WEEK 6 - Microbiota (part 1-3) Flashcards
What is the definition of human microbiota
Inc. Info about microbiota
The total microbial community / microorganisms residing on and in us
- Mostly found within the gut (large intestine)
- can be found in other places e.g. skin, nose BUT NOT in blood (sterile) - Imbalance in normal bacteria composition leads to problems
- Microbiota act as a metabolic organ
- modulate immuensystem, break down non-digestible carbs
NOTE:
- microbiota consists of a wide variety of bacteria, viruses, fungi, and other microorganisms
Understand the role of the human gut microbiota in health and disease
3 key
- Induction of intestinal angiogenesis
- Intestinal angiogenesis - development of capillary networks in digestive system
- Gut microbiota ↑ capillary network generation
- Colonisation bacteria are a barrier to potential pathogens
- trillions of bacteria in and on us that occupy space + available nutrients
= stops potential pathogens colonising space + causing disease- produce antimicrobials
- may alter resisiding environment = pathogens that arent sepcialsied can’t grow / colonise area
- trillions of bacteria in and on us that occupy space + available nutrients
- Metabolise non-digestible carbohydrates and proteins
- bacteria is a metabolic organ (via fermentation process)
- produces short fatty chain acids - diet provides nutrients for host + microbiota
- bacteria is a metabolic organ (via fermentation process)
What is the relation between obesity and gut microbiota
Obese individuals have ↓ bacteroidetes in their gut microbiota compared to lean individuals
- if transfered gut microbiota of lean into obese mouse the obese phenotype was lost
- and if done other way around lean phenotype lost
- Bacteroidetes cause reduced apetite which leads to weight loss
- Propionate triggers production of peptide YY which causes loss of apetite
- a short chain fatty acid produced by gut microflora during the fermentation of dietary fiber (carb.) - BUT also need fibre (30g) and non-digestible carbs in diet to see this effect
- hard to consume 30g daily without GI complications e.g. gas, discomfort
How do we acquire our microbiota profile
Inc. the 2 Ways and when individual microbiota developement occurs
Sterile Womb Paradigm
- womb is sterile therefore birth / delivery is the route of initial host colonisation
- microbiota differs between the 2 routes
- Vaginal delivery
- baby passes through vaginal cavity making contact with it
- predominant bacteria growing in and on you at birth is lactobacillius
- as this is the most dominant bacteria in vaginal cavity - at birth microbiota is similar to vaginal microbiota
- C-section
- baby makes contact with skin + surronding surgical enviroment
- at birth microbiota is similar to mother skin and environment
When does individual development of microbiota occur
6 weeks old:
- Age it first begins
- See clusters of bacteria at specifc body sites
- See more bacteroides in gut (not seen at birth)
- As grow microbiota becomes more complex
3 years old:
- Reached climax microbiota community by this age
- At birth / early weeks not exposed to much but parents, sibilings, breast/ bottled milk
- As grow, exposed to diff. bacterias e.g. other children (nursery), toys, pets, new environments, diet
- Antibiotic exposure e.g. ear infection
- treatment may wipe microbiota
How does microbiota modulate behaviour
Via the gut-brain axis
(interaction through vagal nerve - brain to digestive system)
- Microbiota can effect cognitive development and behaviour
- e.g. animals without microbiota profile are less anxious but cognitively impaired
Via diet
- Diet may alter mating choices e.g. in drosophila flies
- only mated with flies that had same diet = selective breeding
What causes ‘Antibiotic Associated Diarrhoea’ (AAD)
Dysbiosis in gut microbiota i.e. imbalance in normal host gut microbiota
- e.g. c.difficile colonisation
Cause:
1. Loss of commensal bacteria
- removes colonisation resistnace
- NO COMPETITION
- This loss leads to loss of bacterial diversity
- Allows bloom of potenital new pathogens
- as broad-spectrum antibiotic has removed residing natural flora = NO competition
- can cause c.difficile infections
Clostidium Difficile (C.difficile) INFO
(a.k.a. Clostridiodes difficile)
Its is a bacterium
Features:
- Gram positive
- Spore forming
- allows survival on surfaces for years
