Month: March 2018

PROMPT: 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 to. 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.

There will likely always be two sides to getting funding for research that come into play when an agency makes its choice. First, the more obvious one, what are the potential monetary profits from any conclusions of the study? Second, what are the potential benefits, how significant are those benefits (i.e. lifesaving/changing vs very mild improvement) and how many people could potentially benefit from funding this research? Sadly, many times the first consideration will end up overshadowing the second no matter how significant. If there is no profit to be made from the results of the study, or only a small number of people the research targets, it can hard to find the appropriate funding needed. In a perfect world, no quanta of money would be considered more important than any life, and thus thinking in nontraditional manners is crucial to develop the latest and greatest treatment.

We have gone over a multitude of relations and impacts microbes have on human health, with different concepts having a varying reach of impact. If I were to propose a study that I would find to be interesting and would still be potentially highly profitable, I would look at MDROs and the drug resistances epidemic we are facing. As more and more antibiotics are becoming ineffective in treating infections, were running out of options of treatment, potentially at the cost of numerous lives. Since bacteria replicate so quickly and with a high rate of mutation, almost any time a new antibiotic is created, it will become relatively ineffective in some manner of time. Current antibiotics target various stages of bacterial replication, relying on this to make further replication ineffective and in time the bacterial colonies die, and the infection is cured. However, if a mutation occurs in a way which the antibiotic can no longer bind to, or negatively impact the replication, resistance forms.

Modern antibiotics use chemicals, either organic (i.e. in penicillin) or synthesized, to kill the bacteria causing the infection. Interestingly, nature created its own antibiotic organism long before the first animals stepped foot on land. These, are bacteriophages, or virus which infect bacterial cells. (1) The use of bacteriophages to fight infections, known as ‘Phage Therapy’ is no modern concept. It was discovered AND USED in the 1920s and 1930s, years before penicillin or sulfa antibiotics were discovered, and were the only therapy available for a short period of time. Unfortunately, when penicillin was discovered, phage therapy was put on the back burner in western medicine, and to this day is only allowed in a few regions of the world. (2) Antibiotics offered a cheap, relatively harmless cure for the infection, and our limited medical knowledge in the early-mid 20^th century it made a lot more sense to focus on killing the bacteria with cheap medication that could be manufactured easily on a large scale.

However, at the time we were unaware of the epidemic that was looming over our future. With Antibiotic resistance bacteria popping up more and more, and with increasingly tough resistance to even multiple different forms of antibiotics, it’s clear that we must look elsewhere to find future treatments. Further, antibiotics are not harm free, the increasing need for highly specialized antibiotics has caused an increased price and limitations in available amounts, and harsh side effects can often result from antibiotic us from killing more than just the targeted pathogenic bacteria. These are two of the areas where phage therapy can shine.

First, bacteriophages, like bacteria, replicate at an incredibly fast rate and are thus able to potentially counter resistance developed by pathogens through their own mutations. This means that counter resistance could develop as quickly as resistance forms in the first place. Second, since bacteriophages replicate quickly, producing them on a large scale could be relatively cheap and quick with the right equipment. Third, with the phages being viruses, they are incredibly tiny, multiple times smaller than even bacteria. That means that little space is needed to store the bacteriophages used in treatments. Finally, another promising aspect of phage therapy is the fact that bacteriophages can be incredibly specific in the cells they attack, not only being able to be limited to target a single species but even individual strains! (2)

I am not sure exactly why Phage Therapy died out after the introduction of antibiotics, rather than be used concurrently. However, we are reaching a point where our future options are limited. The number of drug-resistant organisms is increasing much quicker than newly designed antibiotics can be developed, tested and put into public use. This is a critical time in medicine, and we must look at all potential avenues to find the light at the end of the tunnel, and not place limitations on the tools we can use. I think this is one area of medicine that will bring about some incredible innovations in the near future.

 

Sources:

1. Lin D, Koskella B, Lin H. 2017. Phage therapy: An alternative to antibiotics in the age of multi-drug resistance. World J Gastrointest Pharmacol Ther. 8(3):162.
2. Wittebole X, De Roock S, Opal S. 2013. A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens. Virulence. 5(1):226-235.

Prompt 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.

-Depression, anxiety, other assorted mental health-related disorders Additional, other cognitive health issues such as Alzheimer’s,

-Obesity, Atherosclerosis, and Diabetes

-G.E.R.D./Stomach Ulcers/IBDs

-Gastric Cancer

-Immune insufficiency

-Asthma

Prompt 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.

