Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability

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Abstract

The gut microbiome plays a key role in human health. This community is dynamic during the first three years of life, before stabilizing to an adult-like state. However, relatively little is known about the impact of environmental factors on the developing human gut microbiome. Here we report a longitudinal study of the gut microbiome based on DNA sequence analysis of monthly stool samples and clinical information from 39 children, approximately half of whom received multiple courses of antibiotics during the first three years of life. While the gut microbiome of most vaginally born children was dominated by Bacteroides species, we found that all four children born by Cesarean section and approximately 20% of vaginally born children lacked Bacteroides in the first six to eighteen months. Our longitudinal sampling, coupled with whole-genome shotgun sequencing, allowed us to detect strain-level variation as well as the abundance of antibiotic resistance (AR) genes. The microbiota of antibiotic-treated children was less diverse at the level of both species and strains, with some species often dominated by single strains. In addition, we observed short-term composition changes between consecutive samples from children treated with antibiotics. AR genes carried on microbial chromosomes showed a strong peak in abundance after antibiotic treatment followed by a sharp decline, whereas some genes on mobile elements persisted longer after the end of antibiotic therapy. Our results highlight the value of dense longitudinal studies with high-resolution strain profiles in studying the establishment and response to perturbation of the infant gut microbiome.

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The comprehensive antibiotic resistance database.

Andrew McArthur, Nicholas Waglechner, Fazmin Nizam … (2013)

The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment.

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Short-Term Antibiotic Treatment Has Differing Long-Term Impacts on the Human Throat and Gut Microbiome

Hedvig E Jakobsson, Cecilia Jernberg, Anders F. Andersson … (2010)

Antibiotic administration is the standard treatment for the bacterium Helicobacter pylori, the main causative agent of peptic ulcer disease and gastric cancer. However, the long-term consequences of this treatment on the human indigenous microbiota are relatively unexplored. Here we studied short- and long-term effects of clarithromycin and metronidazole treatment, a commonly used therapy regimen against H. pylori, on the indigenous microbiota in the throat and in the lower intestine. The bacterial compositions in samples collected over a four-year period were monitored by analyzing the 16S rRNA gene using 454-based pyrosequencing and terminal-restriction fragment length polymorphism (T-RFLP). While the microbial communities of untreated control subjects were relatively stable over time, dramatic shifts were observed one week after antibiotic treatment with reduced bacterial diversity in all treated subjects in both locations. While the microbiota of the different subjects responded uniquely to the antibiotic treatment some general trends could be observed; such as a dramatic decline in Actinobacteria in both throat and feces immediately after treatment. Although the diversity of the microbiota subsequently recovered to resemble the pre treatment states, the microbiota remained perturbed in some cases for up to four years post treatment. In addition, four years after treatment high levels of the macrolide resistance gene erm(B) were found, indicating that antibiotic resistance, once selected for, can persist for longer periods of time than previously recognized. This highlights the importance of a restrictive antibiotic usage in order to prevent subsequent treatment failure and potential spread of antibiotic resistance.