Human milk oligosaccharides(HMOs)are critical bioactive glycans that modulate gut microbiota composition and intestinal mucosal immunity.Among them,2′-fucosyllactose(2′-FL)and lacto-N-neotetraose(LNnT)are predominan...Human milk oligosaccharides(HMOs)are critical bioactive glycans that modulate gut microbiota composition and intestinal mucosal immunity.Among them,2′-fucosyllactose(2′-FL)and lacto-N-neotetraose(LNnT)are predominant structures and major fermentable substrates for microbial production of short-chain fatty acids(SCFAs).To elucidate the downstream immunomodulatory actions of HMOs,this study specifically examined their principal microbial metabolites—SCFAs(acetate,propionate,and butyrate)—which function as central mediators of intestinal barrier integrity and immune homeostasis.This study investigated the protective effects and molecular mechanisms of SCFAs—particularly butyrate—against lipopolysaccharide(LPS)-induced intestinal mucosal immune injury.In a humanized rat model,SCFAs supplementation(acetate,propionate,and butyrate)markedly alleviated body weight loss,reduced disease activity index(DAI)and histological damage,and decreased myeloperoxidase(MPO)activity.SCFAs improved intestinal barrier integrity by upregulating Claudin-1,Claudin-2,ZO-1,and Muc2 expression,while reducing serum D-lactate and diamine oxidase(DAO)levels.They also suppressed pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-2)and enhanced anti-inflammatory cytokines(IL-10,IL-4)and secretory IgA(sIgA)production.Transcriptomic and protein-protein interaction(PPI)analyses revealed that butyrate modulated colonic gene expression enriched in G protein-coupled receptor signaling and IgA immune network pathways,and mitigated inflammation by inhibiting the EGFR/STAT1/CXCL10/CCL2 and IL-6/STAT3 signaling axes.In vitro,butyrate significantly reduced lactate dehydrogenase(LDH)release,downregulated inflammatory gene expression,and inhibited M1 macrophage polarization.Collectively,these findings indicate that HMOs confer intestinal immunoprotective effects primarily through the microbial metabolite butyrate,providing new mechanistic insights into the immunomodulatory potential of HMOs and supporting their development as functional food ingredients.展开更多
The aim of this study was to investigate the effect of different storage temperatures(4℃,25℃ and 45℃,denoted as T-4,T-25 and T-45,respectively)on the physical stability and protein-lipid co-oxidation of whey protei...The aim of this study was to investigate the effect of different storage temperatures(4℃,25℃ and 45℃,denoted as T-4,T-25 and T-45,respectively)on the physical stability and protein-lipid co-oxidation of whey protein functional emulsions during the storage period at storage times of 1,2,3 and 6 months.At the 6th month of storage,samples stored at 45℃ were less physically stable than samples stored at 4℃,as evidenced by an increase in particle size(5.50%),a decrease in zeta potential(7.93%),and a decrease in adsorbed protein concentration(36.8%).The most severe protein-lipid co-oxidation was induced in whey protein functional emulsions under 45℃ temperature conditions with increasing storage time.Protein oxidation products(carbonyls,N′-formyl-L-kynurenine,and sulfhydryl groups)and lipid oxidation products(lipid hydroperoxides,thiobarbituric acid reactive substances)were at their highest levels,and significant molecular changes were observed in the molecules of adsorbed protein or unadsorbed proteins.As the storage temperature rises it exposes the active sites such as internal sulfhydryl and hydrophobic groups in the protein,promoting cross-linking and aggregation.Cluster and correlation analyses showed that protein-lipid co-oxidation of emulsions inevitably occurs during storage,but low-temperature storage can delay this process.This study is of guiding significance for the quality maintenance of functional nutritional emulsions and the selection of storage conditions.In addition,this study may provide clearer solutions to the problems of whey protein denaturation and formation of lipid oxides caused by protein-lipid co-oxidation in the food industry,as well as to the problem of increasing the shelf life of products by choosing the appropriate storage,packaging,and transportation temperatures.展开更多
基金supported by the Hohhot City"Government,Industry,University,Research,Promotion and Application of Silver"Innovation Consortium Project(2023RC-Consortium-7)the"Lutein/DHA-caseinalgal ternary composite small intestine-targeted controlled-release system and its application in eye-protecting functional food"Project(2025YFHH0187)the"Special Funding Project of the China Post-doctoral Science Foundation"(2025T180813).
