Maternal short chain fructo-oligosaccharides supplementation during late gestation and lactation influences milk components and offspring gut metabolome: a pilot study.

Breast milk composition is influenced by maternal diet. This study aimed to evaluate if supplementation of maternal diet with a prebiotic fibre, through its potential effect on milk composition, can be a leverage to orientate the gut microbiota of infants in a way that would be beneficial for their health. Twelve sows received a diet supplemented with short chain fructo-oligosaccharides or maltodextrins during the last month of gestation and the lactation. Oligosaccharidic and lipidomic profiles of colostrum and mature milk (21 days), as well as faecal microbiota composition and metabolomic profile of 21 day-old piglets were evaluated. The total porcine milk oligosaccharide concentration tended to be lower in scFOS-supplemented sows, mainly due to the significant reduction of the neutral core oligosaccharides (in particular that of a tetrahexose). Maternal scFOS supplementation affected the concentration of 31 lipids (mainly long-chain triglycerides) in mature milk. Faecal short-chain fatty acid content and that of 16 bacterial metabolites were modified by scFOS supplementation. Interestingly, the integrative data analysis gave a novel insight into the relationships between (i) maternal milk lipids and PMOs and (ii) offspring faecal bacteria and metabolites. In conclusion, scFOS-enriched maternal diet affected the composition of mature milk, and this was associated with a change in the colonisation of the offspring intestinal microbiota.

Bacteroides salyersiae is a potent chondroitin sulfate-degrading species in the human gut microbiota.

Chondroitin sulfate (CS) has widely been used as a symptomatic slow-acting drug or a dietary supplement for the treatment and prevention of osteoarthritis. However, CS could not be absorbed after oral intake due to its polyanionic nature and large molecular weight. Gut microbiota has recently been proposed to play a pivotal role in the metabolism of drugs and nutrients. Nonetheless, how CS is degraded by the human gut microbiota has not been fully characterized. In the present study, we demonstrated that each human gut microbiota was characterized with a unique capability for CS degradation. Degradation and fermentation of CS by the human gut microbiota produced significant amounts of unsaturated CS oligosaccharides (CSOSs) and short-chain fatty acids. To uncover which microbes were responsible for CS degradation, we isolated a total of 586 bacterial strains with a potential CS-degrading capability from 23 human fecal samples. Bacteroides salyersiae was a potent species for CS degradation in the human gut microbiota and produced the highest amount of CSOSs as compared to other well-recognized CS-degraders, including Bacteroides finegoldii, Bacteroides thetaiotaomicron, Bacteroides xylanisolvens, and Bacteroides ovatus. Genomic analysis suggested that B. salyersiae was armed with multiple carbohydrate-active enzymes that could potentially degrade CS into CSOSs. By using a spent medium assay, we further demonstrated that the unsaturated tetrasaccharide (udp4) produced by the primary degrader B. salyersiae could serve as a "public goods" molecule for the growth of Bacteroides stercoris, a secondary CS-degrader that was proficient at fermenting CSOSs but not CS. Taken together, our study provides insights into the metabolism of CS by the human gut microbiota, which has promising implications for the development of medical and nutritional therapies for osteoarthritis. Video Abstract.

Preparation of ß-galacto-oligosaccharides using a novel endo-1,4-ß-galactanase from Penicillium oxalicum.

Endo-1,4-ß-galactanase is an indispensable tool for preparing prebiotic ß-galacto-oligosaccharides (ß-GOS) from pectic galactan resources. In the present study, a novel endo-1,4-ß-galactanase (PoßGal53) belonging to glycoside hydrolase family 53 from Penicillium oxalicum sp. 68 was cloned and expressed in Pichia pastoris GS115. Upon purification by affinity chromatography, recombinant PoßGal53 exhibited a single band on SDS-PAGE with a molecular weight of 45.0 kDa. Using potato galactan as substrate, PoßGal53 showed optimal reaction conditions of pH 4.0, 40 °C, and was thermostable, retaining >80 % activity after incubating below 45 °C for 12 h. Significantly, PoßGal53 exhibited relatively conserved substrate specificity for (1 â†’ 4)-ß-D-galactan with an activity of 6244 ± 282 U/mg. In this regard, the enzyme is in effect the most efficient endo-1,4-ß-galactanase identified to date. By using PoßGal53, ß-GOS monomers were prepared from potato galactan and separated using medium pressure liquid chromatography. HPAEC-PAD, MALDI-TOF-MS and ESI-MS/MS analyses demonstrated that these ß-GOS species ranged from 1,4-ß-D-galactobiose to 1,4-ß-D-galactooctaose (DP 2-8) with high purity. This work provides not only a highly active tool for enzymatic degradation of pectic galactan, but an efficient protocol for preparing ß-GOS.

