Advances in Microbiome Research Flashcards
What is the microbiome?
A complex microbial community consisting of hundreds of species, The numbers of species depend on several variables, including pH values.
Approx. how many more microbial genes than human ones?
50
What is NB to be considered when attempting microbiome therapies?
The complex interactions between species
Mutualism
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
Hallmarks of coevolution
- 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
Benefits associated with the microbiome
Immune system development Gut tissue development Nutrient acquisition Brain function Neurodevelopment
Gnotobiology
The study of germ-free animals, typically mice with no microbes.
NB in studies to try understand the functional role of the microbiome
Are germ-free mammals good models?
Yes, because the differences that you can see in the other mouse model (conventional) are due to the microbiome.
Examples of diseases in which the gut microbiome is of importance
CVD, colon cancer, obesity, diabetes, allergies, autoimmune disease, chronic inflammation, neurological & mental disorders
Examples of environmental factors that are known to disrupt the gut microbiome and associated with a higher incidence of chronic disease
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
Lots of human pathologies are associated with?
Dysbiosis - altered composition of gut microbiota
What is special about the gut microbiota of rural Papua New Guineans?
They showcase one of the least industrialised populations in the world but have more diversity in their gut microbiota (Martinez et al., 2015)
Dysbiotic microbiomes: more or less diverse?
Often less diverse
Obese individuals that also suffer from metabolic inflammation show? (Le Chatelier et al., Nature, 2013)
A less diverse microbiome & reduction of anti-inflammatory mediators
the Old Friends’ Hypothesis
Changing our environment and the context the microbiome is in disrupts the mutualistic relationship
Relationship between microbiome and IgE
Need microbiome to demyelinate IgE response - germ-free mice more likely to develop IgE-mediated allergies than mice with a normal microbiome
Role of SCFAs in microbiome
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
How does colonocyte metabolism shape the gut microbiota? (Yael Litvak et al.)
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
Examples of microbes produced by the host and modified by the microbiome?
- Bile acids
- Trimethylamine N-oxide (TMAO)
What are likely key mechanisms in chronic diseases associated with dysbiosis?
Diet and lifestyle-induced alterations of microbiome metabolism and host microbiome immune interactions (e.g. inflammation)
Therapeutic modulation of the gut microbiota
- 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
Probiotics: strong evidence for?
Immunomodulation and endocrine system changes
- Less strong evidence that they can alter/ normalise the microbiome
Prebiotics can only be metabolised by
The microbiome, not the human host
i.e. dietary fibre
What are synbiotics?
Pre- and pro-biotics → live microbe + substrates for it
Challenges associated with microbiome studies?
- 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?
Future of Microbiome Research?
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
