The human milk oligosaccharide 3’sialyllactose promotes inflammation resolution and reduces atherosclerosis development.

Chemoproteomic mapping of human milk oligosaccharide (HMO) interactions in cells

“…Our finding that 3SL exhibits maximal interactions with proteins found in murine macrophages is intriguing, given recent findings that it induces transcriptional activation to resolve inflammatory responses, however further investigations are needed to elucidate the underlying molecular mechanisms. 11,41,42 Overall, these probes augment the existing toolkit to study of glycan-protein interactions in solution and in equilibrium, and we expect the datasets herein to facilitate our understanding HMO biological activity as well as other untapped free glycans.…”

“…S3A, ESI†), as the immunomodulatory activities of HMOs have previously been described in these cells. 11,37 In addition to the previously reported immunomodulatory roles, RAW264.7 cells are widely used in immunology due to their phenotypic and functional stability. 38 In brief, cells were treated with each probe, followed by exposure to UV light, harvesting, lysis, coupling of probe-modified proteins to TAMRA-azide and fluorescence visualization.…”

“…As probe 3 engaged most of the proteins detected and its cognate free glycan (3SL) displays important immunomodulatory properties, 11,41,42 we pursued competition experiments to provide additional evidence that the identified targets bind 3SL. In these experiments, cells were pre-treated with excess 3SL prior to incubation with probe 3 plus 3SL and processed for proteomic analysis as described above.…”

“…8,9 While initially believed to be mere nutritional agents, increasing evidence has highlighted HMOs as important signaling molecules involved in the activation of protein receptors 10 and the resolution of inflammation. 9,[11][12][13] Some HMOs also display antimicrobial activity by acting as soluble decoys for pathogenic microbes or through inhibiting biofilm formation. 14,15 HMOs share a common lactose (Galb(1-4)Glc) core structure, which is often decorated with additional modifications, such as fucose or sialic acid residues (Fig.…”

Human Milk Oligosaccharides in Maternal Serum Respond to Oral Glucose Load and Are Associated with Insulin Sensitivity

“…Serum 3′SL is increased in pregnant compared to non-pregnant individuals, and concentrations seem to rise moderately over gestation [ 5 ]. In vivo and in vitro studies have attributed multiple effects to 3′SL, amongst them proangiogenic [ 17 ], anti-inflammatory and anti-atherogenic [ 45 ] effects, as well as effects on ganglioside biosynthesis in the brain. Based on our findings, we can only speculate on the consequence of the 3′SL increase, raising the question of whether 3′SL is protective or detrimental, counterbalancing or aggravating some of the pregnancy-induced unmet metabolic challenges.…”