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

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.