Month: June 2020

Imagine yourself as the head of a funding agency (like the National Institute of Health) in which your job is to look at proposals for research projects and decide what projects to award funding. Based on your readings this term, discuss a research project (or projects) that you would be most excited about funding as they relate to learning more about microbial influences on human health. As part of your response, consider what are we likely to learn from the project and how that might be important in future healthcare decisions.

As the head of the funding agency NIH, I would be most excited in funding research investigating the relationship between microbes and cancer. Cancer adversely affects the lives of millions worldwide. From the project, we are most likely to learn specific DNA-damaging toxins and carcinogenic metabolites produced by microbes that may promote proliferation as well as the mechanisms of action. We are also likely to learn which microbes are associated with cancer; this may be important in future healthcare decisions as health experts can suggest how to promote a healthy microbial community with decreased diversity of cancer-associated microbes. Not only will we gain insight into the relationship between microbes and cancer, but we may gain knowledge about other important aspects of uncontrolled cell growth and proliferation. 

Part 1: Set a timer for 3 minutes and make a list of as many human non-infectious diseases that you can think of that are influenced by microorganisms. (disorders and other health conditions included)

Cancer, IBS, CD, UC, obesity, heart disease, diabetes, seborrheic dermatitis, atopic dermatitis, acne, asthma, COPD, cystic fibrosis, gingivitis, periodontitis, UTIs, allergies, MS, Parkinson’s, Alzheimer’s, rheumatoid arthritis, mood disorders, eating disorders, anxiety disorders

Part 2: Refer back to your Writing Exercise #1 that you completed the first week of class. Reflect and discuss how your responses have changed from week 1 to week 10, and what the most important topics you will take away with you once you have completed the course.

In comparison to Writing Exercise #1, my number of responses increased in Writing Exercise #10. Some diseases, disorders, and conditions that I mentioned in Writing Exercise #10 and not in Writing Exercise #1 were CD, UC, obesity, diabetes, seborrheic dermatitis, atopic dermatitis, acne, asthma, COPD, cystic fibrosis, gingivitis, periodontitis, UTIs, allergies, rheumatoid arthritis, mood disorders, eating disorders, anxiety disorders. I learned the relationship between more specific autoimmune diseases such as rheumatoid arthritis and Type I diabetes. The most important topics that I will take away from this class are the large role that microbes may play in health and disease, the importance of a diverse, pathogen-free, and dynamic microbial community as well as the various metabolic, structural, and protective functions of microbes within the body. 

In W. P. Hanage’s article, he discusses the importance of five key questions when interpreting scientific literature:

• Can experiments detect differences that matter?

Hanage discusses, through an example using microbes, that in order to detect differences that matter researchers need to be able to identify functional differences in closely related genes, genes that they may not be familiar with. This suggests that they first need to know what they are looking for. In a broader sense, researchers must be able to distinguish and define what they intend to compare, otherwise the information gathered could mean anything. 

• Does the study show causation or correlation?

Correlation does not prove causation. Hanage states that all scientists are taught this catechism. He also provides an example of a study whose authors proposed a causal relationship that fit the data clearly but did not explore other factors. One of the other factors that was not considered, which is significant in interpreting scientific literature, was the reverse causality. What is there to determine that this causal factor is not correlated, or even a bystander. 

• What is the mechanism?

Mechanisms provide detail for a hypothesis. When something is well defined, a mechanism will be present. Experiments may seek out this information to understand the true influence of what is being researched. 

• How much do experiments reflect reality?

What good is an experiment if it does not reflect what happens in the real world? First, by controlling the environment, researchers are able to look at specific interactions. Second, researchers acquire reliable data. However, this comes with a price — reliability. While the research may be valid, the reader must consider how well the experiment explains the real world. This is hard. The real world has so many confounding variables, whether influential or not, and as Hanage discusses, with respect to microbes, germ-free mice are often used. The animals and their microbiomes are adapted to a different niche than humans, so the results may not be generalizable. 

• Could anything else explain the results?

This ties in well with do experiments reflect reality. The simple answer is they do not reflect it well. Many other things may help explain the results but were controlled for in the experiment. Hanage states that it is important for a critic to ask whether other contributors to, in this case, disease are considered, compared, and reported.

Which is most helpful when discussing controversy, and why?

I believe that the most helpful question to consider when discussing controversy is the mechanism. Controversy relies on correlation, and, as Hanage explains, the use of careful experiments to determine the mechanism and biochemical activity is crucial for understanding the true causes microbial influences may have. Causation is more likely to be assumed with mechanistic evidence. A close second would be an explanation of results. Sometimes mechanisms may not be found without the adverse effects of other factors. Discussing other contributors also may facilitate explaining real-world consequences. 

Describe how microbial communities in the body could influence brain and mental health states. Then, describe how brain and mental health states could influence microbial communities in the body. In what ways might these promote health and/or disease?

The proposed mechanism of the interaction between the brain and the gut may provide key insight into the relationship between microbes and mental health. Altered microbiota composition may signal for serotonin (5-HT) release by enteroendocrine cells, cytokine release, increased gut epithelium permeability for bacterial molecules (fatty acids, GABA, serotonin precursors), and increased afferent vagal input. All of these molecules play different roles within the brain. For example, serotonin is a neurotransmitter active in constricting smooth muscle and contributing to overall wellbeing and happiness (serotonergic pathway). Mental health disorders, such as depression, are highly reliant on serotonergic pathway functioning. Cytokines, or immune system chemical messengers, facilitate the immune response. GABA is an inhibitory neurotransmitter and decreases activity in the nervous system. With regard to stress and anxiety, germ-free mice have been shown to have an exaggerated stress response which could be rescued by Bifidobacterium. Microbial communities in the body, specifically the gut, may influence the brain and mental health with respect to Autism spectrum disorder (ASD); people with ASD often have IDB or other gastrointestinal problems as they are a common comorbidity in ASD patients.

The brain and mental states may influence and alter the gut microbiome through the communication with the efferent adrenergic nerve which signals for the release of noradrenaline, which has been shown to enhance growth of bacteria. Also, the enteric nervous system comprises a largely efferent network of neurons that spread throughout the gut tissue and may be influential in cellular response to microbes and other cells. Specifically, these neurons have the ability to influence motility, secretion, and nutrient delivery which can affect microbial balance.