In a groundbreaking study, researchers from EMBL Heidelberg have discovered that the effect of human medications on the bacteria in the gut microbiome is reduced when the bacteria form communities. Through investigating how 30 different drugs affect 32 different bacterial species representative of the human gut microbiome, the researchers found that certain drug-resistant bacteria displayed communal behaviors that protected other bacteria sensitive to drugs. This ‘cross-protection’ behavior allowed sensitive bacteria to grow normally within a community in the presence of drugs that would have killed them if they were isolated. The researchers were surprised at the level of resilience seen in these communities when exposed to medications.
Further investigation into the molecular mechanisms underlying this cross-protection revealed that bacteria help each other by taking up or breaking down drugs through strategies known as bioaccumulation and biotransformation. These findings highlight the previously underestimated potential of gut bacteria to transform and accumulate medicinal drugs. However, the study also revealed that there is a limit to the community’s strength, as high drug concentrations can cause microbiome communities to collapse and switch to ‘cross-sensitization’. In this scenario, bacteria that would have been resistant to drugs become sensitive within the community.
The researchers combined their scientific expertise to conduct this study, with each group contributing unique strengths. The Typas Group focused on high-throughput experimental microbiome and microbiology approaches, while the Bork Group provided bioinformatics expertise, the Zimmermann Group conducted metabolomics studies, and the Savitski Group performed proteomics experiments. External collaborators, including EMBL alumnus Kiran Patil’s group at the Medical Research Council Toxicology Unit, University of Cambridge, offered insights into gut bacterial interactions and microbial ecology. The study involved a multidisciplinary approach to better understand how medications impact the gut microbiome and the potential implications for tailored prescriptions and reducing drug side effects.
Using their new knowledge of cross-protection interactions, the researchers were able to assemble synthetic communities that maintained their composition when exposed to drugs. This experiment serves as a stepping stone towards understanding the intricacies of medications on the gut microbiome and how this information can be used to personalize prescriptions and mitigate adverse drug effects. The researchers are also investigating how interspecies interactions are influenced by nutrients to create better models for understanding the interactions between bacteria, drugs, and the human host. This research has broad implications for the field of microbiome studies and drug development, highlighting the importance of considering communal behavior in bacteria when assessing the impact of medications on the gut microbiome.