Week 7: Microbiome Flashcards
Microbiota
Community of microorganisms (eg. fungi, bacteria, viruses)
Microbiome
Collection of all microbial genes
Can exist in mouth, skin, digestive system, urogenital
What makes a healthy microbiome?
DIVERSE
What bacteria make up 90% of microbiome?
Bacteroidetes
Firmicutes
What bacteria make up 10% of microbiome?
Actinobacteria
Proteobacteria
Bacteroidetes
Beneficial effects on human health, anti-inflammatory
Help prevent or mitigate disease such as cancer, diarrhea and IBS
Firmicutes
Carbohydrate metabolism
Reduction in depressive symptoms
Actinobacteria
Gut homeostasis, functions in gut barrier, immune system and metabolism
ex. bifidobacteria
Proteobacteria
Microbial signature of disease
Associated with onset of CV events and IBS
Bacteroidetes and firmicutes ratio
High firmicute:bacteroidete ratio is associated with several pathological conditions such as obesity
Bifidobacterium
+
Reduced abundance in obesity
Lactobacillus
+
Attenuates IBD
Alistipes
-
Associated w disease
Roseburia
+
Reduced abundance in IBD
Eubacterium
+
Reduced abundance in IBD
Faecalibacterium
+
Reduced abundance in obesity and IBD
Enterobacteria
-
Increased abundance in IBD
Framework to study causality of gut microbial components
- Control vs disease population
- Perform metagenomic profiling to create a microbiome correlational network
- Perform faeces transplant
- if phenotype change is observed, there is an association btwn that disease and the microbiome
Microbiome correlational network
Identifies a relationship btwn microbes and can help identify microbial markers associated with diff health conditions
Faeces transplant
Transplant of microbiome from humans to germ-free rat
Germ-free
No microbiome
Microbiota-changing interventions
- Nutrition
- Exercise
- Faecal microbiota transplantation
- Prebiotics
- Probiotics
Function of gut microbiome
- Antimicrobial protection
- Immunomodulation
- Gut-brain axis
- Gut mucosal barrier
- Nutrient metabolism
Antimicrobial protection
Gut microbiota can induce the synthesis of antimicrobial proteins and local immunoglobins
Immunomodulation
Gut microbiota work w innate and adaptive immune systems to modify immune response
Gut-brain axis
Bidirectional communications btwn the central and enteric nervous systems; integrates neural, hormonal and immunological signalling
Gut-brain axis neurological circuit
Cross talk allows gut sensory visceral signals that travel with the vagus nerve to influence the CNS which modifies behaviours and moods and brain can also modulate gut physiology
Enteric nervous system
Complex network of neurons responsible for intrinsic innervation of gut functions
Gut mucosal barrier
Gut microbiota maintains structure and function of GI tract
Nutrient metabolism
Metabolized non-digestible carbs, can produce a variety of vitamins and can synthesize all essential and non-essential amino acids
Example 1 of gut brain axis
Physiological stress and gut microbiota
Examples 2 of gut brain axis
Hunger regulation
Homeostatic hunger regulation
Hormones stimulating hunger or fullness; hypothalamus
Hormones involved in hunger regulation
Ghrelin, leptin, insulin
Reward/hedonic hunger regulation
Desire or cravings; dopamine system
Cognition and hunger regulation
Integration of hedonic and homeostatic food intake regulation; prefrontal cortex
Homeostatic system feedback mechanisms
Metabolic feedback (appetite hormones that go to hypothalamus)
Visceral feedback (Vagus nerve- goes to brainstem)
Hedonic system areas
- Conscious cortical areas
- Unconscious subcortical areas
What type of feedback received by the conscious cortical area of the hedonic system?
Reward feedback- senses such as smell
Nutrient metabolism: dietary fibre
Fibre is broken down in to short chain fatty acids and acts as an indigestible dietary substrate for bacteria in large intestine
Short chain fatty acids
Key bacterial fermentation products
Three main short chain fatty acids
- Butyrate
- Propionate
- Acetate
Role of short chain fatty acids
Line epithelium to protect gut and help form tight junctions btwn cells, preventing permeability
What happens to the tight junctions when the bacteroidete:firmicute ratio is altered
Reduces proteins that form the junctions and lipopolysaccharides can leak through - LEAKY GUT
Butyrate
Key energy source for human coloncytes
Maintains intestinal barrier
Propionate
Energy source for epithelial sources
Transferred to liver
Role in gluconeogenesis
Imp satiety signal
Acetate
Growth of other bacteria
Cholesterol metabolism and lipogenesis
Role in appetite regulation
What SCFA inhibit growth of pathogens in gut?
