Clostridium difficile Colonization in Early Infancy Is Accompanied by Changes in Intestinal Microbiota Composition

Abstract

Clostridium difficile is a major enteric pathogen responsible for antibiotic-associated diarrhea. Host susceptibility to C. difficile infections results partly from inability of the intestinal microbiota to resist C. difficile colonization. During early infancy, asymptomatic colonization by C. difficile is common and the intestinal microbiota shows low complexity. Thus, we investigated the potential relationship between the microbiota composition and the implantation of C. difficile in infant gut. Fecal samples from 53 infants, ages 0 to 13 months, 27 negative and 26 positive for C. difficile, were studied. Dominant microbiota profiles were assessed by PCR-temporal temperature gradient gel electrophoresis (TTGE). Bacterial signatures of the intestinal microbiota associated with colonization by C. difficile were deciphered using principal component analysis (PCA). Resulting bands of interest in TTGE profiles were excised, sequenced, and analyzed by nucleotide BLAST (NCBI). While global biodiversity was not affected, interclass PCA on instrumental variables highlighted significant differences in dominant bacterial species between C. difficile-colonized and noncolonized infants (P ‫؍‬ 0.017). Four bands were specifically associated with the presence or absence of C. difficile: 16S rRNA gene sequences related to Ruminococcus gnavus and Klebsiella pneumoniae for colonized infants and to Bifidobacterium longum for noncolonized infants. We demonstrated that the presence of C. difficile in the intestinal microbiota of infants was associated with changes in this ecosystem's composition. These results suggest that the composition of the gut microbiota might be crucial in the colonization process, although the chronology of events remains to be determined.

Clostridium difficile and the microbiota

“…Another potential reservoir of C. difficile resides in the infant population, in which colonization is estimated to occur in up to 45% of individuals (14,15). The infant microbiome is distinct from adults', and differences in the microbiome may be important in both colonization and disease resistance (16,17). Although high rates of C. difficile colonization are observed in infants, they rarely develop disease.…”

Suppression of Clostridium difficile in the Gastrointestinal Tracts of Germfree Mice Inoculated with a Murine Isolate from the Family Lachnospiraceae

“…Administration of broad-spectrum antibiotics is theorized to destroy this protective function of the indigenous microbiota, allowing C. difficile to proliferate and colonize the GI tract (32,34,39). In support of this hypothesis, mice or hamsters challenged with C. difficile are not readily susceptible to C. difficile colonization or disease (CDI) (5,43,45), while antibiotic administration will render animals susceptible to infection (3,5,12,20,30).…”

Clostridium difficile presence in Spanish and Belgian hospitals

“…However, only eight of the positive patients harboured toxigenic C. difficile strains. It has been described that during early infancy the gut microbiota complexity is poor and asymptomatic colonisation by C. difficile is common [31,32]. However, all the paediatric patient samples analysed in this study were diarrhoeal.…”