microorganisms in a particular environment (including the body or part of a body)
What is the definition of metagenomics
Study of genetic material recovered directly from environmental samples
What is the definition of proteomics (3)
- A branch of biotechnology
- concerned with applying techniques of molecular biology, biochemistry and genetics
- to analyse the structure, function and interaction of proteins produced by genes of a particular cell, tissue or organism
What is the definition of pharmacogenomics (3)
- Study of how genes affect a person’s response to drugs.
- Combines pharmacology (science of drugs) and genomics (study of genes and their functions)
- to develop safe, effective medicines and doses that will be tailored to a person’s genetic makeup
What has metagenomics explored using 300 healthy individuals (5)
- Nasal passages
- Oral cavity
- Skin
- GI tract
- Urogenital tract
What is the Integrative Human Microbiome Project (iHMP) (3)
- Established in 2014
- 2nd phase after the HMP – consists of 3 projects
- Pregnancy and preterm birth
- Inflammatory Bowel Disease – Crohn’s disease and ulcerative colitis
- Prediabetes
- Integrated longitudinal datasets of biological properties from both the microbiome and host
How many species does the stomach include
25
How many species does the intestine include
500-1000
How many species do the mouth, pharynx and respiratory system include
600+
How many species does the skin include
1000
How many species does the urogenital tract include
60
What are the beneficial effects of gut microflora (3)
- Immunity - Provide a physical barrier to invasive microbes and enhance the functionality of the immune system
- Vitamins - Synthesise vitamins B & K as well as absorb calcium and iron
- Metabolism - metabolic activity allows our body to utilise food that would otherwise not be digested
What are the harmful effects of gut microflora (3)
- Obesity - gut bacteria differ significantly in obese patients
- Inflammation - major role in the development of various inflammatory diseases including IBS and colitis
- Autism - a link between autism and decreased gut bacterial diversity
Diseases linked to the microbiome (15)
- Acne
- Antibiotic-associated diarrhoea
- Asthma/allergies
- Autism –
- Autoimmune diseases
- Cancer
- Dental cavities
- Depression and anxiety
- Diabetes
- Eczema
- Gastric ulcers
- Hardening of the arteries
- Inflammatory bowel diseases
- Malnutrition
- Obesity
What is Helicobacter pylori (3)
- Curved gram-negative rod bacteria
- Common precursor of gastritis and peptic ulcers
- Risk factor for gastric carcinoma (cancer)
What does Helicobacter pylori do in the body to survive (2)
- Synthesise urease which produces ammonia that damages the gastric mucosa
- The ammonia neutralises acid pH which allows the organism to live in the stomach
What is Helicobacter pylori treated with (3)
- Omeprazole
- Clarithromycin
- Amoxicillin
What structures are in Helicobacter pylori (5)
- Flagella - mobility & chemotaxis to colonise under mucosa
- Urease - neutralise gastric acid, gastric mucosal injury by ammonia
- Lipopolysaccharides - adhere to host cells, inflammation
- Outer proteins - adhere to host cells
- Type IV secretion system - pilli-like structure for injection of effectors
What do Helicobacter pylori effectors e.g. cagA do (4)
- Actin remodelling
- IL-8 induction
- Inhibit host cell growth
- Inhibit apoptosis
What is the Helicobacter pylori exotoxin (1) and what does it do (1)
- Vacuolating toxin (vacA)
- gastric mucosal injury
What are the Helicobacter pylori secretory enzymes (3) and what do they do (1)
- Mucinase
- Protease
- Lipase
- Gastric mucosal injury
What are the Helicobacter pylori tests (4)
- Test for antibodies in the blood
- Urea breath test
- Test for antigens in stools
- Endoscopic biopsies
What is Clostridium difficile (5)
- Gram +ve rods bacteria
- Anaerobic
- Spore forming
- In the human colon
- pathogenic
What are Clostridium difficile infection symptoms in increasing severity (4)
- Can be asymptomatic
- Mild diarrhoea
- Pseudomembranous colitis
- Toxic megacolon
How are C.difficle infections managed and treated with supportive care (5)
- Symptomatic treatment
- Electrolytes
- hydration
- nutrition
- Don’t give antiperistaltic agents
What may be a risk factor for C.Difficile
PPIs
How are mild/moderate C.difficle infections managed and treated with medication
Metronidazole – 400mg tds for 10-14 days
What accompanies severe C.Difficile infection (3)
- temperature over 38.5°C
- severe colitis
- white cell count over 15 x 10^9/L
How are severe C.difficle infections managed and treated with medication (2)
- Oral Vancomycin – 125mg qds for 10-14 days
- Fidaxomicin - 200mg bd
What are other ways in which C. difficile infections are treated (2)
- Probiotics - Live yoghurts
- Faecal microbiota transplantation (FMT).
