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The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing

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  • Les Dethlefsen
  • Sue Huse
  • Mitchell L Sogin
  • David A Relman

Abstract

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. : The intestinal microbiota is essential to human health, with effects on nutrition, metabolism, pathogen resistance, and other processes. Antibiotics may disrupt these interactions and cause acute disease, as well as contribute to chronic health problems, although technical challenges have hampered research on this front. Several recent studies have characterized uncultured and complex microbial communities by applying a new, massively parallel technology to obtain hundreds of thousands of sequences of a specific variable region within the small subunit rRNA gene. These shorter sequences provide an indication of diversity. We used this technique to track changes in the intestinal microbiota of three healthy humans before and after treatment with the antibiotic ciprofloxacin, with high sensitivity and resolution, and without sacrificing breadth of coverage. Consistent with previous results, we found that the microbiota of these individuals was similar at the genus level, but interindividual differences were evident at finer scales. Ciprofloxacin reduced the diversity of the intestinal microbiota, with significant effects on about one-third of the bacterial taxa. Despite this pervasive disturbance, the membership of the communities had largely returned to the pretreatment state within 4 weeks. The most complete survey to date of bacterial diversity in the human gut shows extensive but temporary changes in the microbial community following ciprofloxacin treatment.

Suggested Citation

  • Les Dethlefsen & Sue Huse & Mitchell L Sogin & David A Relman, 2008. "The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing," PLOS Biology, Public Library of Science, vol. 6(11), pages 1-18, November.
  • Handle: RePEc:plo:pbio00:0060280
    DOI: 10.1371/journal.pbio.0060280
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    1. Ruth E. Ley & Peter J. Turnbaugh & Samuel Klein & Jeffrey I. Gordon, 2006. "Human gut microbes associated with obesity," Nature, Nature, vol. 444(7122), pages 1022-1023, December.
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    2. Bo-Young Hong & Michel V Furtado Araujo & Linda D Strausbaugh & Evimaria Terzi & Effie Ioannidou & Patricia I Diaz, 2015. "Microbiome Profiles in Periodontitis in Relation to Host and Disease Characteristics," PLOS ONE, Public Library of Science, vol. 10(5), pages 1-14, May.
    3. Iyiola Olatunji Oladunjoye & Yusuf Amuda Tajudeen & Habeebullah Jayeola Oladipo & Mona Said El-Sherbini, 2022. "Planetary Health and Traditional Medicine: A Potential Synergistic Approach to Tackle Antimicrobial Resistance," Challenges, MDPI, vol. 13(1), pages 1-10, June.
    4. Chang-Ro Lee & Ill Hwan Cho & Byeong Chul Jeong & Sang Hee Lee, 2013. "Strategies to Minimize Antibiotic Resistance," IJERPH, MDPI, vol. 10(9), pages 1-32, September.
    5. Rebecca Flancman & Ameet Singh & J Scott Weese, 2018. "Evaluation of the impact of dental prophylaxis on the oral microbiota of dogs," PLOS ONE, Public Library of Science, vol. 13(6), pages 1-18, June.
    6. Oliver Aasmets & Kertu Liis Krigul & Kreete Lüll & Andres Metspalu & Elin Org, 2022. "Gut metagenome associations with extensive digital health data in a volunteer-based Estonian microbiome cohort," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    7. Lena Takayasu & Wataru Suda & Eiichiro Watanabe & Shinji Fukuda & Kageyasu Takanashi & Hiroshi Ohno & Misako Takayasu & Hideki Takayasu & Masahira Hattori, 2017. "A 3-dimensional mathematical model of microbial proliferation that generates the characteristic cumulative relative abundance distributions in gut microbiomes," PLOS ONE, Public Library of Science, vol. 12(8), pages 1-20, August.
    8. Eman M Fouda, 2017. "Airway Microbiota and Allergic Diseases: Clinical Implications," International Journal of Pulmonary & Respiratory Sciences, Juniper Publishers Inc., vol. 1(5), pages 1-5, May.
    9. Eman M Fouda, 2017. "Airway Microbiota and Allergic Diseases: Clinical Implications," International Journal of Pulmonary & Respiratory Sciences, Juniper Publishers Inc., vol. 1(5), pages 119-124, May.
    10. Xiaobo Yin & Seiji Kamba & Koki Yamamoto & Atsushi Ogura & Ernest Apondi Wandera & Mohammad Monir Shah & Hirokazu Seto & Takashi Kondo & Yoshio Ichinose & Makoto Hasegawa, 2022. "Analysis of Environmental and Pathogenic Bacteria Attached to Aerosol Particles Size-Separated with a Metal Mesh Device," IJERPH, MDPI, vol. 19(9), pages 1-13, May.

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