Microorganisms and Human Health

I may be biased due to the topic I chose for my final review essay, but I would love to be able to allocate funding for research dedicated to discovering the connection between our microbial populations and brain-related disorders such as Alzheimer’s disease. The amount of people affected by incurable neuro-degenerative disorders is astronomical, with future prospects not looking much better. Delving into the research regarding the pathogen hypothesis, it revealed numerous proof of concept studies that necessitate funding for the next level of research. With the current line of thinking (amyloid cascade hypothesis) bringing no successful treatments to fruition, I believe it is definitely time to broaden our horizons with a new perspective that considers microbes as the possible catalyst and route to treatment. If nothing else, it would certainly give us the opportunity to further understand how microbes could influence the human brain, and vice versa, as there are numerous other disorders that still require answers (e.g., Parkinson’s, Huntington’s, depression, anxiety, etc.).

Non-infectious, microbial-related diseases I can name: asthma, various allergies, some cancers (e.g., gastric cancer), an array of gastrointestinal disorders (e.g., IBD and CD), brain/mental disturbances (e.g., depression, anxiety, Alzheimer’s disease), immunodeficiency diseases (due to lack of proper immune system development in relation to factors such as C-section births).

Looking back at my first post, what I know now about the topic far outweighs what I came into the course with. I could barely name any examples that the writing exercise called for, and I was not aware that microbes and non-infectious diseases were even associated with each other. Having now experienced the course, it’s pretty crazy that not so long ago I was so uninformed about the incredible role microbes can play in our bodies. Learning that this topic has gained such attention recently, even being deemed our “hidden metabolic organ,” makes me wonder how I have gone so long knowing so little. While my BHS major brought me to this course, it is only one of several options I could choose from in a required field.

We read articles that asked us to broaden our horizons and consider the significance of microbes dwelling in our gut, as well as ones that appeal to our analytical nature; asking us to remain cautious and pragmatic before jumping to any conclusions too wild. I think I will take both sides of the argument with me when I leave this course, as they both deserve a place in the reader’s toolbox when encountering new scientific literature and concepts.

• Can experiments detect differences that matter?
  • Many experiments still rely on outdated techniques or standards that fail to meet up to the level of detail and accuracy required by the public and researchers of this era. In that, experiments that aren’t modernly designed might reach conclusions that have neglected important details regarding the subject matter. Specifically, results could lend to generalizations about a certain phyla of bacteria, wherein the multitude of strains it encompasses actually does not meet conclusions made by the researchers.

• Does the study show causation or correlation?
  • Though the two relational classifications are widely acknowledged as important to distinguish between, it can often be a difficult task. Categorizing two variables as having a causal link when they are merely just victims to same-place-at-the-same-time circumstances would be a significant mislabelling that could inspire additional unnecessary research.

• What is the mechanism?
  • It is important to define the process by which the science in question actually works. To outline and understand the cause and effect being published in the study/research will eliminate some mystery as to if the two variables are actually related in a causal way. Determining each step of the mechanism from beginning to end will validate the conclusions reached by the study, rather than simply stating two things are related due to their mutual presence.

• How much do experiments reflect reality?
  • While significant and groundbreaking discoveries can be made during research projects/studies, it is not always clear if the given results/findings hold the same significance when applied to human life. For example, most experiments use specific animals to reach their conclusions, but it must be taken into account that this does not efficiently mirror an experiment carried out on humans. It must be acknowledged in the work and the differences should be explained to better keep the data in perspective.

• Could anything else explain the results?
  • Similar to the question of cause or correlation, an audience should ask if the circumstances hold any variables that could be blamed for the ending data. If there are other influential things present (e.g., environmental, etc.) then it is not a fair assessment or true discovery.

 

Since the substantial, recent increase in attention towards the human gut microbiome, ample amounts of research has been put forth in pursuance of fully understanding the  complex relationship between our metabolic processes and the commensal bacteria dwelling in the gastrointestinal tract. In realizing the many regulatory roles our microflora play in our most significant bodily mechanisms. As more information has accrued, researchers have turned their attention to the possibility that our hidden metabolic organ could influence our most protected organ: the brain.

Through the newly recognized microbiota-gut-brain axis, our microbes have established mechanisms by which they can exert their influence over the brain from their long distance domain. Having shown the ability to secrete numerous chemicals, researchers have further identified that a portion of those produced can be used to communicate with the brain via blood or neurons. In regards to the latter, the tenth cranial nerve, known as the vagus nerve, is the only cranial nerve to leave the brain and penetrate the diaphragm. This gives our microbes a direct line to our nervous system, facilitating action potentials via neurotransmitter release that can show direct consequence to emotions controlled by the central nervous system (1, 2).

A few of the chemicals released by our microbial communities that can regulate our mood (and the disorders caused by its alterations) are serotonin, dopamine, and gamma-aminobutyric acid (a.k.a. GABA). Differing the concentrations of these chemicals can control appetite-related signals, changing one’s perception of fullness and digestion. Manipulation of these chemicals can also contribute to the development of a variety of intestinal disorders that show strong correlation to depression and anxiety, as well as other complex mental disturbances, often treated by medications that oppose the effects relayed by the bacteria (2).

