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1.
Impact of a Plant Sterol- and Galactooligosaccharide-Enriched Beverage on Colonic Metabolism and Gut Microbiota Composition Using an In Vitro Dynamic Model.
Blanco-Morales, V, Garcia-Llatas, G, Yebra, MJ, Sentandreu, V, Lagarda, MJ, Alegría, A
Journal of agricultural and food chemistry. 2020;(7):1884-1895
Abstract
A beverage enriched with plant sterols (1 g/100 mL) and galactooligosaccharides (1.8 g/100 mL) was subjected to a dynamic gastrointestinal and colonic fermentation process to evaluate the effect on sterol metabolism, organic acid production, and microbiota composition. Production of sterol metabolites (coprostanol, methylcoprostanol, ethylcoprostenol, ethylcoprostanol, and sitostenone) was observed in the transverse colon (TC) and descending colon (DC) vessels in general, from 24 and 48 h, respectively. Microbial activity was assessed through the production of organic acids, mainly acetate in all colon vessels, lactate in the AC, and butyrate and propionate in the TC and DC. A higher diversity in the microbial community was found in the TC and DC, in accordance with a higher sterol metabolism and organic acid production. Although the prebiotic effect of galactooligosaccharides was not detected, changes in microbiota composition (an increase in the Parabacteroides genus and the Synergistaceae and Lachnospiraceae families) indicated an enhancement of sterol metabolism.
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2.
Hyaluronan oligosaccharides modulate inflammatory response, NIS and thyreoglobulin expression in human thyrocytes.
D'Ascola, A, Scuruchi, M, Ruggeri, RM, Avenoso, A, Mandraffino, G, Vicchio, TM, Campo, S, Campo, GM
Archives of biochemistry and biophysics. 2020;:108598
Abstract
Autoimmune thyroid diseases, such as Hashimoto's thyroiditis, are characterized by lymphocytic infiltration and altered function of the thyroid. During inflammation, it has been reported a decreased expression in Tg and NIS, accompanied by an increase in HA production that accumulates in the gland. HA fragments produced in different pathological states can modulate gene expression in a variety of cell types and may prime inflammatory response by interacting with the TLR-2, TLR-4 and CD44 that, in turn, induce NF-kB activation finally responsible of inflammatory mediator transcription, such as IL-1β, TNF-α and IL-6. The aim of this study was to investigate the potential inflammatory effect and the biochemical pathways activated by 6-mer HA oligosaccharides in cultured human thyrocytes. 6-mer HA treatment induced up-regulation of TLR-2, TLR-4, CD44 mRNA and related protein levels, increased HA production and NF-kB activation, that in turn increased IL-1β and IL-6 concentrations. Instead, we found evidence of an opposite effect on thyroid specific-gene Tg and NIS, that were decreased after 6-mer HA addition. Thyrocytes exposition to specific blocking antibodies for TLR-2, TLR-4 and CD44 abolished up-regulation of NF-κB activation and the consequent pro-inflammatory cytokine production, while restored Tg and NIS levels. A further goal of this study was demonstrate that also other LMW HA have pro inflammatory proprieties. These data suggest that HA fragments, through the involvement of TLR-2, TLR-4 and CD44 signaling cascade, contribute to prime the inflammatory response in thyrocytes and, by reducing the expression of thyroid-specific genes, could promote the loss of function of gland such as in Hashimoto's thyroiditis.
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3.
Immunomodulation by Human Milk Oligosaccharides: The Potential Role in Prevention of Allergic Diseases.
Zuurveld, M, van Witzenburg, NP, Garssen, J, Folkerts, G, Stahl, B, Van't Land, B, Willemsen, LEM
Frontiers in immunology. 2020;:801
Abstract
The prevalence and incidence of allergic diseases is rising and these diseases have become the most common chronic diseases during childhood in Westernized countries. Early life forms a critical window predisposing for health or disease. Therefore, this can also be a window of opportunity for allergy prevention. Postnatally the gut needs to mature, and the microbiome is built which further drives the training of infant's immune system. Immunomodulatory components in breastmilk protect the infant in this crucial period by; providing nutrients that contain substrates for the microbiome, supporting intestinal barrier function, protecting against pathogenic infections, enhancing immune development and facilitating immune tolerance. The presence of a diverse human milk oligosaccharide (HMOS) mixture, containing several types of functional groups, points to engagement in several mechanisms related to immune and microbiome maturation in the infant's gastrointestinal tract. In recent years, several pathways impacted by HMOS have been elucidated, including their capacity to; fortify the microbiome composition, enhance production of short chain fatty acids, bind directly to pathogens and interact directly with the intestinal epithelium and immune cells. The exact mechanisms underlying the immune protective effects have not been fully elucidated yet. We hypothesize that HMOS may be involved in and can be utilized to provide protection from developing allergic diseases at a young age. In this review, we highlight several pathways involved in the immunomodulatory effects of HMOS and the potential role in prevention of allergic diseases. Recent studies have proposed possible mechanisms through which HMOS may contribute, either directly or indirectly, via microbiome modification, to induce oral tolerance. Future research should focus on the identification of specific pathways by which individual HMOS structures exert protective actions and thereby contribute to the capacity of the authentic HMOS mixture in early life allergy prevention.
