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Our Microbial Frenemies

By Wei Han Chong

How could it be that some of the smallest organisms known to mankind can hold so much influence and cause such calamity in our lives? The significance of these microorganisms have long eluded the greatest microbiologists. But has our perception of these microbes blinded us to their advantages, if any?

Edited by Khoa Anh Tran & Tanya Kovacevic

Issue 1: September 24, 2021

Illustration by Rachel Ko

Throughout human history, diseases and plagues have amassed death tolls reaching hundreds of millions, if not billions. From the Black Death in the 14th century, which killed about 200 million people, or about 30–50% of Europe’s population, to outbreaks of tuberculosis and typhoid fever, resulting in 1.4 million and 200,000 deaths every year, respectively (1, 2, 3). It should come as no surprise then that we have long perceived these microorganisms as a threat to public health and have consequently sought to eradicate these microbes from our environment. But have we been looking at them the wrong way?

First and foremost, we know very little about the microorganisms living around us. In bacterial species alone, some scientists have estimated around a billion species worldwide, though even this value is believed to be a gross underestimation (4).

Before the germ theory, the most widely accepted theories were the spontaneous generation and miasma theories. Spontaneous generation was a simple theory, believing that living organisms could develop from nonliving matter, such as maggots developing from rotting flesh. The miasma theory, on the other hand, was more prevalent throughout both ancient and modern history. From this perspective, “toxic” vapours from rotting organisms or unsanitary locations were believed to have caused disease (5).

This all changed with the germ theory of disease: an idea that would revolutionise our understanding of microorganisms for centuries to come. First theorised as “invisible seeds” by Italian scholar Girolamo Fracastoro in 1546, Fracastoro believed that these seeds could cause disease when spread from infected to healthy individuals (6). For the most part, the basis of the germ theory would continue to follow this logic of a specific microorganism, a “germ”, that could cause a specific disease when invading its host (7).

Yet, it was not until nearly 200 years later that the field of microbiology would see huge developments. In 1861, French scientist Louis Pasteur had disproved the spontaneous generation theory by means of sterilisation and proper sealing of food items, which would prevent microbial growth (8). However, Louis Pasteur would not be the only one contributing to developments in microbiology. In 1884, German scientist Robert Koch would be the first to develop a classification system for establishing a causative relationship between a microorganism and its respective disease, effectively confirming the germ theory of disease (9). Even to this day, Koch’s system is still very much influential in microbial pathogenesis, albeit refined to a higher standard. Now known as Koch’s Molecular Postulates — as opposed to Koch’s Original Postulates — which is a model that places a greater emphasis on the virulence genes causing disease, rather than the microorganism itself (10).

Today, while we have much to thank Pasteur and Koch for in laying the foundation of modern microbiology, undoubtedly one of the biggest discoveries in microbiology was the discovery of the human microbiota. When we think of microbial life, we usually think of diseases and plagues, cleanliness and dirtiness. Rarely do we ever consider the idea of microbes living inside and around us. Yet, even less so can we begin to comprehend the sheer number of microorganisms that live and proliferate all around ourselves. In our gastrointestinal tract, estimates suggest that there are some 100 trillion microorganisms encoding three million genes altogether, which is 130 times more than what we encode ourselves (11).

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Figure 1. Microbes in Food (25)

So, what do we know about the microbiota; specifically, our microbiota? Firstly, we know that the microorganisms occupying our gut do not cause disease, under normal circumstances. Secondly, we know that they can provide us with a multitude of benefits, such as helping us digest complex organic molecules, and preventing invasion of foreign microbes by directly competing for resources and keeping the immune system stimulated. These are just a few of the advantages our microbial allies provide us. However, that is not to say that they pose no danger to ourselves either. Typically, these microorganisms are categorised into being in a beneficial, pathogenic or commensal relationship with its host.

Beneficial microbes, or probiotics, are as the name suggests: these microbes typically provide some form of health benefit to the host and are usually non-pathogenic. Many of the bacterial species found in our gut lumen, for example, have the capability to digest cellulose. As such, without these microbes, digesting vegetables would be a much harder and less rewarding task. Most of the probiotics found in our microflora are of lactic acid bacteria origin and are most common in diets that incorporate fermented dairy products (12). Pathogenic microbes, on the other hand, mostly describe microbes of foreign origin. These microorganisms will infect and exploit the host’s cells, ultimately causing disease. Commensal microorganisms walk an interesting line, in comparison to beneficial and pathogenic microbes. This group of microbes encompasses all of the characteristics described above, depending on circumstance. This ranges from benefiting both the host and microbe, the microbe itself, or even causing disease within its host when given the opportunity. An example of a commensal microorganism is Escherichia coli, or E. coli. It is a bacterium that colonises our gastrointestinal tract as soon as we are born, where it fends off more than 500 competing bacteria species, thanks to its versatility and adaptations to our gut environment (13). Furthermore, the presence of E. coli along our gut epithelium helps to stimulate mucin production, inhibiting any foreign microbes from invading the epithelium (14). However, as is typical of a commensal organism, when given the chance, E. coli is capable of causing intestinal or extraintestinal disease in our bodies. Urinary tract infections due to E. coli are among the most common causes of a microflora-associated infection and often occur when the bacterium is allowed to enter the urinary tract via cross contamination with the anus, where E. coli is typically shed as part of the faeces (15).

