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1.
Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro.
Pham, VT, Calatayud, M, Rotsaert, C, Seifert, N, Richard, N, Van den Abbeele, P, Marzorati, M, Steinert, RE
Nutrients. 2021;(4)
Abstract
Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.
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2.
Changes in HMO Concentrations throughout Lactation: Influencing Factors, Health Effects and Opportunities.
Thum, C, Wall, CR, Weiss, GA, Wang, W, Szeto, IM-Y, Day, L
Nutrients. 2021;(7)
Abstract
Human milk oligosaccharides (HMOs) are important functional biomolecules in human breast milk. Understanding the factors influencing differences in HMO composition and changes in their concentration over lactation can help to design feeding strategies that are well-adapted to infant's needs. This review summarises the total and individual concentration of HMOs from data published from 1999 to 2019. Studies show that the HMO concentrations are highest in colostrum (average 9-22 g/L), followed by slightly lower concentrations in transitional milk (average 8-19 g/L), with a gradual decline in mature milk as lactation progresses, from 6-15 g/L in breast milk collected within one month of birth, to 4-6 g/L after 6 months. Significant differences in HMO composition have been described between countries. Different HMOs were shown to be predominant over the course of lactation, e.g., 3-fucosyllactose increased over lactation, whereas 2'-fucosyllactose decreased. Recent clinical studies on infant formula supplemented with 2'-fucosyllactose in combination with other oligosaccharides showed its limited beneficial effect on infant health.
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3.
The Effect of A Whey-Protein and Galacto-Oligosaccharides Based Product on Parameters of Sleep Quality, Stress, and Gut Microbiota in Apparently Healthy Adults with Moderate Sleep Disturbances: A Randomized Controlled Cross-Over Study.
Schaafsma, A, Mallee, L, van den Belt, M, Floris, E, Kortman, G, Veldman, J, van den Ende, D, Kardinaal, A
Nutrients. 2021;(7)
Abstract
People experiencing sleep problems may benefit from nutrients supporting serotonin metabolism and stress reduction. We studied the effect of a dairy-based product (DP) containing protein, galacto-oligosaccharides, vitamins and minerals, on sleep quality, stress, and gut-microbiota. In a cross-over RCT (three weeks intervention; three weeks washout), adults (n = 70; 30-50 y) with sleep disturbances (Pittsburgh Sleep Quality Index (PSQI) ≥ 9) consumed products 1 h before bed-time. Sleep quality (PSQI) was measured weekly, stress at base- and end-line (Depression Anxiety Stress Scale and saliva cortisol). Fecal samples were collected in the 1st intervention period only. Compared to placebo (skimmed milk), PSQI was only lower at day 14 in the 2nd intervention period in intention-to-treat (ITT) (p = 0.017; n = 69) and per-protocol (PP) (p = 0.038; n = 64) analyses. Post-hoc analysis (modified-PP: n=47, with baseline PSQI ≥ 9, and endline day 14), however, showed a decrease in PSQI (-1.60 ± 2.53; p = 0.034). Early morning saliva cortisol decreased versus placebo (p = 0.045). Relative abundance of Bifidobacterium increased (p = 0.02). Redundancy analysis showed an inverse relationship between baseline microbiota composition and baseline PSQI (p = 0.046). Thus, although DP did not improve sleep quality in ITT and PP populations, it did in the modPP. DP reduced salivary cortisol and stimulated Bifidobacterium, which possibly is important for sleep improvement.
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4.
Human Milk Microbiota and Oligosaccharides: A Glimpse into Benefits, Diversity, and Correlations.
Moubareck, CA
Nutrients. 2021;(4)
Abstract
Human milk represents a cornerstone for growth and development of infants, with extensive array of benefits. In addition to exceptionally nutritive and bioactive components, human milk encompasses a complex community of signature bacteria that helps establish infant gut microbiota, contributes to maturation of infant immune system, and competitively interferes with pathogens. Among bioactive constituents of milk, human milk oligosaccharides (HMOs) are particularly significant. These are non-digestible carbohydrates forming the third largest solid component in human milk. Valuable effects of HMOs include shaping intestinal microbiota, imparting antimicrobial effects, developing intestinal barrier, and modulating immune response. Moreover, recent investigations suggest correlations between HMOs and milk microbiota, with complex links possibly existing with environmental factors, genetics, geographical location, and other factors. In this review, and from a physiological and health implications perspective, milk benefits for newborns and mothers are highlighted. From a microbiological perspective, a focused insight into milk microbiota, including origins, diversity, benefits, and effect of maternal diet is presented. From a metabolic perspective, biochemical, physiological, and genetic significance of HMOs, and their probable relations to milk microbiota, are addressed. Ongoing research into mechanistic processes through which the rich biological assets of milk promote development, shaping of microbiota, and immunity is tackled.
