The Challenges of Hacking the Human Holobiont

At the beginning of this month, a “Brief Report” in OFID (Open Forum of Infectious Diseases) described a case where a woman who suffered from both C. difficile and H. pylori infections was treated and cured with a fecal microbiota transplant (FMT) donated from her daughter.

Certainly, FMT treatment’s popularity is on the rise. A quick search for “fecal transplants” provides a myriad of people who believe the secret to human health resides in our excrement. From PoP to various instructional videos on the web, people are actively exploring the curative properties of human waste. Sometimes with very encouraging results as one mother explains while preparing a fecal enema for her daughter who suffers (or rather, suffered) from a bowel disorder but is now healthy due to twice weekly FMTs.

Use of feces to cure GI disease is nothing new. Though the first fecal transplant referenced in scientific literature occurred in 1958, the Chinese recipe for yellow soup (basically diluted poop) has been around for over a thousand years. Still, intense interest in feces for health didn’t really become a mainstream (if you can use that word here) idea until the late in the 20th Century and the beginning of the 21st Century when clinical research began regularly reporting using fecal transplants to cure persistent C. difficile infections as well as other bowel dysfunctions. Now, studies in the Netherlands are investigating whether FMT can be a solution to metabolic syndrome and obesity to diabetes; while here, the Food and Drug Administration (FDA) is working out regulations to ensure the safety and efficacy of FMT as a routine treatment for persistent and highly pathogenic bacterial infections.

Poop! The new super food! However, before we all begin looking for fecal donors (I predicted in 2010 when I saw my first Gordon study on obese mice and FMTs that we’d eventually be getting shit enemas from supermodels to establish waif-y waistlines), we need to examine what exactly it is about poop that can so powerfully change our health—this examination needs to include not only our cellular bionts (including bacterial and human cells) but our viral ones as well. And many recent studies are moving in intriguing directions as we are learning to look more deeply not just into who lives in our holobiont but what types of jobs they are doing there.

But back to our cured woman: months later, despite a medically supervised diet and exercise regime, this woman whose BMI was 26 before the FMT reported that she could not stop gaining weight and is currently at a BMI of 34.5. The culprit (as insinuated by the reports) is her daughter’s microbiota (she had a BMI of 26.4 at time of donation and though current BMI was not given, apparently weighs about 170lbs now).

My sympathies do lie with this woman. It must be terrible to go from one situation where your body rebels against you, despite all you do, to another situation you also cannot control. One of the researchers claims, “She felt like a switch flipped in her body – to this day she continues to have problems”–which include constipation and other dyspeptic symptoms. It is only natural to want to find a singular instant to blame for the new problem.

Certainly, there are mouse studies that support the conclusion that the new microbial ecosystem is responsible. However, before we can conclude that one woman’s microbiota caused another woman to uncontrollably gain weight, we need to consider a few things.

This woman had a wasting infection. Though her weight at time of treatment was holding steady, a severe C. diff infection such as hers often causes massive weight loss in sufferers because their body is not getting access to nutrient energy. This woman had the benefit of “catching” her infection before he became so severe, but the reports lacks any evidence about what state her ecosystem was in at the time of the FMT other than she was unresponsive to other extensive antibiotic treatments and had established C. diff and H. pylori infections. What is definitive is that she was cured from her infections (the H. pylori took some additional treatment) and has remained so. Perhaps the flipped switch was her transition from an unbalanced ecosystem to one that was more balanced.

Though she was on a medically supervised diet, we do not have any information about energy intake post-FMT. As I have argued before, Calories (or to be more correct: nutrient load) matter. In the West, we are swimming in high-energy foods that drastically effect to our collective ecosystem. The human biont eats an array of diets across the globe and the only real common denominator for obesity in the West is how much we eat rather than what we eat.

But most importantly, and this is noted by the researchers, we don’t have a metagenomic comparison of the woman’s microbiota and her daughter’s, nor of her state before the FMT and after. What such a comparison would show us is what is functionally going on in each woman’s gut and how much they are similar and different in metabolic processing. Further, we don’t have a clear picture of how this woman’s viral bionts and those of her donated microbiota played into her new ecological makeup. This kind of data comes from metagenomics studies that look at the genome of the entire system and what every participant is doing or is capable of doing.  Our scientific and cultural fixation on who (as in species or strains) in our guts is transitioning to a more micro-appropriate view of what jobs are being done.

As Katherine Pollard, a senior researcher at Gladstone Institutes, stated at the AAAS 2015 Annual Meeting “it is the genetic make-up of the different strains of bacteria that are of greater importance. DNA in bacteria differs significantly, sometimes up to 30 percent. To apply this variation to the animal world, this is the difference between the genome of a human being and a mouse. This [difference] means that the examinations of gut bacteria should not simply stop at comparing different species [–] an important point because it is at the genetic level that the functionality of bacteria in terms of processing sugar and fat (key determinants of obesity) takes place” (reported by Tim Sandle).

I’m excited about the possibilities in human health that FMT offers, and I do believe that as we are figuring this stuff out, there will be those treated with side effects that are unpleasant and unexpected. I think that the researchers in this case are doing the wise thing in not using obese (or potentially obese) donors in the future. However, the most valuable lesson we can take away from this report is not that fat people’s poop will make you fat, but that our holobiont is incredibly nuanced and we need to take great care in how we approach treating it and how we analyze the after-effects of treatment.

Posted In

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s