Week 3.1: The role of microbiota in affective disorders Flashcards
The collection of all the microorganisms (bacteria, viruses, fungi, etc.) living in a particular environment, such as the gut.
Often used interchangeably with “microbiota,” though it encompasses a broader context including the microorganisms’ genetic makeup and their interactions with the environment.
Microbiome
What is the connection between microbiome and mental health?
Research suggests that the gut microbiome can influence mood and mental health, potentially contributing to conditions like depression and anxiety.
What is the human body’s microbial population?
The human body hosts trillions of microorganisms, including bacteria, viruses, and fungi.
The community of microorganisms (bacteria, viruses, fungi, etc.) living in a specific environment within the body.
Microbiota
The Boy in the Bubble: A Case Study
David’s Condition: He was born with a severe immune deficiency condition inherited from his parents.
Germ-Free Bubble: David was raised in a sterile, microbe-free environment to protect him from infections.
Isolation: This setup meant David could not experience direct human touch or contact, leading to severe emotional and psychological distress.
Transplant: At the age of 12, David received a bone marrow transplant from his sister.
Complications: Although the transplant itself was not rejected, David died a few months later due to a dormant virus in his sister’s blood that went undetected.
Why are microbes important in immune system development?
Living in a microbe-free environment prevents the immune system from developing properly making one highly vulnerable to pathogens once exposed to the real world.
Exposure to microbes is essential for building a strong and resilient immune system.
The community of microorganisms residing in the gastrointestinal tract.
Gut Microbiota
What are the functions of Gut Bacteria?
1) Nutrient Provision
2) Aid Digestion
3) Defense Against Pathogens
4) Intestinal Architecture
5) Neurotransmitter Production
6) Intestinal Barrier Maintenance
The gut lining that prevents bacteria and other harmful substances from translocating from the gut to the surrounding environment.
Intestinal Barrier
A condition where the intestinal barrier is compromised, allowing bacteria and toxins to pass through, leading to inflammation.
Leaky Gut
A disorder affecting the large intestine, causing symptoms like cramping, abdominal pain, bloating, gas, and diarrhea or constipation.
Irritable Bowel Syndrome (IBS)
Chronic inflammation of the digestive tract, including conditions like Crohn’s disease and ulcerative colitis.
Irritable Bowel Disease (IBD)
A persistent, mild form of inflammation that remains in the body for an extended period, often months or years. Unlike acute inflammation, which is a short-term response to injury or infection, chronic inflammation does not resolve quickly and can cause ongoing damage to tissues and organs
Chronic Low-Grade Inflammation
Also known as the microbiota-gut-brain axis, this term refers to the complex, bidirectional communication between the gut and the brain.
Gut-Brain Axis
The community of microorganisms (bacteria, viruses, fungi, etc.) living in the digestive tracts of humans and other animals.
Gut Microbiota
Research studies that observe and measure outcomes without manipulating variables.
Observational Studies
A method used to identify and compare bacteria within a given sample. It targets the 16s ribosomal RNA gene, which is present in all bacteria but has regions that vary between different species, allowing for identification.
16s rRNA Sequencing
What do we mean when we talk about the composition of the gut microbiota?
Diversity: How many different types of bacteria are there?
Abundance: How much of each type of bacteria is there?
The number of different species present in a given environment. Higher richness means more species.
Richness
This refers to how evenly the different species are represented. Higher evenness means that no single species is overly dominant.
Evenness
High richness (i.e., many different nationalities) and high evenness (i.e., each nationality well-represented).
True Diversity
What is the connection between diversity and symptom severity?
There is a negative correlation between diversity and symptom severity. Lower diversity often means worse symptoms.
The hierarchical classification of organisms. In this context, it ranges from phylum (broadest category) to genus (more specific category).
Taxonomic Rank
A type of bacteria commonly found in the intestines. It is often included in probiotics and supplements due to its health benefits, such as aiding digestion and boosting the immune system.
Bifidobacterium
A beneficial bacterium prevalent in the gut. It has anti-inflammatory properties and is involved in producing short-chain fatty acids like butyrate, which are important for gut health.
Faecalibacterium
Fatty acids produced by the fermentation of dietary fibers by gut bacteria (ex. butyrate).
SCFAs produced by gut bacteria help reduce inflammation
Short-Chain Fatty Acids (SCFAs)
A fatty acid that plays a crucial role in maintaining gut health and reducing inflammation.
Butyrate
Bacteria that can promote inflammation in the body. Increased levels of these bacteria are often associated with various health conditions, including depression.
