How human poop can save lives

Almost a decade ago, American researchers performed experiments with poop to examine its effects, or rather the effects of the microbes in the stool on weight.

They transferred poop from sets of human twins, one obese and the other lean, into mice and found to their amazement that mice with poop from the fat twins grew fat; those with poop from lean twins stayed lean.

Could human obesity be treated in this way?

Back then, we had only a vague understanding of the role that the microbes, or microrganisms, in the gut and hence poop played in human health.

But today, with advances in DNA sequencing and computing (needed as the microbes in our gut collectively comprise about one terabyte, or 1,000 gigabytes, worth of genetic data), we know now that the gut microbiome, the collection of trillions of microbes in one’s digestive tract, plays an important role in human health and multiple conditions.

These include immune disorders, metabolic illnesses and even neurological states such as autism. And we are starting to understand why.

We share a world with innumerable other organisms.

However, the old paradigm of (futilely) attempting to eradicate the microbes has now been replaced by a more nuanced understanding that there are “good” and “bad” microbes that live in and around us, and we are now learning how to optimise the “good” bugs and minimise the “bad” ones.

In the gut, the microbes live in a complex community, helping us to digest the foods we use and use these same foods to produce molecules and other substances that cross our gut wall to exert their effects.

HOW IS A FAECAL TRANSPLANT DONE?

A faecal transplant, as the name suggests, is literally that: Stool from a healthy donor, and hence the microbes from the donor’s gut, is collected and transplanted into the patient’s gut.

This can be done in multiple ways: During colonoscopy where the poop is injected directly into the large intestine; through enemas with the microbes then travelling upwards into the large intestines or through specially coated oral capsules which pass through the stomach unscathed and then release the contents in the intestines.

Whatever the mode of delivery, faecal transplants in essence repopulate the diseased gut with healthy bacteria and enable normal function of the gut including its digestive, absorptive and metabolite producing functions.

The ancient Chinese were the first to use faecal transplants routinely and in remarkably sophisticated ways. Poop from healthy young males was collected and buried 20m deep in a cool climate for a decade or more.

During this low-temperature, slow fermentation, the “bad” bugs (pathogens) decline in numbers and the beneficial bacteria become predominant.

Professor Zhao Liping of Rutgers University and his team have replicated this process and reported this results in an odourless yellow liquid that can be directly administered.

The renowned fourth century physician Hong Ge was one of the earliest of many Chinese physicians to use stool medicinally and China has a long history of using poop in various forms to treat multiple conditions.

Interestingly, the Germans also applied similar concepts in using camel poop during World War II to treat soldiers afflicted with dysentery.

THE RENAISSANCE OF POOP TRANSPLANTS 

After decades in medical purgatory, faecal transplants have enjoyed a resurgence in modern medical practice as a highly effective treatment of severe colitis, an inflammation of the bowel caused by the bacterium Clostridium difficile (C. diff). 

In fact, doctors at the National University Hospital (NUH) in Singapore conducted the first series of faecal transplants back in 2014 to successfully treat C. diff colitis.

However, it may have applications way beyond one disease and faecal transplants and the gut microbiome are now the subject of intense research relating to numerous diseases.

In fact, Dr James Kinross of Imperial College London describes the gut microbiome as the “most important scientific discovery for human health in recent decades”.

For example, the oncology world was taken by storm earlier this year when researchers reported that patients with advanced melanoma (a very aggressive form of skin cancer) unresponsive to therapy became responsive after faecal transplants from patients also with melanoma but who were responsive.

Six out of 15 patients in the trial experienced either tumour reduction or disease stabilisation for more than a year.

Andrey Morgun of Oregon State University told News Medical: “It was pretty dramatic. We found altering the gut microbiome can take a patient with advanced melanoma who has never responded to immunotherapy, which fails about 60 per cent of the time with this kind of cancer, and convert the patient into one who responds to it."

In Singapore, NUH is now planning studies of cancer patients’ microbiome profiles with the intent of subsequently conducting faecal transplant studies.

In autism, 30-50 per cent of patients have gut-related symptoms such as constipation, abdominal cramps and bloatedness and researchers have documented marked improvement in both gut and behavioural symptoms after faecal transplants, with the effects persisting even after two years.

Earlier this year, Polish doctors reported that two patients with severe comorbidities hospitalised for Covid-19 also had C. diff colitis and were thus treated with faecal transplants.

To their utmost surprise, the patients not only recovered rapidly from the colitis but also from Covid-19.  

The doctors were expecting a very difficult hospitalisation with many Covid-19 related complications and speculated that the faecal transplant had boosted the patients’ immune systems, enabling them to fight off the virus quickly.

Polish doctors are now undertaking clinical trials using faecal transplants to treat severe cases of Covid-19.

Do note that despite the overall very good safety profile of faecal transplants, they are a medical procedure not to be undertaken lightly and especially not in a DIY setting as some American Youtubers are promoting them as.

Globally, only 2 per cent of potential donors are eventually found to be suitable, which has been our experience here in Singapore too.

Many potential donors who believe themselves to be healthy, after extensive screening, will be found to have drug-resistant microbes in their stool which are harmless to healthy individuals but may be catastrophic if transplanted into patients with compromised immune systems.

Coming full circle back to the thin and fat mice, it’s not so simple.

Harvard University researchers transplanted poop from thin donors into 12 obese human volunteers and failed to detect any statistically significant changes in weight, lean body mass and insulin sensitivity.

The researchers highlighted the small sample size and also that there were no concurrent dietary or other lifestyle interventions. 

Very likely, faecal transplants can be valuable for complex conditions such as obesity but in the context of a more holistic programme including nutritional and exercise components.

We are in the early days of poop transplants and microbiome application but the science is incredibly exciting. Faecal transplants are only the beginning and admittedly a very crude beginning. 

The Holy Grail will really be about taking the science to the next level of precision, identifying the specific microbial strains and combinations of strains together with the optimal growth conditions for clinical effectiveness.

The immediate future will be one in which more clinical indications for faecal transplants will be discovered and entered into practice.

The longer term future could however be about your doctors prescribing not just the usual chemical-based medicines, but also specific foods rich in probiotics or formulations of probiotics. 

Does poop save lives? Yes, definitely! And we are only beginning.

ABOUT THE AUTHOR:

Associate Professor Jeremy Lim is the founder of AMILI, a precision gut microbiome startup and director of global health at the National University of Singapore's Saw Swee Hock School of Public Health.