Austin Brunson BHS 323 blog

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.

If I was the head of a funding agency and had some control as to what project I could fund, I think I would have to throw some money at the Gut Microbes and the Brain: Paradigm shift in neuroscience.  I think this project should be funded because it’s a new way of thinking about neuroscience. Its pretty amazing that the microbes in our gut have ways of interacting with our brains.  The evolutionary formation of a complex gut microbiota in mammals has played an important role in enabling brain development and perhaps sophisticated social interaction. Genes within the human gut microbiota, termed the microbiome, significantly outnumber human genes in the body, and are capable of producing a myriad of neuroactive compounds.

So how does this communication work? There are several main pathways by which signals from the gut travel through the body and cross the blood-brain barrier. Some of those core pathways include the enteric nervous system (a part of the nervous system located within and governing the function of the gastrointestinal system), the vagus nerve (connecting the brain and gut), the immune system and hormones within the gut. Gut microbes are part of the unconscious system regulating behavior. Recent investigations indicate that these microbes majorly impact on cognitive function and fundamental behavior patterns, such as social interaction and stress management.

These recent investigations look promising as we find out more about this connection. The challenge for scientists is to learn how to manipulate gut-brain communication to treat psychiatric illnesses. Most previous studies on gut bacteria and mental health have focused on probiotics. Live, “good” bacteria that can be ingested in foods like yogurt or in supplement form, which have been shown to have anti-anxiety and anti-depressant effects.  What if we could intervene in an alternative way other then probiotics. While doing more research I found a term called Physcobiotics.  Psychobiotics is a new scientific term referring to any intervention that has an effect on mental health by way of changes in the gut microbiome. The larger question here, in medical, scientific, and legal terms, is that psychobiotics are not currently classified as a treatment. At most they are a dietary supplement. The answer to how and whether they should be regulated will emerge as we learn more about the effects of these substances on the central nervous system.

A great deal more research on humans is needed before real treatments are made available. In the meantime, some medical experts are concerned about the widespread marketing of probiotics to consumers to treat psychiatric issues. Consumers should beware of the many probiotics marketed online as cognitive enhancers or mood boosters. Will the gut microbiome add paradigm-transforming insights to our existing understanding of human brain function in health and disease, resulting in novel therapies, or will it represent an incremental step in understanding the inner workings of our brains (1)? This is were more funding could be useful to figure out just what works and what doesn’t. Human clinical trials are expesnive and time consuming so I would devote my funding to this research topic or this project so we can find out whats around the corner in this area of study.

 

List of as many human non-infectious diseases that I can think of that are influenced by microorganisms.

• Celiac Disease
• Cancer (Stomach,Esophageal, Intestinal, Rectal,Skin, Oral, Etc.)
• Irritable Bowel Syndrome
• Diabetes
• Heart Disease
•  Periodontal disease
• Tooth Decay
• Allergies
• Alzheimer’s
• Obesity
• Asthma
• Atopic Dermatitis

 

Referring back to my writing assignment #1 I have a few more diseases written down here. I think I would have even more if I had more time. This class has given me enough evidence to know that microorganisms are responsible or at least trigger the onset of many non infectious diseases. Looking at this now I am actually quite surprised that there isn’t more diseases that are directly related to the populations of microorganism on the body.

The relationship we share with microorganisms is fascinating. The future of microbiology and the study of how microbes interact with human health is on the rise, If I could go back to freshman year and rethink my degree I might just get into Microbiology so I could focus more of my studies on this topic. Its easy to get overwhelmed by the hype of this field, but there is a reason for the hype and I think we will be seeing many new discovers in the near future.

How to not be effected by the hype or the band wagon effect in science.

1. Can experiments detect differences that matter?
2. Does the study show causation or correlation?
3. What is the mechanism?
4. How much do experiments reflect reality?
5. Could anything else explain the results?

