title: Toxin-producing Clostridium difficile strains as long-term gut colonizers in healthy infants.
abstract: Clostridium difficile is a colonizer of the human gut, and toxin-producing strains may cause diarrhea if the infectious burden is heavy. Infants are more frequently colonized than adults, but they rarely develop C. difficile disease. It is not known whether strains of C. difficile differ in the capacity to colonize and persist in the human gut microbiota. Here, we strain typed isolates of C. difficile that had colonized 42 healthy infants followed from birth to ≥12 months of age by using PCR ribotyping of the 16S-23S rRNA intergenic spacer region. The isolates were also characterized regarding carriage of the toxin genes tcdA, tcdB, and cdtA/B and the capacity to produce toxin B in vitro. Most strains (71%) were toxin producers, and 51% belonged to the 001 or 014 ribotypes, which often cause disease in adults. These ribotypes were significantly more likely than others to persist for ≥6 months in the infant micobiota, and they were isolated from 13/15 children carrying such long-term-colonizing strains. Ribotype 001 strains were often acquired in the first week of life and attained higher population counts than other C. difficile ribotypes in newborn infants' feces. Several toxin-negative ribotypes were identified, two of which (GI and GIII) were long-term colonizers, each found in one infant. Our results suggest that the toxin-producing C. difficile ribotypes 001 and 014 have special fitness in the infantile gut microbiota. Toxin-producing strains colonizing young children for long time periods may represent a reservoir for strains causing disease in adults.
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Adlerberth
authors.forename: Haihui
authors.initials: H
authors.lastname: Huang
authors.forename: Erika
authors.initials: E
authors.lastname: Lindberg
authors.forename: Nils
authors.initials: N
authors.lastname: Åberg
authors.forename: Bill
authors.initials: B
authors.lastname: Hesselmar
authors.forename: Robert
authors.initials: R
authors.lastname: Saalman
authors.forename: Carl Erik
authors.initials: CE
authors.lastname: Nord
authors.forename: Agnes E
authors.initials: AE
authors.lastname: Wold
authors.forename: Andrej
authors.initials: A
authors.lastname: Weintraub
mesh_terms: D001427:Bacterial Toxins / Q000235:genetics / Q000633:toxicity*; D002353:Carrier State / Q000382:microbiology*; D002675:Child, Preschool; D016360:Clostridioides difficile / Q000145:classification / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000382:microbiology*; D015331:Cohort Studies; D021903:DNA, Ribosomal Spacer / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D021521:Ribotyping
chemical_list: D001427:Bacterial Toxins; D021903:DNA, Ribosomal Spacer