Molecular mechanisms for milk glycan influence on the bifidobacterial function

Breast fed infants are typically colonized by bifidobacteria that are thought to protect, feed and communicate with the developing intestine. Human milk contains a large amount of free and bound glycans thought to be involved in this bifidobacterial enrichment and my research has focused on deciphering the molecular mechanisms underlying this glycan-based enrichment. Work from my lab has produced the one of most detailed maps of glycan-degradation by a commensal bacterium, providing a significant new model for host-microbe interactions. More importantly, this work provides a conceptual basis for manipulation of the gut microbiota via synbiotic applications of milk glycans and cognate bifidobacteria—applications with very near-term impacts on human health.

Sample publications from this area:

  • Ehrlich, A. M., A. R. Pacheco, B. M. Henrick, D. Taft, G. Xe; M. N. Huda, D. Mishchuk, M. L. Goodson, C. Slupsky, D. Barile, C. B. Lebrilla, C. B. Stephensen, D. A. Mills, H. Raybould. 2020. Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells. BMC Microbiology 20:357. PMC7681996.
  • Karav, S., A. Le Parc, J. M. L. N. de Moura Bell, S. A. Frese1, N. Kirmiz, D. E. Block, D. Barile, and D. A. Mills. 2016. Oligosaccharides released from milk glycoproteins are selective growth substrates for infant-associated bifidobacteria.  Applied and Environmental Microbiology 82:3622-3630. PMC4959171.
  • Garrido, D., S. Ruiz-Moyano, N. Kirmiz, J. C. C. Davis, S. Totten, D. G. Lemay, J. A. Ugalde, J. B. German, C. B. Lebrilla, and D. A. Mills.  2016.  A novel gene cluster allows preferential utilization of fucosylated milk oligosaccharides in Bifidobacterium longum subsp. longum SC596. Scientific Reports. 6:35045. PMC5069460.
  • Garrido, D., C. Nwosu, S. Ruiz-Moyano, D. Aldredge, J. B. German, C. B. Lebrilla and D. A. Mills. 2012.   Endo-beta-N-acetylglucosaminidases from infant-gut associated bifidobacteria release complex N-glycans from human milk glycoproteins.  Molecular and Cellular Proteomics 11:775-785. PMC3434770
  • Sela, D. A., J. Chapman, A. Adeuya, J.H. Kim, F. Chen, T.R. Whitehead, A. Lapidus, D.S. Rokhsar, C.B. Lebrilla, J.B German, N.P. Price, P.M. Richardson, and D.A. Mills. 2008. The complete genome sequence of Bifidobacterium longum subsp. infantis suggests adaptation for milk utilization within the infant microbiome. Proceedings of the National Academy of Sciences 105:18964-18969. PMC2596198