Pro-Inflammatory Bacteria
What is altered in the microbial composition of people with depression?
Decreased Diversity: Lower richness of bacterial species.
Reduced Levels of Beneficial Bacteria
Increased Levels of Pro-Inflammatory Bacteria
Contain bifidobacterium.
These are marketed for their benefits in improving gut health and boosting the immune system.
Probiotics
A type of research that collects and critically analyzes multiple research studies or papers on a specific topic. It aims to provide a comprehensive summary of the available evidence.
Systematic Review
Observational studies that compare individuals with a specific condition (cases) to individuals without the condition (controls) to identify factors that may contribute to the condition.
Case-control Studies
A statistical technique that combines the results of multiple scientific studies to identify overall trends and draw more robust conclusions.
Meta-Analysis
A pattern or characteristic that is common across multiple psychiatric disorders, rather than being specific to one disorder.
Transdiagnostic Pattern
Can influence mood and behavior. For example, an imbalance in gut bacteria can affect mental health conditions like depression and anxiety
Gut-Brain Axis
What are the main components of the gut-brain axis?
Vagus Nerve
Neurotransmitters
Gut Microbiome
Endocrine System
Immune System
This is the largest nerve connecting the brain to the gut. It plays a crucial role in transmitting signals between the gut and the brain
Vagus Nerve
These are chemical messengers that help regulate various functions, including digestion and emotional well-being.
Examples include serotonin, dopamine, and gamma-aminobutyric acid (GABA), many of which are produced in the gut
Neurotransmitters
These microbes communicate with the brain via the vagus nerve and through the production of neurotransmitters and other chemicals.
Gut Microbiome
This system produces hormones that communicate signals related to hunger, fullness, and stress between the gut and the brain
Endocrine System
The gut-associated lymphoid tissue (GALT) is a critical part of the immune system in the gut. It helps in the immune response and also communicates with the brain
Immune System
What are the two main strategies in studying gut microbiome?
Adding something
OR
Removing something
What are the main methods in studying gut microbiome?
Germ-free studies
These involve using germ-free animal models, which are genetically modified animals raised in sterile conditions without any gut microbiota.
To understand the role of gut microbiota by observing the effects of its absence on biological mechanisms and behavior.
Removing something:
- Germ-free Studies
- Antibiotic Studies
- Bacterial Infection Studies
Adding something:
- Supplement Studies
- Faecal Microbiota Transplant (FMT) Studies
Administering antibiotics to individuals to wipe out their gut microbiota.
While useful for treating infections, it can be harmful to the microbiota.
Antibiotic Studies
Inducing a bacterial infection in the gut by removing healthy bacteria.
Provide insights into how infections impact the gut-brain axis.
Bacterial Infection Studies
Adding supplements like probiotics to the diet.
Probiotics can help restore and maintain a healthy gut microbiome.
Supplement Studies
Transplanting microbiota from one individual to another.
To observe the changes in the recipient’s biology and behavior, providing insights into the role of specific microbiota compositions.
Fecal Microbiota Transplant (FMT) Studies
Produces the stress hormone cortisol.
In affective disorders, this axis is often over-activated, leading to increased cortisol production.
Hypothalamic-Pituitary-Adrenal (HPA) Axis
An essential amino acid for serotonin production. Probiotics can increase tryptophan levels.
Tryptophan
Refers to something that affects the entire body rather than just a specific part
Systemically
Is a steroid hormone produced by the adrenal glands, located on top of the kidneys.
Cortisol
It is often referred to as the “stress hormone” because it is released in response to stress and helps regulate various functions, including metabolism, inflammation, blood pressure, and the sleep-wake cycle
Cortisol
Are small proteins that act as chemical messengers in the immune system.
They help regulate inflammation and immune responses by signaling immune cells to act against infections or other threats.
Cytokines
A protein that supports the growth, development, and maintenance of neurons. It is crucial for learning, memory, and overall brain health.
Increased BDNF levels support brain health by promoting the growth and maintenance of neurons, enhancing learning and memory.
Brain-Derived Neurotrophic Factor
A balanced state where the gut microbiota is diverse and beneficial bacteria are abundant.
Homeostasis in Microbiota
Why is it important to maintain gut health?
Keeping a healthy and diverse gut microbiota is crucial for preventing inflammation and supporting mental health.
A healthy gut-brain axis can help reduce the risk of psychiatric disorders by maintaining low levels of inflammation and stress hormones.
Healthy Gut VS Unhealthy Gut
Healthy State: In a healthy gut, beneficial bacteria maintain balance (homeostasis), the gut lining is strong, and inflammation is low. This supports good mental and physical health.
