To study the variability in human milk oligosaccharide (HMO) composition of Chinese human milk over a 20-wk lactation period, HMO profiles of 30 mothers were analyzed using CE-LIF. This study showed ...that total HMO concentrations in Chinese human milk decreased significantly over a 20-wk lactation period, independent of the mother’s SeLe status, although with individual variations. In addition, total acidic and neutral HMO concentrations in Chinese human milk decreased over lactation, and levels are driven by their mother’s SeLe status. Analysis showed that total neutral fucosylated HMO concentrations in Chinese human milk were higher in the two secretor groups as compared to the nonsecretor group. On the basis of the total neutral fucosylated HMO concentrations in Chinese human milk, HMO profiles within the Se+Le+ group can be divided into two subgroups. HMOs that differed in level between Se+Le+ subgroups were 2′FL, DF-L, LNFP I, and F-LNO. HMO profiles in Dutch human milk also showed Se+Le+ subgroup division, with 2′FL, LNT, and F-LNO as the driving force.
Dietary fibres are believed to reduce subjective appetite, energy intake and body weight. However, different types of dietary fibre may affect these outcomes differently. The aim of this review was ...to systematically investigate the available literature on the relationship between dietary fibre types, appetite, acute and long‐term energy intake, and body weight. Fibres were grouped according to chemical structure and physicochemical properties (viscosity, solubility and fermentability). Effect rates were calculated as the proportion of all fibre–control comparisons that reduced appetite (n = 58 comparisons), acute energy intake (n = 26), long‐term energy intake (n = 38) or body weight (n = 66). For appetite, acute energy intake, long‐term energy intake and body weight, there were clear differences in effect rates depending on chemical structure. Interestingly, fibres characterized as being more viscous (e.g. pectins, β‐glucans and guar gum) reduced appetite more often than those less viscous fibres (59% vs. 14%), which also applied to acute energy intake (69% vs. 30%). Overall, effects on energy intake and body weight were relatively small, and distinct dose–response relationships were not observed. Short‐ and long‐term effects of dietary fibres appear to differ and multiple mechanisms relating to their different physicochemical properties seem to interplay. This warrants further exploration.
Pulmonary cachexia is a prevalent, debilitating, and well-recognized feature of COPD associated with increased mortality and loss of peripheral and respiratory muscle function. The exact cause and ...underlying mechanisms of cachexia in COPD are still poorly understood. Increasing evidence, however, shows that pathological changes in intracellular mechanisms of muscle mass maintenance (i.e., protein turnover and myonuclear turnover) are likely involved. Potential factors triggering alterations in these mechanisms in COPD include oxidative stress, myostatin, and inflammation. In addition to muscle wasting, peripheral muscle in COPD is characterized by a fiber-type shift toward a more type II, glycolytic phenotype and an impaired oxidative capacity (collectively referred to as an impaired oxidative phenotype). Atrophied diaphragm muscle in COPD, however, displays an enhanced oxidative phenotype. Interestingly, intrinsic abnormalities in (lower limb) peripheral muscle seem more pronounced in either cachectic patients or weight loss-susceptible emphysema patients, suggesting that muscle wasting and intrinsic changes in peripheral muscle's oxidative phenotype are somehow intertwined. In this manuscript, we will review alterations in mechanisms of muscle mass maintenance in COPD and discuss the involvement of oxidative stress, inflammation, and myostatin as potential triggers of cachexia. Moreover, we postulate that an impaired muscle oxidative phenotype in COPD can accelerate the process of cachexia, as it renders muscle in COPD less energy efficient, thereby contributing to an energy deficit and weight loss when not dietary compensated. Furthermore, loss of peripheral muscle oxidative phenotype may increase the muscle's susceptibility to inflammation- and oxidative stress-induced muscle damage and wasting.
► Production of monomeric galacturonic acid and arabinose from sugar beet pulp. ► Saccharification conditions are used that are feasible for industrial upscaling. ► Release of 79% galacturonic acid ...and 82% arabinose with 17% cellulose degradation. ► Recalcitrant oligosaccharides obtained after hydrolysis are characterized in detail. ► Lacking enzyme activities for further increase of yield are being discussed.
Enzymatic saccharification of sugar beet pulp was optimized on kg-scale to release the maximum amounts of monomeric galacturonic acid and arabinose with limited concomitant degradation of cellulose, using conditions that are feasible for industrial upscaling. A selected mixture of pectinases released 79% of the galacturonic acid and 82% of the arabinose as monomers from sugar beet pulp while simultaneously degrading only 17% of the cellulose. The recalcitrant structures that were obtained after hydrolysis were characterized using mass spectrometry. The most abundant structures had an average degree of polymerization of 4–5. They were identified as partially acetylated rhamnogalacturonan-oligosaccharides, mostly containing a terminal galacturonosyl residue on both reducing and non-reducing end, partially methyl esterified/acetylated homogalacturonan-oligosaccharides, mostly containing methyl and acetyl esters at contiguous galacturonosyl residues and arabinan-oligosaccharides, hypothesized to be mainly branched. It could be concluded that especially rhamnogalacturonan-galacturonohydrolase, arabinofuranosidase and pectin acetylesterase are lacking for further degradation of recalcitrant oligosaccharides.
