Clinical Research Article | Published:

Enteric dysbiosis and fecal calprotectin expression in premature infants

Pediatric Research (2018) | Download Citation

Subjects

Abstract

Background

Premature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).

Methods

Stool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks’ postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.

Results

We enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.

Conclusion

In premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution.

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Acknowledgments

This research was funded by National Institutes of Health awards NR015446 (M.W.G.), HL124078 (A.M.), and HL133022 (A.M.), and T32GM007281 (A.L.Y.). We thank the research nurses, Judy Zaritt and Marcia Kneusel, for identification of eligible infants, and collection of clinical information and stool samples. We are also indebted to the nursing staff at the NICU at TGH for their constant support.

Author contributions

T.T.B.H. collected and analyzed the data and wrote the manuscript. M.W.G. supervised laboratory process and advised on content of the manuscript. B.K. performed laboratory analysis and advised on laboratory techniques. A.L.Y. analyzed 16S rRNA data. B.A.T. advised on the content of the manuscript. J.A.G. supervised the analysis of 16S rRNA data and advised on the manuscript content. A.M. supervised the data analysis and wrote the manuscript. All authors edited the manuscript and approved the final draft.

Author information

Affiliations

  1. Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    • Thao T. B. Ho
    •  & Benjamin A. Torres
  2. College of Nursing, University of South Florida, Tampa, FL, USA

    • Maureen W. Groer
    •  & Bradley Kane
  3. Department of Surgery, University of Chicago, Chicago, IL, USA

    • Alyson L. Yee
    •  & Jack A. Gilbert
  4. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    • Akhil Maheshwari

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The authors declare no competing interests.

Corresponding author

Correspondence to Akhil Maheshwari.

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DOI

https://doi.org/10.1038/s41390-018-0254-y