Bioptimizers Annual Essay Contest Scholarship Winning Essays

First Place 

How Improving the Microbiome Will Be the Medicine of the Future 

By Enobong Ukpong, University of Calgary, Canada

Fungi, bacteria, virus. When the average person hears words like this, they might immediately conclude these are bad things to be avoided. And this is not an absurd assumption–bacteria, fungi, and viruses cause many diseases. However, they may not know that these microbes naturally live in our bodies in a vast ecosystem known as a microbiome. 

Though microscopic, these one hundred trillion bacteria, fungi, and viruses add so much value to the human body that they cannot be overstated. Lactobacillus Acidophilus, for example, helps us digest food and protects us against harmful pathogens. Likewise, bifidobacteria infantis helps relieve abdominal pain, gas, and bloating. 

The use of bacteria to protect the body is not a new concept. Ancient Egyptians used human and animal stools to treat various illnesses. However, this practice fell out of favor as modern medicine evolved and a focus on hygiene and antiseptic environments were established. 

“The pendulum has swung from a focus on killing pathogenic bacteria to a focus on healthy, symbiotic, and commensal microbes,” said Melissa Melby, Ph.D., co-director of the Humans and the Microbiome Program at the Canadian Institute for Advanced Research (CIFAR) in Toronto. “There has been a shift in clinical care and the popular consciousness with the realization that microbes are not all bad.”

Alterations to the microbiome can seriously affect one’s health. For example, exposing the microbiome to environmental pollutants can lead to health disorders such as type 2 diabetes, cancer, and dysregulation of the immune system.

The microbiome can also be negatively affected by the overuse of antibiotics or antibacterial sanitizers. Preliminary studies have even linked disorders in the microbiome to neurodegenerative disorders, such as Parkinson’s disease, as well as inflammatory and cardiovascular. diseases However, if negative alterations can lead to adverse health effects, does it not stand to read that, in contrast, positive alterations can lead to positive benefits? 

Yes, and indeed there are multiple ways to improve your microbiome, such as improving your diet. Eating vegetables, avoiding sugar and processed foods, and cutting red meat have been 

shown to have positive benefits. Take probiotics, whether in pills or foods such as leeks. Hitting the gym is also a way to improve your microbiome. 

Rapid developments in gene sequencing and innovation in laboratory techniques have led to a rise in microbiome research, which could signal a shift from curative and preventative medicine to optimized medicine. Instead of trying a one-size-fits-all solution approach to medicine, we could be looking at medicine tailored to your specific needs that will end up being more effective and thus cheaper. Improving the microbiome has the potential to be the medicine of the future. 

Why are tailor-made solutions needed? The composition of everyone’s microbiomes is unique and dependent on diet, lifestyle, health, and genes. This means that the same medicine won’t be effective for every person. 

Acetaminophen, the widely used painkiller found in Tylenol, can be highly toxic for some people, depending on their gut microbiome. With the sheer diversity of microbiomes each person has, it would be much more effective for doctors to analyze the composition of their patients’ gut microbiomes to determine what medicine would work best for that individual patient instead of implementing a generalized solution. 

We can already see this starting to happen. In Turkey, doctors were able to use artificial intelligence to analyze the microbiome of people with chronic constipation, relieving them more effectively than laxatives would by implementing AI-recommended changes in diet. 

“The AI tells us what bacteria are and are not lacking in the microbiome of people with chronic constipation and recommends dietary changes to dietitians who then translate this data into personalized advice for the patient,” says Varol Tunali at the Esrefpasa Municipality Hospital in Izmir, Turkey. 

Another avenue of improvement is the use of live bacteria. For example, doctors have found Clostridium difficile can be cured by fecal transplant, taking fecal matter from a healthy person’s colon and transplanting it into the colon of the patient. 20% of C difficile cases involve bacteria that have become immune to antibiotics, so this procedure turns a potentially fatal infection into an illness that is significantly easier to treat. 

These sorts of procedures have been the trailblazers in microbiome medicine, as ten thousand FMT (fecal matter transplant) procedures occur each year. So it’s interesting to see that the Ancient Egyptian medicine theory had some merit. 

