As lack of RCT studies is a main issue for the majority of microbial relationships to health outcomes, I would focus on providing funding for one of those. Specifically, I would allocate the funding to studies involving depression and the microbiome. Mounting evidence indicates that microbes factor into the mental health equation. An appealing thing about focusing research here is the lack of alternatives to alleviate depression symptoms. It is such a frustrating disorder to approach due to its complexity so exploring new, science-based methods for alleviating the symptoms could have huge benefits. I believe this would be a worthwhile area to study as the prevalence of depression continues to rise. Propelling treatment forward with high quality studies on the relationship is the first step in progress in fighting depression. In the beginning, isolating which specific classes or species of microbes have an effect on mental health seems to be the first step.
Non-infectious diseases influenced by microbiome:
Obesity, crohn’s, depression, anxiety, pulmonary disease, diabetes, IBD, heart disease, stroke, cancer, pre term births, allergies, autoimmune disease, MS
Comparing where I was at week one to now, I have gained a lot of factual knowledge while also deepening my understanding of the body as an overall system. This class was definitely a case of answering one question and having it open up 50 other questions instead of giving a satisfactory conclusion. I view this as a good thing and a great reminder to always look at evidence critically and truthfully. That is a broad lesson, but in taking this class alongside microbiology and immunology this summer, I have learned an obscene amount about cells and microbes which contribute to my knowledge of human health. I can definitely take the abstract skills and the concrete knowledge developed in the class into my future career (hopefully) in healthcare.
Can experiments detect differences that matter?
This is the first question listed by Hanage for good reason; it is a basal question. It is relevant because there would be no point to carrying out experiments if they would not be able to lead you to a conclusion. Really, this is more of a question for the researchers than the one reading the article, but it is still valid and calls into question the purpose of the study.
Does the study show causation or correlation?
This question is important to ask as it allows you to gauge how much the results should influence your thinking. If a study is a randomized control sample with a large sample size and clear question, it is more likely to establish a causal result. However, most studies do not meet the strenuous requirements to draw causation so they must be taken with a grain of salt. This ensures an appropriate level of skepticism is applied as it is easy to get carried away when relationships are demonstrated in mice, for example. Though the relationship is very shiny and nice looking it is important to remember it is not proven yet.
What is the mechanism?
This is another important question to ask to ensure an appropriate level of skepticism is applied. This question also allows you to double check if the study makes sense. Some mechanisms are definitely proposed that are far reaching and often data hands us relationships that we cannot explain. Therefore, this is an important factor to think of when considering a scientific study.
How much do experiments reflect reality?
This question’s main purpose is to establish practicality. This is something very applicable to scientific literature as more often than not, lab conditions are far from real conditions. The only way to convert all the knowledge gained from scientific studies into real improvement is by asking this question. This allows us to apply knowledge gained to the real world.
Could anything else explain the results?
Finally, this question ensures the efficacy of results. If a confounding variable could even possibly be at play there is room for criticism. This is healthy as we want to ensure scientific data is reliable and evidence backed. It is not that the study must not have those other possible variables, but it is necessary to consider them when thinking about the study. The question contributes to the overall purpose of the other questions, to ensure data is valid and accurate.
The most helpful question when discussing controversy specifically is the last one. A piece of information cannot be held reliable if there are other explanations that could be drawn from the data. To explain it in a different way, if you could answer question five, Could anything else explain the results, with a confident no, there would be no room for controversy. It was quite disheartening to read Hanage’s editorial as his skepticism made me question many microbe studies, though the skepticism is healthy.
The microbial community in the body influences the brain through systemic and communication and direct communication. Systemically, cytokines, neurotransmitters, and other small signaling molecules are produced by the microbiome either directly or indirectly. These go on to manifest direct consequences for brain function. An example of an indirect and systemic effect the microbiome has on brain function is an increase in BDNF, a protein produced in the hippocampus and involved in cognition, being elevated in those with microbes compared to germ free individuals in mice studies. Aside from systemic effects, the gut is also directly connected to the brain via the vagus nerve and communication occurs through that pathway. This is evidenced by microbiome effects that were demonstrated in mice being non-reproducible following severance of the vagus nerve. The gut microbiome-brain relationship is bidirectional. The brain is shown to modulate gut microbiome via corticosteroids and neurotransmitters, which alter function. The brain also initiates changes in behavior which lead to effects on the microbiome.
This newly discovered interplay allows us to approach health from a different perspective. Probiotics and prebiotics can now be considered by those treating disorders such as autism or depression, ones typically thought to be separate from hard medical science.
The peer review process feels very mean from the reviewers perspective. I wish I could review papers during in person classes as writing criticisms comes off sort of rude whereas talking to the person is easier. Anyways, it is definitely useful to be the reviewer as you gain insight into common mistakes made and learn different revision techniques. Getting in the reviewer mindset is also useful for your own paper as I can now go back and read it objectively, judging if things truly make sense and come together well. It is easy to write something and just submit it without reading but in order to compose a properly good paper reviewing is essential.
One of the most clear lessons I gained from doing peer review is redundancy and concise writing. When doing a draft and getting your thoughts on paper a lot of fluff appears naturally. Trimming that and enhancing your actual ideas will always lead to a higher quality paper that is easier to read.
Scientific peer review is the process by which studies get published in journals. In order to increase the veracity of the journal, all studies in it are sent to other scientists who are experts in that field. Those experts review the paper to ensure that everything is technically correct and the claims that were made are backed up with data. As a concept, there are no real cons to peer review other than it taking time. In terms of pros it increases the reputation of the authors and journal bidirectionally if the study is of high quality. In fact, peer review is like the quality control process of the science factory. It has been shown not to work in certain cases however, such as that of the Bogdanoff twins wherein they were awarded PhDs in physics despite gibberish thesis papers.