The oligosaccharides of Xiasangju alleviates dextran sulfate sodium-induced colitis in mice by inhibiting inflammation.

Xiasangju (XSJ) is a traditional Chinese herbal formula consisted of Prunella spica, Mulberry leaf and Chrysanthemi indici flos, which can be used to treat fever, headache and ulcer. To explore the effects of oligosaccharides from XSJ (OX) on colitis, we used dextran sulfate sodium (DSS) to establish colitis mouse models. After administration of OX with different doses on the control and colitis mice, we measured their body weights, disease activity indexes (DAI), lengths and histopathologic changes of colons, spleen indexes. The inflammatory cytokines and oxidative stress-related factors in serum, and the intestinal microbial community in feces were also detected. We found that colitis mice with oral administration of OX showed higher body weights and lower levels of DAI and spleen index. Tissue damages induced by DSS were also alleviated by OX treatment. The colitis mice with OX treatment exhibited lower levels of AST, ALT, BUN, CR, MDA and a down-regulated expression of IL-6 and IL-1ß, while the activity of SOD was up-regulated. Furthermore, OX improved the relative abundance of gut microbiota and restored the proportions of Bacteroidetes and Muribaculaceae. We found that oligosaccharides from XSJ alleviated the symptoms of colitis mice through its inhibitory effects on inflammation and oxidative stress, and also regulated the composition of intestinal flora, which indicates a beneficial role for patients with colitis.

Selenium-based metabolic oligosaccharide engineering strategy for quantitative glycan detection.

Metabolic oligosaccharide engineering (MOE) is a classical chemical approach to perturb, profile and perceive glycans in physiological systems, but probes upon bioorthogonal reaction require accessibility and the background signal readout makes it challenging to achieve glycan quantification. Here we develop SeMOE, a selenium-based metabolic oligosaccharide engineering strategy that concisely combines elemental analysis and MOE,enabling the mass spectrometric imaging of glycome. We also demonstrate that the new-to-nature SeMOE probes allow for detection, quantitative measurement and visualization of glycans in diverse biological contexts. We also show that chemical reporters on conventional MOE can be integrated into a bifunctional SeMOE probe to provide multimodality signal readouts. SeMOE thus provides a convenient and simplified method to explore the glyco-world.

Xylobiose treatment triggers a defense-related response and alters cell wall composition.

Plant cell wall-derived oligosaccharides, i.e., damage-associated molecular patterns (DAMPs), could be generated after pathogen attack or during normal plant development, perceived by cell wall receptors, and can alter immunity and cell wall composition. Therefore, we hypothesised that xylo-oligosaccharides (XOS) could act as an elicitor and trigger immune responses. To test this, we treated Arabidopsis with xylobiose (XB) and investigated different parameters. XB-treatment significantly triggered the generation of reactive oxygen species (ROS), activated MAPK protein phosphorylation, and induced callose deposition. The combination of XB (DAMP) and flg22 a microbe-associated molecular pattern (MAMP) further enhanced ROS response and gene expression of PTI marker genes. RNA sequencing analysis revealed that more genes were differentially regulated after 30 min compared to 24 h XB-treated leaves, which correlated with ROS response. Increased xylosidase activity and soluble xylose level after 30 min and 3 h of XB-treatment were observed which might have weakened the DAMP response. However, an increase in total cell wall sugar and a decrease in uronic acid level was observed at both 30 min and 24 h. Additionally, arabinose, rhamnose, and xylose levels were increased in 30 min, and glucose was increased in 24 h compared to mock-treated leaves. The level of jasmonic acid, abscisic acid, auxin, and cytokinin were also affected after XB treatment. Overall, our data revealed that the shortest XOS can act as a DAMP, which triggers the PTI response and alters cell wall composition and hormone level.