Of course, we already know the health benefits of bacteria. As stated previously, bacteria such as Lactobacillus Acidophilus help us digest food and protects us against harmful pathogens, and this knowledge is reflected through the use of pro and antibiotics. But eventually, bacteria may even be used in place of chemical treatments. 

“Someday soon, you and I will go into the doctor’s office, and the doctor will prescribe medicine that won’t be a chemical from a lab but may be live bacteria,” says Sarkis Mazmanian, a microbiologist at Caltech in Pasadena, California. This is known as psychobiotics, live bacteria that, when ingested, may provide mental health benefits by affecting the microbiome of the individual ingesting it. While research is still in its preliminary stages, a 2020 literature review suggested that psychobiotics could be a viable option to restore mental health. 

In conclusion, medical studies have shown signs that the direction of medicine is shifting away from its sterile, antiseptic environment towards the acknowledgment that bacteria has helpful functions for decades now. Doctors have gotten the ball rolling with probiotics, but a new avenue of medicine is about to take hold: the microbiome era. Doctors have found that personalizing diets and medication to patients’ gut microbiomes is a more effective way of nursing them back to health than prescribing generalized medication. 

Furthermore, we are seeing a rise in medical practices, such as fecal matter transplants and psychobiotics based on these principles, truly solidifying microbiome improvement as the future medicine.

References:

1. U. S Department of Health and Human Services, Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013.; 2013. Accessed August 13, 2022. https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf
2. Romijn AR, Rucklidge JJ. Systematic review of evidence to support the theory of psychobiotics. Nutr Rev. 2015;73(10):675-693. doi:10.1093/nutrit/nuv025
3. Parshley L. Microbiome science could bring a revolution in medical care. NBC News. Published January 26, 2017. Accessed October 14, 2022. https://www.nbcnews.com/mach/science/microbiome-science-could-bring-revolution-med%20ical-care-n710861
4. Kuai XY, Yao XH, Xu LJ, et al. Evaluation of fecal microbiota transplantation in Parkinson’s disease patients with constipation. Microb Cell Fact. 2021;20(1):98. doi:10.1186/s12934-021-01589-0
5. Gut microbiome: Next frontier of precision medicine. Aacc.org. Accessed October 14, 2022. https://www.aacc.org/cln/articles/2020/may/gut-microbiome-next-frontier-of-precision-medicine
6. Tracy A. A new power couple: The combined impact of the microbiome and chemical exposures on disease susceptibility (Part 2 of 2). EDF Health – Our experts’ views on chemical news. Published December 19, 2011. Accessed October 14, 2022. https://blogs.edf.org/health/2011/12/19/1653/
7. Wong C. AI that recommends diets based on the microbiome relieves constipation. New Sci. Published online August 15, 2022. Accessed October 14, 2022. https://www.newscientist.com/article/2333663-ai-that-recommends-diets-based-on-the-microbiome-relieves-constipation/

Second Place 

How Improving the Microbiome Will Be the Medicine of the Future

By Jonathan Reimche, St Mary’s University, Canada

It seems common sense that your brain would be vital to your mental and physical health. But on the other hand, many people still do not recognize they also have a second brain; it is just as significant to your body’s and brain’s overall health. This second brain is your microbiome, the community of bacteria, fungi, yeasts, parasites, and even viruses in your body, working together to create the beauty of life as we know it. 

As almost anyone would tell you, diet greatly impacts your health and can also help prevent illness and disease.

 Why is it that diet has a large effect on future health? How does this process prevent or cause disease? And why should we care?

In this essay, I will discuss this topic more, touch on these questions, and discuss what benefits this field can provide us for better and more sustainable healthy lifestyles.

Suffice it to say that we are not an autonomous species and most likely never will be, so what

we put into our bodies, that is, our diet is very important. Yet, it seems easy to take for granted a large number of processes constantly happening within our bodies that keep us healthy and alive. 

Microbes are the reason behind these processes; they can break down and produce vital vitamins and nutrients that our genes can not. Microbes also teach our immune systems how to recognize harmful intruders and produce anti-inflammatories that fight off other disease-causing microbes and bacteria. 

