Maternal Fucosyltransferase 2 Status Associates with the Profiles of Human Milk Oligosaccharides and the Fecal Microbiota Composition of Breastfed Infants

2021 ◽  
Vol 69 (10) ◽  
pp. 3032-3043
Author(s):  
Fan Liu ◽  
Jingyu Yan ◽  
Xifan Wang ◽  
Chenyuan Wang ◽  
Lingli Chen ◽  
...  
2015 ◽  
Vol 60 (6) ◽  
pp. 825-833 ◽  
Author(s):  
Mei Wang ◽  
Min Li ◽  
Shuai Wu ◽  
Carlito B. Lebrilla ◽  
Robert S. Chapkin ◽  
...  

Author(s):  
Miriam N. Ojima ◽  
Yuya Asao ◽  
Aruto Nakajima ◽  
Toshihiko Katoh ◽  
Motomitsu Kitaoka ◽  
...  

Human milk oligosaccharides (HMOs), which are natural bifidogenic prebiotics, were recently commercialized to fortify formula milk. However, HMO-assimilation phenotypes of bifidobacteria vary by species and strain, which has not been fully linked to strain genotype. We have recently shown that specialized uptake systems, particularly for the internalization of major HMOs (fucosyllactose (FL)), are associated with the formation of a bifidobacteria-rich gut microbial community. Phylogenetic analysis has revealed that FL transporters have diversified into two clades harboring four clusters within the Bifidobacterium genus, but the underpinning functional diversity associated with this divergence remains underexplored. In this study, we examined the HMO-consumption phenotypes of two bifidobacterial species, Bifidobacterium catenulatum subspecies kashiwanohense and Bifidobacterium pseudocatenulatum , which both possess FL binding proteins that belong to phylogenetic clusters with unknown specificities. Growth assays, heterologous gene expression experiments, and HMO-consumption analysis showed that the FL transporter type from B. catenulatum subspecies kashiwanohense JCM 15439 T conferred a novel HMO-uptake pattern that includes the complex fucosylated HMOs (lacto- N- fucopentaose II and lacto- N- difucohexaose I/II). Further genomic landscape analyses of FL transporter-positive bifidobacterial strains revealed that H-antigen or Lewis antigen-specific fucosidase gene(s) and FL transporter specificities were largely aligned. These results suggest that bifidobacteria have acquired FL transporters along with the corresponding gene sets necessary to utilize the imported HMOs. Our results provide insight into the species- and strain-dependent adaptation strategies of bifidobacteria to HMO-rich environments. Importance The gut of breastfed infants is generally dominated by health-promoting bifidobacteria. Human milk oligosaccharides (HMOs) from breastmilk selectively promote the growth of specific taxa such as bifidobacteria, thus forming an HMO-mediated, host-microbe symbiosis. While the co-evolution of humans and bifidobacteria has been proposed, the underpinning adaptive strategies employed by bifidobacteria require further research. Here, we analyzed the divergence of the critical fucosyllactose (FL) HMO transporter within Bifidobacterium . We have shown that the diversification of the solute-binding proteins of the FL-transporter led to uptake specificities of fucosylated sugars ranging from simple trisaccharides to complex hexasaccharides. This transporter and the congruent acquisition of the necessary intracellular enzymes allows for bifidobacteria to import different types of HMOs in a predictable and strain-dependent manner. These findings explain the adaptation and proliferation of bifidobacteria in the competitive and HMO-rich infant gut environment and enable accurate specificity annotation of transporters from metagenomic data.


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Cilius Esmann Fonvig ◽  
Ingvild Dybdrodt Amundsen ◽  
Louise Kristine Vigsnæs ◽  
Nikolaj Sørensen ◽  
Christine Frithioff-Bøjsøe ◽  
...  

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Janet E Williams ◽  
Mara A Riley ◽  
Sarah L Brooker ◽  
Katherine M Hunt ◽  
Alexandra Szyszka ◽  
...  

2022 ◽  
Vol 9 ◽  
Author(s):  
Sarah Bajorek ◽  
Rebbeca M. Duar ◽  
Maxwell Corrigan ◽  
Christa Matrone ◽  
Kathryn A. Winn ◽  
...  