Three alginate lyases provide a new gut Bacteroides ovatus isolate with the ability to grow on alginate.

Humans consume alginate in the form of seaweed, food hydrocolloids, and encapsulations, making the digestion of this mannuronic acid (M) and guluronic acid (G) polymer of key interest for human health. To increase knowledge on alginate degradation in the gut, a gene catalog from human feces was mined for potential alginate lyases (ALs). The predicted ALs were present in nine species of the Bacteroidetes phylum, of which two required supplementation of an endo-acting AL, expected to mimic cross-feeding in the gut. However, only a new isolate grew on alginate. Whole-genome sequencing of this alginate-utilizing isolate suggested that it is a new Bacteroides ovatus strain harboring a polysaccharide utilization locus (PUL) containing three ALs of families: PL6, PL17, and PL38. The BoPL6 degraded polyG to oligosaccharides of DP 1-3, and BoPL17 released 4,5-unsaturated monouronate from polyM. BoPL38 degraded both alginates, polyM, polyG, and polyMG, in endo-mode; hence, it was assumed to deliver oligosaccharide substrates for BoPL6 and BoPL17, corresponding well with synergistic action on alginate. BoPL17 and BoPL38 crystal structures, determined at 1.61 and 2.11 Å, respectively, showed (α/α)6-barrel + anti-parallel ß-sheet and (α/α)7-barrel folds, distinctive for these PL families. BoPL17 had a more open active site than the two homologous structures. BoPL38 was very similar to the structure of an uncharacterized PL38, albeit with a different triad of residues possibly interacting with substrate in the presumed active site tunnel. Altogether, the study provides unique functional and structural insights into alginate-degrading lyases of a PUL in a human gut bacterium.IMPORTANCEHuman ingestion of sustainable biopolymers calls for insight into their utilization in our gut. Seaweed is one such resource with alginate, a major cell wall component, used as a food hydrocolloid and for encapsulation of pharmaceuticals and probiotics. Knowledge is sparse on the molecular basis for alginate utilization in the gut. We identified a new Bacteroides ovatus strain from human feces that grew on alginate and encoded three alginate lyases in a gene cluster. BoPL6 and BoPL17 show complementary specificity toward guluronate (G) and mannuronate (M) residues, releasing unsaturated oligosaccharides and monouronic acids. BoPL38 produces oligosaccharides degraded by BoPL6 and BoPL17 from both alginates, G-, M-, and MG-substrates. Enzymatic and structural characterization discloses the mode of action and synergistic degradation of alginate by these alginate lyases. Other bacteria were cross-feeding on alginate oligosaccharides produced by an endo-acting alginate lyase. Hence, there is an interdependent community in our guts that can utilize alginate.

The biosynthesis, degradation, and function of cell wall ß-xylosylated xyloglucan mirrors that of arabinoxyloglucan.

Xyloglucan is an abundant polysaccharide in many primary cell walls and in the human diet. Decoration of its α-xylosyl sidechains with further sugars is critical for plant growth, even though the sugars themselves vary considerably between species. Plants in the Ericales order - prevalent in human diets - exhibit ß1,2-linked xylosyl decorations. The biosynthetic enzymes responsible for adding these xylosyl decorations, as well as the hydrolases that remove them in the human gut, are unidentified. GT47 xyloglucan glycosyltransferase candidates were expressed in Arabidopsis and endo-xyloglucanase products from transgenic wall material were analysed by electrophoresis, mass spectrometry, and nuclear magnetic resonance (NMR) spectroscopy. The activities of gut bacterial hydrolases BoGH43A and BoGH43B on synthetic glycosides and xyloglucan oligosaccharides were measured by colorimetry and electrophoresis. CcXBT1 is a xyloglucan ß-xylosyltransferase from coffee that can modify Arabidopsis xyloglucan and restore the growth of galactosyltransferase mutants. Related VmXST1 is a weakly active xyloglucan α-arabinofuranosyltransferase from cranberry. BoGH43A hydrolyses both α-arabinofuranosylated and ß-xylosylated oligosaccharides. CcXBT1's presence in coffee and BoGH43A's promiscuity suggest that ß-xylosylated xyloglucan is not only more widespread than thought, but might also nourish beneficial gut bacteria. The evolutionary instability of transferase specificity and lack of hydrolase specificity hint that, to enzymes, xylosides and arabinofuranosides are closely resemblant.