Inflamed State: In an unhealthy gut, harmful bacteria increase, causing the gut lining to leak. This leads to higher inflammation and stress hormone levels, which can negatively impact mental health.
Plays a crucial role in shaping the gut microbiota, which in turn can influence mental health.
Diet
Live microorganisms that, when consumed in adequate amounts, confer a health benefit on the host.
Probiotics
What are the components of a healthy and more varied diet?
1) Fruits and vegetables
2) Grains
3) Reduced Sugar, Salt, and Saturated Fats
4) Omega-3 Fatty Acids
Provide essential vitamins, minerals, and antioxidants.
Fruits and Vegetables
Whole grains like oats, quinoa, and brown rice.
Grains
Limiting these can help prevent negative health outcomes.
Sugar, Salt, and Saturated Fats
Found in fish, flaxseeds, and walnuts, these are beneficial for brain health.
Omega-3 Fatty Acids
Foods that are heavily processed and often contain added sugars, fats, and preservatives which are linked to an increased risk of depression.
Ultra-Processed Food
Are there super foods or magic supplements?
No single food or supplement can guarantee positive mental health. A balanced, ongoing diet is necessary.
What are the challenges of dietary interventions
1) Adherence Issues
2) Lack of Motivation or Interest
3) Comorbidity
What are the types of Microbiota-Targeted Supplements?
1) Probiotics
2) Prebiotics
3) Synbiotics
4) Psychobiotics
Food supplements containing beneficial bacteria that, when ingested in sufficient quantities, can have positive effects on our bodies.
Ex. Cheeses, sauerkraut, pickled foods, ginger
Probiotics
Non-digestible fibers found in food that promote the growth and activity of beneficial bacteria (probiotics).
Ex. Cocoa, onion, garlic, cabbage, green bananas.
Prebiotics
Supplements that combine both probiotics and prebiotics.
Synbiotics
A term coined by John Cryan and Ted Dinan, referring to supplements (probiotics, synbiotics, etc.) that, when taken in sufficient quantities, can yield positive psychiatric effects.
Psychobiotics
Probiotics that can positively impact mental health by influencing the gut-brain axis.
Psychobiotics
Types of beneficial bacteria commonly used in probiotics.
Lactobacillus and Bifidobacterium
A modern technology that allows for comprehensive analysis of genetic material, including the microbiota.
Next-Generation Sequencing
The tendency to respond to sad mood with negative thoughts.
Cognitive Reactivity
Initial research conducted in cell cultures or animal models to identify compounds with therapeutic potential.
Laboratory Studies
How is the human phase trial conducted?
Phase I:
Purpose: Determine the safety of a drug.
Participants: A small group of healthy volunteers.
Phase II:
Purpose: Study the drug’s efficacy and safety.
Participants: A larger group, generally in the hundreds.
Phase III:
Purpose: Thoroughly assess effectiveness in a more representative population.
Participants: Thousands of people.
Duration: These phases can take up to 10 years.
Ongoing research after a drug is approved and available to the public.
Post-Marketing Phase
How does the Clinical Trials pipeline look like?
1) Laboratory Studies
2) Human Phase Trials
3) Post-Marketing Phase
The ability of a compound to provide medical benefits.
Therapeutic Potential
The ability of a drug to produce the desired therapeutic effect.
Efficacy
Is there a connection between probiotics and antidepressants?
Combining probiotics with antidepressants appears more effective than using probiotics alone
A measure of the strength of the relationship between two variables.
Effect Size
A substance with no therapeutic effect used as a control in testing new drugs.
Placebo
What are the effects of probiotics on other psychiatric disorders?
MDD: Some benefit alleviating depressive episodes
Alzheimer’s: Some improvement in cognitive function, mood and anxiety
Bipolar Disorder: Reduce hospitalization and rehospitalization during manic episodes
Autism: Minor improvements in overall behavior
Schizophrenia: Potential benefits in gastrointestinal functioning and metabolic health
Involve transferring stool from a healthy donor to a recipient to restore healthy gut microorganisms.
Primarily used to treat Clostridium difficile (C. difficile) infections and some bowel diseases
Faecal Microbiota Transplant (FMT)
A bacterium that causes severe diarrhea and other intestinal issues.
Clostridium difficile (C. difficile)
What are the implications of FMT studies?
Causal Role: These studies suggest that an imbalanced microbiota can be a cause, not just a symptom, of psychiatric conditions.
Caution in Clinical Use: Care must be taken when transplanting microbiota, as it can carry the “footprint” of mental illness.