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4.
β-Galactooligosaccharide in Conjunction With Low FODMAP Diet Improves Irritable Bowel Syndrome Symptoms but Reduces Fecal Bifidobacteria.
Wilson, B, Rossi, M, Kanno, T, Parkes, GC, Anderson, S, Mason, AJ, Irving, PM, Lomer, MC, Whelan, K
The American journal of gastroenterology. 2020;(6):906-915
Abstract
INTRODUCTION The low FODMAP diet (LFD) reduces symptoms and bifidobacteria in irritable bowel syndrome (IBS). β-galactooligosaccharides (B-GOS) may reduce the symptoms and increase bifidobacteria in IBS. We investigated whether B-GOS supplementation alongside the LFD improves IBS symptoms while preventing the decline in bifidobacteria. METHODS We performed a randomized, placebo-controlled, 3-arm trial of 69 Rome III adult patients with IBS from secondary care in the United Kingdom. Patients were randomized to a sham diet with placebo supplement (control) or LFD supplemented with either placebo (LFD) or 1.4 g/d B-GOS (LFD/B-GOS) for 4 weeks. Gastrointestinal symptoms, fecal microbiota (fluorescent in situ hybridization and 16S rRNA sequencing), fecal short-chain fatty acids (gas-liquid chromatography) and pH (probe), and urine metabolites (H NMR) were analyzed. RESULTS At 4 weeks, adequate symptom relief was higher in the LFD/B-GOS group (16/24, 67%) than in the control group (7/23, 30%) (odds ratio 4.6, 95% confidence interval: 1.3-15.6; P = 0.015); Bifidobacterium concentrations (log10 cells/g dry weight) were not different between LFD and LFD/B-GOS but were lower in the LFD/B-GOS (9.49 [0.73]) than in the control (9.77 [0.41], P = 0.018). A proportion of Actinobacteria was lower in LFD (1.9%, P = 0.003) and LFD/B-GOS (1.8%, P < 0.001) groups than in the control group (4.2%). Fecal butyrate was lower in the LFD (387.3, P = 0.028) and LFD/B-GOS (346.0, P = 0.007) groups than in the control group (609.2). DISCUSSION The LFD combined with B-GOS prebiotic produced a greater symptom response than the sham diet plus placebo, but addition of 1.4 g/d B-GOS did not prevent the reduction of bifidobacteria. The LFD reduces fecal Actinobacteria and butyrate thus strict long-term use should not be advised.
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5.
Human milk oligosaccharide supplementation in irritable bowel syndrome patients: A parallel, randomized, double-blind, placebo-controlled study.
