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The Species in the Feces

I do not understand the interest many appear to have in their bowels and the movement there of.  But then, I pay little attention to most of my body functions as long they are functioning within  reasonable parameters, and as I get  older the definition of reasonable is increasingly flexible.

The elderly especially seem to obsess about their bowels.  My theory is that since they have often lost taste, smell, hearing and are alone with little direct human touch,  a good BM is the only remaining physical joy left, and when it is compromised they are understandably upset.

Still, the concept of colonics for ‘detoxification’  strikes me as more humorous than repellent, despite the lack of efficacy and documented complications of the procedure.  Under normal circumstances, when it comes to the colon it is probably better to be removing substances than to be introducing them.  I do not pretend to be expert in the human microbiome: the complex ecosystem of bacteria and other organisms that are in and on us. It is of interest but usually not a direct concern in the daily application of infectious diseases.  I spend most of my days trying to kill the odd pathogen, most of whom are not usually part of the human bacterial ecosystem.  There are 1000’s of species in and on us, and we can grow only a small fraction of them in the clinical microbiology lab. There are an estimated 10 to 100 times more bacterial cells in and on you than there are cells of you.  Take your colon. Please.

…it has been estimated that the cumulative human lower intestinal microbiota contains at least 1800 genera and 15 000–36 000 species (depending on a conservative vs liberal classification).

I tend to think that the conservative approach has a larger quantity of lower intestinal material associated with it.  You may think you are hot stuff, but really you are only a sentient transport and feeding mechanism for your bacteria.

A side effect of antibiotics is wiping out large swaths of the normal flora in and on us.  Early in my career it was taught that the benefits of the microbiome were simple: competition for adherence sites and nutrition with a little vitamin K production thrown in for good measure.  It turns out the interactions of the metabiome and the humans is much more complex than  suspected.  There probably is a core microbiome that we share, but the diversity of bacterial flora  is greater than the similarities.

At the national meeting I  last year I attended some lectures on the microbiome, and the two most interesting factoids from my notes were that microbiomes are more similar in people who are related.  My microbiome resembles  that of my parents and children more than that of my wife.  And even more interesting is that the microbiology found on the left upper canine tooth resembles the right upper canine, rather than the tooth below it or the teeth next to it.  Each tooth is a Galapagosian island of separate and sometimes parallel evolution.  Neat.

I mess with the microbiome of others on a daily basis wiping out billions of bacteria and upsetting the human ecology.  Not that I have much choice.  Most of the patients I see would likely die from their infection without antibiotics, although if there is karma for causing the deaths of other creatures, given the huge number of microbial deaths for which I am responsible,  I am destined to come back in the next life as a rabbit in a syphilis laboratory.

What little data exists suggests that the bacterial flora declines dramatically with antibiotics and is slow to recover, often taking months to return to pre-antibiotic diversity.  Each course of antibiotics is, to the bowel bacteria, an almost K-T extinction event.  There would be a less prolonged effect if we were more like mice and were coprophagic, but eating poo is not high on the human consumption list.  Except for those of us that love hot dogs.

The best known and more reliable effect of messing with the bowel flora is diarrhea, which comes in two flavors: antibiotic associated and Clostridia diarrhea.  Some antibiotics, like oral amoxicillin/clavulanic, are arguably better than most laxatives at cleaning out the gastrointestinal tract, and antibiotic associated diarrhea adds to discomfiture and cost of hospitalization, with the upside that you can get more reading done.

Probiotics are useful in prevention of antibiotic associated diarrhea, supported by reasonable studies in the literature.  In my institutions when we instituted yogurt for all our patients on antibiotics our testing for causes of diarrhea fell by half, a reasonable surrogate that the product was effective.

I recommend the yogurt over probiotic pills if possible, despite how unpleasant yogurt can be.  Yogurt has the advantage of a known quantity and distribution of bacteria since its production is overseen by regulatory agencies.  I suggest yogurt that has the more diverse and highest quantities of bacteria, the yogurt closest to stool, a slogan not likely to be used by Dannon anytime soon: “The yogurt that most resembles stool. ”Probiotic pills are problematic, since their contents are not regulated and the organisms can be dead or be species of bacteria other than what is listed on the label.

It is wrong to consider the organisms in probiotics to be ‘good’ bacteria.  They are not part of the normal flora and can incite an inflammatory response or  invade the blood stream in rare circumstances.  It is interesting, but not surprising,  that probiotics can prevent URI’s in children.

Regarding the potential mechanisms through which the reductions in respiratory symptoms and antibiotic usage could be explained, an immune-enhancing effect is a likely explanation, because numerous studies with various probiotic bacteria have demonstrated their ability to modulate immune responses through interactions with toll-like receptor.

As I have mentioned before, “immune-enhancing” is what ID docs call an inflammatory response, which, if activated in advance of a pathogen, primes the immune response against subsequent infections.  The inflammatory response, long term, is bad, being associated short term with increased vascular events (stroke, heart attack and pulmonary embolism) and long term with vascular disease.  Being immune-enhanced may, for example, prevent TB at the price of the metabolic syndrome. As far as I can tell, the immune system is best left alone if not under acute microbial attack

Bacteria are neither good nor bad, but more or less likely to be pathogenic.  Some are collaborators with the enemy, aiding and abetting pathogens in their invasion.  The normal flora, the so called ‘good’ bacteria, may enhance infection from polio,  some worms, and other bacteria.  Not a surprise, for even as we were evolving in tandem with our flora, our pathogens were certainly evolving along us and our microbiome.  Even the ‘good’ bacteria would be happy to consume you if given half an opportunity.  As would some of our pets as I think about it.

