BHS 323 Blog - Zach Herron

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. 

Reflect on the peer-review process with you as the reviewer. How did it feel to read and critique someone else’s writing? What did you learn that you can apply to your own writing as you revise your final essay?

At first, as a reviewer, I felt harsh. I felt that my feedback was constantly negative. However, looking back on the process, and thinking about being a reviewer and a reviewee, I believe this process is very beneficial for both parties. As a reviewer, you find statements, ideas, and critiques that are useful for your own paper. Specifically, I noticed that many ideas were not tied back to the thesis with clarity; they had tied back “accidentally”. I learned that I need to be concise in connecting my points with my thesis which will allow the reader to follow along with more fluency. On the other hand, as a reviewee, you allow others to be critical of your work when you yourself may be reluctant to do so. Overall, this process will supplement my final product greatly.

Describe the process of peer review to someone who does not frequently read scientific articles. In your response, consider the pros and cons of peer review and how that might impact the credibility of the results that come from that scientific article.

The peer review and the scientific writing process consists of multiple steps. First, the author, or authors, develops the manuscript. Next, the authors submit the article to a journal of their selection, determined by connections, subject matter, and the impact factor, or how prestigious the journal is. Next, the manuscript is screened by the journal editor and the editor works with the journal publisher to discuss the direction of the journal and if it “fits” or is rejected. If the article is not rejected, the editor then chooses two to four reviewers who are established, published researchers in the field of work, and sends them the article. The reviewers send their summary of thoughts and responses to the editor. Next, the editor assesses the reviews and decides if the manuscript is rejected, needs to be revised by the authors, or is accepted with no revisions required. The positives of the peer review process are the anonymity of the reviewers to the authors and that the reviewers are experts in the field. The downsides include that there is no anonymity of the author to the reviewers, which could impose bias, as well as the connections that the authors may have with the journal, which can give an unfair advantage for certain research to be published. 

List and describe as many changes in human behaviors as you can think of that contribute to decreased exposure to microbes.

• Nutritional choices
  • Lower dairy product intake
  • Lower fermented product intake
  • Less natural pre- and probiotic intake
• Supplementary choices
  • Little or no pre- and probiotic use
• Bacterial infection
  • Increased antibiotic use
• Pregnancy and infancy practices/changes
  • Immunological changes of the mother may impact immune system development of the child
  • Mode of delivery (C-section)
  • Mode of feeding (formula-fed)
  • Maternal milk bacterial composition
    • Shaped by an infant’s oral bacteria composition and maternal weight
  • Maternal antibiotic treatment during pregnancy and lactation
• Decreased interactions
  • Low exposure to dirt/”germs”
  • No or few pets
  • Decreased siblings
  • Homeschooling
  • No daycare
• Living circumstance
  • Urban rather than rural
  • Home sanitation level

The most interesting thing I have learned so far in regard to microbes and human health is the amount of relation they have to each other. Throughout my courses here at the university, I have learned a lot about molecular processes, biochemistry, and anatomy and physiology of both the human body and microbes, but the classes have failed to discuss the adverse relationship between microbes and the human body. I can honestly say that the amount of correlation between disease states and dysbiosis is astounding. What I am most interested in and would like to learn more about are the mechanisms of action of the role of microbes as both beneficial and harmful.

The role of microbes is adverse in that their health influences. They include metabolic functions, structural functions and protective functions. Some of these aspects that we have briefly discussed are the control of epithelial cell differentiation as well as apical tightening, fermentation of nondigestible foods, and protection against pathogens. This is intriguing to me and I am interested to know more about the mechanisms behind these functions. In fact, it would be even more beneficial to know how these functions may vary by site-specific microbial community. I am taking Principles of Immunology this summer term and hope to learn more of the interaction of the human body and microorganisms.

What I might do to begin to prepare for the final paper, based on the free-write exercises, will most likely be to free write first. I will try to write everything down about the topic that I can come up with, then take to the notes to refine ideas and finally to back them up with sources. I know I will not be able to come up with all the information I will need to develop the paper, so after this, I will most likely browse the texts we have read for more information and find useful articles through a search engine. 

List and describe potential factors that the mother or the infant could be exposed to that could influence the colonization of the microbial community in the newborn infant (in positive or negative ways).

• Immunological changes mother goes through may impact immune system development of the child and alter the types of microbes that will be able to colonize
• Mode of delivery — vaginal birth where infants initial microbial communities reflect mother’s vaginal community and C-section where infants’ initial microbial communities reflect mother’s skin community
• Pre-pregnancy BMI — correlated to neonatal gut microbiota composition in vaginally delivery
• Maternal weight — major influencing factor in shaping milk bacterial composition
• Maternal antibiotic treatment during pregnancy or lactation — may reduce antiviral immune responses in infants
• Prebiotic treatment during pregnancy and lactation — may alter infant cecal microbiome as well as prevent adiposity
• Bacterial infections — may be correlated with pregnancy complications
• Maternal bacteria may be able to enter the GI tract of the fetus
• Mode of feeding (breastmilk vs. formula then solid foods) — food composition and nutrients provided for microbes

All potential factors, except for bacterial infections, may provide both positive and negative consequences. 

Describe your personal philosophy about how and when you have taken, or would take, antibiotics. What experiences or prior knowledge do you have that shaped that personal philosophy?

I have been prescribed antibiotics multiple times when I was younger for recurring ear infections, and once in my first year of college when I had developed bronchitis. I had a persistent cough for nearly a month, minimal mucus production, and some wheezing and shortness of breath and when I was prescribed antibiotics for bronchitis, my only philosophy was to listen to the doctor because they knew what they were doing. My prior knowledge about bacteria and antibiotics was minimal as I had taken a few biology classes in high school and did not feel that I needed to research much into treatment. While I did some research on symptoms and figured I had acute bronchitis, I still felt it was best to just see a professional. With my current knowledge, I would have been more reluctant to take antibiotics because most cases of bronchitis are viral and there is always the risk of bacterial resistance; I would not want to take antibiotics if they are not necessary. I would have like to know the doctor’s reasoning for why they prescribed antibiotics in this situation.