iv. The Human Microbiome

Question 1

• Every part of the human body is covered in _________ – Every surface has a population of a number of different kinds of organisms (Body is not sterile).

The partnership of man and microbe has developed over the entire course of _______. Thus, without these microorganisms humans cannot function properly – Humans have developed a relationship with the microorganisms.

Microorganisms (bacteria, viruses, fungi, archaea, helminths/parasites in our gut) influence
human anatomy and ______.

Answer 1

microrganisms
evolution
physiology

Question 2

• Microbiome:

Answer 2

• Microbiome: Refers to the genes present in all the microorganisms living in association with
  the host.

Question 3

• Microbiota: (2)

Answer 3

• Microbiota: Refers to the actual organisms
• Bacteria (in and on us) outnumber human cell population - Bacteria: human cells probably
  3:1. The large number indicates that they must be playing some role/function.

Question 4

Bacteria are present:
- Very ______ bacteria are present on the human body.

Answer 4

specific

Question 5

The human bacterial microbiota at different anatomical sites: (2)

Answer 5

• Distribution of these bacteria is extremely different in different parts of the body (types and number of bacteria).
• It is postulated that different people have slightly different organisms colonising breast tissue – Contributing factor in breast cancer.
• Most anatomical sites are composed of the same phyla but have different species (within the same phyla) and different proportional representation each phyla.

Question 6

The gut microbiota
The Intestine:
- ____-_____ species of bacteria present in the intestines

• Different ______ dominant in different parts of the intestine – When viewed as a micro-population, the small intestine appears very different to the colon.
• The _____ of _____ increases from the duodenum through to the descending colon and
  rectum (closer you get to the descending colon and rectum, the higher the number of bacteria).

Answer 6

• 500- 1000
• Phyla
• Load of bacteria

Question 7

• Several different factors contribute to bacterial distribution within the GIT: (3)

Answer 7

o pH of the intestinal contents
o Oxygen levels
o Antimicrobial protein production

Question 8

• Several different factors contribute to bacterial distribution within the GIT:

o pH of the intestinal contents:

Answer 8

Very low prior to the bile duct opening up into the duodenum. pH increases steadily throughout the entre intestine. Certain organisms are tolerant to the very acidic environment while others can withstand extremely high pH levels.

Question 9

• Several different factors contribute to bacterial distribution within the GIT:

o Oxygen levels:

Answer 9

High within the proximal parts of the small bowel but further down, the oxygen concentration decreases – favouring the growth of completely different organisms (Anaerobes).

Question 10

• Several different factors contribute to bacterial distribution within the GIT:

o Antimicrobial protein production:

Answer 10

The small bowl produces a number of antimicrobial proteins – Don’t want a lot of bacteria within your small intestine because this is where majority of absorption takes place (want food absorption rather than consumption of the nutrients by a large population of bacteria).

Question 11

2 groups of proteins inhibit the growth of microorganisms: Decrease the concentration of organisms in the small bowel.

What are these proteins? (2)

Answer 11

▪ IgA is secreted into the lumen of the gut, found in high concentrations in the mucus layer

▪ Antimicrobial proteins secreted at the intestinal crypts by basal cells

Question 12

Bacteria in the _____ _____ are very important in providing energy as they breakdown some food we cannot digest (fibre).

Answer 12

large intestine

Question 13

• When considering the transverse distribution of bacteria (previously done longitudinal), different microorganisms live in the centre of the _____/____ as opposed in close association with the epithelium/inter-fold regions of the large intestine. THEREFORE, YOU WILL NOT FIND ALL THE ORGANISMS IN THE GUT WHEN ANALYSING FAECAL MATTER – Inaccurate representation of all organisms, digesta portion mainly. some organisms live in very close association to the epithelium, particularly within the ____ _____ of the intestines.

Answer 13

lumen/digesta
mucus layer

Question 14

• With oxygen level transverse distribution, there is more oxygen close the ______ than there is in the lumen (oxygen can diffuse of from the epithelial cells into the mucus layer)
• The ______ holds a source of microorganisms for repopulating the large bowel (safe space for some organisms to remain – reserve)

Answer 14

epithelium
appendix

Question 15

• There are 2 mucus layers in the large intestine: Very specific organisms are found within each of these layers.
  NOTE: If you are fasting/starving, not providing these organisms with food, the mucosal organisms continue to survive by breaking down and eating the mucus. Composition of the mucus layer in the Git will change during starvation/fasting in order to maintain these populations of bacteria.