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5.
The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome.
Iribarren, C, Magnusson, MK, Vigsnæs, LK, Aziz, I, Amundsen, ID, Šuligoj, T, Juge, N, Patel, P, Sapnara, M, Johnsen, L, et al
Nutrients. 2021;(11)
Abstract
BACKGROUND Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2'-O-fucosyllactose and lacto-N-neotetraose (2'FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. METHODS Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2'FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. RESULTS Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2'FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2'FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. CONCLUSION Supplementation with 2'FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2'FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.
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6.
Computer-aided engineering of a branching sucrase for the glucodiversification of a tetrasaccharide precursor of S. flexneri antigenic oligosaccharides.
Benkoulouche, M, Ben Imeddourene, A, Barel, LA, Lefebvre, D, Fanuel, M, Rogniaux, H, Ropartz, D, Barbe, S, Guieysse, D, Mulard, LA, et al
Scientific reports. 2021;(1):20294
Abstract
Enzyme engineering approaches have allowed to extend the collection of enzymatic tools available for synthetic purposes. However, controlling the regioselectivity of the reaction remains challenging, in particular when dealing with carbohydrates bearing numerous reactive hydroxyl groups as substrates. Here, we used a computer-aided design framework to engineer the active site of a sucrose-active [Formula: see text]-transglucosylase for the 1,2-cis-glucosylation of a lightly protected chemically synthesized tetrasaccharide, a common precursor for the synthesis of serotype-specific S. flexneri O-antigen fragments. By targeting 27 amino acid positions of the acceptor binding subsites of a GH70 branching sucrase, we used a RosettaDesign-based approach to propose 49 mutants containing up to 15 mutations scattered over the active site. Upon experimental evaluation, these mutants were found to produce up to six distinct pentasaccharides, whereas only two were synthesized by the parental enzyme. Interestingly, we showed that by introducing specific mutations in the active site of a same enzyme scaffold, it is possible to control the regiospecificity of the 1,2-cis glucosylation of the tetrasaccharide acceptor and produce a unique diversity of pentasaccharide bricks. This work offers novel opportunities for the development of highly convergent chemo-enzymatic routes toward S. flexneri haptens.
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7.
Nutrient Intake and Gut Microbial Genera Changes after a 4-Week Placebo Controlled Galacto-Oligosaccharides Intervention in Young Females.
Johnstone, N, Dart, S, Knytl, P, Nauta, A, Hart, K, Cohen Kadosh, K
Nutrients. 2021;(12)
Abstract
Recent interest in the gut-brain-axis has highlighted the potential of prebiotics to impact wellbeing, and to affect behavioral change in humans. In this clinical trial, we examined the impact of four-weeks daily supplementation of galacto-oligosaccharides (GOS) on self-reported nutrient intake and relationships on gut microbiota in a four-week two-armed parallel double-blind placebo controlled GOS supplement trial in young adult females. Food diaries and stool samples were collected prior to and following 28 days of supplement consumption. It was found that four weeks of GOS supplementation influenced macronutrient intake, as evident by reduced carbohydrate and sugars and increased fats intake. Further analysis showed that the reduction in carbohydrates was predicted by increasing abundances of Bifidobacterium in the GOS group in comparison to the placebo group. This suggests that Bifidobacterium increase via GOS supplementation may help improve the gut microbiota composition by altering the desire for specific types of carbohydrates and boosting Bifidobacterium availability when fiber intake is below recommended levels, without compromising appetite for fiber from food.
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8.
Gut microbiota comparison of vaginally and cesarean born infants exclusively breastfed by mothers secreting α1-2 fucosylated oligosaccharides in breast milk.
Tonon, KM, Morais, TB, Taddei, CR, Araújo-Filho, HB, Abrão, ACFV, Miranda, A, de Morais, MB
PloS one. 2021;(2):e0246839
Abstract
BACKGROUND Exclusive breastfeeding promotes beneficial modifications on the microbiota of cesarean born infants, but little is known about the role of specific breast milk components in this modulation. Women with an active FUT2 gene (called secretors) secrete α1-2 fucosylated human milk oligosaccharides (HMOs), which promote Bifidobacterium in the infant's gut and may modulate the microbiota of cesarean born infants. OBJECTIVE To compare the microbiota composition of cesarean and vaginally born infants breastfed by secretor mothers. METHODS Maternal secretor status was determined by the occurrence of 4 different α1-2 fucosylated HMOs in breast milk by LC-MS. The fecal microbiota composition from cesarean and vaginally born infants was analyzed by 16S rRNA gene sequencing and qPCR, stratified by the maternal secretor status, and compared. RESULTS Alpha and beta diversity were not significantly different in cesarean born, secretor-fed infants (CSe+) compared to vaginally born, secretor-fed infants (VSe+). There were no significant differences in the fecal relative abundance of Bifidobacterium between CSe+ and VSe+ infants, but the prevalence of the species B. longum was lower in CSe+. The fecal relative abundance of Bacteroides was also lower, while Akkermansia and Kluyvera were higher in CSe+ infants. CONCLUSION Cesarean and vaginally born infants fed with breast milk containing the α1-2 fucosylated HMOs fraction present similar amounts of Bifidobacterium in the feces, but differences are observed in other members of the microbiota.
