Project description:The Human Milk Oligosaccharide 3'Sialyllactose Promotes Selective Modulation of Inflammation and Reduces Atherosclerosis Development in Mice
Project description:Macrophages contribute to the induction and resolution of inflammation and play a central role in the chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. Here, we identify the HMO 3’sialyllactose (3’SL) as a natural inhibitor of TLR4-induced low-grade inflammation in macrophages and endothelium. Transcriptome analysis in macrophages revealed that 3’SL attenuates a selected set of inflammatory gene expression and promotes activity of genomic regions occupied by LXR and SREBP. These acute anti-inflammatory effects of 3’SL were associated with reduced histone H3K27 acetylation at a subset of LPS-inducible enhancers distinguished by preferential enrichment for NFKB, ATF3, IRF2, BCL6, and other transcription factor recognition motifs. In a murine atherosclerosis model, both subcutaneous and oral administration of 3’SL significantly reduced atherosclerosis development and the associated inflammation. This study provides evidence that 3’SL attenuates inflammation by a transcriptional mechanism to reduce atherosclerosis development in the context of cardiovascular disease.
Project description:Macrophages contribute to the induction and resolution of inflammation and play a central role in the chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. Here, we identify the HMO 3’sialyllactose (3’SL) as a natural inhibitor of TLR4-induced low-grade inflammation in macrophages and endothelium. Transcriptome analysis in macrophages revealed that 3’SL attenuates a selected set of inflammatory gene expression and promotes activity of LXR and SREBP. These acute anti-inflammatory effects of 3’SL were associated with reduced histone H3K27 acetylation at a subset of LPS-inducible enhancers distinguished by preferential enrichment for CTCF, IRF2, BCL6, and other transcription factor recognition motifs. In a murine atherosclerosis model, both subcutaneous and oral administration of 3’SL significantly reduced atherosclerosis development and the associated inflammation. This study provides evidence that 3’SL attenuates inflammation by a transcriptional mechanism to reduce atherosclerosis development in the context of cardiovascular disease.
Project description:Macrophages contribute to the induction and resolution of inflammation and play a central role in the chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. Here we identify the HMO 3’sialyllactose (3’SL) as a natural inhibitor of TLR4-induced low-grade inflammation in macrophages and endothelium. Transcriptome analysis in macrophages revealed that 3’SL attenuates a selected set of inflammatory gene expression and promotes activity of LXR and SREBP. Surprisingly, the acute anti-inflammatory effects of 3’SL were associated with reduced histone H3K27 acetylation at a subset of LPS-inducible enhancers distinguished by preferential enrichment for CTCF, IRF2, BCL6 and other transcription factor recognition motifs. In a murine atherosclerosis model, the subcutaneous administration of 3’SL significantly reduced atherosclerosis development and macrophage content in atherosclerotic lesions. This study provides evidence that 3’SL attenuates inflammation by a transcriptional mechanism to reduce atherosclerosis development in the context of cardiovascular disease.
Project description:Sialyllactose supplementation in pig milk replacer could promote cognitive functions in postnatal piglet behaviour experiment. There are 2 groups of 3-day-old postnatal piglets, feeding basal level and sialyllactose. After 35 days feeding, sialyllactose group showed better performance in behaviour experiment. We used microarrays to detail the global programme of gene expression underlying the nervous system development and memory formation.
Project description:Bifidobacteria constitute a specific group of commensal bacteria which inhabit the gastrointestinal tract of humans and other mammals. Bifidobacterium breve UCC2003 has previously been shown to utilise several plant-derived carbohydrates that include cellodextrins, starch and galactan. In the current study, we investigate the ability of this strain to utilise the mucin- and human milk oligosaccharide (HMO)-derived carbohydrate, sialic acid. Using a combination of transcriptomic and functional genomic approaches, we identified a gene cluster dedicated to the uptake and metabolism of sialic acid. Furthermore, we demonstrate that B. breve UCC2003 can cross feed on sialic acid derived from the metabolism of 3’ sialyllactose, a HMO, by Bifidobacterium bifidum PRL2010.