Iribarren, C, Törnblom, H, Aziz, I, Magnusson, MK, Sundin, J, Vigsnaes, LK, Amundsen, ID, McConnell, B, Seitzberg, D, Öhman, L, et al
Neurogastroenterology and motility. 2020;(10):e13920
Abstract
OBJECTIVES Human milk oligosaccharides safely and beneficially impact bifidobacteria abundance in healthy adults, while their effects in patients with irritable bowel syndrome (IBS) are unknown. Hence, we aimed to determine the dose of 4:1 mix of 2'-O-fucosyllactose and Lacto-N-neotetraose (2'FL/LNnT) that increases fecal bifidobacteria abundance without aggravating overall gastrointestinal symptoms in IBS patients in a randomized, double-blind, controlled study. Additionally, the impact of 2'FL/LNnT on the fecal bacterial profile was assessed. METHODS Irritable bowel syndrome patients diagnosed according to the Rome IV criteria received placebo (glucose), or 5 g or 10 g 2'FL/LNnT for 4 weeks followed by a four-week follow-up period. Gastrointestinal Symptom Rating Scale-IBS was used to assess gastrointestinal symptom severity; fecal microbiota composition was evaluated by GA-map™ Dysbiosis Test. RESULTS Of the included 60 patients, two (one placebo and one 10 g) discontinued prematurely. Fecal bifidobacteria abundance was increased at week 4, but not at week 8, in the 10 g group compared to the other groups. Severity of overall or individual gastrointestinal symptoms did not differ between the groups at week 4 or 8, and no symptom deterioration was seen in any of the groups. The 10 g dose influenced overall fecal microbiota composition, and responders-defined as bifidobacteria increase ≥50%-could be discriminated from non-responders based on fecal microbiota modulation. CONCLUSIONS The 10 g dose of 2'FL/LNnT induced an increase in the beneficial Bifidobacterium spp. without aggravating gastrointestinal symptoms in patients with IBS. This approach may be worthwhile to modulate gut microbiota of IBS patients toward a healthier profile.
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6.
The Role of Human Milk Oligosaccharides and Probiotics on the Neonatal Microbiome and Risk of Necrotizing Enterocolitis: A Narrative Review.
Nolan, LS, Rimer, JM, Good, M
Nutrients. 2020;(10)
Abstract
Preterm infants are a vulnerable population at risk of intestinal dysbiosis. The newborn microbiome is dominated by Bifidobacterium species, though abnormal microbial colonization can occur by exogenous factors such as mode of delivery, formula feeding, and exposure to antibiotics. Therefore, preterm infants are predisposed to sepsis and necrotizing enterocolitis (NEC), a fatal gastrointestinal disorder, due to an impaired intestinal barrier, immature immunity, and a dysbiotic gut microbiome. Properties of human milk serve as protection in the prevention of NEC. Human milk oligosaccharides (HMOs) and the microbiome of breast milk are immunomodulatory components that provide intestinal homeostasis through regulation of the microbiome and protection of the intestinal barrier. Enteral probiotic supplements have been trialed to evaluate their impact on establishing intestinal homeostasis. Here, we review the protective role of HMOs, probiotics, and synbiotic combinations in protecting a vulnerable population from the pathogenic features associated with necrotizing enterocolitis.
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7.
Synthetic Oligosaccharides Mimicking Fungal Cell Wall Polysaccharides.
Krylov, VB, Nifantiev, NE
Current topics in microbiology and immunology. 2020;:1-16
Abstract
The cell wall of pathogenic fungi is highly important for the development of fungal infections and is the first cellular component to interact with the host immune system. The fungal cell wall is mainly built up of different polysaccharides representing ligands for pattern recognition receptors (PRRs) on immune cells and antibodies. Purified fungal polysaccharides are not easily available; in addition, they are structurally heterogenic and have wide molecular weight distribution that limits the possibility to use natural polysaccharides to assess the structure of their active determinants. The synthetic oligosaccharides of definite structure representing distinct polysaccharide fragments are indispensable tools for a variety of biological investigations and represent an advantageous alternative to natural polysaccharides. The attachment of a spacer group to these oligosaccharides permits their efficient transformation into immunogenic glycoconjugates as well as their immobilization on plates or microbeads. Herein, we summarize current information on synthetic availability of the variety of oligosaccharides related to main types of fungal cell wall components: galactomannan, α- and β-mannan, α- and β-(1 → 3)-glucan, chitin, chitosan, and others. These data are supplemented with published results of biochemical and immunological applications of synthetic oligosaccharides as molecular probes especially as the components of thematic glycoarrays suitable for characterization of anti-polysaccharide antibodies and cellular lectins or PRRs.
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8.
Determining the optimum model parameters for oligosaccharide production efficiency using response surface integrated particle swarm optimization method: an experimental validation study.