► Characterization of plant cell wall derived oligosaccharides using HILIC–ELSD–MS
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. ► Complex mixtures of neutral and acidic oligosaccharides can be separated. ► Oligosaccharides with same net ...charge but different DP can be separated adequately.
Analysis of complex mixtures of plant cell wall derived oligosaccharides is still challenging and multiple analytical techniques are often required for separation and characterization of these mixtures. In this work it is demonstrated that hydrophilic interaction chromatography coupled with evaporative light scattering and mass spectrometry detection (HILIC–ELSD–MS
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) is a valuable tool for identification of a wide range of neutral and acidic cell wall derived oligosaccharides. The separation potential for acidic oligosaccharides observed with HILIC is much better compared to other existing techniques, like capillary electrophoresis, reversed phase and porous-graphitized carbon chromatography. Important structural information, such as presence of methyl esters and acetyl groups, is retained during analysis. Separation of acidic oligosaccharides with equal charge yet with different degrees of polymerization can be obtained. The efficient coupling of HILIC with ELSD and MS
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-detection enables characterization and quantification of many different oligosaccharide structures present in complex mixtures. This makes HILIC–ELSD–MS
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a versatile and powerful additional technique in plant cell wall analysis.
Colostrum oligosaccharides are known to exhibit prebiotic and immunomodulatory properties. Oligosaccharide composition is species-specific, and equine colostrum has been reported to contain unique ...oligosaccharides. Therefore, equine oligosaccharides (EMOS) from colostrum from different horse breeds were analyzed by CE-LIF, CE-MS n , HILIC-MS n , and exoglycosidase degradation. Sixteen EMOS were characterized and quantified, of which half were neutral and half were acidic. EMOS showed about 63% structural overlap with human milk oligosaccharides, known for their bioactivity. Seven EMOS were not reported before in equine oligosaccharides literature: neutral Gal(β1–4)HexNAc, Gal(β1–4)Hex-Hex, β4′-galactosyllactose, and lactose-N-hexaose, as well as acidic 6′-Sialyl-Hex-Ac-HexNAc, sialyllacto-N-tetraose-a, and disialylacto-N-tetraose (isomer not further specified). In all colostrum samples, the average oligosaccharide concentration ranged from 2.12 to 4.63 g/L; with β 6′and 3′- galactosyllactose, 3′-sialyllactose, and disialyllactose as the most abundant of all oligosaccharides (27–59, 16–37, 1–8, and 1–6%, respectively). Differences in presence and in abundance of specific EMOS were evident not only between the four breeds but also within the breed.
Prebiotic oligosaccharides, including galacto-oligosaccharides (GOS), are used in infant formula to mimic human milk oligosaccharides, which are known to have an important role in the development of ...the intestinal microbiota and the immune system in neonates. The maturation of the intestines in piglets closely resembles that of human neonates and infants. Hence, a neonatal piglet model was used to study the multi-faceted effect of dietary GOS in early life. Naturally farrowed piglets were separated from the mother sow 24–48 h postpartum and received a milk replacer with or without the addition of GOS for 3 or 26 d, whereafter several indicators of intestinal colonisation and maturation were measured. Dietary GOS was readily fermented in the colon, leading to a decreased pH, an increase in butyric acid in caecum digesta and an increase in lactobacilli and bifidobacteria numbers at day 26. Histomorphological changes were observed in the intestines of piglets fed a GOS diet for 3 or 26 d. In turn, differences in the intestinal disaccharidase activity were observed between control and GOS-fed piglets. The mRNA expression of various tight junction proteins was up-regulated in the intestines of piglet fed a GOS diet and was not accompanied by an increase in protein expression. GOS also increased defensin porcine β-defensin-2 in the colon and secretory IgA levels in saliva. In conclusion, by applying a neonatal piglet model, it could be demonstrated that a GOS-supplemented milk replacer promotes the balance of the developing intestinal microbiota, improves the intestinal architecture and seems to stimulate the intestinal defence mechanism.
•Homogalacturonan pectins mainly inhibit TLR2-1.•Pectins with a low DM or intermediate DM with a high DB inhibited TLR2-1 strongest.•TLR2 bound strongest to pectins with a low DM or an intermediate ...DM with a high DB.•TLR2-1 inhibiting pectins also inhibited IL-6 secretion from macrophages.
