title: Overcoming the limited availability of human milk oligosaccharides: challenges and opportunities for research and application.
abstract: Human milk oligosaccharides (HMOs) are complex sugars highly abundant in human milk but currently not present in infant formula. Rapidly accumulating evidence from in vitro and in vivo studies, combined with epidemiological associations and correlations, suggests that HMOs benefit infants through multiple mechanisms and in a variety of clinical contexts. Until recently, however, research on HMOs has been limited by an insufficient availability of HMOs. Most HMOs are found uniquely in human milk, and thus far it has been prohibitively tedious and expensive to isolate and synthesize them. This article reviews new strategies to overcome this lack of availability by generating HMOs through chemoenzymatic synthesis, microbial metabolic engineering, and isolation from human donor milk or dairy streams. Each approach has its advantages and comes with its own challenges, but combining the different methods and acknowledging their limitations creates new opportunities for research and application with the goal of improving maternal and infant health.
authors.affiliation: L. Bode is with the Department of Pediatrics, Mother Milk Infant Center of Research Excellence (MoMI CoRE), University of California, San Diego, La Jolla, California, USA. N. Contractor is with Metagenics, Inc, Gig Harbor, Washington, USA. D. Barile is with the Department of Food Science and Technology, University of California, Davis, Davis, California, USA. N. Pohl is with the Department of Chemistry, Indiana University, Bloomington, Indiana, USA. A.R. Prudden and G.-J. Boons are with the Department of Chemistry and the Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA. Y.-S. Jin is with the Department of Food Science and Human Nutrition, Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. S. Jennewein is with Jennewein Biotechnologie GmbH, Rheinbreitbach, Rhineland Palatinate, Germany. lbode@ucsd.edu.
authors.forename: Lars
authors.initials: L
authors.lastname: Bode
authors.affiliation: L. Bode is with the Department of Pediatrics, Mother Milk Infant Center of Research Excellence (MoMI CoRE), University of California, San Diego, La Jolla, California, USA. N. Contractor is with Metagenics, Inc, Gig Harbor, Washington, USA. D. Barile is with the Department of Food Science and Technology, University of California, Davis, Davis, California, USA. N. Pohl is with the Department of Chemistry, Indiana University, Bloomington, Indiana, USA. A.R. Prudden and G.-J. Boons are with the Department of Chemistry and the Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA. Y.-S. Jin is with the Department of Food Science and Human Nutrition, Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. S. Jennewein is with Jennewein Biotechnologie GmbH, Rheinbreitbach, Rhineland Palatinate, Germany.
authors.forename: Nikhat
authors.initials: N
authors.lastname: Contractor
authors.affiliation: L. Bode is with the Department of Pediatrics, Mother Milk Infant Center of Research Excellence (MoMI CoRE), University of California, San Diego, La Jolla, California, USA. N. Contractor is with Metagenics, Inc, Gig Harbor, Washington, USA. D. Barile is with the Department of Food Science and Technology, University of California, Davis, Davis, California, USA. N. Pohl is with the Department of Chemistry, Indiana University, Bloomington, Indiana, USA. A.R. Prudden and G.-J. Boons are with the Department of Chemistry and the Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA. Y.-S. Jin is with the Department of Food Science and Human Nutrition, Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. S. Jennewein is with Jennewein Biotechnologie GmbH, Rheinbreitbach, Rhineland Palatinate, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Barile
authors.affiliation: L. Bode is with the Department of Pediatrics, Mother Milk Infant Center of Research Excellence (MoMI CoRE), University of California, San Diego, La Jolla, California, USA. N. Contractor is with Metagenics, Inc, Gig Harbor, Washington, USA. D. Barile is with the Department of Food Science and Technology, University of California, Davis, Davis, California, USA. N. Pohl is with the Department of Chemistry, Indiana University, Bloomington, Indiana, USA. A.R. Prudden and G.-J. Boons are with the Department of Chemistry and the Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA. Y.-S. Jin is with the Department of Food Science and Human Nutrition, Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. S. Jennewein is with Jennewein Biotechnologie GmbH, Rheinbreitbach, Rhineland Palatinate, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pohl
authors.affiliation: L. Bode is with the Department of Pediatrics, Mother Milk Infant Center of Research Excellence (MoMI CoRE), University of California, San Diego, La Jolla, California, USA. N. Contractor is with Metagenics, Inc, Gig Harbor, Washington, USA. D. Barile is with the Department of Food Science and Technology, University of California, Davis, Davis, California, USA. N. Pohl is with the Department of Chemistry, Indiana University, Bloomington, Indiana, USA. A.R. Prudden and G.-J. Boons are with the Department of Chemistry and the Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA. Y.-S. Jin is with the Department of Food Science and Human Nutrition, Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. S. Jennewein is with Jennewein Biotechnologie GmbH, Rheinbreitbach, Rhineland Palatinate, Germany.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Prudden
authors.affiliation: L. Bode is with the Department of Pediatrics, Mother Milk Infant Center of Research Excellence (MoMI CoRE), University of California, San Diego, La Jolla, California, USA. N. Contractor is with Metagenics, Inc, Gig Harbor, Washington, USA. D. Barile is with the Department of Food Science and Technology, University of California, Davis, Davis, California, USA. N. Pohl is with the Department of Chemistry, Indiana University, Bloomington, Indiana, USA. A.R. Prudden and G.-J. Boons are with the Department of Chemistry and the Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA. Y.-S. Jin is with the Department of Food Science and Human Nutrition, Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. S. Jennewein is with Jennewein Biotechnologie GmbH, Rheinbreitbach, Rhineland Palatinate, Germany.
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Boons
authors.affiliation: L. Bode is with the Department of Pediatrics, Mother Milk Infant Center of Research Excellence (MoMI CoRE), University of California, San Diego, La Jolla, California, USA. N. Contractor is with Metagenics, Inc, Gig Harbor, Washington, USA. D. Barile is with the Department of Food Science and Technology, University of California, Davis, Davis, California, USA. N. Pohl is with the Department of Chemistry, Indiana University, Bloomington, Indiana, USA. A.R. Prudden and G.-J. Boons are with the Department of Chemistry and the Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA. Y.-S. Jin is with the Department of Food Science and Human Nutrition, Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. S. Jennewein is with Jennewein Biotechnologie GmbH, Rheinbreitbach, Rhineland Palatinate, Germany.
authors.forename: Yong-Su
authors.initials: YS
authors.lastname: Jin
authors.affiliation: L. Bode is with the Department of Pediatrics, Mother Milk Infant Center of Research Excellence (MoMI CoRE), University of California, San Diego, La Jolla, California, USA. N. Contractor is with Metagenics, Inc, Gig Harbor, Washington, USA. D. Barile is with the Department of Food Science and Technology, University of California, Davis, Davis, California, USA. N. Pohl is with the Department of Chemistry, Indiana University, Bloomington, Indiana, USA. A.R. Prudden and G.-J. Boons are with the Department of Chemistry and the Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA. Y.-S. Jin is with the Department of Food Science and Human Nutrition, Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. S. Jennewein is with Jennewein Biotechnologie GmbH, Rheinbreitbach, Rhineland Palatinate, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jennewein
mesh_terms: D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D035843:Biomedical Research; D005818:Genetic Engineering; D006801:Humans; D007223:Infant; D041943:Infant Formula; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D008895:Milk, Human / Q000737:chemistry*; D009753:Nutritive Value; D009844:Oligosaccharides / Q000032:analysis* / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D009844:Oligosaccharides
keywords: bioengineering; carbohydrates; human milk oligosaccharides; milk; pediatrics; synthesis