Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment

Mihai Pop, Joseph N. Paulson, Subhra Chakraborty, Irina Astrovskaya, Brianna R. Lindsay, Shan Li, Héctor Corrada Bravo, Clayton Harro, Julian Parkhill, Alan W. Walker, Richard I. Walker, David A. Sack, O. Colin Stine

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Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in inhabitants from low-income countries and in visitors to these countries. The impact of the human intestinal microbiota on the initiation and progression of ETEC diarrhea is not yet well understood.

We used 16S rRNA (ribosomal RNA) gene sequencing to study changes in the fecal microbiota of 12 volunteers during a human challenge study with ETEC (H10407) and subsequent treatment with ciprofloxacin.

Five subjects developed severe diarrhea and seven experienced few or no symptoms. Diarrheal symptoms were associated with high concentrations of fecal E. coli as measured by quantitative culture, quantitative PCR, and normalized number of 16S rRNA gene sequences. Large changes in other members of the microbiota varied greatly from individual to individual, whether or not diarrhea occurred. Nonetheless the variation within an individual was small compared to variation between individuals. Ciprofloxacin treatment reorganized microbiota populations; however, the original structure was largely restored at one and three month follow-up visits.

Symptomatic ETEC infections, but not asymptomatic infections, were associated with high fecal concentrations of E. coli. Both infection and ciprofloxacin treatment caused variable changes in other bacteria that generally reverted to baseline levels after three months.
Original languageEnglish
Article number440
Pages (from-to)1-11
Number of pages11
JournalBMC Genomics
Publication statusPublished - 8 Jun 2016

Bibliographical note


The authors wish to thank Mark Stares, Richard Rance, and other members of the Wellcome Trust Sanger Institute’s 454 sequencing team for generating the 16S rRNA gene data. Lili Fox Vélez provided editorial support.


IA, JNP, and MP were partly supported by the NIH, grants R01-AI-100947 to MP, and R21-GM-107683 to Matthias Chung, subcontract to MP. JNP was partly supported by an NSF graduate fellowship number DGE750616. IA, JNP, BRL, OCS and MP were supported in part by the Bill and Melinda Gates Foundation, award number 42917 to OCS. JP and AWW received core funding support from The Wellcome Trust (grant number 098051). AWW, and the Rowett Institute of Nutrition and Health, University of Aberdeen, receive core funding support from the Scottish Government Rural and Environmental Science and Analysis Service (RESAS).


  • diarrhea
  • enterotoxigenic Escherichia coli
  • 16S rRNA gene survey
  • microbiota
  • antibiotic treatment


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