The Human Microbiome: Role in Obesity & Diabetes (7/8) Flashcards
Describe the fibre content of ultra-processed food and how this affects the gut.
Lacks fibre
Fibre itself is not digestible by humans but is for gut microbiome
Ultra-processed food can alter the microbiome profile and cause inflammation
Suggest why the same exercise is not equally beneficial for different people.
The benefits of exercise are affected by factors such as diet and the gut microbiome profile.
What is the gut microbiome?
Ecological community of commensal, symbiotic and pathogenic microorganisms within the gut
It makes up 1-3% of total body mass
What is the gut microbiome made up of?
Generally non-pathogenic made up of bacteria (mainly), viruses, protozoa, fungi
Symbiotic with host
How is the gut microbiome studied?
Using 16S rRNA (small subunit of prokaryotic ribosomes) which is highly conserved in bacteria and archaea
Hyper-variable species specific sequences
No horizonal gene transfer - not transferred between species
What is dysbiosis?
An imbalance between the types of organism present in a person’s natural gut microflora
Contributes to a range of conditions of ill health
Can involve and increase in potentially pathogenic bacteria (e.g. campylobacter or salmonella) causing acute illness or a relatively subtle alteration in the richness and/or diversity of bacterial species present in the gut
What is richness in relation to the gut microbiome?
The total number of bacterial species in your gut microbiome
What is diversity in relation to the gut microbiome?
The amount of individual bacteria from each of the bacterial species present in your gut microbiome
How do diversity and richness of the gut microbiota change over time?
Increases during development
Remains stable in adulthood
Can decrease with ageing: inflammation or immunosenescence
Also decreases with chronic poor diet
How can biased diets affect the gut microbiome?
Alteration of the microbiome species
A high fat diet -> alkaline environment tolerance
A high protein diet is the least dangerous
Atkins diet: high carbohydrates and proteins, no fat
How can the gut microbiota affect the brain?
Bacteria communicate with each other by releasing GABA, which is a neurotransmitter that affects the brain
Other microbiota secretions include 5-HT (serotonin) precursors.
There is 2-way communication between the brain and the gut.
- Dysbiosis affects the brain
- Mental issues (stress, anxiety etc.) affect the gut
How do adipose tissue and the liver cope with obesity?
Triglycerides are normally stored in adipose tissue
In obesity, adipose tissue can only cope up to a point
The liver copes with the excess triglycerides
Liver increases in size, becomes fatty
It can also cope up to a point
What happens when the liver can’t cope with excess triglycerides in obesity?
Fatty liver disease will develop due to the build-up of excess triglycerides in the liver
How does microbial dysbiosis contribute to fatty liver disease?
Increased production of intestinal ethanol can be toxic to the liver and can damage the gut permeability by destroying tight junctions
Leaky gut (loss of tight junctions between epithelial cells)
How do pathogen-associated molecular patters (PAMPs) contribute to fatty liver disease?
PAMPs can bind to toll-like receptors in the liver and activates pro-inflammatory pathways. This causes hepatic inflammation and fibrosis
How does choline metabolism contribute to fatty liver disease?
Gut microbiota hydrolyse choline to form dimethylamine and trimethylamine
Increased choline metabolism may cause choline deficiency, which prevents the excretion of very low-density lipoprotein (VLDL)
Initiates the accumulation of triglycerides in liver
How does fasting-induced adipocyte factor (FIAF) contribute to fatty liver disease?
FIAF inhibits endothelial lipoprotein lipase (LPL) which releases triglycerides from VLDLs into the liver
Altered gut microbiota can inhibit the secretion of FIAF
Fasting-induced adipocyte factor (FIAF) = Angiopoietin-related protein 4 (ANGPTL4)
What are the net effects of FIAF inhibition in fatty liver disease?
Inhibition of lipid β-oxidation and increased storage of hepatic triglycerides
What are short chain fatty acids (SCFAs)?
Microbial metabolites that play a critical role in host metabolism and immunity through both local and systemic actions on multiple targets
They have different mechanisms in different organs
How do short-chain fatty acids (SCFAs) contribute to fatty liver disease?
Excessive SCFAs are substrates for gluconeogenesis and fat synthesis in liver
They promote the accumulation of hepatic free fatty acids (FFAs) by inhibiting the activity of adenosine monophosphate activated protein kinase (AMPK)
How do short-chain fatty acids (SCFAs) relate to the gut microbiota health?
A healthy gut microbiome increases the number of SCFAs through the fermentation of fibre
Overproduction of SCFAs is not good
How are short-chain fatty acids (SCFAs) taken in by organs?
Through G-protein coupled receptors
What is the mechanism of GLP-1?
Stimulated by SCFAs
Receptors in gut, liver, pancreas and hypothalamus
Improve insulin sensitivity, decrease gastric emptying, increase glucose uptake/oxidation etc.
What effect does GLP-1 have in the hypothalamus?
It acts on the same neurones as leptin
Decreases gastric emptying to increase satiety signals
