Epidemiological and microbiome associations of Clostridioides difficile carriage in infancy and early childhood

ABSTRACT

There has been an increase in the prevalence of Clostridioides difficile (C. diff) causing significant economic impact on the health care system. Although toxigenic C. diff carriage is recognized in infancy, there is limited data regarding its longitudinal trends, associated epidemiolocal risk factors and intestinal microbiome characteristics. The objectives of our longitudinal cohort study were to investigate temporal changes in the prevalence of toxigenic C.diff colonization in children up to 2 years, associated epidemiological and intestinal microbiome characteristics. Pregnant mothers were enrolled prenatally, and serial stool samples were collected from their children for 2 years. 2608 serial stool samples were collected from 817 children. 411/817 (50%) were males, and 738/817 (90%) were born full term. Toxigenic C.diff was detected in 7/569 (1%) of meconium samples, 116/624 (19%) of 2 m (month), 221/606 (37%) of 6 m, 227/574 (40%) of 12 m and 18/235 (8%) of 24 m samples. Infants receiving any breast milk at 6 m were less likely to be carriers at 2 m, 6 m and 12 m than those not receiving it. (p = 0.002 at 2 m, p < 0.0001 at 6 m, p = 0.022 at 12 m). There were no robust differences in the underlying alpha or beta diversity between those with and without toxigenic C. diff carriage at any timepoint, although small differences in the relative abundance of certain taxa were found. In this largest longitudinal cohort study to date, a high prevalence of toxigenic C. diff carrier state was noted. Toxigenic C. diff carrier state in children is most likely a transient component of the dynamic infant microbiome.

KEYWORDS:

• Epidemiology
• Clostridiodes difficile
• microbiome
• infants
• children

Disclosure statement

No potential conflict of interest was reported by the author(s).

Contributors’ statement page

Dr. Mani conceptualized and designed the study, collected and interpreted data, drafted the initial manuscript, reviewed and revised the manuscript.

Ms. Levy conceptualized and designed the study, designed the data collection instruments, collected data and reviewed and revised the manuscript.

Mr. Fassnacht carried out the Clostridioides difficile PCR analysis and reviewed and revised the manuscript.

Dr. Hazrati carried out the initial epidemiological analyses and reviewed and revised the manuscript.

Dr. Angelova carried out microbiome analysis and reviewed and revised the manuscript.

Dr. Subramanian carried out microbiome analysis and reviewed and revised the manuscript

Ms. Richards collected data and reviewed and revised the manuscript.

Mr. Rice collected data and reviewed and revised the manuscript.

Dr. Niederhuber conceptualized and designed the study and reviewed and revised the manuscript.

Dr. Maxwell conceptualized and designed the study and reviewed and revised the manuscript.

Dr. Hourigan conceptualized and designed the study, collected and interpreted data, drafted the initial manuscript and critically revised the manuscript for important intellectual content.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Data availability statement

The data that support the findings of this study are openly available in https://www.ncbi.nlm.nih.gov/bioproject/PRJNA851805 [ncbi.nlm.nih.gov]

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2203969

Additional information

Funding

This work was supported by a National Institute of Child Health and Human Development of the National Institutes of Health K23 award (No. K23HD099240, Hourigan), the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under the Intramural Research Program (Hourigan) and an Inova Health System Seed Grant (Mani, Hourigan). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Inova expresses its appreciation to the Fairfax County in VA, which has supported Inova’s research projects with annual funding from its Contributory Fund (Fund 10030, Maxwell).