Human Milk Oligosaccharides: Potential Applications in COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a global health crisis with more than four million deaths worldwide. A substantial number of COVID-19 survivors continue suffering from long-COVID syndrome, a long-term complication exhibiting chronic inflammation and gut dysbiosis. Much effort is being expended to improve therapeutic outcomes. Human milk oligosaccharides (hMOS) are non-digestible carbohydrates known to exert health benefits in breastfed infants by preventing infection, maintaining immune homeostasis and nurturing healthy gut microbiota. These beneficial effects suggest the hypothesis that hMOS might have applications in COVID-19 as receptor decoys, immunomodulators, mucosal signaling agents, and prebiotics. This review summarizes hMOS biogenesis and classification, describes the possible mechanisms of action of hMOS upon different phases of SARS-CoV-2 infection, and discusses the challenges and opportunities of hMOS research for clinical applications in COVID-19.

Human Milk Extracellular Vesicles: A Biological System with Clinical Implications

“…Human milk oligosaccharides (hMOS), the third most abundant component of human milk, inhibit binding of pathogens to the intestinal mucosa, stimulate growth of mutualist microbes in the gut (prebiotic), and modulate signaling and inflammation in the intestinal mucosa [ 28 ]. Using liquid chromatography-mass spectrometry, He et al discovered that hMOS are also encapsulated by hMEVs from both colostrum and mature milk.…”

“…For colostrum hMEVs, 2’-fucosyllactose (2’FL), lacto-N-tetraose/neotetraose (LNT/LNnT), lacto-N-difucohexaose (LDFH) were predominant; for mature milk hMEVs, 2’FL, lacto-N-fucopentaose I (LNFP I), and LNT/LNnT predominated [ 136 ]. 2’FL exhibits immunomodulatory and anti-infective properties [ 28 , 136 , 137 , 138 , 139 , 140 , 141 ]. In adherent invasive E. coli -infected mice, hMEV-encapsulated hMOS could attenuate intestinal inflammation comparable to or perhaps superior to that of free solutions of 2’FL [ 136 ].…”

“…Knowledge regarding mechanisms by which human milk components deliver positive health outcomes to children and young adults is growing. The recognized human milk bioactive components include proteins (immunoglobulins, lactoferrin), growth factors, cytokines, adipokines, non-digestible oligosaccharides (2′-fucosyllactose (2′FL), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), sialyllactoses (3SL, 6SL)), leukocytes, and stem cells [ 25 , 26 , 27 , 28 ]. In 2007, Admyr et al [ 29 ] reported that human milk contains EVs harboring major histocompatibility complex (MHC) class I/II, which can be immunosuppressive.…”

The Role of the Gut-Lung Axis in COVID-19 Infections and Its Modulation to Improve Clinical Outcomes

“…In addition, HMOs also act against biofilm formulation to weaken the invasion capacity of pathogens [115]. Recently, HMOs have been proposed to be applied in COVID-19 [116]. As HMOs are rare in the market-place, bovine milk oligosaccharides (BMOs) have been studied for their prebiotic beneficial effects [117].…”

Chemoenzymatic Synthesis of Asymmetrically Branched Human Milk Oligosaccharide Lacto-N-Hexaose

“…Human milk oligosaccharides (HMOs) are a group of structurally complex glycans that are highly abundant in breast milk and are associated with various biological events in the human body ( Chen et al, 2015 ; Cheng et al, 2021 ; Chutipongtanate et al, 2022 ). Several mechanisms of HMOs that provide health benefits, including intestinal microbiome regulation, epithelial and immune cell response modulation, prevention of viral infection, and the provision of nutrients to the brain, have been examined ( Bode, 2012 ; Kulinich and Liu, 2016 ; Kirmiz et al, 2018 ; Fabiano et al, 2021 ; Moore et al, 2021 ; Morrin et al, 2021 ; Rousseaux et al, 2021 ).…”