Fighting Infections in a Microbial World

How your personal bacterial ecosystem protects you from pathogens

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Abstract:

Bacteria can be found everywhere, including in the human body where it plays an important role in our health. Your bacterial ecosystem is referred to as your microbiota and helps protect you from infections. This article discusses how we came to realize the importance of our microbiota, how it helps our immune system, and how this microbial defense system may be at risk.

Main Article:

The Age of Bacteria

Renown paleontologist Stephen Jay Gould wrote that “this is truly the ‘Age of Bacteria’ – as it was in the beginning, is now and ever shall be” (1994). The dinosaurs, in over 150 million years of prowling, were just a passing phase for our fellow microbes. In a world of microbes, we’re just new arrivals.

We are now aware of the extent of bacterial domination. Sure, they are small, but on a global scale we are far outweighed, ten thousand to one. Even in our own bodies, we’re outnumbered – your body has ten times more bacterial cells than human cells – on your skin, in your airways, and in your gut. We call this microbial ecosystem our microbiota, a term that also includes resident fungi, archaea, and protozoa, but is often used to describe our diverse bacterial populations, which include over a thousand species in the average human adult.

This understanding of a bacterial world didn’t come overnight, but developed over the last few centuries like a Copernican revolution, shifting our biological worldview. Credited with the discovery of cells, Robert Hooke, popularized the use of the microscope for scientific research in the 17th century, springing a series of observations that would develop into microbiology. Soon afterwards, the Dutch scientist Antonie van Leeuwenhoek, observing saliva samples, would be the first to identify bacteria in 1676 and begin the cataloging of microbes that still continues today.

Over the next two centuries, developments in microbiology showed that bacteria were the cause of various communicable diseases. Yet, it took a cholera outbreak and the work of scientists including John Snow, Louis Pasteur, and Robert Koch, to convince the medical community of “germ theory” and finally introduce hand-washing to the operating room. The reality of a bacterial world was beginning to sink in, but with good sterile techniques, improved community hygiene, and the later arrival of antibiotics in the 1940’s, we believed that we could defend ourselves from bacteria.

Yet, we were also realizing that while there were “bad” bacteria, or pathogens, there were also “good” bacteria, or commensals. These bacteria, which varied from person to person, could help digest complex nutrients, prevent common gut diseases, and improve our immune system. The influence of our microbial ecosystem on our health led to our microbiota being described as a “forgotten organ” (O’Hara & Shanahan, 2006) and our bodies labelled as a “superorganism – of microbes and men” (Sleator, 2010).

This path of discovery is ongoing, as modern advances in DNA sequencing and microbiological techniques have enabled greater insight into our bacterial communities. Large scale initiatives like the Human Microbiome Project are allowing researchers to observe population-wide patterns and characterize individual bacterial strains that may have health implications for you and the global community.

Microbial Defenders

Your ecosystem of a hundred trillion bacteria serves many important functions, including its key role in nutrient metabolism that contributes to your overall health. But these bacteria are also critical in defending your body from infections. These effects are mediated in two main ways: blocking pathogen growth and training our immune system.

Consider a bacterial neighbourhood. Simply by being present and occupying the houses on your street, your microbiota is a great deterrent preventing pathogens from moving in next door. Your commensals establish this dominance by colonizing ecological niches and producing compounds called bacteriocins that are toxic to other bacteria.

Having this bacterial community established throughout your body is among the first line of defense against a pathogenic invasion. This function explains why antibiotic therapy, which eliminates a lot of your resident microbes, makes individuals more prone to invasions by Clostridium difficile, a difficult-to-treat infection that causes severe diarrhea and possibly death (Brown et al., 2015). C. difficile is a costly problem for hospitals, where the pathogen often spreads among susceptible patients.

In reality, the distinction between good and bad bacteria is less clear, as some commensals may proliferate and “go rogue” if given the opportunity. Furthermore, some bacteria like C. difficile, which are usually pathogenic, may be present in small numbers in a healthy individual, kept in check by its neighbouring bacteria (Kamada et al., 2013).