Communication between the gut and the brain is not limited to one direction, but is in fact a bidirectional relationship. Mental status generated by the structures and chemicals within the brain can also have an effects on the strains of bacteria that constitute our gut microbiome.  In particular, studies have been dedicated to showing how stress can impact microbe populations. Resulting alterations to those present have yielded lowered immune systems (a system that microbes contribute to), decreased protection from gastrointestinal diseases, etc.

In both directions, the relationship can be beneficial or harmful. Detrimental diseases of the psyche can lend to intestinal consequences or be caused by the bacteria there. On the same note, a strong microbiome can help improve mental status as well.

 

(1) Mayer EA, et al. 2014. Gut Microbes and the Brain: Paradigm Shift in Neuroscience. The Journal of Neuroscience, 34(46): 15490-15496

(2) Smith PA. 2015. Can the Bacteria in Your Gut Explain Your Mood? New York Times Magazine, https://www.nytimes.com/2015/06/28/magazine/can-the-bacteria-in-your-gut-explain-your-mood.html

I’ve always known that I am hypercritical or my own writing style and that I find it hard to half-ass large writing assignments like the one assigned to us. This definitely confirmed that I am just as hard on other writers as well.

To begin with, I had a hard time giving much of a review to the first paper at all, because the entirety of the draft was two vague paragraphs and an equally vague outline for the remainder, and a grand total of 3 references. Many of the questions weren’t applicable and I found myself wondering if I would lose points as well for not having much to say about this largely incomplete paper.

The second paper, however, I had to hold myself back from tearing into bits. I tried to be as gentle as I possibly could while critiquing this piece, because it felt rude to come in as an outsider and tell a stranger how I felt about their writing. Except this piece was truly appalling. Despite it being anonymous, the author still included their name on the piece and based of the ethnic origins, I assumed English was their second language so I tried not to be overly critical of the grammar — not much they can do about that. However, the paper felt like I was reading someone’s stream of consciousness. Many topics discussed in class were dumped into the paper and I just wanted to shout “THAT HAS NOTHING TO DO WITH YOUR PAPER! STOP TRYING TO DISTRACT ME!” But that seemed rude so I left that out of the peer review. It was hard to critique individual aspects of a paper that I wanted to tell the author to burn and completely rewrite.

 

That sounds harsh, I’m sorry.

The peer review process is put in place to evaluate the legitimacy of statements made and results found in a study. It is important to be able to distinguish what the purpose of the paper is and what the authors’ thesis statement is going into it (if there is one).

Anything stated by fact needs to be backed up by a legitimate reference to keep false information from being accepted as anything else but false. The entirety of the references list, in fact, should be combed through to ensure the efficacy of the claims they supposedly support within the paper.

Any informal language used should be corrected and any overly scientific language that the author cannot expect the audience to know should be explained.

The benefit of having a peer review system in place is that it can confirm the validity/credibility of the results rendered so that anyone referencing this paper down the line, or just reading it to gain knowledge in general, is not incorrectly informed. It stops false information from essentially snowballing.

Human behaviors that contribute to decreased microbe exposure:

• Having less children
  • With only one or two children playing in the backyard, visiting friends on play-dates, spending time at school or on the playground, etc., the chance of microbes being carried home to be shared is far less.
• Having no pets
  • On a similar note to the prior point, pets would introduce many microbes due to their constant proximity to the ground, time spent outside (in areas humans would not normally be sniffing around/checking out), contrasting hygiene habits, dander, etc.
• Homeschooling children
  • Removing the normal, early exposure to microbes that takes place during a child’s primary education years would eliminate countless immune system-developing, microbial encounters.
• Avoidance of hospitals/clinical settings
  • As the purpose of these facilities is to treat the sick, they are the perfect place to pick up some new (probably pathogenic) microbes.
• Choices regarding food consumption
  • Having a diet comprised of mostly meat or veggies, for example, creates opportunities for the introduction of different microbes, as these types of foods are cultivated, packaged, stored, and prepared in different ways. Cutting out a certain type of food will decrease the likelihood of potentially consuming the associated microbes.
  • Preparing own food at home, as opposed to allowing strangers to prepare it in restaurant/fast food settings that cannot be monitored by you and are naturally heavily trafficked.
• Lack of traveling
  • Staying in one part of the globe means most likely never being exposed to microbes that are commonly found in another area.
•  Choices regarding living environment
  • Living in urban versus suburban areas will differentially expose you to certain amounts of people, certain amounts/types of animals, lack or existence of smog/pollution, etc.

The assigned material this week has enlightened me on numerous variables that can influence the development of microbial communities in newborn infants.

To begin with, an obvious one would seem to be the nutritional (or not so nutritional) intake by the mother. As the food chosen by the mother is the food received by the fetus, the mother can strongly impact the composition of her fetus’s microflora based on her introduction of healthy or unhealthy sustenance.

