scholarly journals Bovine Milk Oligosaccharides and Human Milk Oligosaccharides Modulate the Gut Microbiota Composition and Volatile Fatty Acid Concentrations in a Preclinical Neonatal Model

2021 ◽  
Vol 9 (5) ◽  
pp. 884
Author(s):  
Mei Wang ◽  
Marcia H. Monaco ◽  
Jonas Hauser ◽  
Jian Yan ◽  
Ryan N. Dilger ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Human Milk ◽  
Volatile Fatty Acid ◽  
Bovine Milk ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Human Milk Oligosaccharides ◽  
Microbial Composition ◽  
Milk Oligosaccharides ◽  
The Impact

Milk oligosaccharides (OS) shape microbiome structure and function, but their relative abundances differ between species. Herein, the impact of the human milk oligosaccharides (HMO) (2′-fucosyllactose [2′FL] and lacto-N-neotetraose [LNnT]) and OS isolated from bovine milk (BMOS) on microbiota composition and volatile fatty acid (VFA) concentrations in ascending colon (AC) contents and feces was assessed. Intact male piglets received diets either containing 6.5 g/L BMOS (n = 12), 1.0 g/L 2′FL + 0.5 g/L LNnT (HMO; n = 12), both (HMO + BMOS; n = 10), or neither (CON; n = 10) from postnatal day (PND) 2 to 34. Microbiota were assessed by 16S rRNA gene sequencing and real-time PCR, and VFA were measured by gas chromatography. The microbiota was affected by OS in an intestine region-specific manner. BMOS reduced (p < 0.05) microbial richness in the AC, microbiota composition in the AC and feces, and acetate concentrations in AC, regardless of HMO presence. HMO alone did not affect overall microbial composition, but increased (p < 0.05) the relative proportion of specific taxa, including Blautia, compared to other groups. Bacteroides abundance was increased (p < 0.05) in the AC by BMOS and synergistically by BMOS + HMO in the feces. Distinct effects of HMO and BMOS suggest complementary and sometimes synergistic benefits of supplementing a complex mixture of OS to formula.

scholarly journals Profiles of Human Milk Oligosaccharides and Their Relations to the Milk Microbiota of Breastfeeding Mothers in Dubai

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1727
Author(s):  
Carole Ayoub Moubareck ◽  
Maryam Lootah ◽  
Muna Tahlak ◽  
Koen Venema
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Maternal Nutrition ◽  
Geographic Location ◽  
Rrna Gene ◽  
Human Breast Milk ◽  
Lactation Period ◽  
Human Milk Oligosaccharides ◽  
Microbial Composition ◽  
Milk Oligosaccharides

The composition of human breast milk is affected by several factors, including genetics, geographic location and maternal nutrition. This study investigated the human milk oligosaccharides (HMOs) of breastfeeding mothers living in Dubai and their relations with the milk microbiota. A total of 30 breast milk samples were collected from healthy Emirati and UAE-expatriates at Latifa Hospital. HMO profiling was performed using UHPLC-MS. Microbiota profiles were determined by sequencing amplicons of the V3-V4 region of the 16S rRNA gene. HMO concentrations were significantly higher in Emirati, and dropped with the lactation period in both groups of mothers. The Le (a−b+)-secretor (Le+Se+) type was the most abundant in Dubai mothers (60%), followed by the Le(a−b−)-secretor (Le−Se+) type (23%). Bifidobacterium and Lactobacillus were considerably lower in Dubai-based mothers, while Pseudomonas and Delftia (Hydrogenophaga) were detected at a higher abundance compared to mothers from other countries. Atopobium was correlated with sialyl-lacto-N-tetraose c, Leptotrichia and Veillonella were correlated with 6’-sialyl-lactose, and Porphyromonas was correlated with lacto-N-hexaose. The study highlights the HMO profiles of breastfeeding mothers in Dubai and reveals few correlations with milk microbial composition. Targeted genomic analyses may help in determining whether these differences are due to genetic variations or to sociocultural and environmental factors.

scholarly journals New strategies for profiling and characterization of human milk oligosaccharides

Glycobiology ◽  
2020 ◽  
Vol 30 (10) ◽  
pp. 774-786 ◽  
Author(s):  
Sara Porfirio ◽  
Stephanie Archer-Hartmann ◽  
G Brett Moreau ◽  
Girija Ramakrishnan ◽  
Rashidul Haque ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Milk Composition ◽  
Human Breast Milk ◽  
Human Milk Oligosaccharides ◽  
Bacterial Strains ◽  
Milk Oligosaccharides ◽  
Vast Number ◽  
The Impact