Acetate and butyrate
Factors affecting gut microbiota
- Age
- Stress
- Diet
- Breastfeeding
- Mode of birth
- Medication
Factors affecting microbiome in newborn
- Maternal diet
- Gestational diabetes
- Environmental exposures
- Gestational age
- Delivery mode
Factors affecting microbiome as we age
- Meds
- Diet
- Exercise
- Infection/disease
- Pets
What is the microbiome like when were adults?
More diverse bc were exposed to more
Stable
Human milk microbiota (HMM)
The nutritional and bioactive molecules (microorganisms) present in human milk; second primary source of microbes for infants (30%)
How is breastfeeding associated with microbiota composition?
- Breastfed babies have lower diversity compared to formula fed children
- Cessation of breastfeeding is associated w shift towards mature, adult-like microbiome
Is HMM a prebiotic or probiotic?
Both
Direct (probiotic) property of HMM
Alter gut microbiota through transmission of bacteria
Indirect (prebiotic) property of HMM)
Contains oligosaccharides that promote growth of specific bacteria
Function of breastfeeding
Shapes composition of gut and respiratory microbiota
Promotes intestinal immune homeostasis
Facilitates digestive processes
Resilience
Following a challenge, the microbiota of a healthy individual is able to return to baseline
Dysbiosis- breastfeeding
Occurs when microbiota does not return to baseline after a challenge, leads to negative health outcomes in infants
How does a C-section affect the microbiome?
Leads to dysbiosis of newborn gut microbiome bc of lack of exposure to maternal vaginal and fecal bacteria that occurs in vaginal birth; decreased microbial diversity
What is a C-section a risk factor for?
Allergic outcomes (asthma)
Antibiotics
Eradicate bacteroidetes, firmicutes and actinobacteria leaving an open niche for colonization or proliferation of opportunistic bacteria (often associated w GI disease)
Western diet vs low fat diet- body fat
Western diet resulted in increased body fat %
Western diet vs low fat diet bacteroidete:firmicute ratio
More firmicutes than bacteroidetes
Associated w obesity
Mediterranean diet
Low in animal fat and protein, high in plant fibres
Fermentation and formation of SCFA
What does mediterranean diet lead to?
- Reduced blood glucose
- Increased energy expenditure
- Increased glucose-stimulated insulin secretion
Western diet
High in animal fat, protein and sugar, low in plant fibres
Proteolysis and production of microbiota related to metabolic disease
What does the western diet lead to?
- Increased blood glucose
- Decreased metabolic endotoxemia
- Decreased glucose-stimulated insulin secretion
Western diet vs mediterranean- bacteria
Dysbiosis and reduced total bacteria
Decreased favourable bacteria and increased unfavourable bacteria
Effect of western diet
Inflammation, CVD, IBD, obesity
Effect mediterranean diet
Reduced risk
Protein consumption and microbial diversity
Positively correlated
Why are plant protein sources beneficial?
Increased bifidobacterium and bacteroidetes
Increased SCFA, reduced inflammation and increased gut barrier
Effect of animal protein sources
Increased bifidobacterium and bacteroidetes
Reduced SCFA, increased CVD and IBD
Study on fat and the microbiome
Three conditions
1. Lower fat diet- 20%
2. Moderate fat diet- 30%
3. High fat diet- 40%
- controlled for source of fat, fibre and protein intake
Results of study on fat and microbiome
High fat diet
- high ratio of firmicutes:bacteroidetes
- decreased SCFA
- decreased faecalbacterium
- increased alistipes
- reduced microbiome diversity
Saturated vs unsaturated fat
Saturated fat reduces microbial diversity and abundance
Unsaturated fat increased beneficial bacteria
How does sugar affect the microbiome?
Increased proteobacteria -inflammatory
Decreased bacteroidetes- antiflammatory
What does sugar promote?
Leaky gut which leads to low grade inflammation and metabolic disorders
What is the microbiota gut-brain axis implicated in?