Şensoy, AT, İspirli, H, Dertli, E
Preparative biochemistry & biotechnology. 2020;(8):820-826
Abstract
Glucansucrases (GTFs) catalyzes the synthesis of α-glucans from sucrose and oligosaccharides in the presence of an acceptor sugar by transferring glucosyl units to the acceptor molecule with different linkages. The acceptor reactions can be affected by several parameters and this study aimed to determine the optimal reaction parameters for the production of glucansucrase-based oligosaccharides using sucrose and maltose as the donor and acceptor sugars, respectively via a hybrid technique of Response Surface Method (RSM) and Particle Swarm Optimization (PSO). The experimental design was performed using Central Composite Design and the tested parameters were enzyme concentration, acceptor:donor ratio and the reaction period. The optimization studies showed that enzyme concentration was the most effective parameter for the final oligosaccharides yields. The optimal values of the significant parameters determined for enzyme concentration and acceptor:donor ratio were 3.45 U and 0.62, respectively. Even the response surface plots for input parameters verified the PSO results, an experimental validation study was performed for the reverification. The experimental verification results obtained were also consistent with the PSO results. These findings will help our understanding in the role of different parameters for the production of oligosaccharides in the acceptor reactions of GTFs.
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9.
Human Milk Oligosaccharide Profile Variation Throughout Postpartum in Healthy Women in a Brazilian Cohort.
Ferreira, AL, Alves, R, Figueiredo, A, Alves-Santos, N, Freitas-Costa, N, Batalha, M, Yonemitsu, C, Manivong, N, Furst, A, Bode, L, et al
Nutrients. 2020;(3)
Abstract
Human milk oligosaccharide (HMO) composition varies throughout lactation and can be influenced by maternal characteristics. This study describes HMO variation up to three months postpartum and explores the influences of maternal sociodemographic and anthropometric characteristics in a Brazilian prospective cohort. We followed 101 subjects from 28-35 gestational weeks (baseline) and throughout lactation at 2-8 (visit 1), 28-50 (visit 2) and 88-119 days postpartum (visit 3). Milk samples were collected at visits 1, 2 and 3, and 19 HMOs were quantified usinghigh-performance liquid chromatography with fluorescence detection (HPLC-FL). Friedman post-hoc test, Spearman rank correlation for maternal characteristics and HMOs and non-negative matrix factorization (NMF) were used to define the HMO profile. Most women were secretors (89.1%) and presented high proportion of 2'-fucosyllactose (2ꞌFL) at all three sample times, while lacto-N-tetraose (LNT, 2-8 days) and lacto-N-fucopentaose II (LNFPII, 28-50 and 88-119 days) were the most abundant HMOs in non-secretor women. Over the course of lactation, total HMO weight concentrations (g/L) decreased, but total HMO molar concentrations (mmol/L) increased, highlighting differential changes in HMO composition over time. In addition, maternal pre-pregnancy body mass index (BMI) and parity influence the HMO composition in healthy women in this Brazilian cohort.
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10.
Synthesis of potential prebiotic α-glucooligosaccharides using microbial glucansucrase and their in vitro fecal fermentation.
Hu, X, Song, L, Yang, Y, Jin, Z, Miao, M
Food & function. 2020;(2):1672-1683
Abstract
Novel α-glucooligosaccharides were synthesized by the acceptor reaction of Leuconostoc citreum SK24.002 glucansucrase with maltose and sucrose. The impact of synthesis conditions, including the ratio of sucrose to maltose and the substrate concentration, on the formation of α-glucooligosaccharides was evaluated. Under the optimized experimental conditions, the yield of a mixture of α-glucooligosaccharides with DP 3-5 reached approximately 56.4% with a concentration of 170.7 mg mL-1. Each of these α-glucooligosaccharides was purified, and the structures were assigned as follows: α-D-Glcp-(1,6)-α-D-Glcp-(1,4)-D-Glcp (DP3), α-D-Glcp-(1,3)-α-D-Glcp-(1,6)-α-D-Glcp-(1,4)-D-Glcp (DP4), and α-D-Glcp-(1,6)-α-D-Glcp-(1,3)-α-D-Glcp-(1,6)-α-D-Glcp-(1,4)-D-Glcp (DP5), respectively. For these three structurally different oligosaccharides, the fermentation selectivity by fecal bacteria was determined in anaerobic batch culture. Fructooligosaccharide (FOS) was used as a positive prebiotic control. Similar to FOS, all three α-glucooligosaccharides selectively stimulated the proliferation of Bifidobacteria and Lactobacilli compared with the control. DP3 exhibited the strongest prebiotic ability to increase the Bifidobacterium and Lactobacillus population, whereas DP5 produced the most short-chain fatty acids. In addition, DP4 produced the highest butyrate concentration and resulted in the lowest acetate : propionate ratio. These results suggested that the enzymatically synthesized α-glucooligosaccharides were potential prebiotics, underlining correlations between the structural features of oligosaccharides and their impact on the metabolism of fecal microbiota.