What is the Public Health England guidance on the management and treatment of CDI (6)
CCGs should ensure that trusts have a multidisciplinary clinical review team consisting of:
1. a microbiologist
2. an infectious diseases or infection prevention and control doctor
3. a gastroenterologist or surgeon
4. a pharmacist
5. a dietician
6. an infection prevention and control nurse.
What body area is Lactobacillus associated with (2)
- Stomach
- Intestine
What body area is Malassezia furfur associated with
Skin
What body area is Clostridium associated with
Intestine
What body area is Haemophilus spp associated with
Nose
What body area is Fusobacterium spp associated with
mouth
Gut microbes influences of Pharmacomicrobiomics / Pharmacometabonomics can be categorised into (2)
- Direct
- Indirect
Gut microbes direct mechanisms: Activation of Drugs – Prodrug Concept (2)
- Gut microbes can concert prodrugs into active drugs
- E.g. Sulfasalazine (treats rheumatoid arthritis, UC, Crohn’s disease) is broken down into 5-ASA in the gut.
Gut microbes direct mechanisms: Deactivation of Drugs (2)
- Gut microbes can encode enzymes that detoxify drugs,
- eg, digoxin is inactivated by the gut residing Actinobacterium **(Gram +ve, anaerobic, non sporulating) - Eggerthella lenta
Gut microbes direct mechanisms: Direct binding (2)
- Gut microbes can bind directly with drugs, compromising their bioavailability,
- eg, levadopa (treat Pakinsons) is converted to dopamine in the gut, preventing it from reaching the brain
Gut microbes indirect mechanisms Intermediates (3)
- Some metabolic pathways share steps between host enzymes and those encoded by gut microbes.
- Intermediate microbial products can lead to pathogenesis
- the best known example of this is not a therapeutic drug but a toxin called melamine
Gut microbes indirect mechanisms Altered kinetics (3)
- Gut microbial metabolites compete with drugs for enzyme-binding sites
- leading to alterations in the drug efficacy or toxicity
- e.g. paracetamol
Gut microbes indirect mechanisms Immune response (2)
- The gut microbes can impact drug efficacy by stimulating the host immune system,
- e.g. cyclophosphamide increases gut permeability leading microbes to translocate into the lymph nodes
Gut microbes indirect mechanisms Enterohepatic recycling –
eg irinotecan
research currently for the treatment of colon cancer by modulating the activity of the microbiome
Gut microbes indirect mechanisms gene expression (2)
- Gut microbes can alter the hepatic expression of key host enzymes involved in drug metabolism,
- e.g. CYP450 leading to alterations in drug efficacy or toxicity
Digoxin activation (4)
- Inactivated by gut bacterium (reduces digoxin) Eggerthella lenta.
- Pair of genes (cgr operon) work together to metabolise digoxin
- Research looks at strategies to manipulate the cgr operon - Blocking E lenta’s action to allow more active digoxin to the heart.
- Cgr operon is less active in the presence of the amino acid arginine so could give patients a high protein diet (research on mice led to higher blood digoxin levels