Fibrolamellar carcinomas-growth arrested by paracrine signals complexed with synthesized 3-O sulfated heparan sulfate oligosaccharides.

Fibrolamellar carcinomas (FLCs), lethal tumors occurring in children to young adults, have genetic signatures implicating derivation from biliary tree stem cell (BTSC) subpopulations, co-hepato/pancreatic stem cells, involved in hepatic and pancreatic regeneration. FLCs and BTSCs express pluripotency genes, endodermal transcription factors, and stem cell surface, cytoplasmic and proliferation biomarkers. The FLC-PDX model, FLC-TD-2010, is driven ex vivo to express pancreatic acinar traits, hypothesized responsible for this model's propensity for enzymatic degradation of cultures. A stable ex vivo model of FLC-TD-2010 was achieved using organoids in serum-free Kubota's Medium (KM) supplemented with 0.1% hyaluronans (KM/HA). Heparins (10 ng/ml) caused slow expansion of organoids with doubling times of ∼7-9 days. Spheroids, organoids depleted of mesenchymal cells, survived indefinitely in KM/HA in a state of growth arrest for more than 2 months. Expansion was restored with FLCs co-cultured with mesenchymal cell precursors in a ratio of 3:7, implicating paracrine signaling. Signals identified included FGFs, VEGFs, EGFs, Wnts, and others, produced by associated stellate and endothelial cell precursors. Fifty-three, unique heparan sulfate (HS) oligosaccharides were synthesized, assessed for formation of high affinity complexes with paracrine signals, and each complex screened for biological activity(ies) on organoids. Ten distinct HS-oligosaccharides, all 10-12 mers or larger, and in specific paracrine signal complexes elicited particular biological responses. Of note, complexes of paracrine signals and 3-O sulfated HS-oligosaccharides elicited slowed growth, and with Wnt3a, elicited growth arrest of organoids for months. If future efforts are used to prepare HS-oligosaccharides resistant to breakdown in vivo, then [paracrine signal-HS-oligosaccharide] complexes are potential therapeutic agents for clinical treatments of FLCs, an exciting prospect for a deadly disease.

The effects of protease, xylanase, and xylo-oligosaccharides on growth performance, nutrient utilization, short-chain fatty acids, and microbiota in Eimeria-challenged broiler chickens fed low-protein diet.

A total of 392 Cobb 500 off-sex male broiler chicks were used in a 21-day experiment to study the effect of protease, xylanase, and xylo-oligosaccharides (XOS) on improving growth performance, nutrient utilization (ileal digestibility and total tract retention), gene expression of nutrient transporters, cecal short-chain fatty acids (SCFAs), and microbiota profile of broilers challenged with Eimeria spp. Chicks at 0-day old were allocated to 8 treatments in a 4 × 2 factorial arrangement: 1) corn-soybean meal diet with no enzyme (Con); 2) Con plus 0.2 g/kg protease alone (PRO); 3) Con plus 0.2 g/kg protease combined with 0.1 g/kg xylanase (PRO + XYL); or 4) Con plus 0.5 g/kg xylo-oligosaccharides (XOS); with or without Eimeria challenge. The 4 diets were formulated to be marginally low in crude protein (183 g/kg). Challenged groups were inoculated with a solution containing E. maxima, E. acervulina, and E. tenella oocysts on d 15. Eimeria depressed (P < 0.01) growth performance and nutrient utilization. Supplemental protease improved (P < 0.05) body weight gain and feed intake in the prechallenge phase (d 0-15) but had no effect during the infection period (d 15-21). There was no interaction between infection and feed supplementation for nutrient utilization. The supplementations of either PRO or XOS alone increased (P < 0.01) total tract retention of Ca and tended (P < 0.1) to improve total tract retention of N, P, AME, and AMEn. Eimeria decreased (P < 0.05) expressions of GLUT2, GLUT5, PepT1, ATP2B1, CaSR, Calbidin D28K, NPT2, and ZnT1 but increased (P < 0.01) expression of GLUT1. XOS supplementation increased (P < 0.05) ATP2B1 expression. Protease decreased (P < 0.05) isobutyrate concentration in unchallenged treatments but not in challenged treatments. Eimeria decreased (P < 0.01) cecal saccharolytic SCFAs acetate and propionate but increased (P < 0.01) branched-chain fatty acid isovalerate. The supplementation of PRO + XYL or XOS increased (P < 0.05) cecal butyrate or decreased cecal isobutyrate concentrations, respectively. PRO + XYL and XOS decreased cecal protein levels in unchallenged birds but not challenged ones. Eimeria challenge significantly (P < 0.05) decreased the microbial richness (Observed features) and diversity (Shannon index and phylogenetic diversity) and changed the microbial composition by reducing the abundance of certain bacteria, such as Ruminococcus torques, and increasing the abundance of others, such as Anaerostipes. In contrast, none of the additives had any significant effect on the cecal microbial composition. In conclusion, PRO or XOS supplementation individually improved nutrient utilization. All the additives decreased the cecal content of branched-chain fatty acids, consistent with decreased cecal N concentration, although the effects were more pronounced in unchallenged birds. In addition, none of the feed additives impacted the Eimeria-induced microbial perturbation.