I remember when I first read the prompt for this assignment. I remember the difficulty of thinking about non-infectious diseases in a way associated with microbes. To me, infectious disease and microbes originally had seemed to go exclusively hand-in-hand. I had a such a strong mental schema of microbes causing disease, that it was difficult to conceptualize microbial influence on non-infectious disease.  However, through taking this course, not only have I gained a more expansive knowledge base regarding the Human Health-Microbe connection, but I have also learned new ways to think about their INDIRECT connections.  Additionally, an important take away I got from this class is the bidirectionality causations of these relationships. Just as microbes can cause/influence non-infectious diseases, but the diseases themselves can influence the microbes in turn.

The key message to me is that human health is incredibly complex. They say, ‘The more you know, the more you realize how much you don’t know. Another quote I often hear is told to medical students is “50% of the material we will teach you will be wrong by the time you graduate. The problem is, we don’t know which 50%.” I believe this statement, while likely more of an approximation than an exact specific, holds a lot of merits, and it reminds us to always maintain an appreciable level of skepticism when you learn something new.

More than likely, much of the incorrect information that is taught was never meant to be intentionally deceitful. However, we live in a time of mass media, easy access to (not always credible) information and viral stories, where eye-catching headlines are often incentivized over accuracy. Even if future information comes out debunking the latest media health craze, the damage can still be perpetuated by fears of conspiracy, or even just simply not knowing better. The MMR Vaccine and Autism is the classic example of this.

Originally titled ‘Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children’ the 1998 study published by Andrew Wakefield claimed a connection between receiving the MMR Vaccine and the development of autism in children. While any non-medically educated person would see the article title and not give it a second glance, the media saw a potentially big-selling story and grabbed it and ran. Newspapers quickly became flooded with headlines like “MMR: THE TRUTH” in bold red letters, claiming that the vaccine causes autism. The hysteria created from the study done in 1998 stuck in the minds of consumers, and there are still large anti-vaccine movements today, 20 years later. It didn’t matter that literally HUNDREDS of other studies showing the study to be false, the article being fully retracted from the journal it was published in, Andrew Wakefield himself confessing to foul play and ultimately losing his medical license, a quick google search to this day will still likely be saturated with claims that the vaccine causes autism.

For me, the most important concepts I will take away from this class are to not only maintain an appropriate and professional level of skepticism about new information but to make sure to keep my mind open to think about relationships and connections that may not always be obvious. By thinking outside the box, we may stumble upon life-changing ideas never considered before or lead to new theories/studies to expand on what is found. The human body is indeed highly complex and specialized, but we mustn’t forget that it is still just one body, working, not always in an obvious way, to sustain life in a single being.

PROMPT:  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?

One thing that has become increasingly studied and researched is the relation with the gut microbiome and mental health. Coincidentally, that is the exact topic of my final essay paper. Even though this is a topic which has interested me for a little while now, and I have done some independent reading on the subject, the process of gathering info for my paper has brought many new theories to my attention. Results from studies I have read have provided information about new ways of how the gut microbiota affects the brain and mental health.

The connection between the gut microbiome and the brain is referred to as the ‘Microbiome-gut-brain-axis’ and involves the bidirectional relation between the Central Nervous System, the Enteric Nervous System, and the gastrointestinal tract. (1) The Central Nervous System encompasses the brain and spinal cord and is well known. The Enteric Nervous system involves approximately 500 million nerve cells which can control all the normal functions of digestion even if separated from the brain. (2)  These two nervous systems connect via the Vagus nerve, and thus a direct line is made connecting the brain and gut.

With respect to the gut affecting the brain/mental health, one of the most fascinating facts relates to the percentage of all endogenous neurotransmitters and neuroactive chemicals that are made in the gut. 5-hydroxytryptamine (5-HT), more commonly referred to as ‘serotonin; plays a large role in our mental health. Imbalances and low concentrations of serotonin are believed to cause a wide array of mental disorders, and thus serotonergic drugs are often the most widely used treatment. When one thinks about neurotransmitters, and chemical imbalances of the brain, its easy to assume that all or a significant majority of neurotransmitters are both made and stored solely in the brain. New studies show that this couldn’t be further from the truth. Approximately 90% of ALL endogenous serotonin is synthesized in the gut! (3) A study using mice found that the presents of some microbes regulate the hosts serotonin levels, and having these microbes led to significantly higher serotonin levels than in mice birthed and raised germ free. (3) Since the microbes are able to alter the levels of endogenous serotonin, and serotonin plays a large role in mental health, the microbes have a direct influence on the mental health of their host!

