22. The Owner's Manual: How We Damage the Microbiome

Scene: A medieval castle and the village within its walls are under siege. The ranks of the soldiers have been depleted by injuries. The villagers are weak from days with limited food supplies and now water is low and being rationed. The castle guards are losing the ability to defend the gates and they can’t maintain the strength of the fortifications. The castle walls are failing, crumbling, and the wooden structures inside the walls are on fire or already burned. The entire community is ripe for overthrow and domination by an invading force that seems to get stronger every day…..

Diversity is the key to stability

I'm trying to stress that we, as humans, are not individuals in the sense that we normally think of. We are self-contained mobile ecosystems with limited but strong connections to the outside world. Our bodies are the vehicles that contain and transport a tremendous internal world of life through the external environment surrounding us. If we as individuals feel stress, it is likely the microbiome feels stress; if the microbiome is stressed, it is almost certain that our human bodies are affected.

For a microbiome, stress is anything that reduces the diversity of the ecosystem. We know from studies in ecology that species diversity in communities is the source of strength for those communities. The loss of species (or a great reduction in abundance) results in several negative consequences for the community. The functions that those species offer to the community are reduced or lost. Think of having a computer keyboard where one of the keys has stopped functioning and how that affects spelling, grammar, and meaning in everything you might try to write. The more keys that are missing, the less sense the writing will make.

A reduction of diversity results in reduced resistance to change. That is, in a highly diverse and inter-connected system, it is difficult to change the system by removing a single piece because all of the other connections can bear the change in stress. But if enough of the system’s components are removed or cease to function, the ability of the system to withstand additional stress is lost. (Think about playing Jenga.) Metaphorically speaking, after many subtractions, the loss of one more piece becomes the straw that breaks the camel’s back.

Even in highly diverse and inter-connected systems, a great stress can sometimes occur and push the system in a new direction. However, diversity also lends a great degree of resilience to change and the system can often return to its original state. You’ve undoubtedly seen a slow-motion video of a ball being struck so hard that the shape of the ball is flattened on one side, but once the ball moves away from the striking force, it regains its original shape. The ball is resilient. It recovers its shape when the stress is removed just as diverse ecosystems can absorb an environmental stress and recover.

The ability to absorb stress and continue without a loss of function is a form of plasticity. It is one of the hallmarks of human physiology: this springy, plastic, resilient characteristic of humans that allows us to live in harsh environments, eat a tremendous variety of foods, and withstand a barrage of diseases.

While it’s true that before about 100 years ago, we were often at the mercy of the environment and just making it through childhood was one of the great survival filters we faced, the fact is that humans have survived thousands of years of the stresses associated with life in large communities. Today, we have the advantages of advanced technology to protect us from the ravages of the environment, but these “advantages” may also be working against us.

I hope it is now obvious that technology changes the context of our lives as BIGs. It also changes the context of our microbiome, our BUGs, but they are able to adjust almost immediately. However, in the past 75 years, technology has allowed us to dramatically change the context in important ways, and those changes have become constants in our world. They do not allow for the microbiome to “bounce back”.

We have reached a point where these major changes to the system are reinforcing other changes and we are witnessing a cascading effect on our health. It’s time we recognized that stress after stress after stress to the system may ultimately cause failure of the system.

I am not saying that modern medicine is bad. You and I are alive because of it. However, the obvious positive effects of such technology often mask subtle negative effects that go unnoticed. The accumulation of these smaller, subtle effects is emerging to reveal real problems, but because they are the result of numerous small changes, we are essentially blind to the actual cause-and-effect process.

For example, vaccines were first introduced to the public on a large scale after 1900, and by 1930 a number of serious viral and bacterial childhood killers were under control, including diptheria, typhoid, whooping cough, scarlet fever, and tetanus. The vaccine system is one that introduces some part of the pathogen into the body’s system and the immune system responds. The immune system produces an antigenic response that recognizes the pathogen as foreign and dangerous. That is, we make antibodies against the pathogen and from that point on the system is alerted to any future appearances of the pathogenic proteins.

In a healthy system, the vaccine has educated the immune system concerning a particular pathogen and thereby prevents that pathogen from overcoming the immune system in the future.

In contrast, antibiotics (introduced in 1945 beginning with penicillin) were also intended to defeat bacterial pathogens, but using a different process. A strong immune system will hunt down and destroy pathogens under normal conditions, but in a weakened system, the body’s immune defenses are unable to control the growth of the pathogen and the result is disease. Antibiotics provide the missing service and are essentially an introduced defense system.

However, it is important to recognize the fundamental nature of this interaction. Taking a broad-spectrum antibiotic is akin to hiring a defense contractor who shows up for work only after the walls of the fortress have been breached and many of the houses are already on fire. In addition, the defense contractor shoots indiscriminately at anything resembling the enemy in the belief that collateral damage is not important as long as the enemy is killed. When used appropriately, antibiotics are applied only after the disease has taken hold and they are tremendously effective at controlling and stopping active bacterial infections, and this saves lives, but it also may come at a cost.