Everyone who shapes, edits and publishes scientific content carries a responsibility to remain as unbiased and nuanced as possible. While a critical scientist may catch the flaws in a colleague’s study, someone with less specialized knowledge likely will not. If you can follow the five questions above you have a good chance of avoiding the hype or bandwagon effect. Most people don’t think about the extensive scientific studies that hide behind  media reports, but that shouldn’t be a problem. Responsible science journalism brings important findings to the public so that they don’t have to.

I would like to point out the importance of knowing the difference between causation and correlation.

We experience the world in a time-oriented manner through cause and effect. First Lucy ate that white berry, then she became sick. It is logical enough on the surface. Often, it seems clear that a specific action caused a second event to happen. This is what is known as causation. Many events appear to be the results brought about by identifiable causes, and the human mind is geared to look for these cause/effect relationships.

Correlation is when two or more things or events tend to occur at about the same time and might be associated with each other, but aren’t necessarily connected by a cause/effect relationship. For instance, in sick people, a runny nose and a sore throat correlate to each other–they tend to show up in the same patients. That doesn’t mean runny noses cause sore throats, or that sore throats cause runny noses, however. Forgetting that leads to sloppy thinking and thus sloppy assumptions.

To avoid the hype on a certain research or scientific topic and remain unbiased  it is essential to remember these five questions and see if you can apply them to your situation. unbiased fact based science is good science. Good science is how we innovate and keep progressing as a society so when we assume that everything we read is true or we don’t remember that correlation does not imply causation. Humans are evolutionarily predisposed to see patterns and psychologically inclined to gather information that supports pre-existing views, a trait known as confirmation bias. Avoiding bias in science is key to avoiding the band wagon.

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 human gastrointestinal tract  harbors trillions of microorganisms, consisting of up to 1,000 or so different bacterial species. These bacteria, known collectively as the gut microbiota, perform a number of vital functions in our body. They defend against pathogens, aid in digestion and nutrient absorption, produce vitamins (K and B), and boost our immune system. Some of the products of metabolism by these bacteria have been found to be neurotransmitters and interact with the enteric nervous system. These neurotransmitters can start at the peripheral nervous system and then be transferred to the the central nervous system were they can effect brain chemistry.  Research shows that people suffering from gastrointestinal disorders are more susceptible to anxiety related disorders. Although the underlying mechanism is not fully understood as yet, there is clear evidence of a connection between the microbiota, gut and brain.

These mechanisms can be related in reverse were the brain can effect the environment in the gut. This happens through stress related incidences. Early life stress has been implicated in many psychiatric disorders ranging from depression to anxiety. A research study “Maternal separation as a model of brain-gut axis dysfunction.” describes the components of the brain-gut axis individually and how they are altered by maternal separation. The separated phenotype is characterised by alterations of the intestinal barrier function, altered balance in enteric microflora, exaggerated stress response and visceral hypersensitivity, which are all evident in IBS (1). This is also the case in psychological, sexual and physical abuse which can lead to high amounts of stress or the release of the release of cortisol, which influences many bodily functions such as metabolic, psychological and immunological functions. So this may be because the establishment of stable gut microbiota is disrupted by altered metabolic functions.

This image depicts the Brain-Gut axis and how stress could interrupt the homeostasis between the two.  Probiotics, antibiotics and fecal transplants are all ways to combat the dysbiosis that can take place from stress.

http://www.jpp.krakow.pl/journal/archive/08_15/articles/02_article.html

O’Mahony, S. M., Hyland, N. P., Dinan, T. G., & Cryan, J. F. (2011). Maternal separation as a model of brain–gut axis dysfunction. Psychopharmacology, 214(1), 71-88.

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?

