The crucial drugs can have unintended consequences. Innovative therapies could shield the microbiome from their effects.

Elie Dolgin

Andrés Cubillos-Ruiz’s wife was four months pregnant when she received a course of antibiotics to prevent invasive bacteria from taking up residence in her gums, following a routine dental procedure.

Nature Outlook: The human microbiome

But the bacteria-killing effects of these drugs weren’t confined to her mouth. Like most systemic antibiotics, they also upended the fragile equilibrium of beneficial microorganisms living in the gut — and given the link between maternal gut health and fetal development, Cubillos-Ruiz worried that the antibiotic exposure might be compromising the health of their unborn daughter.

It is a well-known concern: antibiotics are essential for combating dangerous bacterial infections, but they do not discriminate between harmful and beneficial microbes. Gut microbial communities are often knocked off-kilter, and it can take months for them to fully recover. Until they do, people are more vulnerable to opportunistic infections and to a range of immune, metabolic and cognitive complications.

“Deploying an antibiotic is not a benign act,” says Gautam Dantas, a microbial genomics researcher at the Washington University School of Medicine in St. Louis, Missouri. The drugs often cause “collateral damage”, he explains, disrupting microbial ecosystems in ways that can have long-lasting health effects.

Researchers have tried to remedy the problem with compounds that selectively neutralize antibiotics in the gut without affecting the rest of the body, but these efforts have met with limited success. Faced with a lack of a viable solution for his wife, Cubillos-Ruiz, a microbiologist, took it upon himself to confront the issue head-on.

Working in the laboratory of synthetic biologist James Collins at the Massachusetts Institute of Technology (MIT) in Cambridge and the nearby Wyss Institute in Boston, Massachusetts. Cubillos-Ruiz took a bacterium commonly found in fermented foods and engineered it to safely break down a class of antibiotics called β-lactams. These bacteria-killing medications include amoxicillin — the drug that Cubillos-Ruiz’s wife had taken after her dental surgery.

Cubillos-Ruiz and Collins endowed their engineered microbe with the ability to produce a β-lactamase enzyme that degrades amoxicillin. In experiments with mice, this living biotherapeutic released its antibiotic-neutralizing payload directly into the gut, shielding the microbes within from the antibiotic’s effects. But crucially, the antibiotic retained its infection-fighting capabilities elsewhere in the body¹.