Poop Transplants, Is Your Microbiota an Organ System

This is some research (subscription required) I have been meaning to write about for awhile but have not found the time. Now its basically too late because Carl Zimmer has written about it and it has been picked up elsewhere. However, I did still want to throw in my two cents.

First, you have to realize that there are at least 10 times as many microbial cells living in and on you than there are human cells making up your body. That means you are basically a microbial community with some human contamination.

Second, we have long known that certain microbes cause diseases, like Vibrio cholerae causes cholera and Plasmodium falciparum causes malaria. We also know that many microbes are beneficial. This beneficialness is described as being shield. If the "good" microbes are there, the "bad" microbes cannot colonize us easily. However, these microbes play important roles in providing nutrients we have trouble getting otherwise, like vitamin K. They also help regulate our immune system, which must combat pathogens, but not combat all the "normal" microbial flora. When the immune system goes after norma flora bad things can happen, for example chronic mucataneous candidiasis (pictured to the right, from Doctor Fungus).

What we are now learning is that it appears that the microbiota can have significant impacts on human health beyond these more clear cut examples. The link between certain microbes (and I would be remiss not to include viruses here) and cancer is well established. It is also beginning to look like your gut microbiota can affect your chances on pulmonary infections and may affect allergic diseases.

Your microbiota is so important that the suggestion has been made that your microbiota should be considered an organ system. Now the research focus of this post is colitis, an inflammatory disease of the large intestine caused by Clostridium difficile. C. difficile is easily detected in ~10% of the population, which means low level colonization is probably much higher, but few individuals come down with symptomatic colitis. In patients suffering severe colitis, the gut microbiota is completely abnormal. (To be clear there is not a specific gut microbiota that is considered normal, but a range of specific species and numbers of each organism that we are beginning to assess as normal. Kind of like height, people come in a variety of heights and we have a mean and median, but there is no specific normal height.) So Dr. Khoruts and colleagues took a stool sample from "normal" individuals (family members) and transplanted it into the colitis patient. Of 15 patients treated, 13 were cured almost immediately. Also, when analyzed well afterwards the cured patients had a microbiota back in the normal range!

I cannot overemphasize how incredibly cool all this is. Gross? Yes. Totally awesome? Definitely.

I think these research results lead to some interesting follow up questions. For example, if we consider C. difficile exists in people at a low level normally, what leads to overgrowth and/or colitis? Are there specific competing microbes that keep C. difficile in check? This question is important because it could demonstrate an underlying mechanism of health. If you have organisms X, Y, and Z, then you need to have organisms A, B or C, and D or E to be healthy.

The microbiota and allergies/asthma. Huffnagle GB.PLoS Pathog. 2010 May 27;6(5):e100054

Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ. J Clin Gastroenterol. 2010 May-Jun;44(5):354-60.

Conceptualizing human microbiota: from multicelled organ to ecological community. Foxman B, Goldberg D, Murdock C, Xi C, Gilsdorf JR. Interdiscip Perspect Infect Dis. 2008;2008:613979.