Pectins have anti-inflammatory effects via Toll-like receptor (TLR) inhibition in a degree of methyl-esterification-(DM)-dependent manner. However, pectins also vary in distribution of methyl-esters over the galacturonic-acid (GalA) backbone (Degree of Blockiness - DB) and impact of this on anti-inflammatory capacity is unknown. Pectins mainly inhibit TLR2-1 but magnitude depends on both DM and DB. Low DM pectins (DM18/19) with both low (DB86) and high DB (DB94) strongly inhibit TLR2-1. However, pectins with intermediate DM (DM43/DM49) and high DB (DB60), but not with low DB (DB33), inhibit TLR2-1 as strongly as low DM. High DM pectins (DM84/88) with DB71 and DB91 do not inhibit TLR2-1 strongly. Pectin-binding to TLR2 was confirmed by capture-ELISA. In human macrophages, low DM and intermediate DM pectins with high DB inhibited TLR2-1 induced IL-6 secretion. Both high number and blockwise distribution of non-esterified GalA in pectins are responsible for the anti-inflammatory effects via inhibition of TLR2-1.
In muscle cells, the peroxisome proliferator-activated receptor γ co-activator 1 (PGC-1) signaling network, which has been shown to be disturbed in the skeletal muscle in several chronic diseases, ...tightly controls mitochondrial biogenesis and oxidative substrate metabolism. Previously, we showed that inactivation of glycogen synthase kinase (GSK)-3β potently increased Pgc-1α abundance and oxidative metabolism in skeletal muscle cells. The current study aims to unravel the molecular mechanism driving the increase in Pgc-1α mediated by GSK-3β inactivation.
GSK-3β was inactivated genetically or pharmacologically in C2C12 myotubes and the requirement of transcription factors known to be involved in Pgc-1α transcription for increases in Pgc-1α abundance mediated by inactivation of GSK-3β was examined.
Enhanced PGC-1α promoter activation after GSK-3β inhibition suggested a transcriptionally-controlled mechanism. While myocyte enhancer factor (MEF)2 transcriptional activity was unaltered, GSK-3β inactivation increased the abundance and activity of the transcription factors estrogen-related receptor (ERR)α and ERRγ. Pharmacological inhibition or knock-down of ERRα and ERRγ however failed to prevent increases in Pgc-1α mRNA mediated by GSK-3β inactivation. Interestingly, GSK-3β inactivation activated transcription factor EB (TFEB), evidenced by decreased phosphorylation and enhanced nuclear localization of the TFEB protein. Moreover, knock-down of TFEB completely prevented increases in Pgc-1α gene expression, PGC-1α promoter activity and PGC-1α protein abundance induced by GSK-3β inactivation. Furthermore, mutation of a specific TFEB binding site on the PGC-1α promoter blocked promoter activation upon inhibition of GSK-3β.
In skeletal muscle, GSK-3β inactivation causes dephosphorylation and nuclear translocation of TFEB resulting in TFEB-dependent induction of Pgc-1α expression.
•Inactivation of GSK-3β increases PGC-1α abundance and promoter activation.•Inactivation of GSK-3β increases TFEB nuclear translocation.•Increased PGC-1α expression upon GSK-3β inhibition requires TFEB.•GSK-3 inhibition enhances PGC-1α promoter activity dependent on a TFEB binding site.
In the present double-blind, randomised, parallel intervention study, the effects of the intake of galacto-oligosaccharides (GOS) on the gut microbiota of twelve healthy adult subjects (aged 18–45 ...years with a normal BMI (18–25 kg/m2)) receiving amoxicillin (AMX) treatment were determined. All the subjects were treated with AMX (375 mg; three times per d) for 5 d and given either GOS (n 6) or placebo (maltodextrin, n 6) (2·5 g; three times per d) during and 7 d after AMX treatment. Faecal samples were collected twice before starting the treatment and on days 2, 5, 8, 12, 19 and 26. Due to AMX treatment, a decrease in the abundance of Bifidobacterium spp., an overgrowth of Enterobacteriaceae, and a disruption of the metabolic activity of the microbiota (increase in succinate, monosaccharide and oligosaccharide levels in the faecal samples) were observed in both groups (P< 0·05). Positive effects of GOS intake were observed on the levels of bifidobacteria, although not found to be significant. Data revealed that the levels of bifidobacteria were higher upon GOS intake than upon placebo intake, especially after AMX treatment. The activity of bifidobacteria and subsequent cross-feeding activity of the microbiota upon GOS intake compared with those upon placebo intake were reflected by the significant increase in butyrate levels (P< 0·05) in the faecal samples after AMX treatment. Despite the small number of subjects, our findings confirm previous results obtained in vitro, namely that GOS intake supports the recovery of the beneficial bifidobacteria and, indirectly, the production of butyrate after AMX treatment.
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