Antibiotic-associated colitis – Poo transplants!

We’re running out of antibiotics. From methicillin-resistant Staphlycoccus Aureus (also known as Golden Staph) to multi-drug resistant tuberculosis (which is now at the highest levels we’ve ever seen), we are wading in a fast-rising pool of resistant pathogens.

Ampicillin is feeling a bit useless now... (Photo taken by Thomas Tu)

And we’re not walking to shore as quickly as we used to; the number of classes of antibiotics being invented are going down each year. Biotech companies find it hard to profit off of any new antibiotics while others are still semi-effective, so do not fund their research. In the end, it is like ditching water in a leaky boat anyway; pathogens no doubt will find a way around whatever new antibiotics we do end up using. So scientists are looking at alternative ways to control infections, one of which I’ll talk about today.

The problem: Losing bits of intestine.

Clostridium difficile is a close relative to the bacteria that cause tetanus (Clostridium tetani) and botulism (Clostridium botulinum). Like its cousins, C. diff is a hardy organism that forms spores which can survive high temperatures, dryness and changes in pH. C. diff also secretes toxins and thrives in environments with low levels of oxygen. C. diff’s environmental niche is the human gut, where it normally hangs out in ~2-5% of the population and causes not harm.

However, infection with C. diff can cause recurrent diarrhoea and inflammation of the colon (colitis). In some cases (2-3%), massive chunks of the intestine die, requiring surgery to cut away the dead flesh. The treatment for C. diff infection is usually antibiotics. However, C. diff­-associated disease mainly affects patients who have been on long-term antibiotic therapy, e.g. AIDS or chemo/radiotherapy patients. Thus, you get into a spiral where the cure is the cause of the infection.

Moreover, long-term antibiotic treatment also selects for bacteria that are resistant to the antibiotic. So it’s no surprise that our last-ditch antibiotics (e.g. vancomycin) are starting to become useless in this fight. Probiotic therapy have been trialled and are good prophylaxis but tend to not be very good treatment.

The reason why C. diff comes about after antibiotic therapy is a lesson in the overuse of antibiotics. Although it can live with other bacteria in the gut peacefully, C. diff is an opportunistic little devil. When antibiotics are taken, your natural gut flora is knocked down. C. diff, as I said before, has the ability to sense when bad things are going to happen and form spores that can resist the antibiotics pretty well. Once the storm has settled and the antibiotics are gone, C. diff spores crack open and find reduced competition for both space in the gut and nutrients. So they start to multiply and take over the place.

C. diff also secretes many toxins which kill surrounding intestinal cells. The reason for this is two-fold: 1) the cells explode and leak out their nutrients which C. diff uses to multiply even more; and 2) the diarrhoea, which the patient suffers as a result of this massive cell death, spreads the C. diff all around the environment where it can infect new hosts. It’s quite beautiful if you think about it.

The answer: Poo transplants.

So scientists needed a way to combat this because standard treatment was not working. They thought, “Well, if your kidney was failing, you’d do a transplant. Gut flora is basically an organ anyway; all these different cells working together to make a healthy human. Why don’t we just transplant gut flora from a healthy person to a sick person?” And so they did.

Faecal bacteriotherapy (the technical name for poo transplants) are a fairly simple business. First, you need a donor. Preferably someone you’re intimate with; since you swap saliva anyway, it’s a good bet that you’re resistant to any bugs that they might have. If your partner is pregnant however, it may not be such a good idea: there are reports of morning sickness being transferred from donor to donee, although that may be simply being grossed out by the technique.

At the same time, you need to be prepping the donee for the transplant. You are given a high dose of antibiotics to really knock back the C. diff and clear out any existing gut flora. Also, you get a bit of a rinse through (more technically, a colonic lavage) to get rid of any debris. You’ll be starting with a clean slate, so to speak.

Next, collect the sample. Storing it in an ice cream container is fine, but may get you strange looks on the bus. 200-300g should suffice. Once you have it, put into a blender and add saline until you get a 10% faecal solution. Blend til smooth.

Using water bottles to collect samples will only lead to disappointment (Sorry Ash, I was running out of time to find a picture and this was the most relevant in my collection) (Photo taken by Thomas Tu)

To insert the solution into the patient, you can go two ways: 1) backdoor entrance with an enema; or 2) down the gullet by threading a tube through the nose, past the stomach and into the small intestine. Pump that thing for all it’s worth. Once done, place the patient on an angled couch (head facing the ground) so that the solution will be held in the intestines as long as possible. Simmer for 8hrs or until brown. Serve.

What should happen is the new gut flora will colonise the gut and reduce the amount of free nutrients and growing space available, so C. diff cannot recolonise the place. Patients have reported a >95% cure rate with no recurrence, even after further antibiotic therapy.

I find this a beautifully ingenious solution. Even though some people might be disgusted with this technique, using science, we’re able to cure patients and ease suffering with hard rationality. Given the battle against antibiotic resistance we’re facing, it’s good to know we can adapt to keep up with our rivals.

TT

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7 Comments

Filed under Thomas' Corner

7 responses to “Antibiotic-associated colitis – Poo transplants!

  1. Chris Cursaro

    Another beautiful article Tom. Thanks!

  2. Ha! Gross. Damn Clostridium though, they make some mean diseases.

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  6. Xien_Rue

    Very informative, thank you for the article. The poo transplant is very logical solution. Biology ways usually works better than chemistry ways (i.e antibiotic)

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