Advances in Microbiome Research

Question 1

What is the microbiome?

Answer 1

A complex microbial community consisting of hundreds of species, The numbers of species depend on several variables, including pH values.

Question 2

Approx. how many more microbial genes than human ones?

Answer 2

50

Question 3

What is NB to be considered when attempting microbiome therapies?

Answer 3

The complex interactions between species

Question 4

Mutualism

Answer 4

Living in harmony & symbiosis with our microbiome
- Influenced by our make-up but influences our make-up in turn → modulating immune function, nutrition, resistance to other infections

Question 5

Hallmarks of coevolution

Answer 5

• Size of our colon
• Human milk oligosaccharides in breast milk (Zivkovic et al., 2011) - these complex sugars cannot be digested by an infant → select for ‘correct’ microbial species during early colonisation of GIT? HMOs contribute to the development of the infant’s microflora & immune system

Question 6

Benefits associated with the microbiome

Answer 6

Immune system development
Gut tissue development
Nutrient acquisition
Brain function
Neurodevelopment

Question 7

Gnotobiology

Answer 7

The study of germ-free animals, typically mice with no microbes.
NB in studies to try understand the functional role of the microbiome

Question 8

Are germ-free mammals good models?

Answer 8

Yes, because the differences that you can see in the other mouse model (conventional) are due to the microbiome.

Question 9

Examples of diseases in which the gut microbiome is of importance

Answer 9

CVD, colon cancer, obesity, diabetes, allergies, autoimmune disease, chronic inflammation, neurological & mental disorders

Question 10

Examples of environmental factors that are known to disrupt the gut microbiome and associated with a higher incidence of chronic disease

Answer 10

C-sections (Maghzi et al., 2012)
Formula feeding (Conradi et al., 2012 - breastfeeding associated with lower risk for MS)
Early-life antibiotics (Norgaard et al.)
Low fibre diet

Question 11

Lots of human pathologies are associated with?

Answer 11

Dysbiosis - altered composition of gut microbiota

Question 12

What is special about the gut microbiota of rural Papua New Guineans?

Answer 12

They showcase one of the least industrialised populations in the world but have more diversity in their gut microbiota (Martinez et al., 2015)

Question 13

Dysbiotic microbiomes: more or less diverse?

Answer 13

Often less diverse

Question 14

Obese individuals that also suffer from metabolic inflammation show? (Le Chatelier et al., Nature, 2013)

Answer 14

A less diverse microbiome & reduction of anti-inflammatory mediators

Question 15

the Old Friends’ Hypothesis

Answer 15

Changing our environment and the context the microbiome is in disrupts the mutualistic relationship

Question 16

Relationship between microbiome and IgE

Answer 16

Need microbiome to demyelinate IgE response - germ-free mice more likely to develop IgE-mediated allergies than mice with a normal microbiome

Question 17

Role of SCFAs in microbiome

Answer 17

SCFAs are produced from dietary fibre in order to reduce inflammation & contribute to brain function. Butyrate is essential to keep gut mucosa anaerobic.

Early dysbiosis → less butyrate produced → gut mucosal cells start aerobically respiring → O2 present, aerobic microbes can thrive → further dysbiosis

Question 18

How does colonocyte metabolism shape the gut microbiota? (Yael Litvak et al.)

Answer 18

Colonocyte metabolism → epithelial hypoxia → maintains a microbial community dominated by obligate anaerobic bacteria
Conditions that alter metabolism of colonic epithelium increase epithelial oxygenation → expansion of facultative anaerobic bacteria, a hallmark of dysbiosis in the colon

Question 19

Examples of microbes produced by the host and modified by the microbiome?

Answer 19

• Bile acids

- Trimethylamine N-oxide (TMAO)

Question 20

What are likely key mechanisms in chronic diseases associated with dysbiosis?

Answer 20

Diet and lifestyle-induced alterations of microbiome metabolism and host microbiome immune interactions (e.g. inflammation)

Question 21

Therapeutic modulation of the gut microbiota

Answer 21

• Biotherapeutics i.e. live biotherapeutic product (LBP) - essentially probiotics, contain live organisms (bacteria or yeast), e.g. Akkermansia muciniphila
• FMT (faecal microbiota transplantation) - very successful for C. diff infections
• Phages/ genetic approaches
• Food additives/ supplements → probiotics, prebiotics, synbiotics

Question 22

Probiotics: strong evidence for?

Answer 22

Immunomodulation and endocrine system changes

- Less strong evidence that they can alter/ normalise the microbiome

Question 23

Prebiotics can only be metabolised by

Answer 23

The microbiome, not the human host

i.e. dietary fibre

Question 24

What are synbiotics?

Answer 24

Pre- and pro-biotics → live microbe + substrates for it

Question 25

Challenges associated with microbiome studies?

Answer 25

• Low reproducibility
• High confounding by diet
• Difficulty establishing causality → likely that dysbiosis is a consequence of disease and not the other way around
• Poorly characterised mechanisms/ mechanisms of causation (can make it harder to design helpful strategies)
• Need more experiments in human models
• What to target - diversity? composition?
• When do they target it - at birth? later?

Question 26

Future of Microbiome Research?

Answer 26

Carefully controlled human intervention studies with relevant clinical endpoints are needed to determine the value of microbiome modulation, establish the underlying mechanisms, and determine to what degree treatments and nutritional strategies have