In my experience with the peer review process, I though it helped me better understand the main goals for writing the paper. I was surprised how much I learned from just reading another persons paper. When dissecting a paper you must read it multiple times forwards and backwards. This helped me grab the major concepts of the papers and informed me more then just reading it once over.  I can apply the use of references in my paper that were used the papers that I reviewed. I also liked how one of the papers I read tied her conclusion back to her thesis in a way that made the whole paper very informing and easily understandable. Critiquing somebody’s work is always tough because you don’t want to change too much of the paper or review too harshly. I found it much easier to review when we were given a template to go from. I was able to gain some good insight on what could make my paper better by just looking at techniques used in my peers papers. I don’t think a writing class would be complete without having to go through the reviewing process because its a good way to learn techniques and even better way to learn what goes into a legitimate informational paper.

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 process of peer reviewing scientific articles.

 

http://undsci.berkeley.edu/article/howscienceworks_16

Peer-reviewed articles provide a trusted form of scientific communication. Even if you are unfamiliar with the topic or the scientists who authored a particular study, you can trust peer-reviewed work to meet certain standards of scientific quality. We rely on scientific peer reviewed articles to reference for other papers so they must hold up to scrutiny.

Many fields outside of science use peer review to ensure quality. Philosophy journals, for example, make publication decisions based on the reviews of other philosophers, and the same is true of scholarly journals on topics as diverse as law, art, and ethics. There is essentially two types of peer review closed and open.

Closed peer review is a system where the identities of the reviewers are not disclosed in the journal or to authors, and the identities of authors may not be disclosed, during the review process, to the reviewers. Of course, the reviewers can identify the authors after publication. Closed review works in two ways: single-blind and double-blind. Single blind review works by revealing the names of authors to reviewers while withholding the names of reviewers from authors. In double-blind peer review—as described above—identities of authors and reviewers are mutually withheld.

Open peer review, in contrast, operates a more transparent approach to peer review. Identities of authors and reviewers are mutually disclosed and, furthermore, reviews are sometimes published alongside the published articles. This system is becoming increasingly popular and is often applied by open access journals.

Peer reviewing will help develop you as a writer. Just think about all the ideas another person could think of on the topic your writing about. More minds contributing to the same thing the better. I think peer reviewing helps the writer in ways they might not have thought of when first writing. The purpose of writing a paper is having somebody else read it and make sense of it. The best way to make it appealing to many people is having a few people in same field read it and agree that other people should read it to.

The pros  and cons of peer reviewing

There is no consensus on which of these peer review systems is best and it is agreed that both closed and open peer review have good points and bad; likewise single- versus double-blind peer review. The principle behind closed review is to minimize the bias of reviewers who may be influenced by the identity of the authors and to protect the reviewers from authors who may take exception to adverse reviews and rejections. The principle of only protecting reviewers operates in single-blind review. While it is always possible to protect the identity of reviewers during and after the review process, it is often possible for reviewers to identify authors by virtue of the work that is being reviewed.

Moreover, even when the author cannot be identified, reviewers may take exception to a line of work for reasons that are not concerned with the science or because the work competes with or refutes some of their own work. Therefore, the advantages of the system—minimizing bias and protecting identities—may be undermined by prejudice on behalf of reviewers.

As an ‘antidote’ to some of the issues raised by closed review, open review introduces transparency. By mutually revealing identities, the potential for bias by reviewers is attenuated by accountability to authors and readers. The advantages of this system may be outweighed by less-than-honest comments from reviewers who feel unable to be frank about the work.. On the other hand, the potential for unhelpful and inappropriate comments is reduced. Neither of the above systems of review-closed or open-is capable of completely obviating the problems they are designed to address.

The peer review process is extensive and complex. This is by design to make sure that the papers that make it to journals are held in high regard and hold validity across the board.

Photo retrieved from :

(n.d.). Retrieved May 26, 2017, from http://undsci.berkeley.edu/article/howscienceworks_16

Human behaviors that contribute to decreased exposure to microbes.

We now know that microbial exposures could have positive health impacts later on in life. The hygiene hypothesis states that the lack of early childhood exposure to infectious agents microbes and parasites will suppress the natural development of the immune system.  The immune system can be broken down into sub categories the innate and the adaptive immune system. The hygiene hypothesis primary acts on the adaptive immune system. The adaptive immune response is antigen-specific and requires the recognition of specific “non-self” antigens during a process called antigen presentation. Antigen specificity allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in the body by “memory cells”. Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it. In other words if your not exposed to infectious agents then your adaptive immune system has less information to go off in immune response.

