Meet SynCom15: A Synthetic Microbiome that Outsmarts Superbugs

Antibiotic resistance is one of the biggest threats to modern medicine. The WHO warns of a post-antibiotic era, where simple infections could once again become deadly. One of the culprits: multi-drug resistant Klebsiella pneumoniae. This is a pathogen that thrives in the gut and is resistant, increasingly, to our best treatments.

But what if the drug isn’t another drug? What if it could be a community of other microbes?

In our lab, we set out to design a synthetic microbiome. This isn’t a single engineered bacterium, but an entire team of microbes that could kill K. pneumoniae that was multi-drug resistant. We will have a separate blog post on the details of how we engineered such a consortium. But briefly, we started with ~800 gut commensal strains (strains of bacteria that reside in healthy human gut microbiomes). Then, we used a statistical approach that we developed called ‘Constraint Distillation’. The essence of this approach was instead of endless trial-and-error testing (every microbiome person engineering consortia loves to talk about their robotic capabilities…), we learned the rules of what makes certain communities effective: which combinations suppress pathogens, which restore balance, which act well together.

From those rules, we distilled a 15-member community: SynCom15.

When we tested SynCom15 in a clinically relevant model, it didn’t just suppress Klebsiella. It cleared it completely, restoring the gut microbiome to a healthy, post-antibiotic state. Even more remarkably, SynCom15 matched the efficacy of a full fecal microbiome transplant (FMT)—one of the most powerful blunt tools that exist in microbiome-related therapeutics. We also found that it was effective against certain strains of Clostridium difficile and Escherichia coli—two other superbugs that can cause devastating illness in patients.

SynCom15 is proof that we can design microbiomes in a precise manner that could conceivably be manufactured for clinical use in a scalable manner. We are currently putting significant effort towards this goal in our own good manufacturing practice facility (cGMP) within the Duchossois Family Institute at the University of Chicago. If you’re interested in this effort, please reach out and join us!