Typically, these beneficial and commensal bacteria are found all over our body. They can be found in our hair, on our skin, and as we have discussed, in our gut. Malassezia, for example, is a fungus that colonises our scalp, and is what causes dandruff in most people. While dandruff may be a nuisance to those who experience it, do the disadvantages necessarily outweigh the benefits? The presence of Malassezia on our scalps means that other, possibly dangerous, microorganisms will have to compete with Malassezia in order to invade. Additionally, the stimulation of our body’s defenses due to Malassezia aids in repelling foreign invaders (16). Staphylococcus aureus is another example of a commensal microbe, and an even better example of an opportunistic pathogen that can be found living harmoniously on our skin and nasal passages, helping us fend off other competing microbes just as Malassezia does on our scalp. However, when the skin is pierced, whether by means of injury or even medically through surgeries or treatments, the Staphylococcus bacteria will opportunistically attempt to invade and infect its host (17). As such, Staph infections and outbreaks are among some of the most common forms of hospital-related infections (18).

Source: Thomas L Dawson, “What causes dandruff, and how do you get rid of it?” February 10, 2021, Ted-Ed video (19).

Looking to the future, we have begun to see a spike in non-communicable diseases as opposed to microorganism-based diseases. These include most forms of heart diseases, cancers, diabetes, and others. Still, while the rise of non-communicable diseases is arguably a cause for concern, the return of long extinct diseases and antibiotic resistant pathogens may prove costly. Staph infections, as previously mentioned, are extremely common in hospital environments where continued usage of antibiotics such as penicillin or methicillin has produced a “super strain” of Staphylococcus that is resistant to most commercially available drugs (20). Currently, superbugs such as multidrug-resistant mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus are most common in healthcare settings, but community transmissions have become a concern (21). As such, with our current practices of antibiotic overprescriptions and continued reliance on sterilisation, future outbreaks of mutated and resistant pathogens may be inevitable.

That being said, should we redefine what “clean and sterile” means to us? Should “sterile” necessarily be a microbe-free environment? Our perception of microbial life has consistently been “antibacterial” and believed to have been a threat to public health ever since the inception of the germ theory. However, the fact of the matter is that these microorganisms are unavoidable. There are microorganisms living all over us. Our fingers, our phones, even the soles on our shoes carry certain microorganisms. In hospital rooms, the composition of microbes is constantly changing as patients and visitors enter and leave (22). Besides, the composition of microbes in the environment is not determined solely by its occupants. Other factors, such as ventilation and even architecture, can determine what microbes we find in our environment. In fact, hospital rooms with more airflow and humidity were found to have suppressed the growth of potential pathogens and had fewer human-associated bacteria in its microbial composition (23).

Just as the microbe composition in the environment can be determined by architectural and building factors, the microbe composition in our microflora can hold incredible influence over our physiology. Dysbiosis, an imbalance in our microflora, can occur as a result of repeated consumption of antibiotics, and it is a serious illness resulting in a significant loss of beneficial and commensal microbes (24). Consequently, invasion and colonisation capabilities of foreign pathogens is increased; as has been shown in antibiotic-treated mice exposed to M. tuberculosis, where pathogenic colonisation was promoted when in a dysbiotic state (25). Other factors, such as diet and lifestyle, also contribute as “disturbance” factors that influence dysbiosis, as can be seen in typical Western-style diets that mostly consist of high fatty and sugary foods (26).

In the future, while the crises of pandemics originating from drug-resistant superbugs loom over us, our understanding of microbial life has come far; from its humble beginnings as a rejected theory amongst scholars, to the discovery of an extensive microbial ecosystem inside of our guts. Despite that, our comprehension of this “hidden world” remains lacking, and we have yet to fully realise the potential of microbial life. Throughout history we have constantly taken an antimicrobial stance to preserve public health, but in recent times it has become increasingly clear that these microorganisms play a much greater role in health.

References:
1. LePan, Nicholas. “Visualizing the History of Pandemics.” Visual Capitalist. Last modified September 2021. https://www.visualcapitalist.com/history-of-pandemics-deadliest/.

2. World Health Organization. “Tuberculosis.” Published October 2020. https://www.who.int/news-room/fact-sheets/detail/tuberculosis.