Human milk oligosaccharides as prebiotics.

Based on its richness in immune-related components such as human milk, human milk oligosaccharides (HMOs), milk proteins, and lipids, breast milk can be considered the first functional food that humans encounter in their lifetime. According to WHO recommendations breast milk has to be the only food in an infant's diet in the first six months of age which is then continued up to two years of age with the suitable complementary foods. Regarding breast milk balanced composition, it is considered as the best food of infants thus many studies have been carried out to determine the benefits of breast milk. Based on numerous studies breast milk have a tendency to reduce the risk of type 2 diabetes, obesity, allergies, celiac disease, necrotizing enterocolitis (NEC), gastrointestinal tract infections and some type of cancers. The benefits of breast milk can be explained by its special combination which includes; macronutrients, micronutrients and bioactive components such as immunoglobulins, hormones, growth factors and oligosaccharides. One of the essential bioactive compounds of breast milk is known as human milk oligosaccharides (HMOs). HMOs are unique, bioactive carbohydrates which are identified as the most significant components of breast milk. Since they have structural complexity and multifunctional properties, they are one of the most wondered components of breast milk. HMOs promote the development of the neonatal intestinal immune, and nervous systems. This article briefly describes the history, complex structure and different functions of HMOs and highlight the importance of maternal diet for HMO biosynthesis.

Immunostimulatory effect of mannan-oligosaccharides supplementation diet in milkfish (Chanos chanos).

The current study was designed to examine the impacts of dietary mannan-oligosaccharides (MOS) on growth, hemato-biochemical changes, digestive-antioxidant enzyme activity, immune response, and disease resistance of milkfish (Chanos chanos) fed diets contained MOS i.e. 1g, 2g, and 3g MOS. The growth parameters were significantly influence in milkfish fed all MOS diets, whereas the feed conversion ratio (FCR) and protein efficiency ratio (PER) were significantly influence with 2g or 3g MOS diets. The total protein (TP), globulin (GB), and glucose (GLU) levels, amylase, protease, liver enzymes were found significantly high in fish fed 2g or 3g MOS diets; but, lipase, trypsin, and alkaline phosphatase (ALP) enzymes were increased significantly at 3g MOS diet. All MOS inclusion levels were significantly increased total and Lactobacillus intestinal microflora population. The oxidative enzymes activity as superoxide desmutase (SOD) and catalyze (CAT) were progressively increased with all MOS supplementation diet, but the glutathione peroxidase (GPx) and lactate dehydrogenase (LDH) content were found significantly high in fish fed 2g or 3g MOS diets. Similarly, the reduced glutathione (GSH) and glutathione reductase (GR) contents were observed significantly high level in fish fed 3g MOS diet. The phagocytic (PC) and lysozyme (LYZ) activities were found gradually increase in fish fed increasing level of MOS diets, while the respiratory burst (RB) and malondialdehyde (MDA) activities were seen significant in fish fed 2g and 3g MOS diets. The current research work confirmed that C. chanos fed diets contained 3g kg-1 MOS recorded better growth performance, digestive-antioxidant, immune response, and disease resistance.