Potential risk factors could be:

• Formula feeding instead of being exposed to microbes in breast milk
• Infant being born through c-section and not exposed to vaginal microbes in delivery.
• A kid that never plays outside (in dirt).
• Parents that don’t get there kids vaccinated to be exposed to viruses that like virulence factors.
• Antibiotic therapy not being used in the right way.
• Over use of antimicrobial household products like (detergents, soaps, kitchen cleaners etc.)

https://draxe.com/microbiome/

It is important to keep a biodiversity of microbes in and on your body. Certain behaviors can promote and depress the biodiversity of the micro biome.  The adaptive immune system needs to have infectious agents so it can adapt over time and prevent the later onsets of allergies and infection.

Im am fascinated by the sheer number of microbes we coexist with. I was shocked to learn that the body houses specific microbes in certain parts of the body to utilize their metabolic processes or their use as a natural defense to other pathogens. In particular the mouth microbiota is something that interests me as a future dentist. I think that the interaction we have with the outside world ( our environment) and usually the first portal of entry being our mouth we don’t have more problems with dysbiosis and disease. Many people do have some sort of oral disease at any given point including cavities or gingivitis. Its amazing to me that this dysbiosis in the mouth doesn’t create more problems systemically. The more we study the relationship we have with microbes the better we can understand the mechanisms and use them to our advantage to maintain a healthy diversity of microbiota.

dysbiosis in the mouth

Dysbiosis in the mouth of a normal microbial diversity can have effects on a very macroscopic level. I don’t think many people outside of the scientific world understand the complexity of the interactions, including myself and I would like to research and write more about it. The topic of probiotics is sweeping the world and most people think of just ingesting probiotics to help with a healthy gut.  There is also talk of mouth rinses that have probiotics to maintain a healthy diversity of microbes in the mouth. Again this is one of the major entries into our body and if we don’t have good bacteria in our mouth protecting us from the bad we could experience disease that we would otherwise avoid.

I think the topic of oral microbiota would be very interesting for me to write about and I think I could take a lot away from it. The mouth is a perfect environment for many microorganisms to flourish in, good and bad. So how do we keep high levels of beneficial microbes  where they need to be. I think this focus is broad enough to use a lot of the information I have learned from this class and microbiology to write worth while paper. At the same time I think the focus on the mouth would intrigue me more then looking at the microbial community on the skin.

Microbial colonization of the infant occurs during a critical time window for immune and gastrointestinal development. Infant colonization sets the stage for the adult microbiome. The nature of infant environmental exposures, acting through the microbiome, affect the likelihood of developing childhood and adult diseases such as obesity, food allergy, and inflammatory bowel disease. Many bacterial sources for the infant derive from the maternal microbiota. Therefore, beneficial infant colonization is dependent upon maternal genetics, environmental exposures and diet before and during pregnancy as well as during breast feeding.

The mother not only gives the newborn everything for life but she also gives the newborn some of her microbiota through delivery, prebiotics, and breast milk.

Delivery

The current fetus microbial model leads us to believe there are no bacteria present in the fetus (though they are surrounded by microbiota in the womb) and it’s not until childbirth that the first microbes are transferred to the baby through the birth canal during delivery. So according to what we know as of today, if that baby doesn’t come out of that birth canal, the baby does not get inoculated with healthy probiotic bacteria.

As of last month, a study dropped, proving that if a Cesarean-delivered newborn was swabbed with the mothers vaginal fluid, their gut, oral and skin bacterial communities were enriched with vaginal biome! So for all you parents out there who have the best intentions of delivering vaginally, but your life or the life of your unborn baby, or both, are at risk, there is a simple solution that is now officially backed by the science method (1).