Although we have progressed in understanding this fundamental part of our body, we still do not know as much as we would like about it. It was first discovered in the late 16th century but was not understood and studied further until about two centuries later. It is important to note that your microbiome is as unique as your fingerprint; no two are the same. 

We have already been using this information to help us understand the human body and disease for some time now, so it isn’t that new of a concept in the scientific and health communities. What is new is the amount of traction we have been making in recent years with studies and funding.

Present day, we now know of the importance of the microbiome. Without it, our bodies would

not function the way they do. A study named “The Human Microbiome Project” says bacterial protein-coding genes outnumber human genes by approximately 360:1, and the number of bacteria to human cells is about 10:1, which is mind-boggling, knowing that we are just as much the bacteria in our bodies as we are our cells. 

Almost reminds me of something out of a horror movie, but luckily, they are not those kinds of bacteria, viruses, or parasites. Yes, certain microbes can be harmful or even deadly. But, symbiotic one’s help sustains us and protects us from others coming in and setting up shop that would harm us.

Take, for instance, a roundworm; when they set up shop, they normally do not harm us but boost their host’s immune systems. However, when the microbiome becomes dysfunctional, it can cause several issues, such as obesity, renal and liver disease, cardiovascular diseases, and even cancer.

In a more personal case, I have a chronic illness called Crohn’s Disease. I learned that certain species of the parasite could potentially reduce symptoms, along with other diseases such as Type 1 Diabetes and arthritis, changing my life and many more, if further studied. 

For this reason, this field has received huge amounts of funding from groups and venture capitalists; they see the potential, and so should the rest of us. There have also been studies that show alterations in the vaginal microflora are thought to cause what used to be considered spontaneous pregnancy loss or more susceptibility to STIs such as HIV. 

This is a huge potential discovery. I believe most of us know or know someone affected by these issues and diseases. With more time and dedicated teams investigating these, we could potentially save many lives in the short and long term.

Cancer is a very apparent disease in our world, and as I said before, studying our microbiome may prove to be the link that helps us solve this problem.

 We have found evidence through Epidemiological studies that the loss of homeostasis between us (the host) and our microbes can promote diseases such as stomach, breast, skin, and other cancers.

In conclusion, I truly believe studying and treating the microbiome is the medicine of

the future will be more so when we learn more about it in future years. One simple way to show it has this potential is by looking at certain species and how their microbiome has helped them in more obvious ways. In an article by Jason Gilchrist in 2017, he speaks about how the grey squirrels have rapidly eradicated the red squirrels in parts of the UK due to carrying a virus that is deadly to the red squirrel but harmless to themselves. 

This is how bacteria infect and protect us from other harmful bacteria and viruses. Let’s say you are sick, and a certain bacterium is causing this; if it goes untreated, it may be fatal; we may be able to introduce another bacterium to our microbiome that carries a disease harmless to us but lethal to that bacterium, suddenly we have cured ourselves and boosted our immune system in the process. We have only just begun scratching the surface in the last few decades.

As of now, though, our understanding of the microbiome is still very limited, yet we are progressing further every day; with new technologies in the field of biologies such as DNA sequencing and new possibilities of technology in the future, who knows what we can achieve?

Resources

• About the human microbiome. NIH Human Microbiome Project – About the Human Microbiome. (n.d.). Retrieved August 18, 2022, from https://hmpdacc.org/hmp/overview/
• Gilchrist, J. (2017, March 7). In defense of the grey squirrel, Britain’s most unpopular invader. The Conversation.
• Hayes, W., & Sahu, S. (2020). The human microbiome: History and future. Journal of Pharmacy & Pharmaceutical Sciences, 23, 406–411. https://doi.org/10.18433/jpps31525

Third Place 

By Amit Bijlani, York University, Canada

Present largely in the small and large intestines; the microbiome refers to the community of bacteria, fungi, parasites, viruses, and other microscopic organisms present throughout the body. It is even considered a supporting organ because it is connected to the nervous system and other organs. 

