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Peer-reviewedCC BY 4.0PLOS One

The parental intestinal microbiome modulates systemic and local glucocorticoid levels in neonatal mice

  • Jordan E. Hamden1
  • Garrett Ainsworth-Cruickshank2
  • Katherine M. Gray3
  • Jiayu Ye4
  • George V. Kachkovski5
  • Brandon J. Forys6
  • Claire Sie7
  • Jessica A. F. D. Silva8
  • Melody Salehzadeh9
  • Sanjoy Ghosh10
  • Kenneth K. Harder
  • Kiran K. Soma
10 affiliations
  1. 1Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada
  2. 2Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada
  3. 3Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada
  4. 4Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada
  5. 5Department of Biology, University of British Columbia Okanagan, Kelowna, British Columbia, Canada
  6. 6Department of Emergency Medicine, University of Toronto, Toronto, Ontario, Canada
  7. 7Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada
  8. 8Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada
  9. 9Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada
  10. 10Graduate Program in Neuroscience, University of British Columbia, Vancouver, British Columbia, Canada
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Abstract

Glucocorticoids (GCs) are steroid hormones predominately produced by the adrenal glands and secreted into the blood, but are also produced locally within some target tissues. During early development in mice, postnatal day (PND) 2–12, local GC levels in lymphoid organs are higher than blood GC levels. Interestingly, studies in germ-free (GF) and antibiotic-treated mice demonstrate that the intestinal microbiome modulates circulating and local GC levels, possibly through production of short-chain fatty acids (SCFAs). Importantly, GF mice lack all microbes, and antibiotic treatment is a very powerful perturbation that eliminates most intestinal microbes; the effects of more subtle microbiome manipulations on neonatal blood and local GC levels have yet to be determined. To begin to fill this gap, we established two groups of C57BL/6J mice with distinct microbiomes M1 and M2. We then bred adult mice from M1 and M2 and collected blood, bone marrow, thymus, and spleen from neonatal animals at PND5. We measured progesterone, 11-deoxycorticosterone, corticosterone, and 11-dehydrocorticosterone in the blood and lymphoid organs via liquid chromatography tandem mass spectrometry. We also measured nine SCFAs in the blood to determine a possible connection between microbiome and GCs. The adult microbiomes differed in community composition, but not overall community diversity. Mice with M1 had increased corticosterone and 11-dehydrocorticosteorne levels in blood and lymphoid organs. Mice with M1 also had increased levels of six SCFAs in blood, indicating a possible connection between SCFA signaling and GC levels. These data further our understanding of intestinal microbiome modulation of GC physiology by demonstrating that even subtle differences in microbiome composition can influence systemic and local GC levels.

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Cite

BibTeXRIS
BibTeX
@article{hamden2026parental,
  title = {{The parental intestinal microbiome modulates systemic and local glucocorticoid levels in neonatal mice}},
  author = {Jordan E. Hamden and Garrett Ainsworth-Cruickshank and Katherine M. Gray and Jiayu Ye and George V. Kachkovski and Brandon J. Forys and Claire Sie and Jessica A. F. D. Silva and Melody Salehzadeh and Sanjoy Ghosh and Kenneth K. Harder and Kiran K. Soma},
  journal = {PLOS One},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pone.0357469},
  url = {https://doi.org/10.1371/journal.pone.0357469},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The parental intestinal microbiome modulates systemic and local glucocorticoid levels in neonatal mice
AU  - Jordan E. Hamden
AU  - Garrett Ainsworth-Cruickshank
AU  - Katherine M. Gray
AU  - Jiayu Ye
AU  - George V. Kachkovski
AU  - Brandon J. Forys
AU  - Claire Sie
AU  - Jessica A. F. D. Silva
AU  - Melody Salehzadeh
AU  - Sanjoy Ghosh
AU  - Kenneth K. Harder
AU  - Kiran K. Soma
PY  - 2026
DA  - 2026/09/23
JO  - PLOS One
DO  - 10.1371/journal.pone.0357469
UR  - https://doi.org/10.1371/journal.pone.0357469
AB  - Glucocorticoids (GCs) are steroid hormones predominately produced by the adrenal glands and secreted into the blood, but are also produced locally within some target tissues. During early development in mice, postnatal day (PND) 2–12, local GC levels in lymphoid organs are higher than blood GC levels. Interestingly, studies in germ-free (GF) and antibiotic-treated mice demonstrate that the intestinal microbiome modulates circulating and local GC levels, possibly through production of short-chain fatty acids (SCFAs). Importantly, GF mice lack all microbes, and antibiotic treatment is a very powerful perturbation that eliminates most intestinal microbes; the effects of more subtle microbiome manipulations on neonatal blood and local GC levels have yet to be determined. To begin to fill this gap, we established two groups of C57BL/6J mice with distinct microbiomes M1 and M2. We then bred adult mice from M1 and M2 and collected blood, bone marrow, thymus, and spleen from neonatal animals at PND5. We measured progesterone, 11-deoxycorticosterone, corticosterone, and 11-dehydrocorticosterone in the blood and lymphoid organs via liquid chromatography tandem mass spectrometry. We also measured nine SCFAs in the blood to determine a possible connection between microbiome and GCs. The adult microbiomes differed in community composition, but not overall community diversity. Mice with M1 had increased corticosterone and 11-dehydrocorticosteorne levels in blood and lymphoid organs. Mice with M1 also had increased levels of six SCFAs in blood, indicating a possible connection between SCFA signaling and GC levels. These data further our understanding of intestinal microbiome modulation of GC physiology by demonstrating that even subtle differences in microbiome composition can influence systemic and local GC levels.
SN  - 1932-6203
ER  -