Understanding the impact of antibiotic perturbation on the human microbiome

Abstract

The human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome's ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.

Keywords: Antibiotics; Dynamics; Gut microbiome; Perturbation; Recolonization; Resilience; Resistome.

Fig. 1

Antibiotic perturbation to the microbiome needs to be considered in context. Certain factors are important to consider throughout life (overarching factors). Other factors such as diet and the functional and species diversity and redundancy are important to consider when the antibiotic perturbation is applied. The duration, spectrum, and route of antibiotics are vitally important in the context of how the microbiome responds during an intervention. The post-antibiotic environment including availability and colonization of pathogens, frequency of horizontal gene transfer (HGT), MDROs, and beneficial microbes is important to consider the resilience and response after antibiotic cessation. These factors influence the structure and function of the microbiome before, during, and after antibiotics throughout life. Created with BioRender