In this enlightening episode, we welcome Dr. Andrés Cubillos-Ruiz, who takes us into the world of gut health and antibiotics. His pioneering research proposes a compelling solution to antibiotic-induced alterations in the gut microbiota—a problem that contributes to various metabolic and inflammatory diseases, increases the risk of secondary infections, and fuels the emergence of antimicrobial resistance.

Dr. Cubillos-Ruiz introduces us to an engineered strain of Lactococcus lactis that selflessly degrades β-lactams—a widely used class of broad-spectrum antibiotics that disrupt gut flora—through the secretion and extracellular assembly of a heterodimeric β-lactamase. He explains the unique design of this β-lactamase-expression system, which neither confers β-lactam resistance to the producer cell nor is susceptible to dissemination by horizontal gene transfer.

The intriguing part is how this research plays out in vivo. In a mouse model treated with parenteral ampicillin, oral supplementation with this engineered live biotherapeutic minimized gut dysbiosis without affecting the ampicillin concentration in serum. It also prevented the enrichment of antimicrobial resistance genes in the gut microbiome and the loss of colonization resistance against Clostridioides difficile.

Join us as we delve into the potential of engineered live biotherapeutics that safely degrade antibiotics in the gut, a strategy that could revolutionize the prevention of dysbiosis and associated pathologies.

Keywords: Dr. Andrés Cubillos-Ruiz, Gut Microbiota, Antibiotics, β-lactams, Lactococcus lactis, β-lactamase, Dysbiosis, Antimicrobial Resistance, Biotherapeutics, Metabolic Diseases, Inflammatory Diseases.

https://doi.org/10.1038/s41551-022-00871-9 An engineered live biotherapeutic protects the intestinal microbiome.