Not all infants carry specialized gut microbes, meaning they cannot digest human milk oligosaccharides and therefore do not receive complete benefits from human milk. B. infantis EVC001 is equipped to convert the full array of complex oligosaccharides into compounds usable by the infant, making it an ideal candidate to stabilize gut function and improve nutrition in preterm infants. A prospective, open-label study design was used to evaluate the tolerability of B. infantis EVC001 and its effects on the fecal microbiota in preterm infants in a Neonatal Intensive Care Unit. Thirty preterm infants <1,500 g and/or <33 weeks gestation at birth were divided into two matched groups, and control infants were enrolled and discharged prior to enrolling EVC001 infants to prevent cross-colonization of B. infantis: (1) fifteen control infants received no EVC001, and (2) fifteen infants received once-daily feedings of B. infantis EVC001 (8.0 x 109 CFU) in MCT oil. Clinical information regarding medications, growth, nutrition, gastrointestinal events, diagnoses, and procedures was collected throughout admission. Infant stool samples were collected at baseline, Study Days 14 and 28, and 34-, 36-, and 38-weeks of gestation. Taxonomic composition of the fecal microbiota, functional microbiota analysis, B. infantis, and human milk oligosaccharides (HMOs) in the stool were determined or quantified using 16S rRNA gene sequencing, metagenomic sequencing, qPCR, and mass spectrometry, respectively. No adverse events or tolerability issues related to EVC001 were reported. Control infants had no detectable levels of B. infantis. EVC001 infants achieved high levels of B. infantis (mean = 9.7 Log10 CFU/μg fecal DNA) by Study Day 14, correlating with less fecal HMOs (ρ = −0.83, P < 0.0001), indicating better HMO utilization in the gut. In this study, B. infantis EVC001 was shown to be safe, well-tolerated, and efficient in colonizing the preterm infant gut and able to increase the abundance of bifidobacteria capable of metabolizing HMOs, resulting in significantly improved utilization of human milk.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03939546, identifier: NCT03939546.


2019 ◽  
Vol 156 (6) ◽  
pp. S-235 ◽  
Author(s):  
Cristina Iribarren ◽  
Maria K. Magnusson ◽  
Hans Törnblom ◽  
Imran Aziz ◽  
Ingvild Dybdrodt Amundsen ◽  
...  

2021 ◽  
pp. 1-26
Author(s):  
W. Wang ◽  
C. Mu ◽  
N.A. Cho ◽  
E.W. Noye Tuplin ◽  
D.E. Lowry ◽  
...  

Abstract Early life nutrition fundamentally influences neonatal development and health. Human milk oligosaccharides (HMOs) are key components of breast milk, but not standard infant formula that support establishment of the newborn gut microbiota. Using an artificial rearing system, our objective was to test the effect of two HMOs on whole body and organ growth, adiposity, glucose tolerance, and fecal microbiota in young rat pups. From postnatal day 4 to 21, Sprague Dawley rats were randomized to receive one of: 1) CTR (rat milk substitute); 2) 2’FL (CTR +1.2 g/L 2’-fucosyllactose); 3) 3’SL (CTR+1.2 g/L 3’-sialyllactose); 4) 2’FL+3’SL (CTR+0.6 g/L 2’-FL+0.6 g/L 3’-SL). Body weight, bowel movements and food intake were monitored daily, fecal samples collected each week, and oral glucose tolerance, body composition, and organ weight measured at weaning. No significant differences were observed between groups in growth performance, body composition, organ weight and abundance of dominant fecal microbes. A decreased relative abundance of genus Proteus in week1 fecal samples and Terrisporobacter in week3 fecal samples (P<0.05) was suggestive of a potential pathogen inhibitory effect of 3’SL. Longitudinal changes in the fecal microbiota of artificially reared suckling rats were primarily governed by age (P =0.001) and not affected by the presence of 2’-FL and/or 3’-SL in rat milk substitutes (P =0.479). Considering the known protective effects of HMOs, further investigation of supplementation with these and other HMOs in models of premature birth, extremely low body weight, or malnutrition may show more pronounced outcomes.


2016 ◽  
Vol 69 (Suppl. 2) ◽  
pp. 41-51 ◽  
Author(s):  
Sharon M. Donovan ◽  
Sarah S. Comstock

The immune system of the infant is functionally immature and naïve. Human milk contains bioactive proteins, lipids, and carbohydrates that protect the newborn and stimulate innate and adaptive immune development. This review will focus on the role human milk oligosaccharides (HMO) play in neonatal gastrointestinal and systemic immune development and function. For the past decade, intense research has been directed at defining the complexity of oligosaccharides in the milk of many species and is beginning to delineate their diverse functions. These studies have shown that human milk contains a higher concentration as well as a greater structural diversity and degree of fucosylation than the milk oligosaccharides in other species, particularly bovine milk from which many infant formulae are produced. The commercial availability of large quantities of certain HMO has furthered our understanding of the functions of specific HMO, which include protecting the infant from pathogenic infections, facilitating the establishment of the gut microbiota, promoting intestinal development, and stimulating immune maturation. Many of these actions are exerted through carbohydrate-carbohydrate interactions with pathogens or host cells. Two HMOs, 2′-fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT), have recently been added to infant formula. Although this is a first step in narrowing the compositional gap between human milk and infant formula, it is unclear whether 1 or 2 HMO will recapitulate the complexity of actions exerted by the complex mixture of HMO ingested by breastfed infants. Thus, as more HMO become commercially available, either isolated from bovine milk or chemically or microbially synthesized, it is anticipated that more oligosaccharides will be added to infant formula either alone or in combination with other prebiotics.


Sign in / Sign up

Export Citation Format

Share Document