Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment.
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.
Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA.|Department of Computer Science, University of Maryland, College Park, MD, USA.
Mihai
M
Pop
Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA.|Graduate Program in Applied Mathematics & Scientific Computation, University of Maryland, College Park, MD, USA.|Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, MA, USA.|Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
Joseph N
JN
Paulson
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Subhra
S
Chakraborty
Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA.
Irina
I
Astrovskaya
School of Medicine, University of Maryland, Baltimore, MD, USA.|Merck & Co. Inc, North Wales, PA, USA.
Brianna R
BR
Lindsay
School of Medicine, University of Maryland, Baltimore, MD, USA.
Shan
S
Li
Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA.|Department of Computer Science, University of Maryland, College Park, MD, USA.
Héctor Corrada
HC
Bravo
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Clayton
C
Harro
Pathogen Genomics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
Julian
J
Parkhill
Pathogen Genomics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.|Microbiology Group, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK.
Alan W
AW
Walker
PATH, Washington, DC, USA.
Richard I
RI
Walker
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
David A
DA
Sack
School of Medicine, University of Maryland, Baltimore, MD, USA. ostin001@umaryland.edu.
O Colin
OC
Stine
D000328:Adult; D002939:Ciprofloxacin / Q000494:pharmacology / Q000627:therapeutic use*; D003967:Diarrhea / Q000188:drug therapy / Q000382:microbiology; D054307:Enterotoxigenic Escherichia coli / Q000187:drug effects* / Q000502:physiology*; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D054892:Metagenome; D056186:Metagenomics / Q000379:methods; D008875:Middle Aged; D012336:RNA, Ribosomal, 16S; D012372:ROC Curve; D016896:Treatment Outcome; D055815:Young Adult
D012336:RNA, Ribosomal, 16S; D002939:Ciprofloxacin
16S rRNA gene survey; Antibiotic treatment; Diarrhea; Enterotoxigenic Escherichia coli; Microbiota