Obesity (metabolic health)
Mental processes (mental health)
Disease onset and prevention (immunological health)
Dysbiosis
Imbalance in bacterial composition, changes in bacterial metabolic activities or changes in bacterial distribution in the gut
What does gut dysbiosis lead to?
- Loss of beneficial bacteria
- Overgrowth of potentially pathogenic bacteria
- Loss of overall bacterial activity
Main roles of intestinal barrier
- Absorption of water, electrolytes, essential dietary nutrients from intestinal lumen into circulation
- First line of defense against external pathogens
Structure of intestinal barrier
- Outer mucus layer
- Inner mucus layer
Outer mucus layer
Contains microbiota, antimicrobial proteins and secretary immunoglobin A molecules
Inner mucus layer
Physical barrier that covers epithelial cells
How does the intestinal barrier affect the microbiome?
Mucus barrier provides a habitat and nutrients for microbiome
Breached barrier invokes inflammatory response that affects gut microbiota composition
How does the microbiome affect the intestinal barrier?
Butyrate maintains intestinal barrier but those with IBD lack it, leading to lesions in tight junctions and impaired intestinal permeability
Microbiome helps repair injured mucosa
Gut microbiota modulates production and secretion of mucins and stratification of mucus layers
LPS- lipopolysaccharide
Component of outer cell wall of gram-negative bacteria
What is the main source of LPS?
Microbiota
What in LPS involved in?
Macrophage activation which stimulates inflammation
Septic shock, sepsis and organ failure
What does leaky gut/impaired gut barrier lead to?
LPS in circulatory system
Over-activation of gut immune system, inducing chronic systemic inflammation or an impaired immune response, promoting progressing of metabolic diseases
High circulating levels of LPS
Metabolic endotoxemia; associated w obesity and related metabolic disorders
Conditions associated with dysbiosis
- Pulmonary disorders
- Metabolic disorders
- Cognitive disorders
- Cardiovascular disorders
- Gastrointestinal disorders
Inflammatory bowel syndrome (IBS)
GI disorder characterized by chronic recurrent abdominal discomfort and pain with changes in bowel habits
SCFA producing bacteria and IBS
IBS patients have a lower abundance of butyrate producing bacteria (risk for leaky gut)
Methanogens (archea)
Microbes responsible for removing excess hydrogen by converting it to methane
What is methane production linked to?
Low transit time and anti-inflammatory effects in colon
Methanogens and IBS
IBS patients have lower methanogens- reduced ability for hydrogen gas removal leading to excess gas in abdomen
Small intestinal bacterial overgrowth
Leads to GI symptoms such as malabsorption through effects on GI motility, visceral sensation, immune activation and intestinal permeability
What can small intestinal bacterial overgrowth lead to?
IBS
**bidirectional- IBS can also lead to small intestinal bacterial overgrowth
Microbiome and T2D
Attempts to transfer gut microbiota from drug naive individuals with T2D to germ mice to preproduce T2D phenotype failed
Microbiome and obesity study
Studies twins- one obese one lean
Performed faecal transplantation
Mice that received microbiota from obese doner gained weight
How to enhance gut microbiome
- Eat a diverse range of food
- Eat fibre
- Eat fermentable food
Why is fibre beneficial in diet?
- It is a prebiotic
- Promotes growth and activity of beneficial bacteria in GI tract by acting as a source of nutrition
- Increases microbiome diversity and SCFA-producing bacteria in gut
Fermentation
Process whereby alcohols, carbon dioxide, and/or organic acids are produced by microorganisms from carbohydrates for energy production
Benefits of fermented foods
- Provide nutrients that promote growth of gut microbes
- Microbes survive gastric transit and become a component of gut microbiome
- Enhance digestibility of carbs and proteins
- Produce antioxidants
- produce bioactive compounds
Health benefits of fermented foods
Reduce BP, cholesterol and CVD
Improve metabolic syndromes and immune function
Anti-cancer effects
Weight management
Bioactive compounds
Food derived compounds that exert physiological effect on body
High fermented food diet benefits
- Increase microbiome diversity
- Reduce inflammatory signals and activity
Problem with microbiome research
Diificult to establish causal rather than associative relationship btwn specific microbes and physiological or diseased state