文摘Human milk oligosaccharides(HMOs)are critical bioactive glycans that modulate gut microbiota composition and intestinal mucosal immunity.Among them,2′-fucosyllactose(2′-FL)and lacto-N-neotetraose(LNnT)are predominant structures and major fermentable substrates for microbial production of short-chain fatty acids(SCFAs).To elucidate the downstream immunomodulatory actions of HMOs,this study specifically examined their principal microbial metabolites—SCFAs(acetate,propionate,and butyrate)—which function as central mediators of intestinal barrier integrity and immune homeostasis.This study investigated the protective effects and molecular mechanisms of SCFAs—particularly butyrate—against lipopolysaccharide(LPS)-induced intestinal mucosal immune injury.In a humanized rat model,SCFAs supplementation(acetate,propionate,and butyrate)markedly alleviated body weight loss,reduced disease activity index(DAI)and histological damage,and decreased myeloperoxidase(MPO)activity.SCFAs improved intestinal barrier integrity by upregulating Claudin-1,Claudin-2,ZO-1,and Muc2 expression,while reducing serum D-lactate and diamine oxidase(DAO)levels.They also suppressed pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-2)and enhanced anti-inflammatory cytokines(IL-10,IL-4)and secretory IgA(sIgA)production.Transcriptomic and protein-protein interaction(PPI)analyses revealed that butyrate modulated colonic gene expression enriched in G protein-coupled receptor signaling and IgA immune network pathways,and mitigated inflammation by inhibiting the EGFR/STAT1/CXCL10/CCL2 and IL-6/STAT3 signaling axes.In vitro,butyrate significantly reduced lactate dehydrogenase(LDH)release,downregulated inflammatory gene expression,and inhibited M1 macrophage polarization.Collectively,these findings indicate that HMOs confer intestinal immunoprotective effects primarily through the microbial metabolite butyrate,providing new mechanistic insights into the immunomodulatory potential of HMOs and supporting their development as functional food ingredients.
基金financially supported by the National Key Research and Development Program of China(2022YFF1100402)the National Natural Science Foundation of China(No.31801518 and 31601450)the China Postdoctoral Science Foundation(2024T170256).
文摘The aim of this study was to investigate the effect of different storage temperatures(4℃,25℃ and 45℃,denoted as T-4,T-25 and T-45,respectively)on the physical stability and protein-lipid co-oxidation of whey protein functional emulsions during the storage period at storage times of 1,2,3 and 6 months.At the 6th month of storage,samples stored at 45℃ were less physically stable than samples stored at 4℃,as evidenced by an increase in particle size(5.50%),a decrease in zeta potential(7.93%),and a decrease in adsorbed protein concentration(36.8%).The most severe protein-lipid co-oxidation was induced in whey protein functional emulsions under 45℃ temperature conditions with increasing storage time.Protein oxidation products(carbonyls,N′-formyl-L-kynurenine,and sulfhydryl groups)and lipid oxidation products(lipid hydroperoxides,thiobarbituric acid reactive substances)were at their highest levels,and significant molecular changes were observed in the molecules of adsorbed protein or unadsorbed proteins.As the storage temperature rises it exposes the active sites such as internal sulfhydryl and hydrophobic groups in the protein,promoting cross-linking and aggregation.Cluster and correlation analyses showed that protein-lipid co-oxidation of emulsions inevitably occurs during storage,but low-temperature storage can delay this process.This study is of guiding significance for the quality maintenance of functional nutritional emulsions and the selection of storage conditions.In addition,this study may provide clearer solutions to the problems of whey protein denaturation and formation of lipid oxides caused by protein-lipid co-oxidation in the food industry,as well as to the problem of increasing the shelf life of products by choosing the appropriate storage,packaging,and transportation temperatures.