Regulatory effects mediated by ulvan oligosaccharide and its zinc complex on lipid metabolism in high-fat diet-fed mice.

Obesity-induced lipid metabolism disorders are risk factors for hyperlipidemia, atherosclerosis, and non-alcoholic fatty liver disease. Seaweed oligosaccharides and Zn supplements are potential alternatives to alleviate obesity. Herein, ulvan oligosaccharide (UO) was used as a ligand to prepare a novel Zn supplement (UO-Zn). Subsequently, we explored potential mechanisms underlying UO- and UO-Zn-mediated improvements in lipid metabolism in mice fed a high-fat diet. We found that UO enhanced the abundance of key species (Blautia and Turicibacter) and functions (glycolytic, pentose phosphate, and histidine/lysine biosynthesis pathways) in the gut microbiota, thereby increasing the production of short-chain fatty acids and activating AMPK. Accordingly, UO treatment regulated the transcription of lipid metabolism genes, including ACOX1, ACC, and FASN, thereby reducing blood lipid levels and hepatic lipid accumulation. Zn could act synergistically with UO, enhancing the reversal of cholesterol transport and fatty acid ß-oxidation via the MTF1/PPARα pathway, markedly reducing body and adipose tissue weights.

Process and applications of alginate oligosaccharides with emphasis on health beneficial perspectives.

Alginates are linear polymers comprising 40% of the dry weight of algae possess various applications in food and biomedical industries. Alginate oligosaccharides (AOS), a degradation product of alginate, is now gaining much attention for their beneficial role in food, pharmaceutical and agricultural industries. Hence this review was aimed to compile the information on alginate and AOS (prepared from seaweeds) during 1994-2020. As per our knowledge, this is the first review on the potential use of alginate oligosaccharides in different fields. The alginate derivatives are grouped according to their applications. They are involved in the isolation process and show antimicrobial, antioxidant, anti-inflammatory, antihypertension, anticancer, and immunostimulatory properties. AOS also have significant applications in prebiotics, nutritional supplements, plant growth development and others products.

Impact of fermentable fiber, xylo-oligosaccharides and xylanase on laying hen productive performance and nutrient utilization.

This study evaluated the impact of feeding xylo-oligosaccharides (XOS), fermentable fiber in the form of wheat bran (WB), and xylanase (XYL) on laying hen productive performance and nutrient digestibility. The hypothesis was that the WB would provide the microbiota in the hindgut with fermentable dietary xylan, and the XOS and XYL would further upregulate xylan fermentation pathways, resulting in improved nutrient utilization. Isa Brown hens (n = 96) were obtained at 39 wk of age. They were fed 12 dietary treatments, 8 hens per treatment, for 56 d. A commercial laying hen ration was fed, and for half of the treatments 10% of this ration was directly replaced with WB. The diets were then supplemented with either 1) no supplements; 2) XOS 50 g/t; 3) XOS 2000 g/t; 4) XYL (16,000 BXU/kg); 5) XYL + XOS 50 g/t, or 6) XYL + XOS 2,000 g/t. Hen performance and egg quality were measured every 14 d. On d56, ileum digesta samples were collected for determination of starch, nonstarch polysaccharide (NSP), XOS, protein, energy, and starch digestibility. Ceca digesta samples were also collected for analysis of XOS, short chain fatty acid (SCFA), xylanase and cellulase activity and microbial counts. Feeding 2,000 g/t XOS increased ileal protein digestibility. Combined 2,000 g/t XOS and XYL increased cecal Bifidobacteria concentration. This combination also increased cecal xylanase activity in birds fed the control diet. Cecal cellulase activity was improved by feeding WB, XYL, and 2,000 g/t XOS. XYL increased cecal lactate production. Feeding 2,000 g/t XOS with WB increased insoluble NSP degradability and shell breaking strength at d56. In summary, supplementing laying hen diets with fermentable fiber, XYL and XOS increases utilization of dietary xylan, improving nutrient utilization, performance, and gastrointestinal health.

Preventive effect of pectic oligosaccharides on acute colitis model mice: modulating epithelial barrier, gut microbiota and Treg/Th17 balance.

