The Scoop on Poop

At home, we flush it away as quickly as possible. But what we usually consider waste is helping scientists understand how the colony of microbes called your gut microbiome is relevant to your skin health and skin cancer.

Sometimes, the smallest things have the biggest effect (especially when it comes to science). Over the past two decades, researchers have been studying the gut microbiome — the community of microscopic living things that have made your intestines their home. And it turns out that these tiny organisms can impact nearly every aspect of human health.

By comparing the gut microbiomes of patients who have a disease to those who don’t have the disease, scientists have often found that a difference in the relative abundance of certain species in patients’ microbiomes was associated with having the disease — or not. More recently, researchers discovered that the gut microbiomes of patients who do not respond to immunotherapy treatments for melanoma are different than the gut microbiomes of those patients who do respond.

But how do scientists determine what is in your gut microbiome? It would be difficult to do if it weren’t for the waste that your body eliminates (before it gets flushed): Yep, the proof is in the poop — though “stool” is the preferred medical term. Using stool samples, scientists can analyze key differences between the gut microbiomes of individuals. (If you’re wondering how stool samples are collected, see “A Better Poop Collection System,” below.)

If the microbiome lives on in your poop, and differs between healthy people and those with a certain disease, could the poop of a healthy person be used to help heal someone who is sick? Well, yes. (Ew.) Treatments that alter the gut microbiome go back to 4th century China, and something — unappetizingly — called yellow soup. Today, the methods have been standardized into a process called fecal microbial transplant (FMT).

This procedure is basically the microbial equivalent of a blood transfusion. A stool sample from a healthy donor, containing elements of their gut microbiome, is transplanted into a patient, usually via colonoscopy. Don’t try this at home, though, as the sample is carefully processed and checked for any potentially dangerous organisms before transplantation.

FMT had its first modern success treating patients with an infection known as C. diff, named for the bacteria that causes it — Clostridioides difficile. As its name suggests, C. diff is notoriously tricky to treat. The bacteria can be antibiotic-resistant, and the infection often begins after a patient has been on a strong course of antibiotics for a separate issue. Before the advent of FMT, about half of patients would die from recurrent C. difficile infections in their digestive tract. Now, between 80 and 90 percent of recurrent C. diff patients are cured with a single FMT treatment. On the heels of this success, FMT has shown promising results in clinical trials for treating other gastrointestinal disorders, such as Crohn’s disease and ulcerative colitis, two types of inflammatory bowel disease.

FMTs for Skin Cancer?

Now, researchers are testing FMT for melanoma patients, taking a sample of the microbiome from patients who have responded to immunotherapy and transplanting it into nonresponders. In 2021, two studies proved that it could help. Six out of 15 patients in one study, and three out of 10 in the other (both published in the journal Science), went from having no response to having a positive response to treatment after FMT. “They’re very small phase 1 studies, but it was incredibly compelling,” says Alena Pribyl, PhD, senior scientist and research officer at Microba, an Australia-based company that is doing groundbreaking research into the microbiome.

“It was a proof of concept that you could improve a patient’s response to immune checkpoint inhibitors by changing their gut microbiome.”

This could be hugely beneficial since only 30 to 40 percent of patients currently respond to immunotherapies.

While this is great news, Dr. Pribyl, who was not involved in either study, also cautions that FMT is a crude mechanism. “You’re basing it on, ‘I’ve got a healthy donor stool,’ but that’s a big black box because we still don’t know all of the different bacteria that are present in that sample and what they are doing,” she says. Labs around the world, including at Microba, are working on decoding this black box, and have started to identify some candidate species through observational and clinical trials, though more research is needed. Once the key species responsible for improving response to immunotherapy are identified, safer therapies using only purified forms of those species can be developed. Down the road, this and other research could allow immunotherapy to help more patients and save more lives. (See clinicaltrials.gov for more information on studies focusing on the gut microbiome.)

To read more about the future of microbiome research and what we can do for our health now, check out “The Future of Skin Health May Be Inside You.”  If you want to read more about the background of the microbiome, see “What Does Gut Health Have to Do with Skin Health?”  And did you know that there’s a skin microbiome, too?

A Better Poop Collection System

No doubt you’re wondering how researchers get the stool samples they need. Let’s just say the transport methods are getting better than they used to be. Often, stool sample collection at home involves a plastic shallow bucket or pan, a scoop and a test tube. One new technology that Microba uses is called a FLOQSwab. About the size and shape of a lip-gloss applicator, it doesn’t look that different from the swabs used for COVID tests. To collect a sample for microbiome analysis, you swipe the swab along a piece of (used) toilet paper, then stick it into the tube. Done. “The tube contains silica gel to dry out the sample, which helps preserve the DNA,” Dr. Pribyl explains. In 2021, she and colleagues published a paper in the journal Nature that found the FLOQSwab more accurately preserved the microbial community than other methods. Silica gel absorbs moisture from the air (it is what fills those packets with a “do not eat” warning that come in many products), and a better-preserved sample allows Microba to capture a more complete picture of what is living in your gut microbiome.

---