Natural Prebiotics

The vernix caseosa, the waxy skin coating of a fetus, is shed into the amniotic fluid as the fetus approaches term. While still in utero, the near-term fetus swallows amniotic fluid containing pieces of vernix. While not digestible by human enzymes the vernix caseosa provides a good medium for bacteria to grow on. Once the infant begins to breastfeed, breast milk contains additional prebiotics. Colostrum contains especially high concentrations of human milk oligosaccharides (HMOs), which are indigestible by human enzymes alone. Their synthesis requires up to ten percent of the total energy expended to produce human milk. These oligosaccharides, like the vernix, promote growth of intestinal microbes (2).

 

Breast Milk

Breast milk contains both innate and adaptive immune components that inhibit pathogens from colonizing the infant gut. As part of the innate immune system, breast milk contains antibacterial peptides, such as lactoferrin and lysozyme. These antibacterial peptides provide broad spectrum bacteriostatic and bacteriocidal checks on microbial growth. Breast milk contains glycans that mimic cell surface adhesion molecules on the infant’s intestinal epithelium. These glycans act as decoy receptors to specific intestinal pathogens, providing a further level of protection for the infant.

Breast milk has long been known to contain bacterial DNA. Modern culture-independent techniques identified gut-associated obligate anaerobes in addition to facultative anaerobes in the breast milk as a source of diversity in the infant gut (3). Through these prebiotic and probiotic mechanisms, breast milk shapes the intestinal microbiome. Exclusively breast-fed infants have overall greater diversity of the microbiome when compared to exclusively formula-fed infants

1. Bromberger, P., Lawrence, J. M., Braun, D., Saunders, B., Contreras, R., & Petitti, D. B. (2000). The influence of intrapartum antibiotics on the clinical spectrum of early-onset group B streptococcal infection in term infants. Pediatrics, 106(2), 244-250.
2. Newburg DS, Walker WA. Protection of the neonate by the innate immune system of developing gut and of human milk. Pediatr Res. 2007;61(1):2–8.
3. Jost T, Lacroix C, Braegger C. Assessment of bacterial diversity in breast milk using culture-dependent and culture-independent approaches. Brit J Nutr. 2013;110:1253–1262.

Antibiotic personal philosophy

In my life I have only had to take antibiotics a hand full of times, once for a staff infection and another for when I had strep throat. Personally I have always been under the impression that if you can fight off the infection without antibiotics to do it that way. I remember the doctor telling me when I was younger that its a good thing that I haven’t had to take many antibiotics through out my life.

Antibiotics, also known as antimicrobial drugs, are drugs that fight infections caused by bacteria in both humans and animals. Antibiotics fight these infections either by killing the bacteria or making it difficult for the bacteria to grow and multiply. Antibiotics do not have any effect on viruses. Antibiotics are fundamental to modern medicine, essential for treating everything from routine skin infections to strep throat, and for protecting vulnerable patients receiving chemotherapy or being treated in intensive care units. This also poses the question of what type of infection should be treated with antibiotics.

Which infections are caused by viruses and should not be treated with antibiotics?

• Colds
• Flu
• Most sore throats
• Most coughs and bronchitis (“chest colds”)
• Many sinus infections
• Many ear infections

Antibiotics are necessary when infections are to fierce for the body to get rid of by itself. That being said when doctors do prescribe an antibiotic the full round should be taken to prevent antibiotic resistance. Although antibiotic resistance is not a new problem, its scope now constitutes a major threat to human health. According to the Centers for Disease Control and Prevention, at least 2 million Americans fall sick every year with antibiotic-resistant infections—and 23,000 die.

To avoid antibiotic resistant organisms from manifesting, a few precautions should be considered:

• Ensure that antibiotics are only prescribed when necessary in human health care settings.
• End the overuse of antibiotics in food animals.
• Remove the regulatory economic and scientific obstacles that impede antibiotic discovery and development.
• Dont save antibiotics for the next time you get sick.