The Intestinal Microbiome

Question 1

what is the intestinal microbiome?

Answer 1

a complex network of microorganisms that live synergistically in the colon, but can reside in the small intestine as well.
The microorganisms include: bacteria, viruses, fungi, phages (bacterial viruses) yeast and archaea (single celled organisms).
The microbiome is relatively stable in composition, but can shift after an environmental trigger. (Its plasticity makes it a therapeutic target)

Question 2

how does someone acquire their intestinal microbiome?

Answer 2

• there’s evidence to suggest that there are bacteria in the amniotic fluid
• then during birth, we acquire most of our microbes as we pass through the vaginal canal (more reflective of the mother’s intestinal microbiome) and the early stages of breastfeeding.
  Therefore, you see differences in the composition of the microbiome between babies deliver by c-section compared to those delivered by normal delivery.
  These differences have a big influence on develop of immune systems.
  in our teens it remains stable, it won’t change much (unless you have diseases)

Question 3

what is the hygiene hypothesis regarding IM?

Answer 3

• our immune systems have not seen many microbes, pathogens or bacteria
• we’ve been over hygienic
• so our exposure has been dampened
• for example, if someone has been on a farm, they are exposed to pollen so they won’t sensitive to pollen
• we have an ill-trained immune system at a young age

Question 4

what is the purpose and function of the intestinal microbiome?

Answer 4

• Host defence/pathogen invasion
• Nutrient/digestion/vitamin production/metabolic processes
• Intestinal epithelial maintenance cell renewal
• Host Immune system development

Question 5

what are Enterotypes?
what are the specific types?

Answer 5

The composition of bacterial populations in the intestinal microbiome
We all fall into a specific enterotype.
Enterotype 1: High abundance of Bacteroides bacteria. People who eat a lot of red meat have this enterotype.
Enterotypes 2: High abundance of Prevotella. People who eat lots of carbohydrates and veggies have this enterotype.
Enterotypes 3: High abundance of Ruminococcus bacteria. It is unknown what distinct diet is associate with this enterotype.

• different enterotypes can react to differently to antibiotics
• Knowing what enterotype someone falls into can be clinically important as it could influence how a person metabolises a drug etc.

Question 6

where does the IM live?

Answer 6

• most of them lives in our colon
• live there because the pH is optimal
• less antimicrobial being produced , which allows them to grow
• the colon is anaerobic
• this is because the ones that need oxygen used the oxygen, so they made it anaerbic, this allows anaerobes to thrive
• some bacteria like the lumen, some like poo, some like other
• all these conditions make perfect for some bacteria to thrive

Question 7

what are the diff types of bacteria that live in the intestine?

Answer 7

• some just like to live there
• good bacteria (symbiotes) → we feed them and they give us smth back
• pathogenic bacteria

Question 8

what is the purpose of good bacteria?

Answer 8

• pathogenic resistance/antimicrobial action
• Nutrient/metabolism digestion
• Cell maintenance
• Immunodilation/immune system training
• Mental-wellbeing

Question 9

explain pathogenic resistance/antimicrobial action as an eg of good bacteria function

Answer 9

they suppress pathogenic organism from expanding, as the bacteria living there is like “Hey there’s no room, and we’ve got a good thing going rn,”

Question 10

explain Nutrient/metabolism digestion as an eg of good bacteria function

Answer 10

sometimes our pancreas is unable to digest certain things that are messed up, some bacteria digest them, ferment them and they produce smth that’s useful to us. For example short-chain fatty acids (maintain the integrity of mucosa), enzymes, vitamins

Question 11

explain Cell maintenance as an eg of good bacteria function

Answer 11

without bacteria the, wall of our intestine would be leaky, cells would be all over the place, it would be unhealthy. Why→ Bacteria produce short-chain fatty acids, which improve the integrity of the mucosa, they also improve mucin secretion.

Question 12

explain Immunodilation/immune system training as an eg of good bacteria function

Answer 12

our immune system has been trained by our microbiome, it basically said to the immune system “Hey, hey, hey I’m good for you you shouldn’t destroy me.” and to make sure it regulates t cells etc (kinda like Wakanda and Taolkan

Question 13

explain Mental-wellbeing as an eg of good bacteria function

Answer 13

Bacteria produce serotonin and neurotransmitters that are important for enteric CNS communication, we know what are bacteria produce influences how we feel and our mental well-being,

Question 14

what is the purpose of short chain fatty acids?