3. Centers for Disease Control and Prevention. “Typhoid Fever and Paratyphoid Fever.” Last modified March 2021. https://www.cdc.gov/typhoid-fever/health-professional.html.

4. Dykhuizen, Daniel. “Species Numbers in Bacteria.” Supplement, Proceedings. California Academy of Science 56, no. S6 (2005): 62-71. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160642/.

5. Kannadan, Ajesh. “History of the Miasma Theory of Disease.” ESSAI 16, no. 1 (2018): 41-43. https://dc.cod.edu/essai/vol16/iss1/18/.

6, 8. Greenwood, Michael. “History of Microbiology – Germ Theory and Immunity.” News-Medical. Last modified May 2020. https://www.news-medical.net/life-sciences/History-of-Microbiology-e28093-Germ-Theory-and-Immunity.aspx.

7. Britannica. “Germ theory.” Last modified April 2020. https://www.britannica.com/science/germ-theory.

9, 10. Gradmann, Christoph. “A spirit of scientific rigour: Koch’s postulates in twentieth-century medicine.” Microbes and Infection 16, no. 11 (2014): 885-892. https://doi.org/10.1016/j.micinf.2014.08.012.

11. Valdes, Ana M, Jens Walter, Eran Segal, and Tim D Spector. “Role of the gut microbiota in nutrition and health.” BMJ 361, no. k2179 (2018): 36-44. https://doi.org/10.1136/bmj.k2179.

12, 24. Martín, Rebeca, Sylvie Miquel, Jonathan Ulmer, Noura Kechaou, Philippe Langella, and Luis G Bermúdez-Humarán. “Role of commensal and probiotic bacteria in human health: a focus on inflammatory bowel disease.” Microbial Cell Factories 12, no. 71 (2013): 1-11. https://doi.org/10.1186/1475-2859-12-71.

13, 15. Leimbach, Andreas, Jörg Hacker, and Ulrich Dobrindt. “E. coli as an All-rounder: The Thin Line Between Commensalism and Pathogenicity.” In Between Pathogenicity and Commensalism, edited by Ulrich Dobrindt, Jörg Hacker and Catharina Svanborg, 3-32. Springer: Berlin, 2013.

14. Libertucci, Josie, and Vincent B Young. “The role of the microbiota in infectious diseases.” Nat Microbial 4, no. 1 (2019): 35-45. https://doi.org/10.1038/s41564-018-0278-4.

15. Harvard Medical School. “When urinary tract infections keep coming back.” Published September 2019. https://www.health.harvard.edu/bladder-and-bowel/when-urinary-tract-infections-keep-coming-back.

16. Saunders, Charles W, Annika Scheynius, Joseph Heitman. “Malassezia Fungi Are Specialized to Live on Skin and Associated with Dandruff, Eczema and Other Skin Diseases.” PLoS pathogens 8, no. 6 (2012): 1-4. https://doi.org/10.1371/journal.ppat.1002701.

17. Cogen, A. L., V. Nizet, and R. L. Gallo. “Skin microbiota: a source of disease or defence?” British journal of dermatology 158, no. 3 (2008), https://doi.org/10.1111/j.1365-2133.2008.08437.x.

18, 20. Klein, Eili, David L Smith, and Ramanan Laxminarayan. “Hospitalizations and Deaths Caused by Methicillin-Resistant Staphylococcus aureus, United States, 1999–2005.” Emerging infectious diseases 13, no. 12 (2007): 1840-1846. https://doi.org/10.3201/eid1312.070629.

19. Dawson, Thomas L. “What causes dandruff, and how do you get rid of it?” February 10, 2021. Ted-Ed video, 5:04. https://youtu.be/x6DUOokXZAo.

21. Better Health. “Antibiotic resistant bacteria.” Last modified March 2017. https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/antibiotic-resistant-bacteria#bhc-content.

22, 23. Arnold, Carrie. “Rethinking Sterile: The Hospital Microbiome.” Environmental health perspective 122, no. 7 (2014): A182-A187. https://doi.org/10.1289/ehp.122-A182.

25. Khan, Rabia, Fernanda C Petersen, and Sudhanshu Shekhar. “Commensal Bacteria: An Emerging Player in Defense Against Respiratory Pathogens.” Frontiers in Immunology 10, no. 1 (2019): 1203-1211. https://doi.org/10.3389/fimmu.2019.01203.

26. Schippa, Serena, and Maria P Conte. “Dysbiotic Events in Gut Microbiota: Impact on Human Health.” Nutrients 6, no. 12 (2014): 5786-5805. https://doi.org/10.3390/nu6125786.

27. Sottek, Frank. Microbes in Food. c. 1904. The Tacoma Times, Tacoma. https://commons.wikimedia.org/wiki/File:Sottek_cartoon_about_microbes_in_food.jpg.

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