Pectin as a dietary fiber supplement has shown emerging potential in clinical ulcerative colitis (UC) adjuvant therapy. In this study, the preventive and prebiotic effects of enzymatically degraded pectic oligosaccharides (POS) were further explored in dextran sodium sulfate (DSS)-induced colitis mice. The POS supplement (400 mg kg-1) was significantly effective at improving preventive efficacy, promoting colonic epithelial barrier integrity and reducing inflammatory cytokines. Meanwhile, the changes in T regulatory (Treg) cells and T helper 17 (Th17) cells indicated that POS treatment regulated the Treg/Th17 balance. Gut microbiota analysis showed that the POS supplement reshaped the dysfunctional gut microbiota. Further Spearman's correlation coefficient analysis indicated that the changes of the gut microbiota were highly associated with modulating the epithelial barrier, promoting the development of Treg cells and suppressing the differentiation of pro-inflammatory Th17 cells. All of these results suggest that enzymatically- degraded POS is a promising therapeutic agent for UC prevention and adjuvant treatment by maintaining intestinal homeostasis.

Acidic oligosaccharide sugar chain combined with hyperbaric oxygen delays D-galactose-induced brain senescence in mice via attenuating oxidative stress and neuroinflammation.

Aging is fundamental to neurodegeneration and dementia. Preventing oxidative stress and neuroinflammation are potential methods of delaying the onset of aging-associated neurodegenerative diseases. The acidic oligosaccharide sugar chain (AOSC) and hyperbaric oxygen (HBO) can increase the expression of antioxidants and have a neuroprotective function. In this study, we investigate the ability of AOSC, HBO, and AOSC + HBO to prevent D-gal-induced brain senescence. The Morris water maze and Y-maze test results showed that all three therapies significantly attenuated D-gal-induced memory disorders. A potential mechanism of this action was decreasing elevated levels of oxidative stress and neuroinflammation. The western blot and morphological results showed that all three therapies decreased D-gal-induced neuroinflammation and downregulated inflammatory mediators including the nuclear factor κ-light-chain-enhancer of activated B cells, cyclooxygenase-2, interleukin-1ß, and tumor necrosis factor alpha. Taken together, our results indicated that AOSC, HBO, and AOSC + HBO therapies attenuated D-gal-induced brain aging in mice by repressing RAGE/NF-KB-induced inflammation, the activation of astrocytes and microglia, and a decrease in neuronal degeneration. These could be useful therapies for treating age-related neurodegenerative diseases such as Alzheimer's disease. Furthermore, HBO combined with AOSC had a better effect than HBO or AOSC alone.

Complementary Role of GlcNAc6ST2 and GlcNAc6ST3 in Synthesis of CL40-Reactive Sialylated and Sulfated Glycans in the Mouse Pleural Mesothelium.

Sialyl 6-sulfo Lewis X (6-sulfo sLeX) and its derivative sialyl 6-sulfo N-acetyllactosamine (LacNAc) are sialylated and sulfated glycans of sialomucins found in the high endothelial venules (HEVs) of secondary lymphoid organs. A component of 6-sulfo sLeX present in the core 1-extended O-linked glycans detected by the MECA-79 antibody was previously shown to exist in the lymphoid aggregate vasculature and bronchial mucosa of allergic and asthmatic lungs. The components of 6-sulfo sLeX in pulmonary tissues under physiological conditions remain to be analyzed. The CL40 antibody recognizes 6-sulfo sLeX and sialyl 6-sulfo LacNAc in O-linked and N-linked glycans, with absolute requirements for both GlcNAc-6-sulfation and sialylation. Immunostaining of normal mouse lungs with CL40 was performed and analyzed. The contribution of GlcNAc-6-O-sulfotransferases (GlcNAc6STs) to the synthesis of the CL40 epitope in the lungs was also elucidated. Here, we show that the expression of the CL40 epitope was specifically detected in the mesothelin-positive mesothelium of the pulmonary pleura. Moreover, GlcNAc6ST2 (encoded by Chst4) and GlcNAc6ST3 (encoded by Chst5), but not GlcNAc6ST1 (encoded by Chst2) or GlcNAc6ST4 (encoded by Chst7), are required for the synthesis of CL40-positive glycans in the lung mesothelium. Furthermore, neither GlcNAc6ST2 nor GlcNAc6ST3 is sufficient for in vivo expression of the CL40 epitope in the lung mesothelium, as demonstrated by GlcNAc6ST1/3/4 triple-knock-out and GlcNAc6ST1/2/4 triple-knock-out mice. These results indicate that CL40-positive sialylated and sulfated glycans are abundant in the pleural mesothelium and are synthesized complementarily by GlcNAc6ST2 and GlcNAc6ST3, under physiological conditions in mice.