A person is first exposed to microorganisms as an infant, during delivery in the birth canal, and through the mother’s breast milk. Later, the microbiome changes, such as an increase in density and diversity and the emergence of organ-specific communities. Factors affecting the microbiome include genetics, diet, environment, antibiotics, and method of child delivery.

Most of these microorganisms are symbiotic, and some are pathogenic. In a healthy body, pathogenic and symbiotic microbiota coexist without problems. For example, they stimulate the immune system, break down potentially toxic food compounds, and synthesize certain vitamins (including B and K) and amino acids that may not be found in plants or animals.

The microbiota breaks down complex carbohydrates and fibers that aren’t easily digested with their digestive enzymes. The end-product is short-chain fatty acids (SCFA), as well as metabolites such as butyrate, acetate, and propionate, that act as a nutrient source, promote the growth of villi, enhance the production of mucin and play an important role in muscle function and possibly the prevention of chronic diseases, including certain cancers and bowel disorders. 

Clinical studies have shown that SCFA may be useful in treating ulcerative colitis, Crohn’s disease, and antibiotic-associated diarrhea. Moreover, fermentation of dietary fibers lowers the pH, limiting the growth of harmful bacteria like Clostridium difficile.

The metabolite butyrate is specifically important as clinical studies have shown that oral intake of butyrate in mice could directly activate thermogenesis in brown adipose tissue to increase energy expenditure and reduce body weight. Hence, fermentation of larger quantities of dietary fiber allows for more butyrate production, thereby being a notable treatment option for obesity. 

Butyrate also performs anticancer and anti-inflammatory functions by suppressing the activity of specific immune cells. This helps in preventing colorectal cancer and inflammation. Furthermore, reducing the gut’s inflammatory capacity creates an environment that allows the microbiome to exist within humans without stimulating an acute immune response. Butyrate also regulates colonic motility, natural movements of the gut that move food through it, and increases blood flow in the colon.

Microbiota can also break down dietary choline, which produces TMA that gets oxidized to TMAO. TMAO is positively correlated with atherosclerosis and diabetes and is an important biomarker.

A balanced microbiome is necessary for the prevention of various diseases. However, a disturbance in this balance causes dysbiosis, which results in higher susceptibility of the body to diseases. This could be due to a change in diet. 

For example, the short-term consumption of an animal-based diet rapidly increased the abundance of bile-tolerant Alistipes and Bilophila. At the same time, it reduced the abundance of carbohydrate-metabolizing Firmicutes such as Roseburia, Eubacterium rectale, and Ruminococcus bromii over 1–2 days in humans. 

Another contributing factor is the method of delivery. For example, several studies have shown that birth by C-section is associated with an increased colonization rate by opportunistic pathogens and several immune-mediated diseases, including inflammatory bowel disease, asthma, and juvenile arthritis.

 In addition, children delivered by primary c-section exhibit a higher risk of developing food allergies in later life. In other cases, dysbiosis may result in negative physiological effects within the host and our nervous system. For example, Dysbiosis could strongly affect organ-specific communities such as the liver, which is crucial given the liver’s various functions. Understanding this will help professionals improve the delivery method to avoid these consequences. Therefore, a person needs to consider a person’s microbiome when avoiding or treating diseases.

There is increasing evidence suggesting that the human commensal microbiome is involved in the etiopathogenesis of cancers. Commensal bacteria produce certain ligands like lipopolysaccharides (LPS) and lipoteichoic acid (LTA) that are sensed by toll-like receptors (TLRs) in the gut epithelium and protect the intestinal epithelium against injury. 

However, they may also bring out negative physiological effects. For example, a commensal bacterium, Fusobacterium nucleatum, indirectly promoted human colorectal cancer cell proliferation, thereby leading to colorectal cancer. Another microbiome species present in the gut, Bacteroides fragilis, could destroy the colonic mucosal protective layer by releasing toxins that lead to tumorigenesis. 

In addition, dysbiosis is shown to be a causative factor of bladder, kidney, and prostate cancers.

