Antibiotics and some other drugs can disrupt gut bacteria, killing beneficial microbes and allowing harmful ones to expand. New research suggests that nutrient competition determines how gut microbial communities respond to drugs.

The findings, published in Cell, could help predict and manage microbiota changes after drug treatment.

“Human gut bacteria are routinely exposed to stresses, and community-level responses are difficult to predict,” the authors say. In particular, how antibiotics and other drugs influence complex microbial communities and how interactions among species shape overall community responses is unclear.

The team, led by Handuo Shi at Stanford University in California, used simplified human gut microbial communities—lab-grown mixtures of gut bacteria from a human donor—to study how drugs affect the gut microbiota.

Community responses

The researchers tested how simplified human gut microbial communities respond to 707 different drugs, most of which can be taken orally. They found that many antibiotics reduced community growth, while non-antibiotic drugs had weaker effects. 

Drugs that inhibited growth also changed which species thrived: dominant species were suppressed, allowing rare species to expand. These changes in microbiota composition were linked to how the community consumed nutrients.

Next, the researchers studied how gut bacteria respond to drugs when they are in isolation or when they’re part of a community. While some species were similarly affected in both settings, other species thrived in the community if competitor bacteria were depleted. The effects observed were mostly due to nutrient competition, likely because when dominant species are depleted, the nutrients they normally use become available to other species. 

Predicting drug effects

After drug treatment, gut microbial communities could recover partially or fully, but recovery was more complete when missing species were reseeded, the researchers found.

When communities were treated with drugs multiple times, most species showed similar responses across treatments, while only a small fraction of bacteria, including Flavonifractor plautii, developed resistance. Combining these data with computational models could predict many community-level drug responses. 

Although real gut environments involve additional factors such as interactions with the host, “nutrient competition provides a predictive framework to anticipate and potentially mitigate drug side effects on the gut microbiota,”  the authors say.