Let’s Talk About Microbes

I know that a lot of you have expressed interest in the upcoming flu shot discussion, but I feel the need to do a little background work before launching into that particular discussion. As many of you know, I don’t generally decide that something so pervasive as flu shots is goofy without giving it some real thought first. And it’s hard to put down in a paragraph or two all of the thinking I’ve done about flu shots. Besides, microbes have become really interesting. So, a little background first.

I mentioned Ed Yong’s book “I Contain Multitudes” just a little bit ago. I can’t overemphasize how important and fascinating this book is to me. Here’s why: it isn’t often that a book makes you reconsider your fundamental understanding of how the world works. Honestly, it usually seems to happen with really good science fiction. I’m thinking in particular of “Altered Carbon” by Richard K. Morgan, but I think a couple of the Neal Stephenson books work that way too (“Snow Crash”, “Diamond Age”, “Seven Eves”). So to find that truly paradigm shifting experience in a book of non-fiction is extraordinary made even more so because it’s true.

Let me paraphrase a bit from the beginning of Ed Yong’s book. The concept of the entire history of planet earth expressed as a 12 month time line. It’s a way to illustrate the enormity of geologic time as opposed to our puny concept of time, where time spent on hold with Comcast can seem like an epoch. A couple of highlights from the year:

  • January 1 @ midnight: the earth coalesces from matter in space
  • March 4: the oldest rocks we know of form
  • March 20: algae arrive on the scene
  • July 17: the first cells with nuclei arrive (this would be microbes)
  • November 18: the first basic organisms start to form, including plants
  • December 1: the first insects
  • December 2: the first amphibians
  • December 5: the first reptiles
  • December 13: the first dinosaurs
  • December 14: the first mammals
  • December 22: the first flowering plants
  • December 31 @11:02 pm, just 58 minutes to midnight and the first direct human ancestor makes an appearance.
  • December 31 @11:59 pm: the Revolutionary War

As you can see from this simple illustration, not much seems to have happened in the first 11 months. But, don’t miss that July 17 entry of the first microbes. In this way of looking at the evolution of all animal life on earth, we came on the scene almost 6 months after the microbes. Or, to put it differently, we evolved in an environment that had been completely occupied by microbes for a very, very long time. As mammals, we are Johnny come latelys. As hominids, we are the late coming party crashers, arriving, literally, in the last hour. More to the point, we evolved in the world of microbes.

When I did my medical training (medical school in the late 1980s, surgery training 89–97) I was inducted into the entrenched belief system that the only good “bug” is a dead “bug”. Microbes cause pestilence and disease and are to be eradicated. Almost all of the significant medical advances had involved conquering diseases caused by microbes and this was all the proof anyone needed to know that microbes were nothing but trouble. We didn’t even call them microbes, we called them “germs” in a classic example of demonization. Our medical distrust of microbes spread to the general public and germophobia ran rampant as hand sanitizers and antimicrobial soaps popped up like unwanted mushrooms in a damp field. This may have reached it pinnacle when I saw a dispenser for antimicrobial wipes at a gas pump. I’m not sure I can imagine a much more inhospitable environment for microbes than a gasoline pump handle, but there they were. (As a complete aside, it has always bothered me that we talked about “normal flora” when we talked about microbes that lived in & on our bodies, but we microbes that are pathogens are generically called “germs” and most doctors call them bugs. I should have know this internal inconsistency hid a lot of misinformation!)

Fortunately, not everyone was buying the hype. There were intrepid researchers out there who took a more broad look at microbes and have slowly begun to put together a much more nuanced picture of how we interact with them and the important roles microbes play in everything from planetary health to our day to day health. Not just in disease states, but the ways we co-exist with these partners that have been present long long before multicellular organisms ever existed on planet Earth.

As some of you know, I’ve prattled on a bit about the “gut micro biome” in several posts. Worry not, I will be writing about this for years to come as new and fascinating things come to light. But for those who are wondering if there’s really any practical use to all of this ridiculous micro biome thing, let me close with a little talk about Clostridium difficile colitis. Known as C. diff. colitis in the medical world, this is a disease that is a significant problem that is occasionally fatal and costs us untold millions of dollars to diagnose and poorly treat. And it’s a micro biome problem through and through.

Most people who get C. diff. colitis get it after exposure to antibiotics. That is, they are given antibiotics to treat some problem (whether the antibiotics were a good idea or not in the first place is not the point of this particular discussion, but, as you’ll see, it’s an increasingly germane discussion) and, as a result of the antibiotics, they develop abdominal pain, cramping and diarrhea. Particular to C. diff colitis is a smell, which is hard to forget once you’ve experienced it and is virtually diagnostic. Severe cases can develop breakdown of the lining of the colon (large intestine) which allows bacteria access to the blood stream and can be fatal. Suffice to say, it’s not a problem to be taken lightly. So what happens? How does a dose or two of antibiotic cause such havoc? The answer is that we have trillions of bacteria living in our intestines. All mammals do. These bacteria live in a fairly balanced relationship with our body and immune system and play some pretty important roles. One of the many species residing there is C. diff. But C. diff is resistant to most of the antibiotics you might receive. So as you take antibiotic tablets for that sinus infection, upper respiratory infection, urinary tract infection, etc. the antibiotic can also kill off a large number of the bacteria in your large intestine. As the other bacteria disappear, C. diff has an opportunity to reproduce and take over a bigger role in the gut and, if conditions are right, it will do so. Doctors call this an “opportunistic infection”.

So what’s the treatment for C. diff colitis, a disease caused by the use of antibiotics? Why, more antibiotics, of course! This time specific (and expensive) antibiotics that are generally active in killing off the C. diff as well as the rest of your gut bacteria with the hope that, if you clear everything out, what grows back *should* be more or less normal. It’s like treating your house fire with a couple of cans of gasoline. No wonder some physicians describe this sort of therapy as “flaming the landscape”. In retrospect, probably the most remarkable thing of all is that it has worked more often than not. But it doesn’t always work and some very unfortunate people are left with a chronic C. diff infection that is very hard to shake.

Enter new thinking and a miracle cure. If you take a big step back from the germs as enemies way of thinking and instead think about the colon as an ecology, interesting things start to happen. In the setting of C. diff, the fundamental problem is not that C. diff is there, it has always  been there. The problem is that the other bacteria, that usually keep C. diff in check, are gone. So, can anyone think of a way you might replace the other bacteria that people with C. diff colitis are missing? Or, to reframe the problem in a different language, how could you restore the normal micro biome of the gut? The pretty cheap answer to this conundrum is to transplant a normal micro biome back into the disease colon. Where could you find normal micro biome to transplant? Sorry to say, if you hadn’t already seen this coming, but that’s pretty much what the feces from a healthy person is. So the answer, it turns out, is fecal transplantation. It works, it’s cheap, and it treats the problem in a way that those mired in old “germs are our enemy” thinking have a hard time accepting. Imagine the thought of transplanting trillions of active microbes into a diseased colon and hoping it will cure the problem.

It turns out that it works so well that there is now a preparation for instilling into the colon of people with C. diff colitis. It is a mixture of the bacteria found in a normal, healthy colon grown in the lab and capsulized for easy delivery. The best part? It’s called RePOOPulate. I shit you not. Read about it here.

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