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Wise-Oringer BK, Burghard AC, Park H, et al. Salivary microbiome differences in prepubertal children with and without adrenal androgen excess. Pediatr Res. 2021;doi: 10.1038/s41390-021-01661-w.
Wise-Oringer, B. K., Burghard, A. C., Park, H., Auchus, R. J., Oberfield, S. E., & Uhlemann, A. C. (2021). Salivary microbiome differences in prepubertal children with and without adrenal androgen excess. Pediatric research, . https://doi.org/10.1038/s41390-021-01661-w
Wise-Oringer, Brittany K, et al. "Salivary microbiome differences in prepubertal children with and without adrenal androgen excess." Pediatric research vol. (2021). doi: https://doi.org/10.1038/s41390-021-01661-w
Wise-Oringer BK, Burghard AC, Park H, Auchus RJ, Oberfield SE, Uhlemann AC. Salivary microbiome differences in prepubertal children with and without adrenal androgen excess. Pediatr Res. 2021 Aug 02; doi: 10.1038/s41390-021-01661-w. Epub 2021 Aug 02. PMID: 34341500.
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Pediatr Res. 2021 Aug 02; doi: 10.1038/s41390-021-01661-w. Epub 2021 Aug 02.

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

Pediatric research

Brittany K Wise-Oringer, Anne Claire Burghard, Heekuk Park, Richard J Auchus, Sharon E Oberfield, Anne-Catrin Uhlemann

Affiliations

  1. Division of Pediatric Endocrinology, Diabetes and Metabolism, Columbia University Irving Medical Center, New York, NY, USA.
  2. Department of Medicine and Microbiome & Pathogen Genomics Collaborative Center, Columbia University Irving Medical Center, New York, NY, USA.
  3. Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
  4. Division of Pediatric Endocrinology, Diabetes and Metabolism, Columbia University Irving Medical Center, New York, NY, USA. [email protected].

PMID: 34341500 DOI: 10.1038/s41390-021-01661-w

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.

© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

References

  1. Witchel, S. F., Pinto, B., Burghard, A. C. & Oberfield, S. E. Update on adrenarche. Curr. Opin. Pediatr. 32, 574–581 (2020). - PubMed
  2. Turcu, A. F. & Auchus, R. J. Clinical significance of 11-oxygenated androgens. Curr. Opin. Endocrinol. Diabetes Obes. 24, 252–259 (2017). - PubMed
  3. Rege, J. et al. 11-Ketotestosterone is the dominant circulating bioactive androgen during normal and premature adrenarche. J. Clin. Endocrinol. Metab. 103, 4589–4598 (2018). - PubMed
  4. Wise-Oringer, B. K. et al. The unique tole of 11-oxygenated C19 steroids in both premature adrenarche and premature pubarche. Horm. Res Paediatr. 2, 1–10 (2021). - PubMed
  5. Voutilainen, R. & Jääskeläinen, J. Premature adrenarche: etiology, clinical findings, and consequences. J. Steroid Biochem. Mol. Biol. 145, 226–236 (2015). - PubMed
  6. Ribeiro, F. A. et al. Metabolic and hormonal assessment of adolescent and young adult women with prior premature adrenarche. Clinics (Sao Paulo) 74, e836 (2019). - PubMed
  7. Kaya, G. et al. Body mass index at the presentation of premature adrenarche is associated with components of metabolic syndrome at puberty. Eur. J. Pediatr. 177, 1593–1601 (2018). - PubMed
  8. Silfen, M. E. et al. Elevated free IGF-I levels in prepubertal Hispanic girls with premature adrenarche: relationship with hyperandrogenism and insulin sensitivity. J. Clin. Endocrinol. Metab. 87, 398–403 (2002). - PubMed
  9. Ibanez, L. et al. Hyperinsulinemia in postpubertal girls with a history of premature pubarche and functional ovarian hyperandrogenism. J. Clin. Endocrinol. Metab. 8, 1237–1243 (1996). - PubMed
  10. Bäckhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718–15723 (2004). - PubMed
  11. Lee, C. J., Sears, C. L. & Maruthur, N. Gut microbiome and its role in obesity and insulin resistance. Ann. NY Acad. Sci. 1461, 37–52 (2020). - PubMed
  12. Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006). - PubMed
  13. Guo, Y. et al. Association between polycystic ovary syndrome and gut microbiota. PLoS ONE 11, e0153196 (2016). - PubMed
  14. Kelley, S. T., Skarra, D. V., Rivera, A. J. & Thackray, V. G. The gut microbiome is altered in a letrozole-induced mouse model of polycystic ovary syndrome. PLoS ONE 11, e0146509 (2016). - PubMed
  15. Yurtdaş, G. & Akdevelioğlu, Y. A new approach to polycystic ovary syndrome: the gut microbiota. J. Am. Coll. Nutr. 39, 371–382 (2020). - PubMed
  16. Insenser, M. et al. Gut microbiota and the polycystic ovary syndrome: influence of sex, sex hormones, and obesity. J. Clin. Endocrinol. Metab. 103, 2552–2562 (2018). - PubMed
  17. Tetel, M. J., de Vries, G. J., Melcangi, R. C., Panzica, G. & O’Mahony, S. M. Steroids, stress and the gut microbiome-brain axis. J. Neuroendocrinol. 30, https://doi.org/10.1111/jne.12548 (2018). - PubMed
  18. Sherman, S. B. et al. Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis. Gut Microbes 9, 400–421 (2018). - PubMed
  19. Gulan, T., Yeernuer, T., Sui, S. & Mayinuer, N. A rat model of maternal polycystic ovary syndrome shows that exposure to androgens in utero results in dysbiosis of the intestinal microbiota and metabolic disorders of the newborn rat. Med Sci. Monit. 25, 9377–9391 (2019). - PubMed
  20. Barroso, A. et al. Neonatal exposure to androgens dynamically alters gut microbiota architecture. J. Endocrinol. 247, 69–85 (2020). - PubMed
  21. Mammadova, G., Ozkul, C., Yilmaz Isikhan, S., Acikgoz, A. & Yildiz, B. O. Characterization of gut microbiota in polycystic ovary syndrome: findings from a lean population. Eur. J. Clin. Invest. 51, e13417 (2021). - PubMed
  22. Jobira, B. et al. Obese adolescents with PCOS have altered biodiversity and relative abundance in gastrointestinal microbiota. J. Clin. Endocrinol. Metab. 105, e2134–e2144 (2020). - PubMed
  23. Torres, P. J. et al. Gut microbial diversity in women with polycystic ovary syndrome correlates with hyperandrogenism. J. Clin. Endocrinol. Metab. 103, 1502–1511 (2018). - PubMed
  24. Liu, R. et al. Dysbiosis of gut microbiota associated with clinical parameters in polycystic ovary syndrome. Front. Microbiol. 8, 324 (2017). - PubMed
  25. Vrieze, A. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143, 913–6.e7 (2012). Erratum in: Gastroenterology. 144, 250 (2013). - PubMed
  26. Zeng, B. Structural and functional profiles of the gut microbial community in polycystic ovary syndrome with insulin resistance (IR-PCOS): a pilot study. Res. Microbiol. 170, 43–52 (2019). - PubMed
  27. He, F. F. & Li, Y. M. Role of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome: a review. J. Ovarian Res. 13, 73 (2020). - PubMed
