# A Natural Glycan Array of the Human Milk Glycome

> **NIH NIH R43** · NATGLYCAN, LLC · 2020 · $139,301

## Abstract

In addition to essential nutrients and bioactive antibodies, human milk is unique in providing a rich pool of free-
reducing human milk glycans (HMG) that are minimally digested in the upper GI tract and transported intact into
the lower intestine, where, they have well-known pre- and probiotic effects and interfere with pathogen
attachment by acting as soluble decoy receptors. HMGs also appear in the circulation, suggesting they
participate systemically in physiological processes. HMGs may enhance the epithelial barrier function of the gut
and regulate neuronal dependent gut motility and perhaps enhancement of cognition via the gut-brain axis.
Benefits of breastfeeding stimulated manufacturers of nutritionals to develop supplements to infant formula that
provide the beneficial effects of mother's milk. Abbott Nutrition and Nestle Nutrition recently introduced infant
formula containing LNnT and/or 2'-FL. These HMG are now commodities manufactured as supplements using
fermentation process to supply a global market. Although HMG are beneficial to infants, we know little about the
biological mechanisms of any of the hundreds of HMG. A primary function of glycans in living organisms is their
specific recognition by glycan binding proteins (GBPs), and protein-glycan interactions have been investigated
for many years. Currently the most effective technology for investigating protein-glycan interactions is the printed
glycan microarray where glycans are attached to a glass microscope slides and interrogated with GBP to
discover and characterize protein-glycan interactions. We have discovered several potentially important
interactions of viruses, antibodies, galectins and DC-SIGN using the first HMG glycan microarrays, believe that
these discovery platforms can reveal therapeutically relevant protein-glycan interactions. Using our HMG glycan
array with the glycan binding domain (VP8*) of rotavirus adhesins, we discovered, for the first time, several
glycan determinants that may function as anti-adhesins, and the HMG structures carrying these determinants
had never been identified in spite of 60 years of study on the structure of HMG. These studies led us to look at
HMG as a subset of the larger human glycome. We developed a method to predict what structures make up
HMG glycome, compiled these structures in a database that we can use for a new approach to glycan
sequencing that could be a model for the more monumental task of sequencing the larger human glycome.
Having constructed 2 version of an HMG glycan microarray, we know the difficulties of constructing and
maintaining the required glycan libraries in an academic setting, and here we propose a commercial solution
using large-scale processes developed by NatGlycan to build a sustainable HMG library of pure structures and
construct a comprehensive array of completely defined glycans that represent the complete HMG glycome,
which will be a discovery, screening platform for relevant protein-glycan inter...

## Key facts

- **NIH application ID:** 9878891
- **Project number:** 5R43GM131534-02
- **Recipient organization:** NATGLYCAN, LLC
- **Principal Investigator:** David Fletcher Smith
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $139,301
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878891

## Citation

> US National Institutes of Health, RePORTER application 9878891, A Natural Glycan Array of the Human Milk Glycome (5R43GM131534-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9878891. Licensed CC0.

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