Abstract Human breast milk is an incredibly rich and complex biofluid composed of proteins, lipids and complex carbohydrates, including a diverse repertoire of free human milk oligosaccharides (HMOs). Strikingly, HMOs are not digested by the infant but function as prebiotics for bacterial strains associated with numerous benefits. Considering the broad variety of beneficial effects of HMOs, and the vast number of factors that affect breast milk composition, the analysis of HMO diversity and complexity is of utmost relevance. Using human milk samples from a cohort of Bangladeshi mothers participating in a study on malnutrition and stunting in children, we have characterized breast milk oligosaccharide composition by means of permethylation followed by liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-MS/MS) analysis. This approach identified over 100 different glycoforms and showed a wide diversity of milk composition, with a predominance of fucosylated and sialylated HMOs over nonmodified HMOs. We observed that these samples contain on average 80 HMOs, with the highest permethylated masses detected being &gt;5000 mass units. Here we report an easily implemented method developed for the separation, characterization and relative quantitation of large arrays of HMOs, including higher molecular weight sialylated HMOs. Our ultimate goal is to create a simple, high-throughput method, which can be used for full characterization of sialylated and/or fucosylated HMOs. These results demonstrate how current analytical techniques can be applied to characterize human milk composition, providing new tools to help the scientific community shed new light on the impact of HMOs during infant development.

scholarly journals Linking Human Milk Oligosaccharides, Infant Fecal Community Types, and Later Risk To Require Antibiotics

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Bernard Berger ◽  
Nadine Porta ◽  
Francis Foata ◽  
Dominik Grathwohl ◽  
Michèle Delley ◽  
...  
Keyword(s):  
Human Milk ◽  
Reference Group ◽  
Association Studies ◽  
Medication Use ◽  
Test Group ◽  
Rrna Gene ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Term Infants ◽  
Community Types

ABSTRACT Human milk oligosaccharides (HMOs) may provide health benefits to infants partly by shaping the development of the early-life intestinal microbiota. In a randomized double-blinded controlled multicentric clinical trial, healthy term infants received either infant formula (control) or the same formula with two HMOs (2′-fucosyllactose and lacto-N-neotetraose; test) from enrollment (0 to 14 days) to 6 months. Then, all infants received the same follow-up formula without HMOs until 12 months of age. Breastfed infants (BF) served as a reference group. Stool microbiota at 3 and 12 months, analyzed by 16S rRNA gene sequencing, clustered into seven fecal community types (FCTs) with marked differences in total microbial abundances. Three of the four 12-month FCTs were likely precursors of the adult enterotypes. At 3 months, microbiota composition in the test group (n = 58) appeared closer to that of BF (n = 35) than control (n = 63) by microbiota alpha (within group) and beta (between groups) diversity analyses and distribution of FCTs. While bifidobacteriaceae dominated two FCTs, its abundance was significantly higher in one (FCT BiH for Bifidobacteriaceae at high abundance) than in the other (FCT Bi for Bifidobacteriaceae). HMO supplementation increased the number of infants with FCT BiH (predominant in BF) at the expense of FCT Bi (predominant in control). We explored the association of the FCTs with reported morbidities and medication use up to 12 months. Formula-fed infants with FCT BiH at 3 months were significantly less likely to require antibiotics during the first year than those with FCT Bi. Previously reported lower rates of infection-related medication use with HMOs may therefore be linked to gut microbiota community types. (This study has been registered at ClinicalTrials.gov under registration number NCT01715246.) IMPORTANCE Human milk is the sole and recommended nutrition for the newborn infant and contains one of the largest constituents of diverse oligosaccharides, dubbed human milk oligosaccharides (HMOs). Preclinical and clinical association studies indicate that HMOs have multiple physiological functions largely mediated through the establishment of the gut microbiome. Until recently, HMOs were not available to investigate their role in randomized controlled intervention trials. To our knowledge, this is the first report on the effects of 2 HMOs on establishing microbiota in newborn infants. We provide a detailed description of the microbiota changes observed upon feeding a formula with 2 HMOs in comparison to breastfed reference infants' microbiota. Then, we associate the microbiota to long-term health as assessed by prescribed antibiotic use.

scholarly journals Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2808
Author(s):  
Tanja Šuligoj ◽  
Louise Kristine Vigsnæs ◽  
Pieter Van den Abbeele ◽  
Athanasia Apostolou ◽  
Katia Karalis ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Human Milk ◽  
Barrier Function ◽  
Distal Colon ◽  
Human Milk Oligosaccharides ◽  
Gut Barrier ◽  
Milk Oligosaccharides ◽  
Caco2 Cell ◽  
Gut Barrier Function ◽  
The Impact

Human milk oligosaccharides (HMOs) shape the gut microbiota in infants by selectively stimulating the growth of bifidobacteria. Here, we investigated the impact of HMOs on adult gut microbiota and gut barrier function using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), Caco2 cell lines, and human intestinal gut organoid-on-chips. We showed that fermentation of 2’-O-fucosyllactose (2’FL), lacto-N-neotetraose (LNnT), and combinations thereof (MIX) led to an increase of bifidobacteria, accompanied by an increase of short chain fatty acid (SCFA), in particular butyrate with 2’FL. A significant reduction in paracellular permeability of FITC-dextran probe was observed using Caco2 cell monolayers with fermented 2’FL and MIX, which was accompanied by an increase in claudin-8 gene expression as shown by qPCR, and a reduction in IL-6 as determined by multiplex ELISA. Using gut-on-chips generated from human organoids derived from proximal, transverse, and distal colon biopsies (Colon Intestine-Chips), we showed that claudin-5 was significantly upregulated across all three gut-on-chips following treatment with fermented 2’FL under microfluidic conditions. Taken together, these data show that, in addition to their bifidogenic activity, HMOs have the capacity to modulate immune function and the gut barrier, supporting the potential of HMOs to provide health benefits in adults.

