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

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 u...

Full description

Bibliographic Details
Main Authors: Les Dethlefsen, Sue Huse, Mitchell L Sogin, David A Relman
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-11-01
Series:PLoS Biology
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19018661/?tool=EBI
_version_ 1818435643475230720
author Les Dethlefsen
Sue Huse
Mitchell L Sogin
David A Relman
author_facet Les Dethlefsen
Sue Huse
Mitchell L Sogin
David A Relman
author_sort Les Dethlefsen
collection DOAJ
description 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.
first_indexed 2024-12-14T16:56:09Z
format Article
id doaj.art-7e4d5efb210d4a7da52cebf4ac34f38e
institution Directory Open Access Journal
issn 1544-9173
1545-7885
language English
last_indexed 2024-12-14T16:56:09Z
publishDate 2008-11-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Biology
spelling doaj.art-7e4d5efb210d4a7da52cebf4ac34f38e2022-12-21T22:53:57ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852008-11-01611e28010.1371/journal.pbio.0060280The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.Les DethlefsenSue HuseMitchell L SoginDavid A RelmanThe 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19018661/?tool=EBI
spellingShingle Les Dethlefsen
Sue Huse
Mitchell L Sogin
David A Relman
The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.
PLoS Biology
title The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.
title_full The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.
title_fullStr The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.
title_full_unstemmed The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.
title_short The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.
title_sort pervasive effects of an antibiotic on the human gut microbiota as revealed by deep 16s rrna sequencing
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19018661/?tool=EBI
work_keys_str_mv AT lesdethlefsen thepervasiveeffectsofanantibioticonthehumangutmicrobiotaasrevealedbydeep16srrnasequencing
AT suehuse thepervasiveeffectsofanantibioticonthehumangutmicrobiotaasrevealedbydeep16srrnasequencing
AT mitchelllsogin thepervasiveeffectsofanantibioticonthehumangutmicrobiotaasrevealedbydeep16srrnasequencing
AT davidarelman thepervasiveeffectsofanantibioticonthehumangutmicrobiotaasrevealedbydeep16srrnasequencing
AT lesdethlefsen pervasiveeffectsofanantibioticonthehumangutmicrobiotaasrevealedbydeep16srrnasequencing
AT suehuse pervasiveeffectsofanantibioticonthehumangutmicrobiotaasrevealedbydeep16srrnasequencing
AT mitchelllsogin pervasiveeffectsofanantibioticonthehumangutmicrobiotaasrevealedbydeep16srrnasequencing
AT davidarelman pervasiveeffectsofanantibioticonthehumangutmicrobiotaasrevealedbydeep16srrnasequencing