The Gut Microbiome in Metabolic Disorders Flashcards
What is the microbiome?
Collection of microorganisms and their genes and proteins living within our mucosae, skin, and secretions
What is the exposome?
Environment
What are the two most dominant phyla in the colons of healthy adults?
Firmicutes
Bacteroidetes
What are the Firmicutes mainly made of?
Gram positive Clostridia
What are the Bacteroidetes mainly made of?
Gram negative Bacteroides
Are the less important phyla functionally important?
Yes
What are the two approaches to sequencing the microbiome?
16S ribosomal sequencing
Metagenomic shotgun sequencing
How does 16S ribosomal sequencing work?
Takes areas common to most bacteria in 16S ribosomal subunit gene and amplifies it
Those areas that are different are also amplified
On this basis, bacteria can be separated
What is the speed and ease of 16S ribosomal sequencing?
Simple
Fast
Straightforward to analyse
What does 16S ribosomal sequencing report?
Operational taxonomic units, not sequences of species
Does 16S ribosomal sequencing resolve well at the species level?
No
What are the shortcomings of 16S ribosomal sequencing?
May fail to resolve substantial fraction of diversity
Not ID novel/highly diverged microbes
Can’t resolve biological functions associated with taxa
How does metagenomic shotgun sequencing work?
Microbial and human DNA separated
Microbial DNA randomly sheared into short segments > sequenced > re-assembled
Does metagenomic shotgun sequencing reveal microbial genes that are active?
No, only those that are present
What is alpha diversity?
Measure of species diversity within sample
What is beta diversity?
Measure of diversity between samples
What is dysbiosis?
Disturbance/imbalance in biological system
How is a newborn baby seeded with microbiota?
Vagina
Gut
Skin
Breast milk
What are the dominant species in the vagina with which the baby is seeded?
Lactobacillus
Prevotella
What does a healthy microbiome do in a baby?
Induces maturation and maintains integrity of - Gut - Immune system - Neurological system - Others Protects against infection Produces nutrients and vitamins Utilises energy > regulates metabolism and weight
What happens to the breast milk microbiome after elective C-section?
Altered
What childhood diseases is C-section associated with?
Allergic rhinitis
Asthma
Coeliac disease
Type 1 diabetes
What evidence is there to show that the microbiome regulates development of type 1 diabetes?
Incidence of T1D in wild mice very low
More than half of mice reared in specific pathogen free environments developed T1D
All mice reared in germ-free environment, and had no microbiome, developed T1D
What does diet protection against autoimmune diabetes need?
Microbiome
What is the relationship between gut microbial diversity and seroconversion to clinical type 1 diabetes?
Decrease in diversity with seroconversion
Significant decrease in diversity with diagnosis T1D compared to controls
How does the gut microbiome change in children with type 1 diabetes?
Diversity decreases
Actinobacteria and Firmicutes decreased
Bacteriodetes increased
Butyrate-producing species within Clostridium decreased
How are short-chain fatty acids, such as butyrate, produced?
Bacteria ferment undigested starch
What do short-chain fatty acids do?
Maintain epithelial integrity Absorbed > go to - Liver - Muscle - Brain - Etc Anti-inflammatory - Bind and activate GTRs - Inhibit histone deacetylases
How does a fast food diet change the gut microbiome?
Decreases diversity
Has many additives affecting microbiome
What is the gut microbiome like in type 2 diabetes?
Fewer butyrate-producing bacteria
More opportunistic pathogens > can cause infections
What is a better predictor of insulin resistance than BMI?
Metagenomic signature
Is there evidence that a faecal microbiota transplant cures anything?
No clear evidence that it cures anything except recurrent C difficile infection
How did things change in people with metabolic syndrome with the transfer of gut microbiota from lean donors?
Increased insulin sensitivity
Increased diversity in faecal microbiome
Butyrate-producing bacteria increased
Is obesity transmissible by gut bacteria?
Yes
What are the issues with probiotics?
Contain only few bacteria
Evidence for passage to large bowel
Varying resistance to acid and bile across species and strains
Lack of randomised clinical trials
What are prebiotics?
Food parts that promote specific changes in growth/activity of gut bacteria to confer health benefit to host
Examples
- Non-digestible carbohydrates
- Phytochemicals = chemicals in plants
