Microbiome Flashcards
Learning outcomes
- Apply standard microbiological terms appropriately, including bacteria; virus; infection; contagious; commensal and pathogen
- Map key components of the human microbiome to specific body sites
- State likely and possible functions of the microbiome in healthy people
- Identify critical times, disease states and environmental factors which will affect the microbiome
- Explain how appropriate use of antimicrobials reduces the emergence of Anti-Microbial Resistance (AMR) and reduces disruptive effects on host normal flora, which may lead to, for example, C. difficile infection, Candida infection
Where is the microbiome in the body?
At the interface with our environment Gastrointestinal tract Skin Mouth Vagina Conjunctiva Respiratory tract
Where is it not?
Blood
CSF
Tissues/ Organ parenchyma
State likely and possible functions of the microbiome in healthy people.
- Nutrition/ metabolism
- Immunomodulation
- Innate immunity
- Gut brain axis
What is the relationship of Nutrion/ Metabolism with the microbiome?
- The greatest density of organisms is in the gut.
- Greater density further down the GI tract
- Colonic bacteria ferment foods and other material
- The products of this fermentation include short chain fatty acids (SCFA)
- SCFA feed other bacteria and colon cells
What is immunomodulation?
Change in the body’s immune system, caused by agents that activate or suppress its function.
SCFA (butyrate, acetate, proprionate) can:
- Modulate inflammatory cytokines;
- Decrease response to allergens
Alterations in microbiome (‘dysbiosis’) associated with asthma, allergic rhinitis and coeliac disease
SCFAs are produced by the fermentation of indigestible complex carbohydrates from diet. Colonic bacteria also ferment epithelial cell debris, mucous, bile acids and other material found in the colon. These SCFA can interact with T-helper lymphocytes and dendritic cells (part of pathophysiology of allergy.)
Altered microbiome diversity is observed in patients with allergies and inflammatory disease, particularly GI inflammatory diseases such as a Crohns.
What is innate immunity/ how does it differ from adaptive immunity?
•Barrier function in the gut enhanced by bacteria derived SCFA
•Fatty acids on the skin inhibit pathogens
•‘Resident’ microbiome outcompetes for environmental niches
•Stimulation of innate immune cells such as Natural killer cells and phagocytes
- Innate immunity includes the range of cells, cytokines and barriers which we have against any potential pathogen. This innate immunity is the first and most rapid form of immunity we have. It includes phagocytic cells which will eat foreign (non-self) cells or cells that have become infected with bacteria or viruses.
-The adaptive immune response involves cells (T-lymphocytes) and antibodies (immunoglobulins). The adaptive immune system ‘learns’ after first exposure to a pathogen and then develops memory cells and antibodies to rapidly respond to later exposures to those pathogens.
What is the gut-brain axis?
See diagram microbiome lecture
A complex interplay between the gut microbiota, the gut cells, the enteric nervous system and the CNS. The hypothalamic-Pituitary-Adrenal axis is involved.
Interplay is mediated by the metabolic products of gut organisms, immune system modulators, systemic and enteric hormones and neurochemicals. Microbial antigens such as LPS can induce immune cytokines such as TNF alpha, which pass the blood brain barrier and alter neurological functioning. Some data from RCTs using probiotics (organisms) and prebiotics (nutrients that favour specific organisms, typically oligosaccharides) show gut microbiota can modulate stress response and may be involved in anxiety and depressive states
Identify critical times, disease states and environmental factors which will affect the microbiome.
- Perinatal
- Diet
- Drugs
- Diseases, dysbiosis and direction of causations
What is the relationship between the perinatal period and how it affects the microbiome?
Birth Critical: vaginal microbiota
Prenatal -Maternal diet, maternal GI and vaginal microbiota, antibiotics
Perinatal-Mode of delivery, skin, antibiotics
Postnatal-Environment, people, feeding (bottlefeeding vs breastfeeding) , antibiotics
What is the relationship between diet and drugs and how it affects the microbiome?
•Diet
•Probiotics- bacteria taken as supplements
•Prebiotics- nutritional elements, like oligosaccharides, which are favoured by specific gut organisms
•Antibiotics- broad vs narrow spectrum bacteria: even most narrow spectrum will tend to cause ecological damage to organisms in microbiome
-Other drugs such as Proton Pump Inhibitors (PPIs)- used to treat gastritis/ peptic ulcer disease, stopping gastric acid production. The GA barrier living in mouth etc will get into lower GI tract, significant alteration to microbiome
Why is antibiotic resistance an inevitability?
Bacteria are excellent at adapting to, and colonising new and hostile environments
•Antibiotics are a hostile environment for bacteria•Most antibiotic drugs are closely related to naturally occurring antimicrobial substances
•Therefore resistance is inevitable
•People are covered in bacteria, therefore people tend to share resistant bacteria with one another
What is antimicrobial stewardship?
Antimicrobial stewardship is a series of actions and behaviours to use antibiotics wisely and only when benefit outweighs risk
Definitions can be- “the optimal selection, dosage, and duration ofantimicrobialtreatment that results in the best clinical outcome for the treatment or prevention of infection, with minimal toxicity to the patient and minimal impact on subsequent resistance” Or “an organisational or healthcare-system-wide approach to promoting and monitoring judicious use of antimicrobials to preserve their future effectiveness” (be aware)
What are the 2 main concepts a doctor should consider when approaching infection?
One is to recognise that sepsis is a high mortality condition and assess and treat sepsis rapidly.
The second is to preserve antibtioics to limit microbiome damage and resistance.
These two concepts can pull the doctor in different directions, and cause tension.
What conditions indicate microbiome damage as a result of antibiotics?
Clostridium difficile: anaerobic gram positive rod -Associated strongly with antibiotic use
-Suppression of normal colonic microbiome then overgrowth of toxin producing C. difficile.
Candida albicans, a yeast (Fungi) present in low numbers in microbiome of mouth, moist skin and vagina
- Candidiasis, known as Thrush
- Common side effect of any antibiotic therapy
- Suppression of normal mouth or vaginal microbiome allowing overgrowth of C. albicans
Why is appropriate antibiotic use important?
Antibiotics will affect the microbiome and lead to resistance
At the same time many infections are life-threatening and are helped with antibiotics
Antibiotics allow risky things like surgery or immuno-suppressive cancer chemotherapy
Antimicrobial stewardship is a series of actions and behaviours to use antibiotics wisely and only when benefit outweighs risk
