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How Clostridium difficile takes advantage when we weaken our microbiome.
20 years ago I suffered from a serious and dangerous bacterial infection. I had already described this in the article "Antibiotics - the molecular atom bombs". On a visit to Seattle, I got the full force of the symptoms of a Clostridium difficile infection. Bloody diarrhea, bloody sputum, and rapidly rising fever. I was lucky that my visiting friend was a medical doctor, so I was able to get treated quickly. Other people are not so lucky.
Each year in the U.S. alone, approximately 450,000 people contract Clostridium difficile infection. 35,000 of them die (2015 figures). In Germany, an average of 30,000 people become infected each year, 10% of whom die.
But I wasn't just lucky that I didn't die. I was also lucky that C. difficile did not come back. That is not something that can be taken for granted. That's because a disastrous and self-reinforcing cycle often develops as a result of infestation with this bacterium. More on this later.
C. difficile is actually a bacterium that can only establish itself in a host with difficulty. This is because the gram-positive rod is strictly anaerobic. Oxygen kills it. This makes it almost impossible for the bacterium to infect a human, because normally you move in an oxygenated environment. But C. difficile has one major advantage: it can form spores.
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Spores and Vampires
Spores are special states of bacteria that enable them to survive in life situations that are unfavorable for them. The bacteria go into hibernation, so to speak, which can last hundreds or even thousands of years. A spore-forming bacterium notices that the current living conditions are extremely unfavorable for its survival and starts to form spores. These special forms of life contain the complete genetic information for this bacterium, but are otherwise like a vault. It can also be compared to a vampire, which can lie death-like in its coffin for thousands of years until it is suddenly reawakened. The spore can survive extreme situations such as radiation, heat, cold, etc. and requires hardly any energy for its existence. However, as soon as the living conditions become favorable again, the spore starts to germinate, i.e. a complete cell is formed, which can then divide again.
The spores are never dead
One of the oldest spores came from the abdomen of a bee, which was enclosed in amber and thus preserved for 25-40 million years. Even 250 million years old spores were discovered in salt crystals.
In America, there is the Alcor Life Extension Foundation, which for 200,000 USD freezes a body shortly after death by means of a special procedure in order to bring it back to life sometime in the future. It can also be done cheaper: for 80,000 USD, only the brain is preserved. The intention is the same as with the spores: to save the body from decay until living conditions are so favorable and technological progress is so immense that a disease can be cured. In contrast, however, the spores are never dead - they live, albeit at a very low energetic level.
The C. difficile infection
C. difficile usually infects humans via spores. These can settle in the intestine and do no harm at first - they wait. And wait. Approximately 5% of all adults carry such spores. In hospitals, the number is much higher. There, C. difficile can be detected in 20 - 40 % of all patients. However, our healthy microbiome prevents their germination and the growth of vegetative C. difficile. But as soon as the microbiome is severely damaged and in the worst case collapses, the C. difficile spores "notice" that their environment has changed positively and germinate. This happens furiously. Within a very short time, they colonize the intestine.Through the formation of their toxins, they lead to severe inflammation of the colon, the so-called peudomembranous colitis. This can also lead to a life-threatening rupture of the intestinal wall. 10% of all patients die.
So here again we have the case of a pathogenic, even deadly bacterium being kept at bay by our microbiome. It prevents it from multiplying in the intestine.From this we see how enormously important it is not to damage our microbiome.
It is enormously important to have a diverse and stable microbiome
But what causes the breakdown of a microbiome? In most cases, a broad-spectrum antibiotic, which unspecifically is supposed to kill only one germ, but in fact destabilizes the entire microbiome in the worst case so that germs that otherwise have no chance can grow. In the case of C. difficile, it takes 4-6 weeks.
Therefore, it is enormously important to have a diverse and stable microbiome. The more diverse it is, the more difficult it will be for an antibiotic to do massive damage.
But another factor can also support the development of a C. difficile infection.
Proton pump inhibitors: The new addiction
I previously reported how widespread control of one of our oldest residents, Helicobacter pylori, has increased reflux worldwide. This pushes stomach acid into the esophagus, causing a burning sensation and can develop into Gastroesophageal Reflux Disease (GERD) in the long term. Helicobacter is known to activate a number of hormones that play a role in the regulation of gastric acid. If this regulation falls away, stomach acid can increase dramatically, causing reflux and further resulting disease. In these cases, doctors like to prescribe proton pump inhibitors (PPi), which suppress the formation of stomach acid. Therefore, they are also called acid blockers.
This is where the whole problem becomes apparent, when humans influence the natural cell - bacteria symbiosis. If Helicobacter is eradicated with antibiotics, there is an increase in gastric acid. This in turn is combated with PPi. The strong decrease of the pH-value in turn leads to the fact that the stomach can become a new gateway for other bacteria. These would otherwise have no chance. By fighting a bacterium, medicine creates new problems, for which it in turn offers new drugs. And one of the bacteria that benefits from this is C. difficile.
