Dysbiosis + disease

Question 1

Define Dysbiosis

Answer 1

Imbalance in the human microbiota

Question 2

What are the causes of dysbiosis?

Answer 2

Microbiota availability in youth (hygiene, hospitals)

Human genetics (immune system communication)

Diet

Antibiotics

Pathogenic infections

Question 3

What are the diseases that are associated with Intestinal Dysbiosis?

Answer 3

Clostridum difficile infection

Inflammatory bowel disease

Rheumatoid arthritis

Metabolic syndrome (Obesity, type II diabetes + heart disease)

Question 4

What disturbs the immunological balance in the intestine?

Answer 4

Accumulation of pathobionts disturbs the immunological balance in the intestine

Gut pathobionts may affect the inflammatory state of the inflammatory state of the intestine by increasing in numbers relative to the symbionts

Question 5

How can we identify good or bad bacteria?

Answer 5

Estimated by DNA analysis of stool samples

Proving that a disease is due to the increase of a pathobiont or decrease of a symbiont is difficult, because it is the numbers rather than presence or absence that causes problems

Question 6

Discuss Clostridium difficile

Answer 6

Gram-positive bacterium present in the gut microbiota

Growth inhibited by normal microbiota

If microbiota is killed off by antibiotics, C.difficile can proliferate

Elderly patients are vulnerable

C.difficile secretes toxins, leading to diarrhoea

Also leading to pseudomembranous colitis

Diarrhoea increases chance of infection to other individuals - hygiene is essential

Treatment = metronidazole/vancomycin

Reoccurs in 25% of patients

Life-threatening = can cause colectomy with stoma

Question 7

Discuss alternative therapy for recurring C.difficile

Answer 7

Oral probiotics

• limited benefits due to low gut colonisation rates

Faecal Matter/microbiota transplant

• use fresh stool from healthy donor (relative)
• introduced by infusion (enema, capsule)
• successful in 85% of cases

Question 8

What are the problems with faecal microbiota transplants?

Answer 8

Patient reluctance

Potential contamination with pathogens

Lack of guidelines

Insufficient data on long term effects

No pure cultivated bacteria available yet, may not work as well

Guidelines are now available, but too few treatment centres

Question 9

What is Metabolic Syndrome?

Answer 9

This is the name for the frequent co-occuring conditions of:

• Central obesity
• Insulin resistant diabetes
• Hypertension and cardiovascular disease
• Non-alcoholic hepatic steatosis (fatty liver disease)

5^th leading cause of death worldwide

Question 10

How could the gut microbiota cause metabolic syndrome?

Answer 10

1. The microbiome increases caloric intake by increasing digestion
2. Compounds synthesised by the microbiome change the regulation of metabolism and appetite, causing fat storage and increased calorie intake. The evidence for this mechanism is increasing.

Chronic acetate production by the obesity associated microbiome causes increased insulin secretion + increased appetite

Question 11

How to improve metabolic syndrome + dysbiosis therapy?

Answer 11

Drugs

Probiotics

Diets

Supplements

They are tailored to change the microbiota, rather than reduce calorific intake. It should improve metabolic syndrome by changing both metabolism + appetite

Question 12

Fill in the gaps

Answer 12

Question 13

What are the modes of horizontal gene transfer?

Answer 13

Question 14

What is Evolution?

Answer 14

The accumulation of genetic changes in a biological population over time

Evolution requires genetic variation:

• generated by mutation, recombination + gene transfer
• mutations are harmful to the organism + beneficial ones occur rarely, gene transfer + recombination

Evolution is driven by natural selection:

• Natural selection is the interaction of the environment with the genome
• Genetic variations that increase reproduction become more common over time