The Antibiotic Revolution

No one can argue that antibiotics were not a revolution. The invention of these molecules have saved more lives that one can imagine. In fact, it is likely that antibiotics have saved you from something that was deadly less than 250 years ago (think strep throat). However, as with everything, great power comes at a cost. In the case of antibiotics, we are just now coming to realize the toll they may be taking on our bodies and our healthcare systems.

Most antibiotics are considered broad-spectrum. This simply means that the antibiotic molecule is not specific to a single pathogen; it will inhibit the growth of all microbes it comes in contact with. While this is useful to combat unknown bacterial pathogens quickly, it also means that our microbiomes pay a price.

Whenever we consume an antibiotic, a significant portion of it makes contact with our gut bacteria before getting absorbed. Thus, the stability of our microbiomes gets significantly disrupted as populations of bacteria rapidly get wiped out. This effect varies by the type of antibiotic consumed. For example, vancomycin is known to eliminate more Firmicutes bacteria than any other phylum, thus changing the delicate species ratios of bacteria in your gut. In contrast, amoxicillin does not seem to have this particular effect.

Tipping the Symbiotic Balance

This disruption of the balance of microbes is especially concerning. Our microbiome is a symbiotic community. This means that each bacteria relies on other bacteria for their survival. Just like you rely on people to grow your food and make your clothes, our gut bacteria rely on each other to detoxify molecules and generate their food. When an antibiotic is ingested, it may wipe out one of these essential bacterial species, resulting in the death of countless dependent bacterial species.

For example, one of the essential classes of bacteria in our small intestines are responsible for detoxifying the bile acids our body secretes to digest fats. Without them, all of the bacteria living in the area would be wiped out by the toxic molecule. Some of these bacteria are sensitive to antibiotics and get wiped out upon ingestion of the molecule. If enough of these bacteria die, the resulting flood of toxic molecules would wipe out the entire community living in the area.

On the same note, further modification of these bile salts happens in the large intestine. This final modification is essential to inhibit the growth of the pathogen Clostridium difficile. Elimination of these bile-modifying bacteria has made C. diff. infection the leading cause of antibiotic associated diarrhea.

Microbiome Response to Antibiotics

Just like pathogens develop antibiotic resistance, so do gut bacteria. This initially may sound like a good thing, but there is a catch. The only bacteria that develop this resistance are the ones that can survive the initial exposure to antibiotics. For the sensitive bacteria that get wiped out upon the first encounter with this medication, there is no chance to develop resistance. This significantly reduces the diversity of your gut microbiome.

Horizontal Gene Transfer and Antibiotic Resistance

Bacteria are very cooperative organisms. Just like us humans share information through electronics (i.e. this blog post), bacteria share information through genes. Unlike other organisms, bacteria are able to transfer genes to their neighbors with relative ease. This process is known as horizontal gene transfer and deserves a blog post of its own.

In the context of our antibiotic situation, this means bacteria that evolve antibiotic resistance in our guts will share that new “technology” with their neighbors. These neighbors are basically all the bacteria that scraped by during the initial few antibiotic dosages. These bacteria will receive the antibiotic gene so that the next time you swallow an antibiotic, they will be better prepared and suffer fewer losses. These newly resistant bacteria will now grow unhindered as you continue your antibiotic treatment, taking over the habitats that the sensitive bacteria inhabited.

This explains it is hard to restabilize your gut after antibiotic treatment. The bacteria that survive in your gut grow resistant to antibiotics and take over the dead bacteria’s habitat, altering the structure of the gut community.

Antibiotic-Induced Metabolic Changes in the Gut

Since the general effect of antibiotic treatment is a reduction in the total number of bacteria present in the gut, it is important to understand what kind of effects this basic alteration has on your body. First of all, a reduction in total bacteria means a reduction in fiber metabolism. Bacteria break down fibers into short chain fatty acids (SCFAs), which are absorbed by our bodies. These SCFAs are also important signalling molecules which tell the body that the gut is healthy.

As levels of SCFAs are reduced, the body prepares for gut infection by becoming inflamed. This happens because the body correctly infers that a drop in SCFA means a reduction in good bacteria and an increase in uninhabited gut surfaces. The inflammation is possibly a proactive response to colonization from potential invaders.

Antibiotics and Immune Signalling

Another important effect of antibiotics is on the signalling pathways between microbes and the human immune system. In normal situations, your gut bacteria are constantly telling your body to secrete molecules that are toxic to pathogenic organisms. When antibiotics wipe out your microbiome, these signals are significantly reduced. As a result, pathogens have an opportunity to colonize your gut before the good bacteria can repopulate. When the numbers of bacteria are low, your gut immune system grows lazy. This is because it does not need to be as alert when there are fewer bacteria to keep track of. This reduction in signaling molecules thus reduces the number of immune cells present in the gut lining.

Systemic Immune Changes

In fact, the gut immune system is not the only part of your body’s defenses that gets lazy. Reduction in gut signalling also reduces the number of neutrophils (a type of whit blood cell) in your blood and bone marrow. In your lungs, numbers of macrophages drop, production of the antiviral molecule interferon slows, and levels of the antibody IgA also fall. All of these things probably happen because your entire immune system is concerned about your gut bacteria. After all, the gut is the organ that poses the highest risk for infection. Your body has to constantly monitor your microbiome to make sure no bacteria are misbehaving or damaging the body. Thus, when levels of gut bacteria drop, the entire immune system relaxes for a while.

Countermeasures to Antibiotic Drawbacks

Thankfully there are a few countermeasures everyone can take to reduce the effects of antibiotic use. The most obvious one is to only take antibiotics when there is a clear need for them. If you are a doctor, then it is important to use good judgment when prescribing these molecules to patients. That said, when you are prescribed antibiotics, it is important to complete the entire course of antibiotics prescribed to you. If you don’t, the (now potentially resistant) pathogenic bacteria might bounce back and force you to take even more antibiotics.

While you are on antibiotics, it is important to take probiotic supplements. As discussed in an earlier post, while probiotics often don’t help colonize your gut, they do stimulate your immune system. As the probiotic bacteria pass through the gut, your immune system has to remain vigilant and scan for intruders. This will help combat the immune-relaxing effect of these medications. Perhaps in the future, we will be able to take an oral supplement of gut-signalling molecules during antibiotic treatment but we are not there yet. In extreme cases of microbiome population loss, a fecal transplant from a healthy donor is an effective way of restoring diversity to your gut microbiome.

Conclusion

Antibiotics are a very powerful tool that humanity has developed to combat our natural enemies. However, our evolutionary allies are unfortunately caught in the crossfire. It is important to know exactly how antibiotic treatments are affecting your body in the long run. Equipped with this information, people can make decisions to mitigate the negative aspects of antibiotic treatment and preserve their long term health. After all, proactive action always trumps reactive action.