Differential effects of antibiotic therapy on the structure and function of human gut microbiota

Abstract

The human intestinal microbiota performs many essential functions for the host. Antimicrobial agents, such as antibiotics (AB), are also known to disturb microbial community equilibrium, thereby having an impact on human physiology. While an increasing number of studies investigate the effects of AB usage on changes in human gut microbiota biodiversity, its functional effects are still poorly understood. We performed a follow-up study to explore the effect of ABs with different modes of action on human gut microbiota composition and function. Four individuals were treated with different antibiotics and samples were taken before, during and after the AB course for all of them. Changes in the total and in the active (growing) microbiota as well as the functional changes were addressed by 16S rRNA gene and metagenomic 454-based pyrosequencing approaches. We have found that the class of antibiotic, particularly its antimicrobial effect and mode of action, played an important role in modulating the gut microbiota composition and function. Furthermore, analysis of the resistome suggested that oscillatory dynamics are not only due to antibiotic-target resistance, but also to fluctuations in the surviving bacterial community. Our results indicated that the effect of AB on the human gut microbiota relates to the interaction of several factors, principally the properties of the antimicrobial agent, and the structure, functions and resistance genes of the microbial community.

Figure 1. Microbiota composition of patients A, B, C, and D.

(A) total microbiota (16S rRNA gene) (B) active microbiota (16S rRNA transcripts). The mode of action for each AB used is indicated.

Figure 2. Heat map and clustering based on taxon composition and abundance.

(A) total microbiota, (B) active microbiota. Colors in the figure depict the percentage range of sequences assigned to main taxa (abundance >1% in at least one sample).

Figure 3. Canonical Correspondence Analysis (CCA) of the patients A, B, C and D in the follow-up study.

(A) total microbiota, (B) active microbiota, (C) genes and (D) gene taxonomy. The antimicrobial effect is represented as a vector with two levels (bactericidal and bacteriostatic). The mode of AB action is represented as a vector with three levels (cell envelop synthesis inhibitor, cell replication inhibitor and protein synthesis inhibitor).

Figure 4. Resistance gene profiles.

(A) The dashed lines represent the relative abundance of the total number of resistance genes for patients A, B, C, and D. (B) Relative abundance of the resistance genes throughout AB treatment for patients A, B, and C. The symbol "*" highlights the resistance gene profiles which coincide with the antibiotic administered to patients C, A and B, respectively.