As mentioned when describing the Microbiome-gut-brain-axis as a ‘bidirectional’ relation, the connection and influences go both ways. Mental health can have an impact on the make up of gut microbiomes in a few ways. Chronic stress and Anxiety due to various mental disorders can lead to an increase in stomach acid production. This changes the acidity of the stomach and intestines and impacts which microbes can successfully colonize the area. Depression can lead to a lack of personal hygiene, and poor dietary habits, which both can have an impact on an individual’s microbiota. Bulimia Nervosa, an eating disorder characterized by binge eating followed by forced self-induced emesis to prevent the absorption of the caloric contents of the food, can introduce microbes to new areas of the digestive tract as they are physically relocated during episodes of vomiting.

The microbiome of our gut, the enteric nervous system, and the central nervous system are connected in ways never thought of or studied before. Its amazing learning how two incredibly different specialized regions of the body can have such a collaborative impact on each other. As technology advances and new studies are done, its almost certain that new connections between the organs never thought of before will be discovered, and new ways of indirectly treating diseases and illness affecting different organs will be designed and target the connected organs.

 

1. Mayer E, Tillisch K, Gupta A. 2015. Gut/brain axis and the microbiota. Journal of Clinical Investigation 125:926-938.
2. https://www.youtube.com/watch?v=_PLD5RLLvfQ
3. Yano J, Yu K, Donaldson G, Shastri G, Ann P, Ma L, Nagler C, Ismagilov R, Mazmanian S, Hsiao E. 2015. Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis. Cell 161:264-276.

PROMPT: 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?

It was an interesting process for sure. It was difficult to critique someone else’s writing effectively without feeling rude. It was very informative, however. I feel that it helped me learn a few things to look out for as I revise my own final essay. First, I need to make sure that my language is appropriate for the audience. One way I can do this is by having someone who has no biology background read through my essay and highlight any areas they either didn’t understand or needed to really read in depth and use context to understand. If there are things they highlighted that I feel is still appropriate, I don’t have to change it, but it will still provide a useful source of information to give me an idea of how appropriate my essay is in general. Second, I am going to make sure I really emphasize the importance of thesis, and why it matters to the reader. It’s easy to just start writing when you have an idea. It’s easy to get fixated on making a solid argument to back up your claims, and completely forget to explain exactly why my thesis is important in the first place. One other thing I am going to really make sure to keep in mind as I revise my essay is making sure that I provide any background info needed to explain why it’s important, and to define exactly what I am discussing. It’s easy to assume other people will know your own definition of subjective terminology (for example, over-weight/obese can mean completely different things to different people. My classification may not match exactly what other people think.) Also, if there is a set objective number/quantity, I will be sure to provide it and explain it so I’m sure the reader and myself are on the same page.

The peer-review process was really beneficial in regard to improving my own essay. It helped highlight some things for myself to make sure to check and gave me a good idea about how to make my argument as strong as possible. It is a little scary having someone else read my paper though! Even if their response is anonymous, I still know that another human is critiquing my work, and it’s a little frightening! I look forward to finding out their thoughts and incorporating their feedback into my work though. I am sure it will help me write a stronger essay, and give some ideas where I could expand on, or where I spent too much time talking about.

PROMPT: 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.

Peer review provides a proof-read and a check to make sure claims being made are properly backed up with evidence. By having a qualified person review your article, it increases the credibility because they don’t carry the same beliefs, and if they agree with your points and evidence after reading your article it provides additional credibility. It also allows errors to be corrected, and suggestions for small changes. When writing an article, its easy to get caught up in your argument and lose yourself to small internal, unconscious biases. You make believe in a point you make and don’t feel the need for specific evidence to back it up. However, by having a fresh set of eyes look over your article, these unconscious biases can better be avoided, and any additional evidence necessary can be added. Another advantage to having a peer review your article is that they may be able to provide suggestions about additional sources, evidence, or areas to expand on which can lead to a stronger argument. They may also give ideas about additional potential explanations, or where to look for beneficial information to add to your article. However, having a peer review your article can have its disadvantages. First, it could cause you to question the strength of your claims/thesis to an amount not necessary to ensure an accurate paper. This could potentially cause someone to scrap their entire proposal/article for poor reasons because of self-doubt. Additionally, they could provide inaccurate input or additional biases that can take away from the strength of your argument. So it is wise to take any advice with a grain of salt and to double-check any claims they make and look into their sources to ensure that the information is up-to-date and accurate.