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Aberrant colon metabolome and the sudden infant death syndrome

Pediatric Research volume 95, pages 634–640 (2024)Cite this article

A Comment to this article was published on 16 October 2023

Abstract

Background

The Sudden Infant Death Syndrome (SIDS) has been associated with increased peripheral serotonin and an abnormal colonic microbiome, suggesting the colonic metabolome may also be abnormal. This study addresses this potential correlation by comparing colonic autopsy tissue from SIDS to age-matched non-SIDS controls.

Methods

Untargeted metabolomic analysis by mass spectrometry is used to assess human colonic metabolomic differences including serotonin. Expression of genes associated with colonic serotonin synthesis and transport (TPH1, TPH2, DDC, SCL6A4) is measured by qRT-PCR. Microbiome analysis is performed to compare the SIDS and non-SIDS colonic microbiome.

Results

Unsupervised hierarchical cluster and principal component analyses of metabolomic data shows increased variability in the SIDS cohort and separation of SIDS cases from the non-SIDS controls. There is a trend toward increased serotonin in the SIDS cohort but there is no significant difference in expression of the serotonin synthesis and transport genes between SIDS and non-SIDS control cohorts. Microbiome analysis shows no significant difference between the SIDS and non-SIDS control cohorts.

Conclusions

This study demonstrates increased variability in the colonic metabolome and a trend towards increased colonic serotonin in SIDS. The underlying cause of colon metabolomic variability, and its potential role in SIDS pathogenesis, warrants further investigation.

Impact Statement

  • The key message of this article is that SIDS is associated with an aberrant colonic metabolome.

  • This is a novel observation suggesting another component in the pathophysiology underlying SIDS.

  • Investigation of why the colonic metabolome is aberrant may offer new insights to SIDS pathogenesis and new strategies to reduce risk.

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Fig. 1: Measures of colonic metabolome similarity.
Fig. 2: Colonic tissue concentrations of serotonin and tryptophan.
Fig. 3: Expression of serotonin metabolism genes in colonic tissue.
Fig. 4: Measures of diversity in microbiome associated with colonic mucosa.

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Data availability

The microbiome analysis FASTQ files are available in the NIH BioProject database under ID PRJNA89917. The MS and qRT-PCR datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Human tissue was obtained from the NIH NeuroBiobank’s Brain and Tissue repository at the University of Maryland, Baltimore. The authors appreciate those who provided consent and assistance with biobanking of these tissues and make this valuable resource available. The authors thank Michelle Dittrick and Kendall Plant for administrative and technical assistance.

Funding

This study is funded by British Columbia Children’s Hospital Research Institute Pathology and Laboratory Medicine SIDS research grants and the authors thank Steps for SIDS and the donors who made these grants possible.

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Authors and Affiliations

  1. Department of Pathology, British Columbia Children’s and Women’s Hospitals, Vancouver, BC, Canada

    Jefferson Terry

  2. Analytical Core for Metabolomics and Nutrition, British Columbia Children’s Hospital Research Institute, Vancouver, BC, Canada

    Roger A. Dyer

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  1. Jefferson Terry
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Contributions

Both authors (J.T. and R.A.D.) were involved conception and design, acquisition of data, analysis and interpretation of data, drafting and revising the article, and final approval of the version to be published.

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Correspondence to Jefferson Terry.

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Terry, J., Dyer, R.A. Aberrant colon metabolome and the sudden infant death syndrome. Pediatr Res 95, 634–640 (2024). https://doi.org/10.1038/s41390-023-02847-0

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