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Di Huang, Kexin Yang, Jia Liu, Yingying Xu, Yuanyuan Wang, Ru Wang, Bin Liu, Lu Feng
Fucosyllactoses, including 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL), are important oligosaccharides in human milk that are commonly used as nutritional additives in infant formula due to their biological functions, such as the promotion of bifidobacteria growth, inhibition of pathogen infection, and improvement of immune response. In this study, we developed a synthetic biology approach to promote the efficient biosynthesis of 2'-FL and 3-FL in engineered Escherichia coli. To boost the production of 2'-FL and 3-FL, multiple modular optimization strategies were applied in a plug-and-play manner...
March 9, 2017: Metabolic Engineering
Clarissa Schwab, Hans-Joachim Ruscheweyh, Vera Bunesova, Van Thanh Pham, Niko Beerenwinkel, Christophe Lacroix
Fucosyllactoses (2'- or 3'-FL) account for up to 20% of human milk oligosaccharides (HMOs). Infant bifidobacteria, such as Bifidobacterium longum subsp. infantis, utilize the lactose moiety to form lactate and acetate, and metabolize L-fucose to 1,2-propanediol (1,2-PD). Eubacterium hallii is a common member of the adult gut microbiota that can produce butyrate from lactate and acetate, and convert 1,2-PD to propionate. Recently, a Swiss cohort study identified E. hallii as one of the first butyrate producers in the infant gut...
2017: Frontiers in Microbiology
E Vazquez, A Santos-Fandila, R Buck, R Rueda, M Ramirez
Human milk oligosaccharides (HMO) are involved in many biological functions influencing infant health. Although HMO act locally at the intestine, recent evidence has demonstrated that HMO are partially incorporated into the systemic circulation of breast-fed infants. In the last few years, a large amount of research has been conducted using preclinical models to uncover new biological functions of HMO. The aim of this study was to evaluate the absorption and urine excretion of HMO in rats. We administered a single oral dose of the following HMO: 2'-fucosyllactose (2'-FL), 6'-sialyllactose and lacto-N-neotetraose at different concentrations to adult rats...
February 9, 2017: British Journal of Nutrition
Young-Wook Chin, Ji-Yeong Kim, Jae-Han Kim, Sang-Min Jung, Jin-Ho Seo
2'-Fucosyllactose (2-FL) is one of most abundant oligosaccharides in human milk, which is involved in many biological functions for infant health. Since 2-FL has a great potential in application to functional food materials and pharmaceuticals, several microbial systems for mass production of 2-FL have been developed in recent years. Microbial production of 2-FL was suggested to be influenced by a number of factors including fucosylation activity of α-1,2-fucosyltransferase. In the present study, the wcfB gene coding for α-1,2-fucosyltransferase from Bacteroides fragilis was screened from eleven candidates of putative α-1,2-fucosyltransferase...
December 2, 2016: Journal of Biotechnology
Enrique Vazquez, Alejandro Barranco, Maria Ramirez, Agnes Gruart, Jose M Delgado-Garcia, Maria L Jimenez, Rachael Buck, Ricardo Rueda
2´-fucosyllactose (2´-FL) is an abundant human milk oligosaccharide (HMO) in human milk with diverse biological effects. We recently reported ingested 2´-FL stimulates central nervous system (CNS) function, such as hippocampal long term potentiation (LTP) and learning and memory in rats. Conceivably the effect of 2´-FL on CNS function may be via the gut-brain axis (GBA), specifically the vagus nerve, and L-fucose (Fuc) may play a role. This study had two aims: (1) determine if the effect of ingested 2´-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2) confirm if oral 2´-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy...
2016: PloS One
Karen C Goehring, Barbara J Marriage, Jeffery S Oliver, Julie A Wilder, Edward G Barrett, Rachael H Buck
BACKGROUND: Evidence suggests that human milk oligosaccharides (HMOs) provide multiple benefits to infants, including prebiotic effects, gut maturation, antimicrobial activities, and immune modulation. Clinical intervention studies with HMOs are required to confirm these benefits in infants. OBJECTIVE: Our objective was to investigate the effects of feeding formulas supplemented with the HMO 2'-fucosyllactose (2'-FL) on biomarkers of immune function in healthy term infants...
December 2016: Journal of Nutrition
Vera Bunesova, Christophe Lacroix, Clarissa Schwab
BACKGROUND: Human milk oligosaccharides (HMOs) are one of the major glycan source of the infant gut microbiota. The two species that predominate the infant bifidobacteria community, Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum, possess an arsenal of enzymes including α-fucosidases, sialidases, and β-galactosidases to metabolise HMOs. Recently bifidobacteria were obtained from the stool of six month old Kenyan infants including species such as Bifidobacterium kashiwanohense, and Bifidobacterium pseudolongum that are not frequently isolated from infant stool...
