Unveiling the genes linked to the synthesis of many complex Human Milk Oligosaccharides (HMOs)

The complex carbohydrates in human milk (Human Milk Oligosaccharides or HMOs) are important to infant development. Studies supporting this claim continue to pile up, including a study led by UC San Diego researchers showing that one of the biggest killers of preterm infants, necrotising enterocolitis, is blocked by having enough of one complex sugar in particular.

There are hundreds of different molecular structures of these HMOs in human milk and several are being tied to neurodevelopment, immunity development, and modulation of the infant microbiome. One big challenge is that researchers don't know all the biochemical details of how HMOs are made in the mom. This makes it hard for researchers to understand why some moms make little or none of some important HMOs, or how we can metabolically engineer microbes to produce HMOs as nutraceutical additives or therapeutics in infants and people of all ages

In a study in Nature Communications published on May 4, 2022 entitled "Elucidating Human Milk Oligosaccharide biosynthetic genes through network-based multi-omics integration," a cross-disciplinary team led by UC San Diego researchers used a systems biology approach to integrate gene expression data and HMO composition data to discover the genes linked to the synthesis of many complex HMOs.

“In our study,” said UC San Diego professor Nathan Lewis, the corresponding author of this work, “we were able to decipher the details of the HMO biosynthetic pathway. This will help researchers link maternal genetics to differences in milk composition and guide metabolic engineering for HMO production in efforts to improve infant development and for further nutritional applications.” Lewis holds appointments in the Department of Pediatrics at UC San Diego Health and the Department of Bioengineering at the UC San Diego Jacobs School of Engineering. He is Co-Director of the CHO Systems Biology Center at the UC San Diego Jacobs School of Engineering and an alumnus of the bioengineering graduate program at UC San Diego. 

The paper includes authors from the Department of Pediatrics at UC San Diego Health; the Bioinformatics and Systems Biology Graduate Program at UC San Diego; the Department of Bioengineering at the UC San Diego Jacobs School of Engineering; the Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), UC San Diego; the Complex Carbohydrate Research Center, University of Georgia, Athens; and the Department of Pediatrics, Children’s Nutrition Research Center, US Department of Agriculture/Agricultural Research Service, Baylor College of Medicine.