The important difference between vaccines and antibiotics is this: vaccines strengthen our immune system and antibiotics temporarily replace it. By using antibiotics, we supplant the multiple natural abilities of the biological system with the single ability of a technological system. It works, but only in the sense that a dangerous pathogen has been stopped. It does not work in the sense that the immune system is strengthened by the experience. Instead, the immune system has been bypassed and perhaps even damaged.

If we accept the recent and compelling research that the microbiome plays an integral role in educating and informing our immune system, and we understand that broad-spectrum antibiotics indiscriminately wipe out any bacteria that have basic similarities to the target pathogen, then the frequent use of antibiotics is weakening our innate ability to defend ourselves from disease.

This happens because by greatly reducing the diversity of the bacteria in our microbiome, we reduce our resistance and resilience, we reduce our immune system’s ability to learn and respond, we reduce our communication with the source of our plasticity, the microbiome. And I say “we” because we as individuals are not separate from the vast bacterial community within us. “We” are one and the same and what happens to them also happens to us.

The actions of antibiotics on our microbiome are indisputable. Martin Blaser[i] has written an eloquent denunciation of antibiotic overuse and misuse and the possible connections with the emergence of certain “modern diseases”, such as acid reflux and esophageal cancer. In another review, Pajau Vangay and colleagues[ii] summarized the growing evidence for links between disruptions to the microbiome and childhood obesity, autoimmune diseases, allergies, and susceptibility to infectious diseases.

Of particular importance is the evidence that if antibiotic use, and the resulting impairment of the microbiome, occurs during critical developmental stages in infants, the consequences can be permanent. If there was a suspicion that the emergence of modern diseases is directly related to the loss of microbes and microbial diversity in the human microbiome, I think it’s safe to say that it is no longer a suspicion.....we know it to be true, although we do not know many details.

Since 1945, antibiotics have become an ingrained part of our lives from birth to death. In 2010, 70 billion antibiotic doses were prescribed and the number is growing. Many individuals are taking a course of antibiotics more than once a year. As a species, we had a long and negative history with communicable bacterial diseases and we adopted antibiotics just as quickly as, well, humanly possible. We now fear NOT taking antibiotics when we are faced with an infection or even the possibility of an infection. And the known damage to our system that antibiotics have is considered a reasonable risk compared to the risk of not taking them.

Antibiotics do one thing and do it well: they kill bacteria. After the slow replacement of the Miasma Theory with the Germ Theory of disease from the mid-1800s to the early 1900s, the deployment of antibiotics in 1945 was probably the single most important event in modern medical history. Unfortunately, we prefer to use broad-spectrum antibiotics because we aren’t always sure who the villainous bacterium might be, so we shoot with a shotgun rather than a sniper rifle. Yes, there may be collateral damage, but we know we hit the intended target.

Unfortunately, we are learning, rather slowly and painfully, that the long-term effects of such an approach are, in fact, bad. The effects of the use of broad-spectrum antibiotics can range from zero measurable long-term effects to (potentially) catastrophic influences on health in infants, children, adults, and the elderly by affecting digestion, neural development, and the immune system. But even when it appears there have been zero carryover effects of antibiotic overuse or misuse, we can’t ever be sure because those effects may take years to manifest or, more importantly, they may react with other factors in the environment in unpredictable ways.

As stated before, this is not to say antibiotics are evil. Quite the contrary! Like vaccines, antibiotics are the reason almost all of us are alive today. At issue is our dependency on a one-size-fits-all battering ram approach for dealing with infections, most of which are not lethal or disabling even when left untreated.

At issue is our love affair with a technology that is applied prophylactically when someone is feeling ill, just in case, to prevent the patient from developing a secondary bacterial infection.[iii]

And now, we are finding an additional issue in the fact that we have a built-in defense system, the microbiome, that should be working on our behalf to support our health, prevent infections, and strengthen our immune systems, and the antibiotics we so casually take may damage the ability of that system to function properly. Thus, while the use of antibiotics for serious infections can be lifesaving, the routine use of antibiotics should always be tempered by a consideration of the lasting effects it might have on the microbiome.

[i] Martin J. Blaser. 2014. Missing Microbes (Picador Press). Blaser, M.J., 2016. Antibiotic use and its consequences for the normal microbiome. Science 352:544-545. [ii] Vangay, P., Ward, T., Gerber, J.S. and Knights, D. 2015. Antibiotics, pediatric dysbiosis, and disease. Cell Host & Microbe 17:553-564. [iii] For example, I recently had minor oral surgery and the periodontist prescribed a broad-spectrum systemic antibiotic to prevent an infection at the site of the surgery which was between my two front teeth. It is my hope that such prophylactic prescriptions will be strongly discouraged by all medical associations within a few years. A second hope would be for the development of bacteria-specific antibiotics that can be applied directly to the site of infection.

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