scholarly journals Oligosaccharides Released from Milk Glycoproteins Are Selective Growth Substrates for Infant-Associated Bifidobacteria

2016 ◽  
Vol 82 (12) ◽  
pp. 3622-3630 ◽  
Author(s):  
Sercan Karav ◽  
Annabelle Le Parc ◽  
Juliana Maria Leite Nobrega de Moura Bell ◽  
Steven A. Frese ◽  
Nina Kirmiz ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Human Milk ◽  
Bifidobacterium Longum ◽  
Bovine Milk ◽  
Selective Growth ◽  
Whey Protein Concentrate ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Content Type ◽  
Growth Substrates

ABSTRACTMilk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intactN-linked glycans. We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. We demonstrated that EndoBI-1 releasedN-glycans from concentrated bovine colostrum at the pilot scale. EndoBI-1-releasedN-glycans supported the rapid growth ofBifidobacterium longumsubsp.infantis(B. infantis), a species that grows well on human milk oligosaccharides, but did not support growth ofBifidobacterium animalissubsp.lactis(B. lactis), a species which does not. Conversely,B. infantisATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. Mass spectrometry-based profiling revealed thatB. infantisconsumed 73% of neutral and 92% of sialylatedN-glycans, whileB. lactisdegraded only 11% of neutral and virtually no (<1%) sialylatedN-glycans. These results provide mechanistic support thatN-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. Moreover, releasedN-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. Finally, the variety ofN-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides.IMPORTANCEIt has been previously shown that glycoproteins serve as growth substrates for bifidobacteria. However, which part of a glycoprotein (glycans or polypeptides) is responsible for this function was not known. In this study, we used a novel enzyme to cleave conjugatedN-glycans from milk glycoproteins and tested their consumption by various bifidobacteria. The results showed that the glycans selectively stimulated the growth ofB. infantis, which is a key infant gut microbe. The selectivity of consumption of individualN-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip–quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal thatB. infantiscan consume the range of glycan structures released from whey protein concentrate.

scholarly journals Human Milk Oligosaccharides Influence Neonatal Mucosal and Systemic Immunity

2016 ◽  
Vol 69 (Suppl. 2) ◽  
pp. 41-51 ◽  
Author(s):  
Sharon M. Donovan ◽  
Sarah S. Comstock
Keyword(s):  
Human Milk ◽  
Infant Formula ◽  
Bovine Milk ◽  
Complex Mixture ◽  
Structural Diversity ◽  
Host Cells ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Immune Development ◽  
Breastfed Infants

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.

scholarly journals Activation of the G-protein coupled receptor GPR35 by human milk oligosaccharides through different pathways

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Francis Foata ◽  
Norbert Sprenger ◽  
Florence Rochat ◽  
Sami Damak
Keyword(s):  
Human Milk ◽  
G Protein ◽  
Bovine Milk ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Gpcr Activation ◽  
Host Microbe Interactions ◽  
Receptor Assays ◽  
G Protein Coupled

Abstract Numerous benefits of breastfeeding over infant formula are fully established. The superiority of human milk over bovine milk-based formula is partly due to human milk oligosaccharides (HMOs), a family of over 100 molecules present specifically and substantially in human milk that resemble mucosal glycans. To uncover novel physiological functions and pathways of HMOs, we screened a panel of 165 G-protein coupled receptors (GPCRs) using a blend of 6 HMOs (3′-O-sialyllactose (3′SL), 6′-O-sialyllactose (6′SL), lacto-N-tetraose (LNT), lacto-N-neo-tetraose (LNnT), 2-O-fucosyllactose (2′FL), and difucosyllactose (diFL)), and followed up positive hits with standard receptor assays. The HMO blend specifically activated GPR35. LNT and 6′SL individually activated GPR35, and they showed synergy when used together. In addition, in vitro fermentation of infant stool samples showed that 2′FL upregulates the production of the GPR35 agonist kynurenic acid (KYNA) by the microbiota. LNT + 6′SL and KYNA showed additive activation of GPR35. Activation by 6′SL and LNT of GPR35, a receptor mediating attenuation of pain and colitis, is to our knowledge the first demonstration of GPCR activation by any HMO. In addition, we demonstrated a remarkable cooperation between nutrition and microbiota towards activation of a host receptor highlighting the close interplay between environment and host-microbe interactions.

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