Potential factors in decreased microbial community:
- Formula fed as opposed to breast fed- Breast milk contains microbes which can colonize the newborns body or act as a microbiome while they are still developing. Moving to formula feeding reduces this exposure.
- Caesarean section delivery- C section delivery bypasses the vagina, which contains many microbes.
- Poor diet- Diet has a huge effect on your microbiome and will determine which microbes are able to thrive. Logically this makes sense as your diet will provide for the microbes who live in you. As a specific example, a study mentioned in the Vieira et al. review showed that a diet lacking in plant derived substances will alter the type of bacteria present in the gut.
- Overuse of antimicrobial agents- Increased sanitation overall will lower our exposure to microbes as surfaces simply have less bacteria on them. This means we are picking up less and less microbes throughout our lives.
- Early antibiotic use- Antibiotic use in kids can have harmful long term effects wherein an attack occurs on their microbiome early on and it may never fully recover.
- Extended antibiotic use- If antibiotic tracks are used for too long, resistance can increase in microbes that still survive, as they tend to replicate quickly. This facilitates greater antibiotic resistance in microbes as well, another pressing health issue.
- Lack of human contact- Smaller overall family size or home schooling will result in less human contact. Humans transmit microbes to each other, as we know from infectious diseases being common. Thus, lower human contact will result in reduced microbe exposure.
- Lack of animal contact- With much the same reasoning as above, lack of animal and dirt contact will confer less microbes.
- Loss of microbes in previous generation (vertical transfer)- With the widespread use of antibiotics and sanitation being much increased, certain microbes are rapidly disappearing. Less microbes is harmful for an individual but the effects do not stop there as when they lose microbes they also lose the ability to transfer them.
- Clean drinking water- Although the widespread availability of clean water would be regarded as a good thing by most, it certainly contributes to decreased microbe exposure. This is another logical association. The less microbes in our water, the less microbes that we consume and thus the less we are exposed to.
i) Mother’s Microbiome- A study cited by Nuriel-Ohayon et al. demonstrated the ability of the mother to pass on bacteria to the child by giving a mouse a certain species of bacteria and examining the offspring’s GI tract, finding said bacteria present there. Obviously this makes sense due to the intimate nature of mother and child where they are interacting and touching, allowing for transference of microbes, the first that the baby is exposed to.
ii) Mode of delivery- Studies have shown that newborns delivered vaginally adopt the microbiome of the mother’s vagina early on, where as those delivered by C-section adopt that of the mother’s skin. The difference was present all the way to the oral microbiome of the baby, where the same results were found. The Nuriel-Ohayon et al. paper cited studies that demonstrated increased risk of negative outcomes such as asthma in C-section babies.
iii) Breastfeeding vs Formula- Breast milk contains many microbes in it which are introduced to the baby during breatfeeding. This provides an early microbiome to the child who otherwise would not have been exposed to the many microbes of a mature human. Additionally, increased contact with the mother is made during breastfeeding, furthering the effect.
iv) Antibiotic exposure- Mother and baby exposure to antibiotics will effect the newborn’s microbiome. Logically, this makes sense as taking antibiotics is known to lower diversity of microbes.
The most fascinating thing for me so far has been the link between obesity and gut microbiome. Many people all over the world struggle with body image and dieting is one of the hardest subjects to find consistent information on. There are always fad diets and other things which just serve to confuse. I would like to further my understanding of obesity and how it can be attenuated through microbial means. I also enjoy the difficulties that are associated with studying the human microbiome and its interaction. The fact that it is so difficult to establish if the microbes are there as a cause or effect is so fascinating and opens up the possibility for a lot of theories and things to test, which is awesome from the perspective of a scientists. A third thing I quite enjoy studying in microbial influences is dysbiosis and disease states. The surgery complications article that was required piqued my interest in improving care through manipulating the microbiome.
The link between obesity and the gut microbiome is one that I feel has a lot of data to look through. It is frustrating to find two perfectly good peer reviewed article with no conflict of interests which conflict each other. Regarding microbiome effects in humans, that is the case for nearly every link! There is always one paper which finds this bacteria and another which find a different one, or the same one doing something different. It seems as though the microbiome is highly diverse from person to person which could cause the issue, where the immune system or hormones generally are consistent. Other microbial topics I find personally interesting are the link between dysbiosis and IBD, as well as the use of microbes in treatment and therapy.
To prepare for my final paper, I will definitely start by researching microbial effects on obesity in humans. This is the most fascinating subject to me and the link between digestion and insulin resistance, which are both important factors in obesity, and gut microbiome is well established. There is also a plethora of studies on the subject, so research will be engaging and insightful. I am excited to begin the paper as there is a lot of room for opinion and debate with results open to interpretation. Finally, if the obesity topic does not work out, I have identified several other topics of interest above as back ups.
I would only take antibiotics if prescribed them, with no alternative therapies available. The main reasoning behind this is the boom in studies on our microbial communities and the influence they have on our health. As I was going through school and taking science classes, the idea that antibiotics have been abused and could actually be harming our health as well as creating stronger, more resilient bacteria was emerging. This has given me an overall view of antibiotics as an outdated treatment, which should only be used as a last resort. Luckily, this thinking has prevailed and I was only prescribed antibiotics as single time, with strict instructions on when to stop taking them.
Overall, antibiotics are a vital treatment that has advanced medicine greatly, but they need to be taken with caution and special care behind them. Antibiotic abuse is a real issue and we must tread carefully while we understand so little about our microbiome.