  28. Belstrøm, D. The salivary microbiota in health and disease. J. Oral. Microbiol. 12, 1723975 (2020). - PubMed
  29. Xiao, J., Fiscella, K. A. & Gill, S. R. Oral microbiome: possible harbinger for children’s health. Int J. Oral. Sci. 12, 12 (2020). - PubMed
  30. Mameli, C. et al. Taste perception and oral microbiota are associated with obesity in children and adolescents. PLoS ONE 14, e0221656 (2019). - PubMed
  31. Wu, Y., Chi, X., Zhang, Q., Chen, F. & Deng, X. Characterization of the salivary microbiome in people with obesity. PeerJ 16, e4458 (2018). - PubMed
  32. Triosi, J. et al. Metabolomic salivary signature of pediatric obesity related liver disease and metabolic syndrome. Nutrients 11, 274 (2019). - PubMed
  33. Janem, W. F. et al. Salivary inflammatory markers and microbiome in normoglycemic lean and obese children compared to obese children with type 2 diabetes. PLoS ONE 12, e0172647 (2017). - PubMed
  34. Lindheim, L. et al. The salivary microbiome in polycystic ovary syndrome (PCOS) and its association with disease-related parameters: a pilot study. Front Microbiol 7, 1270 (2016). - PubMed
  35. Akcalı, A. et al. Association between polycystic ovary syndrome, oral microbiota and systemic antibody responses. PLoS ONE 9, e108074 (2014). - PubMed
  36. Pappa, E., Kousvelari, E. & Vastardis, H. Saliva in the “omics” era: a promising tool in paediatrics. Oral. Dis. 25, 16–25 (2019). - PubMed
  37. Chou, J. H., Roumiantsev, S. & Singh, R. PediTools electronic growth chart calculators: applications in clinical care, research, and quality improvement. J. Med. Internet Res. 22, e16204 (2020). - PubMed
  38. Shypailo, R. J. Age-Based Pediatric Blood Pressure Reference Charts. Baylor College of Medicine, Children’s Nutrition Research Center, Body Composition Laboratory, Houston, TX. https://www.bcm.edu/bodycomplab/BPappZjs/BPvAgeAPPz.html (2019). - PubMed
  39. Fernández, J. R., Redden, D. T., Pietrobelli, A. & Allison, D. B. Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents. J. Pediatr. 145, 439–444 (2004). - PubMed
  40. Wright, C., O’Day, P., Alyamani, M., Sharifi, N. & Auchus, R. J. Abiraterone acetate treatment lowers 11-oxygenated androgens. Eur. J. Endocrinol. 182, 413–421 (2020). - PubMed
  41. de Ferranti, S. D. et al. Prevalence of the metabolic syndrome in American adolescents: findings from the Third National Health and Nutrition Examination Survey. Circulation 110, 2494–2497 (2004). - PubMed
  42. Callahan, B. J. et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581–583 (2016). - PubMed
  43. DeSantis, T. Z. et al. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ. Microbiol. 72, 5069–5072 (2006). - PubMed
  44. McMurdie, P. J. & Phyloseq, H. S. An R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE 8, e61217 (2013). - PubMed
  45. Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014). - PubMed
  46. Westfall P. H. & Young S. S. Resampling-Based Multiple Testing: Examples and Methods for P-Value Adjustment (Wiley, 1993). - PubMed
  47. Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009). - PubMed
  48. Le Chatelier, E. et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541–546 (2013). - PubMed
  49. Riggio, M. P., Lennon, A. & Smith, A. Detection of peptostreptococcus micros DNA in clinical samples by PCR. J. Med. Microbiol. 50, 249–254 (2001). - PubMed
  50. Zhou, J. et al. Exploration of human salivary microbiomes—insights into the novel characteristics of microbial community structure in caries and caries-free subjects. PLoS ONE 11, e0147039 (2016). - PubMed
  51. Gross, E. L. et al. Beyond Streptococcus mutans: dental caries onset linked to multiple species by 16S rRNA community analysis. PLoS ONE 7, e47722 (2012). - PubMed
  52. Alauzet, C., Marchandin, H. & Lozniewski, A. New insights into Prevotella diversity and medical microbiology. Future Microbiol. 5, 1695–1718 (2010). - PubMed
  53. Larsen, J. M. The immune response to Prevotella bacteria in chronic inflammatory disease. Immunology 151, 363–374 (2017). - PubMed
  54. Zhu, C. et al. The predictive potentiality of salivary microbiome for the recurrence of early childhood caries. Front, Cell Infect. Microbiol. 8, 423 (2018). - PubMed
  55. Porwal, S., Tewari, S., Sharma, R. K., Singhal, S. R. & Narula, S. C. Periodontal status and high-sensitivity C-reactive protein levels in polycystic ovary syndrome with and without medical treatment. J. Periodontol. 85, 1380–1389 (2014). - PubMed
  56. Rahiminejad, M. E. et al. Comparison of prevalence of periodontal disease in women with polycystic ovary syndrome and healthy controls. Dent. Res J. (Isfahan) 12, 507–512 (2015). - PubMed

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