October 26, 2016: BMC Microbiology
Daniel Garrido, Santiago Ruiz-Moyano, Nina Kirmiz, Jasmine C Davis, Sarah M Totten, Danielle G Lemay, Juan A Ugalde, J Bruce German, Carlito B Lebrilla, David A Mills
The infant intestinal microbiota is often colonized by two subspecies of Bifidobacterium longum: subsp. infantis (B. infantis) and subsp. longum (B. longum). Competitive growth of B. infantis in the neonate intestine has been linked to the utilization of human milk oligosaccharides (HMO). However, little is known how B. longum consumes HMO. In this study, infant-borne B. longum strains exhibited varying HMO growth phenotypes. While all strains efficiently utilized lacto-N-tetraose, certain strains additionally metabolized fucosylated HMO...
October 19, 2016: Scientific Reports
Emma Elison, Louise K Vigsnaes, Laura Rindom Krogsgaard, Julie Rasmussen, Nikolaj Sørensen, Bruce McConnell, Thierry Hennet, Morten O A Sommer, Peter Bytzer
The gut microbiota has been established as an important player influencing many aspects of human physiology. Breast milk, the first diet for an infant, contains human milk oligosaccharides (HMO) that shape the infant's gut microbiota by selectively stimulating the growth of specific bacteria, especially bifidobacteria. In addition to their bifidogenic activity, the ability of HMO to modulate immune function and the gut barrier makes them prime candidates to restore a beneficial microbiota in dysbiotic adults and provide health benefits...
October 2016: British Journal of Nutrition
Austin T Mudd, Jaime Salcedo, Lindsey S Alexander, Stacey K Johnson, Caitlyn M Getty, Maciej Chichlowski, Brian M Berg, Daniela Barile, Ryan N Dilger
BACKGROUND: Milk oligosaccharides (OSs) are bioactive components known to influence neonatal development. These compounds have specific physiological functions acting as prebiotics, immune system modulators, and enhancing intestine and brain development. OBJECTIVES: The pig is a commonly used model for studying human nutrition, and there is interest in quantifying OS composition of porcine milk across lactation compared with human milk. In this study, we hypothesized that OS and sialic acid (SA) composition of porcine milk would be influenced by stage of lactation...
2016: Frontiers in Nutrition
Zhuo-Teng Yu, N Nanda Nanthakumar, David S Newburg
BACKGROUND: Campylobacter jejuni causes diarrhea worldwide; young children are most susceptible. Binding of virulent C. jejuni to the intestinal mucosa is inhibited ex vivo by α1,2-fucosylated carbohydrate moieties, including human milk oligosaccharides (HMOSs). OBJECTIVE: The simplest α1,2-fucosylated HMOS structure, 2'-fucosyllactose (2'-FL), can be predominant at ≤5 g/L milk. Although 2'-FL inhibits C. jejuni binding ex vivo and in vivo, the effects of 2'FL on the cell invasion central to C...
October 2016: Journal of Nutrition
Misty Good, Chhinder P Sodhi, Yukihiro Yamaguchi, Hongpeng Jia, Peng Lu, William B Fulton, Laura Y Martin, Thomas Prindle, Diego F Nino, Qinjie Zhou, Congrong Ma, John A Ozolek, Rachael H Buck, Karen C Goehring, David J Hackam
Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2'-fucosyllactose (2'FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2'FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture...
October 2016: British Journal of Nutrition
J Salcedo, S A Frese, D A Mills, D Barile
The composition of porcine milk oligosaccharides (PMO) was analyzed during early lactation and their relation to piglet gut microbiome was investigated. Pigs are considered ideal intestinal models to simulate humans because of the striking similarity in intestinal physiopathology to humans. The evolution of PMO was investigated in the milk from 3 healthy sows at prefarrowing, farrowing, and d 7 and 14 postpartum by Nano-LC Chip Quadrupole-Time-of-Flight mass spectrometer (Agilent Technologies, Santa Clara, CA)...
October 2016: Journal of Dairy Science
Malene S Cilieborg, Stine B Bering, Mette V Østergaard, Michael L Jensen, Łukasz Krych, David S Newburg, Per T Sangild
Human milk decreases the risk of necrotising enterocolitis (NEC), a severe gastrointestinal disease that occurs in 5-10 % of preterm infants. The prebiotic and immune-modulatory effects of milk oligosaccharides may contribute to this protection. Preterm pigs were used to test whether infant formula enriched with α1,2-fucosyllactose (2'-FL, the most abundant oligosaccharide in human milk) would benefit gut microbial colonisation and NEC resistance after preterm birth. Caesarean-delivered preterm pigs were fed formula (Controls, n 17) or formula with 5 g/l 2'-FL (2'-FL, n 16) for 5 d; eight 2'-FL pigs (50 %) and twelve Controls (71 %) developed NEC, with no difference in lesion scores (P=0·35); 2'-FL pigs tended to have less anaerobic bacteria in caecal contents (P=0·22), but no difference in gut microbiota between groups were observed by fluorescence in situ hybridisation and 454 pyrosequencing...
