Microbiomes Mini-Exam 2 Study Guidance

Study Guide - Smart Notes

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Q1. Define biological (taxonomic and functional) diversity and explain why it is an important metric in microbiome studies.

Background

Topic: Microbial Diversity in Microbiome Research

This question tests your understanding of the concepts of taxonomic and functional diversity, and their significance in analyzing microbiome data.

Key Terms and Concepts:

Taxonomic Diversity: Refers to the variety and abundance of different microbial taxa (such as species, genera, or phyla) present in a community.
Functional Diversity: Refers to the range of different biological functions or metabolic capabilities present in a microbial community, regardless of which taxa perform them.
Alpha Diversity: Diversity within a single sample or environment.
Beta Diversity: Diversity between different samples or environments.

Step-by-Step Guidance

Start by defining taxonomic diversity in your own words, focusing on the variety of microbial species or groups present in a sample.
Next, define functional diversity, emphasizing the different metabolic or biochemical functions that the microbiome can perform.
Explain why measuring both types of diversity is important in microbiome studies (e.g., understanding ecosystem stability, resilience, or disease associations).
Consider examples of how changes in diversity might impact host health or ecosystem function.

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Q2. Given a movie from class that depicted the changing human infant microbiome, explain the components of the moving plot and how the plot data were obtained.

Background

Topic: Visualization and Data Collection in Microbiome Studies

This question assesses your ability to interpret dynamic data visualizations and understand how microbiome data are collected and represented.

Key Terms and Concepts:

Longitudinal Study: Sampling the same subjects over time to observe changes.
Stacked Bar Plot: A common way to show relative abundances of taxa over time.
Sequencing Data: Data obtained from sequencing microbial DNA (e.g., 16S rRNA gene sequencing).

Step-by-Step Guidance

Identify the main components of the plot (e.g., x-axis = time, y-axis = relative abundance, colors = different taxa).
Describe how the data for the plot were likely obtained (e.g., collecting stool samples, extracting DNA, sequencing, and analyzing taxonomic composition).
Explain what the movement or changes in the plot represent (e.g., shifts in dominant taxa as the infant ages).
Discuss why such visualizations are useful for understanding microbiome development.

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Q3. Comparing datasets from the HMP1, interpret body site differences in taxonomic composition versus function.

Background

Topic: Human Microbiome Project (HMP1) Data Interpretation

This question tests your ability to analyze and interpret differences in microbial communities across body sites, considering both taxonomic and functional perspectives.

Key Terms and Concepts:

Taxonomic Composition: The specific microbial taxa present at each body site.
Functional Redundancy: Different taxa may perform similar functions.
Metagenomics: Sequencing all genetic material to assess both taxonomy and function.

Step-by-Step Guidance

Review the types of body sites sampled in HMP1 (e.g., gut, skin, oral cavity, vagina).
Describe how taxonomic composition can differ greatly between sites (e.g., skin vs. gut).
Explain how functional profiles may be more similar across sites, even if the taxa differ, due to functional redundancy.
Consider why both types of data are important for understanding microbiome roles in health.

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Q4. Comparing datasets shown in class from studies of Amerindians and Hadza peoples, interpret plots that show microbiome differences.

Background

Topic: Comparative Microbiome Analysis Across Populations

This question evaluates your ability to interpret comparative plots and understand how lifestyle, diet, and environment influence the microbiome.

Key Terms and Concepts:

Principal Coordinates Analysis (PCoA): A method to visualize differences between microbial communities.
Alpha/Beta Diversity: Measures of within- and between-sample diversity.
Dietary Influence: How traditional vs. Western diets affect microbiome composition.

Step-by-Step Guidance

Identify the axes and groupings in the plots (e.g., clusters by population).
Describe the main differences observed between Amerindian and Hadza microbiomes (e.g., higher diversity, presence of specific taxa).
Relate these differences to lifestyle factors such as diet, environment, and antibiotic exposure.
Discuss the implications for health and microbiome research.

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Q5. Match up the most commonly used microbiome sequencing strategies with the molecule type that is sequenced and the types of information obtained.

Background

Topic: Microbiome Sequencing Methods

This question tests your knowledge of different sequencing approaches and what each reveals about the microbiome.

Key Terms and Concepts:

16S rRNA Gene Sequencing: Targets the 16S ribosomal RNA gene to identify bacteria and archaea.
Metagenomic Shotgun Sequencing: Sequences all DNA in a sample, providing both taxonomic and functional information.
Metatranscriptomics: Sequences RNA to study gene expression in the microbiome.

Step-by-Step Guidance

List the main sequencing strategies (e.g., 16S rRNA, shotgun metagenomics, metatranscriptomics).
For each, specify the molecule type sequenced (DNA or RNA).
Describe the type of information each method provides (e.g., taxonomic identification, functional potential, gene expression).
Consider the strengths and limitations of each approach.

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Q6. Identify microbiome-based treatments discussed thus far that can cure certain diseases.

Background

Topic: Microbiome-Based Therapeutics

This question assesses your understanding of how manipulating the microbiome can be used to treat diseases.