Currently, the mechanisms by which the microbiome affects cancer include genotoxicity, inflammation, and immunity. For example, the disruption to gut microbiota homeostasis could generate many inflammatory substances, such as some subtypes of bile acids, which were secreted and transported into the liver and induced an inflammatory immune response, eventually causing hepatocellular carcinoma genesis.

Gut microbiota also seemed to affect other types of cancer distant from the gut, such as lung and prostate carcinomas. In addition, recent studies suggest that gut microbiota dysbiosis is associated with many metabolic disorders such as obesity, hyperglycemia, dyslipidemia, and others. Such studies made it clear that gut microbial dysbiosis is involved in the regulation of fat storage within the human body and, consequently, the occurrence of obesity.

Dysbiosis in the gut, caused by altered intestinal permeability and damaged bile acid metabolism, could reach the liver and lead to systemic inflammation. It has been proven that the severity and type of chronic liver disease strongly depend on the progression of gut dysbiosis. Several chronic liver diseases result from such alterations: chronic hepatitis B, chronic hepatitis C, alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma.

Some studies showed that patients with NASH had increased  Firmicutes with decreased  Bacteroidetes. In these chronic liver diseases, pathogen-associated molecular patterns (PAMPs) are more exposed to oxidative stress, leading to further inflammation by the production of cytokines through TLRs. Another key player in these diseases is bile acid. Due to microbiota dysbiosis, bile salts are preserved, leading to the permeability of gut microbiota and bacterial growth.

In light of the advancements made in microbiome research, modulation of the host microbiome has been proposed as a potential treatment or prevention for many health disorders. For example, it has been found that there is a bidirectional relationship between microbiota and chemotherapeutic agents on chemotherapeutic efficacy. Collectively, these results highlight the immune system regulatory function of the microbiome and the promise of microbiome therapy in combination with cancer therapy.

Another way of improving the microbiome involves the consumption of certain dietary foods. Diets rich in fiber promotes carbohydrate metabolism and diversify the microbiome. High fruit intake accumulated Faecalibacterium prausnitzii, Akkermansia muciniphila, Ruminococcaceae, Clostridiales, and Acidaminococcus in the gut microbiome, which may benefit insulin sensitivity through increasing production of SCFAs.

In the medical field, one method is fecal microbiota transplantation (FMT) which involves introducing stool from a healthy donor into a recipient’s colon. FMT has become increasingly and rapidly accepted and medically performed because of its success in treating bacterial infections, mainly C. difficile, but also, intriguingly, in treating other disorders like obesity and diabetes, as well as metabolic syndrome. 

Scientists are also looking into using microbiota transplants for various disorders, such as insomnia, Parkinson’s disease, HIV, chronic fatigue, multiple sclerosis, obesity, insulin resistance, metabolic syndrome, and autism. Another emerging indication to perform fecal microbiota transplantation (FMT) is gastrointestinal (GI) tract colonization by antibiotic-resistant bacteria (ARB). Bilinski et al. first reported the high efficacy of FMT, reaching 60–100% of different ARB decolonization rates after one month of FMT.

The microbiome can be used as a low-cost diagnostic tool for inflammatory bowel disease and, irritable bowel syndrome, progression of diabetes. Since the microbiome is a diseased state biomarker, examining microbiomes and metagenomics is necessary to determine the processes. 

Present biomarkers will be the future theragnostic which could outline the suggested diagnostic therapy for the patients and test the new probable medication methods to find the best treatment based on the screening results. There is promising potential in targeted microbiota therapy becoming a treatment method for different diseases.

Across various research institutes, several projects have started which involve modifying the microbiome for treating gluten sensitivity, rheumatoid arthritis, bacterial vaginosis, and even predicting cancer risk. 

The presence of specific strains may have the ability to modulate cancer progression and therapeutics. This increases the likelihood of precision medicine in relation to microbiota in terms of treatment and prognosis. 

Having established the role of the microbiome in maintaining a healthy body, ensuring a balance will be necessary to avoid multiple diseases. Therefore, microbiota is a next-generation medicine and may develop a novel therapeutic role in this field.