Our gut microbes also play a role in immune system development. Our immune system directs our body’s response against pathogens, but fails us when it overreacts, causing an undesired immune response, or under reacts, allowing pathogens to invade. The microbiota is able to fine-tune our immune response, first by training our immune system to become more tolerant to its bacterial population. Not only does this tolerance prevent attacks to our commensal bacteria, this training also suppresses allergic reactions and reduces the chances of developing autoimmune conditions like Crohn’s disease (Campbell, 2014).

Also, by fine-tuning our immune system to recognize resident microbes, the body is sensitized to targeting foreign invaders. A 2012 study demonstrated that the presence of the commensal Staphylococcus epidermidis allowed mice to defend an infection from the pathogen Leishmania major (Naik et al.).

The more we know about our microbiota’s immune functions, the more we can incorporate these microbes in our medical treatments. For example, a strain of Clostridium scindens has recently been shown to have protective effects against C. difficile infections (Buffie et al., 2015). In all, it is important to realize that we don’t face pathogens alone: our microbiota helps us to fight these microbial battles.

Managing Microbes

Like any part of our body, our microbiota can be compromised, making us more vulnerable to immune diseases and infection. The developed world has seen a marked increase in conditions like asthma and allergies, which has been attributed to a reduction in microbial exposure in a cleaner, more sterile, society. This phenomenon has been termed the hygiene hypothesis.

Martin J. Blaser, author of Missing Microbes, specifically attributes the deterioration of our microbial ecosystem to modern medicine. Our extensive use of antibiotics and increased reliance on elective Caesarean deliveries, which prevents newborns from being exposed to their mother’s vaginal microbiota, have led to reduced diversity in our microbial communities and a loss of certain bacterial strains that may have protective effects (Blaser, 2014).

So what can we do to maintain our microbial defenses? Most importantly, being aware of our microbiota allows us to be more informed about our health care decisions. For example, while antibiotics are used in the life-saving treatment of bacterial infections, they are often prescribed unnecessarily for cold symptoms that are more often caused by viruses unaffected by these bacteria-targeting drugs. This overuse has led to other pressing problems like antibiotic resistance, but also disrupt your microbiota, potentially interfering with its protective effects.

Other treatments, including probiotics and prebiotics, are also being developed to introduce good bacteria into our gut and maintain a stable, healthy microbiota. Yet, manipulating the microbiota remains a developing science, and claims of commercial probiotic benefits require further study. Thus, it is important to stay up to date and well-informed about ongoing microbiota research and to ask your healthcare provider if you have any questions about treatment decisions that may affect your microbiota.

In the age of bacteria, these developments are just another small step for mankind as we reorient ourselves in a microbial world. Our ability to steer our own health by managing our microbiota will only improve as we learn more about our microbial neighbours and their role in pathogen defense.

References:

Blaser, M. (2014). Missing Microbes: How The Overuse Of Antibiotics Is Fueling Our Modern Plagues. New York: Henry Holt and Company.

Buffie, C. G., Bucci, V., Stein, R. R., McKenney, P. T., Ling, L., Gobourne, A., … Pamer, E. G. (2015). Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature, 517, 205-208.

Brown, K., Valenta, K., Fisman, D., Simor, A., & Daneman, N. (2015). Hospital ward antibiotic prescribing and the risks of Clostridium difficile infection. JAMA Internal Medicine, 175(4):626-633.

Campbell, A. W. (2014). Autoimmunity and the gut. Autoimmune Diseases, 3, 152428.

Gould, S. J. (1994). The evolution of life on the earth. Scientific American, 271(Oct), 85-91.

Kamada, N., Chen, G. Y., Inohara, N., & Núñez. (2013). Nature Immunology, 14, 685-609.

O’Hara, A. M. & Shanahan, F. (2006). The gut flora as a forgotten organ. EMBO Reports, 7(7), 688-693.

Shruti, N., Bouladoux, N., Wilhelm, C., Molloy, M. J., Salcedo, R., Kastenmuller, W., … Belkaid, Y. (2012). Compartmentalized control of skin immunity by resident commensals. Science, 337(6098), 1115-1119.

Sleator, R. D. (2010). The human superorganism – of microbes and men. Medical Hypotheses, 74(2), 214-215.

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