Urea is a dynamic and functional component of mammalian breast milk

Veerus, L.; Sun, H.; Almet, A. A.; Levin, E. R.; Battaje, R. R.; Dam, V. S.; Shah, D.; Clerk, R.; Chang, B.; Woortman, M. A.; Stuckey, J. E.; Shumaker, M. J.; Yin, Y. S.; Kundu, A.; Talaue-Weeast, M.; Cardenas, V.; Nyangahu, D. D.; Jaspan, H. B.; Manhart, M.; Nie, Q.; Barrett, E.; Nejsum, L. N.; Dominguez-Bello, M. G.; Blaser, M. J.; New Jersey Kids Study team,

doi:10.64898/2026.09.28.755206

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bioRxiv · 10.64898/2026.09.28.755206

Urea is a dynamic and functional component of mammalian breast milk

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Abstract

Urea is a constituent of human milk, yet its regulation and interactions with the infant gut microbiome remain unclear. Combining three human cohorts, a controlled mouse model, and complementary microbiome analyses, we show that milk urea increases across lactation, is conserved across mammals, and is not explained by circulating urea levels or maternal diet. Instead, we identify lactation-dependent remodeling of mammary urea-metabolism and transport pathways, including dynamic AQP3 localization in secretory epithelium, indicative of regulated transfer of circulating urea into breast milk. Alongside urea, maternal milk and stool provide complementary reservoirs of urea-metabolizing bacteria that help establish the infant "ureabiome", whose urea-utilization capacity is supported by metagenomics. This maternal-infant axis is context-dependent: infant formulas provide substantially higher urea levels than human milk, while functional assays show that urea supports both commensal and opportunistic bacteria in a concentration-dependent manner. Together, these findings define a maternal nitrogen axis through which lactation can shape the assembly and function of the infant gut microbiome.

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Veerus, L., Sun, H., Almet, A. A., Levin, E. R., Battaje, R. R., Dam, V. S., Shah, D., Clerk, R., Chang, B., Woortman, M. A., Stuckey, J. E., Shumaker, M. J., Yin, Y. S., Kundu, A., Talaue-Weeast, M., Cardenas, V., Nyangahu, D. D., Jaspan, H. B., Manhart, M., Nie, Q., Barrett, E., Nejsum, L. N., Dominguez-Bello, M. G., Blaser, M. J., New Jersey Kids Study team,. 2026-09-29. Urea is a dynamic and functional component of mammalian breast milk. https://doi.org/10.64898/2026.09.28.755206

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