Antibiotic use and its consequences for the normal microbiome

Abstract

Anti-infectives, including antibiotics, are essentially different from all other drugs; they not only affect the individual to whom they are given but also the entire community, through selection for resistance to their own action. Thus, their use resides at the intersection of personal and public health. Antibiotics can be likened to a four-edged sword against bacteria. The first two edges of the antibiotic sword were identified immediately after their discovery and deployment in that they not only benefit an individual in treating their infection but also benefit the community in preventing the spread of that infectious agent. The third edge was already recognized by Alexander Fleming in 1945 in his Nobel acceptance speech, which warned about the cost to the community of antibiotic resistance that would inevitably evolve and be selected for during clinical practice. We have seen this cost mount up, as resistance curtails or precludes the activities of some of our most effective drugs for clinically important infections. But the fourth edge of the antibiotic sword remained unappreciated until recently, i.e., the cost that an antibiotic exerts on an individual's own health via the collateral damage of the drug on bacteria that normally live on or in healthy humans: our microbiota. These organisms, their genes, metabolites, and interactions with one another, as well as with their host collectively, represent our microbiome. Our relationship with these symbiotic bacteria is especially important during the early years of life, when the adult microbiome has not yet formed.

Figure 1. Models of microbiota change in different societies

The decline in microbiota diversity in the United States happened simultaneously with the early introduction of sanitation, including filtered and chlorinated drinking water, and early antibiotic use. The scale is arbitrary and reflects the aggregate of species and strain losses. The numbers shown represent the generations since the earliest population-wide microbiota species and strain losses and show progressive and cumulative loss of diversity. Each line represents an average; within every generation, there is variation in individual positions, based on their founding populations, exposures, and timing. In a country with late modernization, the diversity loss occurred later, but generation times are shorter, and the steps more irregular and increasing, which reflects the effects of the accelerated pace of modernization in recent years on human microbiota biodiversity loss in developing countries. For the future, three trajectories are shown for the developed country.