Your Other Half

Tom Easton

In the last few years, the human microbiome has been drawing a great deal of attention. It consists of the bacteria, viruses, and fungi that occupy your guts (generating about a third of your poop), as well as your skin, mouth, nose, and other niches.  Its many species make up a population of microbial cells more numerous than (if not as massive as) your own cells, thus justifying the title of this essay, and they communicate with your brain, immune system, heart, and other organs in ways that have a great deal to do with your health. We’re still working out the details, but it is already clear that messing with the microbiome can be very bad for you.

I became aware of the importance of this topic in January 2013, when the New England Journal of Medicine published a very interesting paper on the treatment of Clostridium difficile infections.  These “C. diff” infections often follow antibiotic treatments that destroy the normal intestinal microbe population.  They affect some 700,000 Americans every year and kill about 14,000.

The researchers planned to enlist 120 patients in the study.  Half would get the experimental treatment, half would be split into two control groups.  But after 43 patients, the study was halted on the grounds that it would be unethical to continue.  94 percent of the experimental group were cured, compared to about a quarter of each control group.  “Enough,” they said. “Let’s give everyone the good stuff!”

If a big pharmaceutical company had a new drug with a 94 percent cure rate, they would be beating the marketing drums and watching stock values soar.  In this case, well… Just what was the “good stuff”?

In a word, poop.

Fecal transplantation therapy, now also known as fecal microbiota transplant, has been around for awhile, but it has been one of those things only the desperate will try.  It involves flushing the intestines, more or less the way one prepares for a colonoscopy, and then restoring the intestinal microbes with a preparation obtained by blenderizing a stool sample from a healthy person. The preparation can be administered by enema, or through a tube pushed down the back of the throat to the upper intestine.  The technique has been used for C. diff infections, Crohn’s disease, irritable bowel syndrome, ulcerative colitis, and other illnesses.  The best results show when people who have been ill for months, and whom doctors have been unable to help, leave the hospital feeling great within days.  Sometimes a patient may need a second dose from a different donor.

It sounds simple, and it is.  Indeed, you can find instructions on the Internet on how to do it yourself (https://www.webmd.com/digestive-disorders/news/20151209/diy-fecal-transplant#1).[1]  It is of course better to work with medical professionals who can make sure the donor is healthy and the sample holds no hidden surprises.[2] 

In the C. diff study, the experimental treatment was precisely a fecal transplant.  In one control group, patients received the potent antibiotic vancomycin.  In the other control group, patients had their intestines flushed out (but not “rebooted”) and were given vancomycin.  So for C. diff, poop is better than antibiotics.

But it’s still poop, and the ICK! or YUCK! factor is very strong in most folks’ responses to the idea of using it.  At least until they come down with one of the conditions for which an intestinal reboot has been shown to work and grow desperate enough to try anything.

Is it possible to take the ICK! out of it? Several groups are working on isolating the important bacteria and culturing them to make a poop-less preparation that amounts to a super-probiotic.  In Canada, one project is called RePOOPulate.  In Minnesota, a company called Rebiotix (www.rebiotix.com) is developing a “microbiota restoration therapy” for C. diff cases; the Food and Drug Administration (FDA) fast-tracked their phase II clinical trials, which produced very positive results; phase III trials are under way now. In Cambridge, Massachusetts, Seres Therapeutics (http://www.serestherapeutics.com/) has developed an algorithmic approach to identifying and concentrating poop bacteria that may correct conditions such as C. diff infections.  Their preparation was given “breakthrough” status by the FDA, and to raise money for Phase III trials, they went public in April 2015.  Investors hoped to do well.

How well?  Consider a paper by Vanessa K. Ridaura, et al., “Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice” (Science, September 6, 2013). They chose eight women, four twin pairs who were “discordant” for weight (in each pair, one was heavy, one was not), and transferred fecal bacteria from each woman into germ-free mice.  Mice that received bacteria from the obese twins gained weight.  Mice that received bacteria from the lean twins did not.  And to top it, when the resulting fat and thin mice were caged together, the “lean” bacteria infected the fat mice, which then lost weight.

Would this procedure help humans lose weight?  I’m sure that entrepreneurs are drooling at the thought that it might (weight-loss products are a gold mine, especially if they work), but there is nothing in this study that says it would.  Still, there have been a number of studies that indicate that obese and lean people have different gut bacterial populations and manipulating those populations may do some good (https://www.sciencedirect.com/science/article/pii/S2352939318300162).

The entrepreneurs thus may well have something to drool over.  But a good deal of research remains to be done before we see fecal transplants (or bacterial preparations derived from stool samples) available to treat obesity as well as debilitating intestinal conditions.  That research is already under way, with researchers testing fecal transplant therapy on many diseases.

Among those many diseases are some that outfits like Rebiotix and Seres are already working on. They include Crohn’s disease, ulcerative colitis, irritable bowel syndrome, metabolic syndrome, multidrug resistant urinary tract infections, and hepatic encephalopathy. Seres is also developing preparations to help cancer immunotherapy be more effective and prevent infections and immunity issues after organ transplants.

A little further in the future, there may be hope for preventing at least some cases of autism. In 2018, Catherine R. Lammert, et al., of the University of Virginia published a report indicating that a major autism risk factor may be the condition of the mother’s intestinal microbiota (https://www.sciencedaily.com/releases/2018/07/180718113343.htm).  Because that microbiota can be modified easily by changing diet or administering probiotics or even fecal transplants, it may be possible to reduce the risk.

In 2017, W. H. Wilson Tank and Stanley L. Hazen published an assessment (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354081/) of the possible link between the intestinal microbiota and cardiovascular conditions such as atherosclerosis, noting that though a great deal of work remains to be done, “novel diagnostic, therapeutic, and preventive strategies that leverage their identification may become part of our arsenal for halting and reversing cardiovascular diseases.”

The day may thus not be far off when the drug of choice for many diseases is a preparation derived from poop and designed to reset the intestinal bacterial population to a pattern more consistent with good health, or even with the good health of the baby in the womb 

It will surely help if we can either learn to hold our noses or get rid of the ICK! factor.  Using cultured bacteria and wrapping them up in “super probiotic” capsules is surely the better way to go.

But it still comes from your other half.


[1] Don’t let the kids read this article—if they do, playing “doctor” could take some very weird turns.

[2] We learned the importance of testing natural products such as blood in the 1980s, when AIDS had appeared but no one yet knew it was caused by a virus. Isaac Asimov was only one of many people who developed AIDS from blood transfusions.  Today, donated blood is routinely tested for HIV and many other viruses and parasites.  A similar approach to stool samples would be wise, and some doctors are already stockpiling frozen stool samples that have tested clean.  In Massachusetts, OpenBiome (http://www.openbiome.org) collects and screens stool samples from healthy, thin volunteers for distribution to doctors.

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