The utility of probiotics in the prevention and treatment of probiotics for C. difficile diarrhea is problematic, and the literature can be read either way, I tend to think the glass is half full (of stool) and is of little utility.  It is a problem as C. difficile can be a difficult disease to treat with antibiotics and has a high relapse rate.  Some patients go through multiple courses of different antibiotics without resolution of their disease, each antibiotic more expensive than the last.  The newest agent for C. difficile, fidaxomicin, has set a new record for price gouging with a 10 day course costing round $2800. Yep.  Two thousand eight hundred.

The best therapy, best being the highest cure rate,  for C. difficile is the stool transplant, and I get puky just writing about it.  The stool of spouse (although it should be the parents or children) is pureed and given either down a nasogastric tube or as an enema.  Efficacy is almost 100%.  There are worries about disease transfer, as some infections are spread by the fecal-oral route. Ick.  But most spouses, unlike other relatives, probably share most infections anyway.  I have yet to send a patient for stool transplant, but my partner and the  GI docs have done a handful with good results.

Imagine my surprise when the local weekly had  an article on stool transplants being used by a naturopath  as part of a 3000 to 7000 dollar treatment, depending on whether you want to do receive it at home or as part of a colon health retreat.  According to the Willamette Week, the practitioner is self taught and the stool is obtained from a 13 year old who was chosen as he had never had prior antibiotics.  The kid is paid for his donations. I had a paper route and it also was a …, no I’m not going there. Nope.

According to the web site,

FMT is over 90% effective at treating C. difficile infections, and is 50-90% effective at significantly decreasing or eliminating symptoms of ulcerative colitis and IBS-C.

The first number is legit, the second?  At best I can find a half dozen case reports for ulcerative colitis  and a similar number for irritable bower syndrome.

For non C. difficile bowel disease stool transplant is an intriguing idea, and given the interactions of the colonic microbiome and the gut, I would not dismiss the idea out of hand. How alterations in gut flora plays a role in IBS, UC, or even weight gain or loss are interesting concepts.  The understanding of these interactions is in their infancy and may be a fruitful therapeutic option someday.  I would be cautious since it is also reasonable that  that giving someone a strangers poo could conceivably  set them up for chronic inflammation with resultant stroke and heart attack, increase their risk for polio or even put them at long term risk for bowel cancer, given the curious association between toxigenic Bacteroides fragilis and colorectal cancer.

There are likely to be subtleties in different microbiomes and an individuals immune system’s interactions with that microbiome that will alter the risk or benefit of a random stool transplant.  At least with a kidney they try and match it to the recipient.  I would not be surprised if a similar process would optimize the benefits of a stool transplant, although a complication of organ rejection is infection, and how would you tell in a stool transplant.   While it is medicine that is accused of not treating the individual, it is often the SCAM practitioners who have a one size fits all in their treatments with no consideration of the potential ramifications of the practice.  In the practice of medicine you learn early that no good deed ever goes unpunished; everything has downsides.

I would be disinclined to recommend that a patient spend thousands of dollars based on an interesting idea.  I would not have though someone could beat out Big Pharma and charge more than fidaxomicin for a 10 day course for bowel therapy, but evidently I lack the imagination.  I also lack the insight to realize the importance of the colon for so many extra-colonic processes, except I will admit my health did improve markedly for the better when I had my colon removed.

…using fecal microbial transplantation for other health problems, including autoimmune disease, eczema, asthma, multiple sclerosis and depression… and detoxifies the body and improves mood.

Interesting. The comments write themselves.  To say there is even biologic plausibility to treating MS or depression with stool transplants requires a biology I was never taught and cannot imagine. The opportunity for placebo effects to predominate with stool transplant would be enormous. But there are those who, well, like that sort of thing.  To each their own.

I do not see why squirting another’s poo in your colon would not be, in the world of colonic detox, the equal to giving a toxin enema. If there is anyone with toxins in their colon, it would be a 13 year old boy.  I have seen what mine will eat if given half a chance.

As for performing an unregulated procedure as unproven therapy, Davis says, “The FDA hasn’t said not to.”

The FDA also hasn’t said not to jump off a bridge, and damn I am getting old resorting to that trope.  That’s how to choose interventions for patients: if the powers that be don’t say not to, it is OK.  That is the approach to life of my teenage kids and I have found it to be a reliable technique for them to learn from really stupid decisions.

The practice of medicine is always in flux* and off the wall ideas today are tomorrows standard of care.  For fecal transplant and some colonic diseases, it is an intervention that, outside of C. difficile, is still unproven, although a promising idea.   For diseases outside the colon, biologic plausibility makes stool transplant unlikely to have any benefit with real potential downsides.  Stool transplants are unlikely to be of widespread to benefit,  but when all you have to offer is crap, everything is a toilet.

* an old term for diarrhea.

Posted in: Basic Science, Naturopathy, Science and Medicine

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