The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing

Study information

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study design

Citation

PMID PubMed identifier for scientific articles.

19018661

DOI Digital object identifier for electronic documents.

10.1371/journal.pbio.0060280

URI Uniform resource identifier for web resources.

Authors

Dethlefsen L, Huse S, Sogin ML, Relman DA

Journal

PLoS biology

Year

2008

The human intestinal microbiota is essential to the health of the host and plays a role in nutrition, development, metabolism, pathogen resistance, and regulation of immune responses. Antibiotics may disrupt these coevolved interactions, leading to acute or chronic disease in some individuals. Our understanding of antibiotic-associated disturbance of the microbiota has been limited by the poor sensitivity, inadequate resolution, and significant cost of current research methods. The use of pyrosequencing technology to generate large numbers of 16S rDNA sequence tags circumvents these limitations and has been shown to reveal previously unexplored aspects of the "rare biosphere." We investigated the distal gut bacterial communities of three healthy humans before and after treatment with ciprofloxacin, obtaining more than 7,000 full-length rRNA sequences and over 900,000 pyrosequencing reads from two hypervariable regions of the rRNA gene. A companion paper in PLoS Genetics (see Huse et al., doi: 10.1371/journal.pgen.1000255) shows that the taxonomic information obtained with these methods is concordant. Pyrosequencing of the V6 and V3 variable regions identified 3,300-5,700 taxa that collectively accounted for over 99% of the variable region sequence tags that could be obtained from these samples. Ciprofloxacin treatment influenced the abundance of about a third of the bacterial taxa in the gut, decreasing the taxonomic richness, diversity, and evenness of the community. However, the magnitude of this effect varied among individuals, and some taxa showed interindividual variation in the response to ciprofloxacin. While differences of community composition between individuals were the largest source of variability between samples, we found that two unrelated individuals shared a surprising degree of community similarity. In all three individuals, the taxonomic composition of the community closely resembled its pretreatment state by 4 weeks after the end of treatment, but several taxa failed to recover within 6 months. These pervasive effects of ciprofloxacin on community composition contrast with the reports by participants of normal intestinal function and with prior assumptions of only modest effects of ciprofloxacin on the intestinal microbiota. These observations support the hypothesis of functional redundancy in the human gut microbiota. The rapid return to the pretreatment community composition is indicative of factors promoting community resilience, the nature of which deserves future investigation.

Experiment 1

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Curated date: 2021/09/24

Curator: Mmarin

Revision editor(s): WikiWorks753, Mmarin

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled (if applicable): Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: urinary tract infection INFECTION, URINARY TRACT,TRACT, INFECTION OF URINARY,urinary tract infection,urinary tract infection (disease)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Antibiotic treated
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Healthy adults who had not taken any antibiotics within the previous year were recruited to donate stool samples before, during, and after a short course of ciprofloxacin (Cp) (500 mg twice a day for 5 d).
Group 1 sample size Number of subjects in the case (exposed) group: 3
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 1 year

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V6

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Roche454

Statistical Analysis

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased
Richness Number of species: decreased