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The development of intestinal dysbiosis in anemic preterm infants

Abstract

Objective

Anemia and Proteobacteria-dominant intestinal dysbiosis in very low birth weight (VLBW) infants have been linked to necrotizing enterocolitis, a severe gut inflammatory disease. We hypothesize that anemia of prematurity is related to the development of intestinal dysbiosis.

Study design

Three hundred and forty-two weekly stool samples collected prospectively from 80 VLBW infants were analyzed for bacterial microbiomes (with 16S rRNA). Linear mixed-effects model was used to determine the relationships between the onsets of anemia and intestinal dysbiosis.

Results

Hematocrit was associated with intestinal microbiomes, with lower Hct occurring with increased Proteobacteria and decreased Firmicutes. Infants with a hematocrit <30% had intestinal microbiomes that diverged toward Proteobacteria dominance and low diversity after the first postnatal month. The microbiome changes were also related to the severity of anemia.

Conclusions

This finding supports a potential microbiological explanation for anemia as a risk factor for intestinal dysbiosis in preterm infants.

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Fig. 1: Hematocrit is associated with stool microbiome in VLBW infants.
Fig. 2: Bacterial balance of Enterobacteriaceae in relative to important genera between anemic and nonanemic groups.
Fig. 3: Anemic VLBW infants develop different stool microbiome over time.

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Data availability

Our 16S sequence data are uploaded and available to public at this website: https://www.ncbi.nlm.nih.gov/sra/?term=SRP136661.

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Acknowledgements

We thank the research nurses, Judy Zaritt and Marcia Kneusel, for their valuable contributions with recruitment, data and stool collection; Tampa General Hospital NICU nurses for stool collection; laboratory technician, Bradley Kane, for his assistance with sample processing; Dr Michael Georgieff for scientific inputs and editing; and Dr Jane Carver for editing the manuscript.

Funding

Funding sources: R01 NR015446 (PI Groer), T32GM007281 (ALY).

Author information

Authors and Affiliations

Authors

Contributions

TTBH designed the study, collected clinical data, analyzed the 16S rRNA data, analyzed descriptive statistics, and prepared the manuscript. MWG advised on the study design, data collection, and microbiome analysis and revised the manuscript. AK advised on the study design, performed the statistical analysis on patient clinical and microbiome data, and revised the manuscript. ALY analyzed the 16S data into taxonomic percentages and diversity indices and revised the manuscript. AFLJ performed literature review and manuscript preparation. LJD was advisor in the study design and manuscript preparation. All authors approved the final manuscript as submitted.

Corresponding author

Correspondence to Thao T. B. Ho.

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Conflict of interest

The authors declare that they have no conflict of interest.

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Ho, T.T.B., Kumar, A., Louis-Jacques, A.F. et al. The development of intestinal dysbiosis in anemic preterm infants. J Perinatol 40, 1066–1074 (2020). https://doi.org/10.1038/s41372-020-0599-z

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