Answer 14

• mucus secretion
• epithelial barriers
• energy stores
• dampen inflammatory cytokine production
• important in the blood-brain barrier
• regulate blood pressure have cardioprotective effects

Question 15

how do we influence our bacteria?

Answer 15

• can alter the composition of our bacteria
  
  • we are what we eat, what we eat defines the composition
  • age decreases or declines with age
  • antibiotics this can lead to dysbiosis

Question 16

define Dysbiosis

Answer 16

a shift in the usual microbial communities present to one that is associated with a disease or negative effects

Question 17

what is Microbial dysbiosis?

Answer 17

In many diseases we find that composition of the intestinal microbiome has been altered after the onset of a disease.
A healthy microbiome is one that regardless of composition, promotes well-being in the host.
It is considered that an intestinal dysbiosis could in fact be one of the environmental trigger components that are involved in the development of IBD
In IBD patients we observe an overall:
DECREASE in the diversity/number of bacteria

Question 18

What is a healthy microbiome then?

Answer 18

• One that is diverse and rich (but a highly diverse vaginal microbiome is unhealthy!)
• Ability to resist change easily – has a core set of ‘members’ (they are consistent bacteria)
• Undertakes required metabolic processes (eg SCFA production)
• Is different for different people

Question 19

how is C.diff an example of microbial dybiosis?

Answer 19

• diahorreal diseases
• after antibiotics
• antibiotics deplete usual bacteria
• c.difficle grows and grows
• then they grow and end up having diarrhoea
• a real-life example of dysbiosis

Question 20

how do you reverse the Dysbiosis?

Answer 20

• pre and probiotics are a way getting our bacteria back in
  
  • pre: feed bacteria that are there
  • pro: contain living ones

There are three routes to try to re-establish the ‘healthy’ microbiome and overcome the dysbiotic state:
Prebiotics: Specific bacterial strains in the microbiome have the ability to ferment fibrous substrates , and this in turn can promote the growth of such strains.
This can be adopted in a way to support the growth of selective bacteria within the colon.
Prebiotics: nutrients (carbohydrates and oligosaccharides) are delivered to the colon in a formulation to support the growth of bacteria.
This do not contain microorganisms, only selective fermentation components.

Probiotics: formulations that contain microorganisms, which when taken in appropriate doses and protected in certain ways, can reach the colon intact and viable. They are able to engraft, colonize and promote intestinal health.
Probiotics are able to compete with pathogenic bacteria for colonization niches.
The probiotic E. Coli Nissle is able to inhibit pathogenic microbes.
Specific bacterial strains can be delivered to achieve a desired effect.
For example, probiotic Bifidobacterium can improve intestinal barrier integrity and have anti-inflammatory effects.
NB: there is no evidence supporting the benefits of commercially available probiotics (e.g. Actimel)

Question 21

what is Faecal microbial Transplantation (FMT)?

Answer 21

the transfer of a processed stool obtained from a healthy donor into a patient. The aim is to correct the underlying dysbiosis by attempting to restore the intestinal microbial community.
In this case, the transplant of a whole heterogenous microbial communities is happening, rather than delivering select microbes (probiotic) or encouraging specific bacterial to grow (already present) using a prebiotic.
FMT can be delivered by several routes including:
- colonoscope
- Naso-gastric tube

Question 22

what are problems associated with FMT?

Answer 22

1. Pathogenic transmission: Transplantation of FMT can have significant adverse effects since whole faecal material can contain pathogens.
   Strict inclusion criteria: A very small number of individuals (2.8 %) are eligible to act as a faecal donor in FMT.
2. Routes of delivery: colonoscope or nasogastric-intubation are currently the only successful engraftment routes. Both are invasive, costly, require hospitalisation, associated with complications and negatively impact on patient compliance.
3. Dedication: Some FMT trials require a regime of repeated administration (in some cases 1 per day) which is impractical within the healthcare setting if FMT is to become routine.
4. Heterogenous nature: FMT is a very complex, heterogenous “medicine”. It is difficult to point out what exactly the bioactive agent is and how could we ensure it is in each ‘dose’. Therefore, imposing standardised production procedures will be difficult. Therefore getting MHRA approval will also be difficult.