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Salivary microbiome differences in prepubertal children with and without adrenal androgen excess

Abstract

Background

Premature adrenarche is a condition of childhood adrenal androgen excess (AAE) in the absence of gonadotropin-dependent puberty, and has been linked to insulin resistance and progression to metabolic syndrome. Microbial dysbiosis is associated with progression of inflammatory states and chronic diseases. Here, we aimed to examine the salivary microbiomes of children with AAE and assess the relationship with adrenal androgens and metabolic parameters.

Methods

In a prospective cross-sectional study of children with AAE and healthy controls, adrenal and metabolic parameters were characterized and salivary microbiome was profiled using V3–V4 16S rDNA gene amplicon sequencing.

Results

There was increased α-diversity in AAE (5 M, 15 F) compared to controls (3 M, 8 F), with positive correlation of 11OHA4, 11KA4, testosterone, androstenedione, DHEA, and DHEAS. Subanalyses showed increased α-diversity in both overweight/obese AAE and normal weight AAE compared to normal weight controls. Genus Peptostreptococcus, Veillonella, and Streptococcus salivarius were increased in normal weight AAE. Genus Prevotella, Abiotrophia, and Neisseria were increased in overweight/obese AAE.

Conclusion

These pilot data demonstrate differences in salivary microbiome profiles of children with and without AAE. Further studies are needed to assess the causal relationships between adrenal androgens, metabolic dysfunction, and salivary microbiome composition.

Impact

  • This study is the first to report the salivary microbiome of prepubertal children with adrenal androgen excess (AAE).

  • α-Diversity is increased in the salivary microbiome of children with AAE independent of weight status, and in this study cohort several serum androgens are positively associated with α-diversity.

  • Several taxa that have been associated with periodontal disease and inflammation are found to be significantly increased in AAE.

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Fig. 1: Bacterial diversity in AAE and controls.
Fig. 2: Differential abundant ASV in children with AAE and controls by weight status.

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Acknowledgements

We thank the members of the Division of Pediatric Endocrinology, Diabetes and Metabolism at Columbia University Irving Medical Center (New York, NY) for their referral of eligible subjects, and the subjects and their families for agreeing to participate. We thank the members of the Microbiome & Pathogen Genomics Collaborative Center for technical support. We thank Rachel Tao, B.A., for her initial help with patient recruitment and coordination of study visits. We also thank Ismael Castaneda, R.N. and the staff of the Clinical Research Resource at Columbia Irving Institute for Clinical and Translational Research (UL1TR001873) for their valuable help in conducting the study visits. With gratitude we acknowledge Esoterix Laboratory and the Columbia Biomarkers Core Laboratory for performing laboratory measurements for this study. This work was supported in part by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grant 5T32DK065522-14 (to B.K.W.-O. and S.E.O.) and by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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Contributions

B.K.W.-O., A.C.B., H.P., R.J.A., S.E.O., and A.-C.U. made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data. B.K.W.-O., A.C.B., H.P., S.E.O., and A.-C.U. were involved in drafting the article or revising it critically for important intellectual content. R.J.A., S.E.O., and A.-C.U. provided final approval of the version to be published.

Corresponding author

Correspondence to Sharon E. Oberfield.

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Informed consent was obtained for all study subjects prior to enrollment. For patients less than 7 years of age, informed consent was obtained from the parent or legal guardian. For patients 7 years or older, informed consent and assent were obtained.

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Wise-Oringer, B.K., Burghard, A.C., Park, H. et al. Salivary microbiome differences in prepubertal children with and without adrenal androgen excess. Pediatr Res 91, 1797–1803 (2022). https://doi.org/10.1038/s41390-021-01661-w

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