WHAT ARE THE 2 LAYERS?

Answer 15

o Tight inner mucus layer which is firmly attached to epithelium

o Looser mucus layer allowing the flow of solid faecal material to the distal part of the
intestine.

Question 16

Development of the individual GIT microbiota: (6)

Answer 16

Question 17

Factors that affect the GIT Microbiota: (3)

Answer 17

• Diet
• Environment
• Host Immune system

Question 18

Diet and environment are responsible for reduction in _____ and _______.

Answer 18

diversity
dysbiosis

Question 19

Factors that affect the GIT Microbiota:
- Diet:

Answer 19

Question 20

Factors that affect the GIT Microbiota:
- Environment:

Answer 20

Question 21

Factors that affect the GIT Microbiota:
- Host Immune system:

Answer 21

Difficult to quantify in humans but some major examples

Example: IgA deficiency will lead to drastically different control over their small intestine microbiota.

Question 22

Function of the gut bacterial microbiota
Actions of microbiota: (2)

Answer 22

Question 23

Diet is extremely important - Have to support the right bacteria in our gut to have these effects. Depending on bacteria present, you will have particular _______ and structural components of bacteria present. These structural components and metabolites can have negative and positive effects:

Answer 23

metabolites

Question 24

A number of different tissues and organs are affected: Adipose tissue, Liver (non-alcoholic fatty liver disease association), Intestine, Brain, CVS, Lungs (allergic Asma).

How are these tissues and organs affected? (3)

Answer 24

• LPS/endotoxin:
  Can be absorbed and cause inflammation
• Short chain fatty acids/SCFAs:
• Trimethyamine
  Comes from choline in the diet and has been assoaited with the development of atherosclerosis which leads to strokes and heart attacks.

Question 25

Energy and metabolism:
- One of the first effects of the microbiota was noted to involve energy and metabolism. An early experiment involved taking germ-free mice with no microbiota associated, and reconstitute their microbiota from various sources. Reconstituted some mice with microbiota taken from obese humans (mice became obese) and other mice were reconstituted with _______ taken from lean humans (mice were thin).
- Adds hundreds of ______ _______ to the gut, making extra energy available especially from fibre. SERIOUS PUBLIC HEALTH PROBLEM – LOW FIBRE DIETS.
- Upregulates _______ of CHO and lipid in the gut.
- Influences glucose ________
- Affects bile salt metabolism
- Affects appetite by altering secretion of gut hormones and increasing _____ sensitivity

Answer 25

microbiota
digestive enzymes
transporters
homeostasis
leptin

Question 26

The immune system:
- The physical development and function of the entire immune system depends on the presence of the microbiota.

What are the control mechanisms involved?

Answer 26

• Control of the epithelium microbiota interface:
  Normal microbiota controls what other organisms can gain access to the epithelium of the gut. Therefore, presence of normal microbiota will prevent a large proportion of gut infections.
• Colonization Resistance: The mechanism whereby the intestinal microbiota protects itself against incursion by new and often harmful microorganisms.
  A depleted microbiota will lead to infections occurring more easily and frequently.

Question 27

Bacteria can not only activate but can also suppress the immune system:

What is the metabolite involved?

Answer 27

Metabolite: Shot Chain Fatty Acids (SCFAs)

Question 28

Metabolite: Shot Chain Fatty Acids (SCFAs)
- Acetate, Butyrate and _______
NOTE: Butyrate is the major source of energy for normal colon epithelial cells – therefore if you do not eat enough fibre to produce butyrate, you will not get enough energy to colon cells. Other sources of butyrate include cheese and butter.
- Produced by bacteria from ____ in the diet and act in the gut as well as being absorbed.

Answer 28

Propionate
fibre

Question 29

What are the effects of SCFAs? (2)

Answer 29

Question 30

Bacteria can not only activate but can also suppress the immune system:

What is the microbial component?

Answer 30