- spores go into dormant state + coat itself in protective coating
- spores are resistant to heat, UV and dessication
- Obligate anaerobe = can NOT grow in presence of O2
- grows in guts (in large intestine)
NOTE:
- caused inflammation of digestive system + death in hamsters
- c.difficile associated diarrohea became a bug problem, causing death in UK
Explain C.Difficile Colonisation / CDAD development
CDAD = C.Difficile Associated Diarrhoea
- Broad spectrum antibiotic use
- antibitoics wipe out commenstal bacteria
= removes colonisation resitance + competition
- esp. 3rd gen. cephlasporins
2a. C.Difficile spores PRESENT or ingest spores from environment
- usually sporolates in human guts but causes no issues as commensal bacteria is present
- spores survive antibiotics
- when antibiotics wear off will have reduced commensal bacteria = C.Diff can flourish in gut
2b. C.Difficle NOT PRESENT = NO CDAD
- C.Diff spores germinate and produce toxins A and B
- B is most virulent, A is unable to cause CDAD on its own - CDAD is acquired and will experince symptoms e.g. diarrohea
- Spores from diarrhoea may cause envrironmental contamination = outbreak
CDAD
- Most cases are mild + self-limiting so treatment isn’t required
- commensal hut microbiota will compete
-
Explain the role of C.Difficile toxins
3 Toxins
When c.diff reaches a threshold toxin production will begin
- amount of toxin secreted depends on how seevre infection is
AIM of both toxin A and B:
- Attach to epithelia, enter intestinal cells (endocytosis) and inactivate RHO and RAC GTPase
- RHO and RAC are involved in epithelial integrity + tight junctions
Removal of RHO and RAC causes:
- Damgaged tight junctions
- Damged epithelail integrity
- Leaky intestinal epethelial cells
ISSUE:
- immune cells can enter = inflammtion
- loss of fluid into large intestine = diarrohea
AIM of CDT (binary toxin):
- Only produced by hypervirulent c.diff
- Endocytosed into epithelial cell and inhibits polymerisation of actin
= cell’s normal architecture (cytoskeleton) is ruined
- movement across cell is affected
- causes firbonectin protrusion which allows ↑ c.diff to attach =
NOTE
- Toxin A (TcdA)
- Toxin B (TcdB)
Explain how the undisturbed microbiota works
- Have lots of commensal bacteria
- Glycosylated mucus layer is attached to intestinal epithelial layer taking up all availale space and nutrients
- Some of mucus layer is getting cleaved = making sialic acid available
- s.acids are used by commensal bacteria - Liver makes primary bile acids
- bile acids enter small intestine and commensal gut microbiota convert into secondary bile acids
- this is a colonisation resistance function as primary bile acids are used by c.diff to germiniate into viable cells = preventing this conversion is bad
Explain how antibiotic disturbed microbiota works
- Antibiotics take out commensal bacteria = reduced no. of bacteria growing on surface of intestine
- Sialic acid previously used by commensal bacteria is converted into succinate and now used by c.diff
- due to ↓ competition - Now no commensal bacteria availbe to convert primary bile salts into secondary salts
= c.diff use primary salt as nutrient to germinate from spores into viable cells + flourish
Risk Factors and Symptoms of CDAD
2 risk factors and 3 symptoms
Risk Factors:
- Over 65
- Antibiotic (broad-spectrum) consumption
SYMPTOMS:
- Mild to severe explosive diarrhoea
- explosive diarrohea aids spore transmission
- Severe inflammation of inner lining of large intestine
- may develop yellow fluid filled sacs on lining - Toxic mega colon (fatal)
- severe inflammtion of colon
How was transmission of CDAD controlled
- New infection control policies implemented
- prevent transmission of organism
- Antibiotic stewardship
- prevent inappropriate use of broad-spectrum antibiotics
- these antibiotics took out commensal gut microbiota
3.
Antibiotic Treatment options for CDAD
Inc. why re-occurence can happen
1st Line - Oral Vancomycin
- 125mg QDS for 10 days
- if treatment fails increase dose to 500mg + can add IV metronidazole
2nd Line - Oral Fidaxomicin
- 200mg BD for 10 days
- associated with ↓ CDAD re-occurence
- also used as relapse treatment
Why may it re-occur
- Treating with antibiotics to kill associated c.diff BUT this takes out normal gut microbiota
- If antibiotic doesn’t kill c.diff but has removed commensal microbiota = no competition = c.diff will just come back