This negative spiral leads to a high percentage of patients relapsing
But it gets worse. So when an antibiotic and the use of proton pump inhibitors dramatically weaken the microbiome and an infestation of C. difficile occurs, with the spores germinating and overgrowing the intestine, an antibiotic, metronidazole or vancomycin, is again used to combat it. These strong antibiotics destroy the vegetative C. difficile cells, but in turn weaken the microbiome, which is already considerably destabilized. Thus, an antibiotic is used to combat a germ that was able to prevail against the rest of the bacteria in the first place through the use of antibiotics. This negative spiral leads to a high percentage of patients relapsing once the antibiotic is discontinued. This is because, of course, there is no longer a sufficiently diverse microbiome left to stand in the way of the spores germinating again.
To avoid death, a colectomy is then used in many cases, resulting in complete removal of the intestine. The patient may survive but his quality of life is severely diminished forever.
A new glimmer of hope?
Therefore, treatment options had been sought to break this negative downward spiral and also found: Fecal transplantation. Here, the stool of a healthy donor is transmitted into the intestine of the diseased person. This can be done by endoscopy or capsules. This fecal transfer has had resounding success in combating C. difficile infections. On average, relapse was avoided in most cases (90%). The patient became healthy and his microbiome recovered. But at what cost? Long-term studies are not yet available. So the chain continues: the use of antibiotics leads to an infection, which is first treated by another antibiotic. If this is unsuccessful, a part of a foreign microbiome is implanted, which is successful in the first instance, but can in turn lead to a significant change in the original microbiome. This again leads to new dangers, which will be discussed in another article.
The ghosts I called, I will not get rid of now.
We see that by human intervention in the microbiome we always trigger a chain of events that is difficult to control. Freely according to the motto of Goethe "the ghosts I called, I will not get rid of now."
What can be done?
The C. difficile infection cycle clearly shows that a stable microbiome is the best protection against pathogens. So it is essential that we try to maintain a diverse and healthy microbiome. I will show strategies for this in some later articles. In addition, we need to be aware that the use of an antibiotic always carries imponderable risks, so we need to think carefully with our treating physician about whether its use is necessary. It can go well - but it doesn't have to. My experience in Seattle had clearly shown that to me.
We have to keep our microbiome diverse and alive by all means.
Last but not least, the practice of massively prescribing proton pump inhibitors needs to be questioned. My former family doctor told me "he prescribes the stuff like crazy because people eat it like candy every day." You don't have to be an expert to realize that this can't be healthy in the long run.
Yet many patients will be completely unaware that they are interfering with the composition of their microbiome by swallowing proton pump inhibitors.
Although it may seem demanding, there is no way around the fact that people have to take personal responsibility to keep their microbiome healthy and stable. This may not correspond to the mentality of leaving one's own "repair" to the doctor and not taking care of it. But this way of looking at things leads out of the role of a defenseless victim into a position where active shaping of health is possible.
The human being and his processes are complex. Many things are directly or indirectly related to each other. Just as we destroy soil fertility through monoculture in agriculture, if we do not take care of our microbiome or weaken it with medications, we make ourselves vulnerable to disease. We have to keep our microbiome diverse and alive by all means.
Otherwise we are unguarded.
Further reading and sources:
Bagdasarian N, Rao K, Malani PN (2015) Diagnosis and Treatment of Clostridium difficile in Adults: A Systematic Review. Jama 313:398–408. https://doi.org/10.1001/jama.2014.17103
Green JE, Davis JA, Berk M, et al (2020) Efficacy and safety of fecal microbiota transplantation for the treatment of diseases other than Clostridium difficile infection: a systematic review and meta-analysis. Gut Microbes 12:1854640. https://doi.org/10.1080/19490976.2020.1854640
Lessa FC, Mu Y, Bamberg WM, et al (2015) Burden of Clostridium difficile Infection in the United States. New Engl J Medicine 372:825–834. https://doi.org/10.1056/nejmoa1408913
Ma Y, Yang JY, Peng X, et al (2020) Which probiotic has the best effect on preventing Clostridium difficile-associated diarrhea? A systematic review and network meta-analysis. J Digest Dis 21:69–80. https://doi.org/10.1111/1751-2980.12839
Sholeh M, Krutova M, Forouzesh M, et al (2020) Antimicrobial resistance in Clostridioides (Clostridium) difficile derived from humans: a systematic review and meta-analysis. Antimicrob Resist Infect Control 9:158. https://doi.org/10.1186/s13756-020-00815-5
Smits WK, Lyras D, Lacy DB, et al (2016) Clostridium difficile infection. Nat Rev Dis Primers 2:16020. https://doi.org/10.1038/nrdp.2016.20
This article does not contain any medical advice. Please read the full disclaimer.