September 2016: British Journal of Nutrition
Takahiro Matsuki, Kana Yahagi, Hiroshi Mori, Hoshitaka Matsumoto, Taeko Hara, Saya Tajima, Eishin Ogawa, Hiroko Kodama, Kazuya Yamamoto, Takuji Yamada, Satoshi Matsumoto, Ken Kurokawa
Recent studies have demonstrated that gut microbiota development influences infants' health and subsequent host physiology. However, the factors shaping the development of the microbiota remain poorly understood, and the mechanisms through which these factors affect gut metabolite profiles have not been extensively investigated. Here we analyse gut microbiota development of 27 infants during the first month of life. We find three distinct clusters that transition towards Bifidobacteriaceae-dominant microbiota...
June 24, 2016: Nature Communications
Sean Austin, Carlos A De Castro, Thierry Bénet, Yangfeng Hou, Henan Sun, Sagar K Thakkar, Gerard Vinyes-Pares, Yumei Zhang, Peiyu Wang
Breastfed infants tend to be less prone to infections and may have improved cognitive benefits compared to formula-fed infants. Human milk oligosaccharides (HMO) are the third most abundant component of human milk, but are absent from formulae. They may be partially responsible for the benefits of breastfeeding. In this cross-sectional observational study, the HMO composition of milk from Chinese mothers was studied to determine the impact of stage of lactation, mode of delivery and geographical location. The content of 10 HMO was measured by HPLC in 446 milk samples from mothers living in three different cities in China...
June 8, 2016: Nutrients
Malene S Cilieborg, Per T Sangild, Michael L Jensen, Mette V Østergaard, Lars Christensen, Stine O Rasmussen, Anne L Mørbak, Claus B Jørgensen, Stine B Bering
OBJECTIVES: Infectious diarrhea, a leading cause of morbidity and deaths, is less prevalent in breastfed infants compared with infants fed infant formula. The dominant human milk oligosaccharide (HMO), α-1,2-fucosyllactose (2'-FL), has structural homology to bacterial adhesion sites in the intestine and may in part explain the protective effects of human milk. We hypothesized that 2'-FL prevents diarrhea via competitive inhibition of pathogen adhesion in a pig model for sensitive newborn infants...
February 2017: Journal of Pediatric Gastroenterology and Nutrition
Young-Wook Chin, Nari Seo, Jae-Han Kim, Jin-Ho Seo
2'-Fucosyllactose (2-FL) is one of the key oligosaccharides in human milk. In the present study, the salvage guanosine 5'-diphosphate (GDP)-l-fucose biosynthetic pathway from fucose was employed in engineered Escherichia coli BL21star(DE3) for efficient production of 2-FL. Introduction of the fkp gene coding for fucokinase/GDP-l-fucose pyrophosphorylase (Fkp) from Bacteroides fragilis and the fucT2 gene encoding α-1,2-fucosyltransferase from Helicobacter pylori allows the engineered E. coli to produce 2-FL from fucose, lactose and glycerol...
November 2016: Biotechnology and Bioengineering
Chloe A Autran, Margriet H C Schoterman, Evelyn Jantscher-Krenn, Johannis P Kamerling, Lars Bode
Necrotising enterocolitis (NEC) is one of the most frequent and fatal intestinal disorders in preterm infants and has very limited treatment options. Breast-fed infants are at a 6-10-fold lower NEC risk than formula-fed infants, and we have previously shown that human milk oligosaccharides (HMO) improved survival and reduced pathology in a rat NEC model. The HMO disialyllacto-N-tetraose (DSLNT) was most effective, and sialylation was shown to be essential for its protective effect. Galacto-oligosaccharides (GOS), currently added to some infant formula, but not containing sialic acid, had no effect...
July 2016: British Journal of Nutrition
Elena Oliveros, María Ramirez, Enrique Vazquez, Alejandro Barranco, Agnes Gruart, Jose Maria Delgado-Garcia, Rachael Buck, Ricardo Rueda, Maria J Martin
Human milk oligosaccharides have been proposed to exert beneficial effects on brain development. During the last decades, most of the studies have focused on the evaluation of sialylated structures but recent experiments have also tested fucosylated oligosaccharides, i.e. 2'-fucosyllactose (2'-FL). The present study aimed to determine whether oral 2'-FL has an effect on the development of newborn brain, contributing to enhance cognitive skills later in life. Rat pups received an oral supplementation of 2'-FL (2'-FL group) or water (control group) during the lactation period...
May 2016: Journal of Nutritional Biochemistry
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