On a similar note, where the mother chooses to acquire her food could have direct impact as well. There are a multitude of facilities offering fast and easy food, and while this is a totally normal occurrence in every day life, the introduction of pathogenic microbes via unsanitary conditions would be more significant for a fetus, compared to someone who has established their gut composition and the commensals there.

Something made aware to me just this week is that the mode of birth could potentially shape the fetus’s microbial composition. In a seemingly simple choice between vaginal birth or cesarean section, the newborn’s early stage health could be determined.

The environment around us holds innumerable chances for exposure to a range of microbes and the environment that the parent chooses to raise the newborn in would have understandably large impact on their species diversity and which taxa would be most dominant.

Nutrition continues to be an important factor after birth for both mother and newborn. Nutritional intake on the mother’s part is directly incorporated into the breast milk received by the newborn. With full vulnerability in a brand new world, nutritional values may be even more important to the newborns in this stage more than ever.

I can only recall being prescribed antibiotics a few times in my life, due to my family’s tendency to feel like hospitals/clinics were reserved for dire circumstances. Usually choosing to “sweat it out” over a hospital bill and prescription medication, I didn’t know much about antibiotics in general prior to coming to college and becoming a pharmacy technician. I’m much more familiar with them now, in terms of how they are prescribed, the various kinds, the side effects, etc., due to my exposure to them in the pharmacy.

I am still fairly set in my ways when it comes to pursuing professional medical opinions on my health, typically assuming I can handle things on my own. Overall, I’ve developed the mindset that in most cases it isn’t necessary to rush to antibiotics to treat something that your own body could overcome and potentially strengthen your immune system from. There certainly are more serious circumstances where I would accept antibiotics as a course of treatment, but I think there are more important factors to take into consideration when battling something that while inconvenient, can soon be fought off by your body’s own natural defense system.

Since learning about the recent increase in concern over bacterial acquisition of antibiotic resistance, I’m even more wary of potentially overusing our first line of defense. I wouldn’t want to contribute to this widespread problem by giving any pathogenic bacteria the chance to familiarize, mutate, and adapt to antibiotics when the infection could be resolved with time or by other means.

One aspect of antibiotic use that still surprises me is in the minimal education given to the patients. I can’t recall having doctors ever stress to me in the past the importance of finishing the treatment regimen. In fact, I was sorting through a tub of old medications not too long ago and found an vial for antibiotics, prescribed to me my first year of college, with two tablets still inside—a full day’s worth of the seven day course. It’s only been a few years since then and I was shocked that I didn’t even know that long ago what the consequences of stopping early could be.

Doctor’s aren’t the only culprits of failing to stress the importance of a completed regimen, though. I am constantly listening to the pharmacists counsel on ciprofloxacin, levofloxacin, cephalexin, clarithromycin, amoxicillin, penicillin, sulfa antibiotics, etc., all day long at my job. While finishing the course is almost always mentioned, I don’t feel like the patients are made fully aware of the significance of this suggestion. Other than the simple direction to finish it, customers aren’t educated on the reasons why and the possible consequences. If the doctors are not educating the patients, and our pharmacists aren’t, patients will never learn and the bacterial resistance predicament will continue to worsen.

When first reading this prompt, a choice that I make almost every week immediately popped into my head—to fast food or not to fast food? The most obvious point of discussion would be the lack of nutritional value in our popular drive-thru/delivery choices. Failing to provide much nutritional benefit to the one consuming it, I would not expect it give much nourishment to our commensal gut bacteria either, which would only hamper their ability to survive and thrive.

However, something that I have been considering as I become more microbially aware, is what invisible pathogenic microbes could be hitching a ride from an unsanitary food facility to a comfortable new home in my metabolic organ, via my burrito. Accidental consumption of an undesirable bacterial strain could certainly disrupt the balanced microbiome (dysbiosis) and displace the commensal microorganisms dwelling there. Though the outcome is unintentional, our inability to trust how our food is being prepared and handled before it reaches us could yield potentially fatal consequences and any lapse in judgement made by the food handler could contribute to their likelihood.

A popular topic these days, choosing to receive treatment by antibiotics could have the desired result with unintended fallout. At the very least, the antibiotics will eradicate the infection, but at the expense of preexisting microflora that were either beneficial or not harmful. With so much real estate becoming available, the door is left open for unfamiliar and potentially pathogenic microorganisms to fill in those vacancies, leaving the host at risk for even more health problems.

On the other hand, the introduction of antibiotics could lead to a far worse outcome that has become a rather large concern recently: bacterial acquisition of antibiotic immunity. If the patient chose to discontinue treatment, or if the treatment were to fail altogether, the invasive bacteria have the chance to increase their tolerance against our first line of defense. Furthermore, this advancement isn’t a personal hurdle presented to each bacterium—once earned, bacteria can spread their resistance to others via horizontal gene transfer or binary fission and selection (“vertical”). Once resistant, the offending bacteria will be able to dominate the microbiome and the host much more easily.