Preterm Infant Fecal Microbiota and Metabolite Profiles Are Modulated in a Probiotic Specific Manner.

OBJECTIVES: To compare the impact of two probiotic supplements on fecal microbiota and metabolites, as well as on gut inflammation in human milk-fed preterm infants. METHODS: In this single-center observational cohort study, we assessed the effects of Bifidobacterium longum subsp. infantis or Lactobacillus reuteri supplementation on the infant gut microbiota by 16S rRNA gene sequencing and fecal metabolome by 1 H nuclear magnetic resonance spectroscopy. Fecal calprotectin was measured as a marker of enteric inflammation. Aliquots of human or donor milk provided to each infant were also assessed to determine human milk oligosaccharide (HMO) content. RESULTS: As expected, each probiotic treatment was associated with increased proportions of the respective bacterial taxon. Fecal HMOs were significantly higher in L. reuteri fed babies despite similar HMO content in the milk consumed. Fecal metabolites associated with bifidobacteria fermentation products were significantly increased in B. infantis supplemented infants. Fecal calprotectin was lower in infants receiving B. infantis relative to L. reuteri ( P < 0.01, Wilcoxon rank-sum test) and was negatively associated with the microbial metabolite indole-3-lactate (ILA). CONCLUSIONS: This study demonstrates that supplementing an HMO-catabolizing Bifidobacterium probiotic results in increased microbial metabolism of milk oligosaccharides and reduced intestinal inflammation relative to a noncatabolizing Lactobacillus probiotic in human milk-fed preterm infants. In this context, Bifidobacterium may provide greater benefit in human milk-fed infants via activation of the microbiota-metabolite-immune axis.

The combined impact of xylo-oligosaccharides and gamma-irradiated astragalus polysaccharides on the immune response, antioxidant capacity, and intestinal microbiota composition of broilers.

The present study investigated the individual and combined effects of xylo-oligosaccharides (XOS) and gamma-irradiated astragalus polysaccharides (IAPS) on the immune response, antioxidant capacity and intestinal microbiota composition of broiler chickens. A total of 240 newly hatched Ross 308 chicks were randomly allocated into 5 dietary treatments including the basal diet (control), or the basal diet supplemented with 50 mg/kg chlortetracycline (CTC), 100 mg/kg XOS (XOS), 600 mg/kg IAPS (IAPS), and 100 mg/kg XOS + 600 mg/kg IAPS (XOS + IAPS) respectively. The results showed that birds in the control group had lower the thymus index and serum lysozyme activity than those in the other 4 groups (P < 0.05). Moreover, there was an interaction between XOS and IAPS treatments on increasing the serum lysozyme activity (P < 0.05). Birds in the CTC and XOS + IAPS groups had lower serum malondialdehyde concentration and higher serum total antioxidant capacity activity and mucosal interleukin 2 mRNA expression of jejunum than those in the control group (P < 0.05). In addition, birds in the control groups had lower duodenal and jejunal IgA-producing cells number than these in other 4 groups (P < 0.05). As compared with the CTC group, dietary individual XOS or IAPS administration increased duodenal IgA-producing cells number (P < 0.05). Meanwhile, there was an interaction between XOS and IAPS treatments on increasing duodenal and jejunal IgA-Producing cells numbers (P < 0.05). Dietary CTC administration increased the proportion of Bacteroides, and decreased the proportion of Negativibacillus (P < 0.05). However, dietary XOS + IAPS administration increased Firmicutes to Bacteroidetes ratio, the proportion of Ruminococcaceae, as well as decreased the proportion of Barnesiella and Negativibacillus (P < 0.05). In conclusion, the XOS and IAPS combination could improve intestinal mucosal immunity and barrier function of broilers by enhancing cytokine gene expression, IgA-producing cell production and modulates cecal microbiota, and the combination effect of XOS and IAPS is better than that of individual effect of CTC, XOS, or IAPS in the current study.