The Human Milk Glycome As a Defense Against Infectious Diseases: Rationale, Challenges, and Opportunities

Each year over 3 million people die from infectious diseases with most of these deaths being poor and young children who live in low- and middle-income countries. Infectious diseases emerge for a multitude of reasons. On the social front, reasons include a breakdown of public health standards, international travel, and immigration (for financial, civil, and social reasons). At the molecular level, the modern rise of infectious diseases is tied to the juxtaposition of drug-resistant pathogens and a lack of new antimicrobials. The consequence is the possibility that humankind will return to the preantibiotic era wherein millions of people will perish from what should be trivial illnesses. Given the stakes, it is imperative that the chemistry community take leadership in delivering new antibiotic leads for clinical development. We believe this can happen through innovation in two areas. First is the development of novel chemical scaffolds to treat infections caused by multidrug-resistant pathogens. The second area, which is not exclusive to the first, is the generation of antibiotics that do not cause collateral damage to the host or the host's microbiome. Both can be enabled through advances in chemical synthesis. It is with this general philosophy in mind that we hypothesized human milk oligosaccharides (HMOs) could serve as novel chemical scaffolds for antibacterial development. We provide herein a personal account of our laboratory's progress toward the goal of using HMOs as a defense against infectious diseases.