Poop Pill’s Surprise Failure Shows That the Microbiome is Still a Mystery

The human microbiome remains a mystery. That is the hard lesson to take from Seres Therapeutics’ shocking announcement today that its experiment in using gut bacteria to treat a deadly infection has failed.

Data published earlier this year by Seres suggested its pill for treating cases of Costridium difficile could radically alter treatment of the gastrointestinal illness that in 2011 claimed 29,000 lives in the U.S. That made the company one of the most promising in a field of biotech startups hoping to harness some of the trillions of bacteria living on or in the human body to treat disease.

Seres’ drug, SER-109, is designed to treat patients with recurring C. difficile infections, which can be hard to treat. Antibiotics can sometimes worsen the condition by killing good bacteria and allowing C. difficile to thrive.

An illustration of a C. difficile bacterium that the SER-109 drug aimed to treat.

Previously, researchers demonstrated that a fecal transplant—taking a healthy person’s stool and putting it in another person—results in a remarkably successful treatment of C. difficile infections. But scientists don’t really know why it works.

The ick-factor of receiving a fecal enema resulted in the creation of the nonprofit stool bank OpenBiome, which aimed to create pills that could be taken orally instead. Seres Therapeutics took the idea a step further by creating the SER-109 pill. Here, spores from good bacterial species are isolated and encapsulated in pill form, while disease-spreading microbes like Listeria and Salmonella are eliminated.

The goal is to reintroduce the diverse population of microbes that normally live in the gut, which is disrupted during a C. difficile infection. Researchers from Seres Therapeutics, Mayo Clinic, and Massachusetts General Hospital published a paper in The Journal of Infectious Diseases earlier this year saying that the SER-109 treatment was effective for preventing C. difficile infections in an early stage trial.

But results from a more advanced trial released today indicate that there was no significant difference in the outcome of patients receiving the therapy compared to those who got a placebo. In a press release, Seres noted this was “inconsistent” with their expectations.

The microbiome is having a moment, as biotech firms like Vedanta Biosciences, Synlogic, Second Genome, Enterome, and others, are all working on therapies centered around human-hosted bacteria. Seres Therapeutics themselves received $120 million in funding from Nestlé and had a market capitalization of $1.4 billion before their stock fell 78 percent on the news of the failed trail. The company has two other treatments in clinical trials—one for ulcerative colitis and a second C. difficile medication.

SER-109’s surprising flop is a humbling reminder of the microbiome’s complexity. But even if the treatment had been successful, its creators would’ve been hard-pressed to present a concrete reason why. Many microbiologists have called for a healthy dose of skepticism in microbiome studies. Its potential may be great, but for now it looks like the good old-fashioned fecal transplants still have the drugs beat out.

(Read More: “Companies Aim to Make Drugs from Bacteria That Live in the Gut,” “Unraveling the Mysterious Function of the Microbiome,” “Seres Therapeutics stock plunges on disappointing drug trial results”)