Key Terms and Concepts:

Fecal Microbiota Transplantation (FMT): Transferring stool from a healthy donor to a patient to restore microbiome balance.
Probiotics: Live microorganisms administered to confer a health benefit.
Prebiotics: Substrates that promote the growth of beneficial microbes.

Step-by-Step Guidance

Recall examples of diseases where microbiome-based treatments have been effective (e.g., recurrent Clostridioides difficile infection).
Describe the treatment method (e.g., FMT, probiotics) and how it works.
Explain the evidence supporting its use as a cure or therapy.
Consider limitations or risks associated with these treatments.

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Q7. Recognize the sources and effects of important short-chain fatty acids associated with microbiomes and dysbiosis-associated diseases.

Background

Topic: Microbial Metabolites and Host Health

This question tests your knowledge of short-chain fatty acids (SCFAs), their microbial origins, and their roles in health and disease.

Key Terms and Concepts:

Short-Chain Fatty Acids (SCFAs): Metabolites such as acetate, propionate, and butyrate produced by microbial fermentation of dietary fibers.
Dysbiosis: Disruption of the normal microbiome balance, often linked to disease.
Gut Health: SCFAs play roles in maintaining gut barrier function and modulating inflammation.

Step-by-Step Guidance

List the main SCFAs produced by gut microbes and their dietary sources (e.g., fiber fermentation).
Describe the beneficial effects of SCFAs on host physiology (e.g., anti-inflammatory effects, energy source for colonocytes).
Explain how dysbiosis can alter SCFA production and contribute to disease.
Provide examples of diseases associated with altered SCFA levels.

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Q8. Describe the mechanistic links between microbiomes and cancers.

Background

Topic: Microbiome and Cancer Mechanisms

This question evaluates your understanding of how the microbiome can influence cancer development and progression.

Key Terms and Concepts:

Carcinogenesis: The process by which normal cells become cancerous.
Microbial Metabolites: Some can promote or inhibit cancer (e.g., SCFAs, secondary bile acids).
Immune Modulation: Microbes can influence immune responses relevant to cancer.

Step-by-Step Guidance

Identify ways in which the microbiome can contribute to or protect against cancer (e.g., production of carcinogenic compounds, modulation of inflammation).
Describe specific mechanisms (e.g., DNA damage, immune suppression, altered metabolism).
Provide examples of cancers linked to microbiome changes (e.g., colorectal cancer).
Discuss how understanding these links can inform prevention or treatment strategies.

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Q9. Based on graphs shown in class, compare alternative explanations for differences in skin microbiomes leading to acne based on new data on Cutibacterium phylotypes versus previous data on C. acnes (P. acnes) bacteriophage.

Background

Topic: Skin Microbiome and Acne Pathogenesis

This question tests your ability to interpret data and compare hypotheses about the role of microbes and phages in acne.

Key Terms and Concepts:

Cutibacterium (Propionibacterium) acnes: A common skin bacterium implicated in acne.
Phylotypes: Genetically distinct strains or groups within a species.
Bacteriophage: Viruses that infect bacteria, potentially influencing bacterial populations.

Step-by-Step Guidance

Summarize the new findings regarding Cutibacterium phylotypes and their association with acne.
Contrast these findings with earlier hypotheses focusing on bacteriophage involvement.
Discuss how the data support or refute each explanation.
Consider the implications for acne treatment or prevention.

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Q10. Describe the important information that we can gain from studies of monozygotic and dizygotic twin microbiomes.

Background

Topic: Twin Studies in Microbiome Research

This question assesses your understanding of how twin studies help disentangle genetic and environmental influences on the microbiome.

Key Terms and Concepts:

Monozygotic Twins: Identical twins sharing nearly all their genes.
Dizygotic Twins: Fraternal twins sharing about half their genes.
Heritability: The proportion of variation in a trait attributable to genetic factors.

Step-by-Step Guidance

Explain why comparing monozygotic and dizygotic twins is useful for studying the microbiome.
Describe what similarities and differences in their microbiomes can reveal about genetic vs. environmental influences.
Discuss examples of traits or taxa with high or low heritability.
Consider limitations of twin studies in microbiome research.

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Q11. What are the major processes that regulate microbe-to-brain communication in the gut-brain-axis?

Background

Topic: Gut-Brain Axis

This question tests your knowledge of the mechanisms by which the gut microbiome can influence brain function and behavior.

Key Terms and Concepts:

Gut-Brain Axis: The bidirectional communication network between the gut microbiota and the central nervous system.
Neural Pathways: Vagus nerve signaling.
Immune Pathways: Cytokine production and inflammation.
Metabolic Pathways: Microbial metabolites (e.g., SCFAs, neurotransmitter precursors).

Step-by-Step Guidance

List the main communication routes (neural, immune, metabolic).
Describe how each pathway allows microbes to influence the brain (e.g., vagus nerve stimulation, cytokine signaling, production of neuroactive compounds).
Provide examples of specific microbial metabolites or signals involved.
Discuss the relevance to health and disease (e.g., mood disorders, neurodegeneration).

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Q12. What does the “Hygiene Hypothesis” propose to explain increased incidence of various diseases in urbanized/developed societies?

