Simulating single versus cocktail antibiotic effects on the human gut microbiome

The human microbiome is an ecosystem of diverse microorganisms that reside within the body. It includes several stable and abundant bacterial species that define an individual’s gut enterotype. These bacteria play a critical role in regulating metabolism and immune function. Antibiotics are intended to treat pathogenic bacterial infections, but they often act non-selectively, killing commensal bacteria in the gut microbiome. Antibiotics exert a selective pressure that promotes the development of antibiotic resistance through random bacterial mutations. Combining multiple antibiotics into a cocktail increases the number of mutations required for bacteria to become resistant to the treatment. However, these cocktails may also eliminate commensal species in the microbiome. We hypothesized that antibiotic cocktails composed of broad-spectrum drugs would lead to a more substantial reduction in gut microbial diversity compared to single-drug treatments. We used SimulATe, a computational model of the gut microbiome, to simulate the effects of penicillins, quinolones, tetracyclines, and trimethoprims administered individually and in combination across three gut enterotypes. We found that most single antibiotics preserved a subset of bacterial species within the microbiome. In contrast, we identified that antibiotic cocktails rapidly eliminated nearly all bacterial species, demonstrating the strong consequence of combinatorial treatments on the gut microbiome. Our findings underscore the importance of considering gut microbiome dynamics in antibiotic therapy, suggesting that antibiotic cocktails should be optimized to balance effective infection control with the preservation of microbiome integrity. These insights could inform clinical strategies to enhance patient outcomes and combat the growing challenge of antibiotic resistance.