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9.
Production of β-galactosidase by Trichoderma sp. through solid-state fermentation targeting the recovery of galactooligosaccharides from whey cheese.
de Jesus, LFMC, Guimarães, LHS
Journal of applied microbiology. 2021;(3):865-877
Abstract
AIMS: Optimization of β-galactosidase production by Trichoderma sp. under solid-state fermentation using wheat bran as solid substrate through an experimental design and its application targeting the recovery of galactooligosaccharides (GOS) from whey cheese. METHODS AND RESULTS The β-galactosidase production by Trichoderma sp. increased 2·3-fold (2·67 U g-1 of substrate) culturing the fungus at 30°C for 187 h, at an inoculum of 105 spores per ml, and a 1 : 1·65 (w/v) ratio of wheat bran to tap water. The best enzyme activity was obtained at 55°C and pH 4·5. The catalytic activity was maintained for up to 180 min incubating at 35-45°C, and above 50% at acidic or alkaline pH for up to 24 h. It also presented resistance to chemical compounds. β-galactosidase catalysed the hydrolysis of the lactose and the transgalactosylation reaction leading to the production of GOS. CONCLUSION Trichoderma sp. produced β-galactosidase with transgalactosylation activity that may be used to recover GOS, products with high added value, from whey cheese. SIGNIFICANCE AND IMPACT OF THE STUDY β-galactosidases are used in different industrial sectors. Therefore, the Trichoderma β-galactosidase is a promising alternative for the production of GOS as prebiotic from the dairy effluents, contributing to the reduction in the environmental impact.
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10.
Galacto-oligosaccharides supplementation in prefrail older and healthy adults increased faecal bifidobacteria, but did not impact immune function and oxidative stress.
Wilms, E, An, R, Smolinska, A, Stevens, Y, Weseler, AR, Elizalde, M, Drittij, MJ, Ioannou, A, van Schooten, FJ, Smidt, H, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3019-3031
Abstract
BACKGROUND & AIMS Ageing is associated with an increased risk of frailty, intestinal microbiota perturbations, immunosenescence and oxidative stress. Prebiotics such as galacto-oligosaccharides (GOS) may ameliorate these ageing-related alterations. We aimed to compare the faecal microbiota composition, metabolite production, immune and oxidative stress markers in prefrail elderly and younger adults, and investigate the effects of GOS supplementation in both groups. METHODS In a randomised controlled cross-over study, 20 prefrail elderly and 24 healthy adults received 21.6 g/day Biotis™ GOS (containing 15.0 g/day GOS) or placebo. Faecal 16S rRNA gene-based microbiota and short-chain fatty acids were analysed at 0, 1 and 4 weeks of intervention.Volatile organic compounds were analysed in breath, and stimulated cytokine production, CRP, malondialdehyde, trolox equivalent antioxidant capacity (TEAC) and uric acid (UA) in blood at 0 and 4 weeks. RESULTS Principle coordinate analysis showed differences in microbial composition between elderly and adults (P≤0.05), with elderly having lower bifidobacteria (P≤0.033) at baseline. In both groups, GOS affected microbiota composition (P≤0.05), accompanied by increases in bifidobacteria (P<0.001) and decreased microbial diversity (P≤0.023). Faecal and breath metabolites, immune and oxidative stress markers neither differed between groups (P ≥ 0.125) nor were affected by GOS (P ≥ 0.236). TEAC values corrected for UA were higher in elderly versus adults (P<0.001), but not different between interventions (P ≥ 0.455). CONCLUSIONS Elderly showed lower faecal bifidobacterial (relative) abundance than adults, which increased after GOS intake in both groups. Faecal and breath metabolites, parameters of immune function and oxidative stress were not different at baseline, and not impacted by GOS supplementation. CLINICALTRIALS. GOV WITH STUDY ID NUMBER NCT03077529.