Background

Topic: Hygiene Hypothesis and Disease Incidence

This question evaluates your understanding of the hygiene hypothesis and its implications for immune-related diseases.

Key Terms and Concepts:

Hygiene Hypothesis: The idea that reduced exposure to microbes in early life leads to increased susceptibility to allergies and autoimmune diseases.
Immune System Development: Importance of microbial exposure for proper immune regulation.
Urbanization: Associated with cleaner environments and altered microbiome exposure.

Step-by-Step Guidance

State the main premise of the hygiene hypothesis.
Explain how reduced microbial exposure can affect immune system development.
Discuss examples of diseases with increased incidence in developed societies (e.g., allergies, asthma, autoimmune diseases).
Consider alternative explanations or supporting evidence.

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Q13. What are the underlying molecular mechanisms in immune dysregulation driven by the microbiome that lead to allergies and autoimmune diseases?

Background

Topic: Microbiome and Immune Dysregulation

This question tests your understanding of how changes in the microbiome can disrupt immune tolerance and promote disease.

Key Terms and Concepts:

Immune Tolerance: The ability of the immune system to avoid attacking self or harmless antigens.
Regulatory T Cells (Tregs): Immune cells that help maintain tolerance.
Microbial Metabolites: Such as SCFAs, which can modulate immune responses.

Step-by-Step Guidance

Describe how a healthy microbiome supports immune tolerance (e.g., induction of Tregs).
Explain how dysbiosis can lead to loss of tolerance and increased inflammation.
Discuss specific molecular pathways or signals involved (e.g., SCFA signaling, cytokine production).
Provide examples of resulting diseases (e.g., allergies, type 1 diabetes).

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Q14. Based on the mini-presentation in class that focused on prediction of breast cancer using the blood microbiome, describe the major differences in microbes and identify the type of sample or tissue that was sequenced.

Background

Topic: Blood Microbiome and Cancer Prediction

This question assesses your ability to recall and interpret findings from a specific study on the blood microbiome and its association with breast cancer.

Key Terms and Concepts:

Blood Microbiome: Microbial DNA detected in blood samples.
Biomarkers: Microbial signatures that may predict disease.
Sequencing Sample Type: Identifying whether plasma, serum, or whole blood was analyzed.

Step-by-Step Guidance

Recall the main findings regarding differences in microbial taxa between breast cancer patients and controls.
Identify the type of blood sample that was sequenced in the study.
Discuss how these microbial differences could be used for disease prediction.
Consider limitations or challenges in using blood microbiome data.

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Q15. Based on the mini-presentation in class that focused on metagenomics of the gut microbiome in Parkinson’s disease, explain the meaning of the dots in the species network and the major conclusions based on the red and blue network clusters.

Background

Topic: Network Analysis in Microbiome Studies

This question tests your ability to interpret network plots and understand their implications for disease-associated microbiome changes.

Key Terms and Concepts:

Species Network: A graphical representation where nodes (dots) are microbial species and edges represent associations.
Network Clusters: Groups of species that are more closely associated with each other.
Metagenomics: Sequencing all microbial DNA to assess community structure and function.

Step-by-Step Guidance

Explain what each dot in the network represents (i.e., a microbial species).
Describe what the red and blue clusters indicate (e.g., groups of species associated with disease or health).
Summarize the main conclusions drawn from the network analysis regarding Parkinson’s disease.
Discuss the potential implications for understanding disease mechanisms or identifying biomarkers.

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Bonus Question: History Game – Focused on 2 Important Events of Your Choice.

Background

Topic: History of Microbiome Research

This question allows you to demonstrate your knowledge of key historical events in microbiome or microbiology research.

Key Terms and Concepts:

Landmark Discoveries: Such as the invention of the microscope, discovery of antibiotics, or the launch of the Human Microbiome Project.
Impact on Science: How these events shaped our understanding of microbes.

Step-by-Step Guidance

Choose two significant events in microbiome or microbiology history.
Briefly describe each event and its importance.
Explain how each event contributed to advances in microbiome research or public health.
Consider the broader impact on science or society.

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Graduate Students Only: Compare two different human diseases with a microbiome component and (1) first explain how microbial taxa or microbiome functions are similar and different in the disease dysbiosis, and (2) describe a very simple experiment for one of these diseases that would provide strong evidence of causation (either the microbiome dysbiosis causing the disease or the disease causing the microbiome dysbiosis).

Background

Topic: Comparative Microbiome Dysbiosis and Experimental Design

This question tests your ability to compare microbiome changes across diseases and design experiments to test causality.

Key Terms and Concepts:

Dysbiosis: Disruption of the normal microbiome associated with disease.
Microbial Taxa: Specific groups of microbes present or absent in disease states.
Germ-Free Mice: Animal models used to test causality by transferring microbiomes.

Step-by-Step Guidance

Choose two diseases with known microbiome involvement (e.g., inflammatory bowel disease and obesity).
Compare and contrast the microbial taxa or functions altered in each disease.
Design a simple experiment (e.g., fecal transplant into germ-free mice) to test causation for one disease.
Explain what results would support causality in either direction.