Hanne Frokiaer

Hanne Frokiaer
University of Copenhagen · Faculty of Life Sciences

About

133
Publications
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Publications

Publications (133)
Article
The immunomodulatory potential of probiotics and (poly)phenols (PP) is recognized; however, studies regarding microorganisms-PP synergisms are yet to be explored. Here, we investigated the cooperation between probiotics and berry-derived PP extracts in modulating the cytokine responses in dendritic cells. Bacteria elicited immune responses in a str...
Article
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Methicillin resistant Staphylococcus aureus (MRSA) has developed resistance to most β-lactam antibiotics leaving few treatment options against infections with MRSA. Through mannose receptors, mannan potentiates IL-12 production induced by Gram-positive bacteria, a cytokine crucial in the clearance of S. aureus infection. We investigated the IL-12 p...
Article
Methicillin resistant Staphylococcus aureus (MRSA) constitute a serious health care problem worldwide. This study addresses the effect of β-lactam treatment on the ability of clinically relevant MRSA strains to induce IL-12 and IL-23. MRSA strains induced a dose-dependent IL-12 response in murine bone-marrow-derived dendritic cells that was depende...
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Some oligosaccharides induce growth of anti-inflammatory bacterial species and induce regulatory immunity in humans as well as animals. We have shown that the equine gut microbiota and the immune-microbial homeostasis largely stabilize within the first 50 days of life. Furthermore, we have previously established that certain bacterial species in th...
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Diet is an important component in weight management strategies, but heterogeneous responses to the same diet make it difficult to foresee individual weight-loss outcomes. Omics-based technologies now allow for analysis of multiple factors for weight loss prediction at the individual level. Here, we classify weight loss responders (N = 106) and non-...
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Elevated postprandial plasma glucose is a risk factor for development of type 2 diabetes and cardiovascular disease. We hypothesized that the inter-individual postprandial plasma glucose response varies partly depending on the intestinal microbiome composition and function. We analyzed data from Danish adults (n = 106), who were self-reported healt...
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This study examines different factors influencing the 13-valent pneumococcal conjugate vaccine (PCV13) specific antibody response in 8–13 months old Danish children starting in day care. We present secondary findings to the ProbiComp study, which included nose swabs, buccal swabs and blood samples from the children before entering day care (baselin...
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The mannose receptor (MR) is a C-type lectin involved in endocytosis and with a poorly defined ability to modulate cellular activation. We investigated the effect of mannan treatment prior to stimulation of murine bone marrow-derived dendritic cells with the Gram-positive bacteria Lactobacillus acidophilus NCFM (L. acidophilus) on the induction of...
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Shortly after birth the mammalian gut is colonized, by a transient microbiota, highly susceptible to environment and diet, that eventually stabilizes and becomes the resident gut microbiota. In a window of opportunity during the colonization, oral tolerance is established towards resident bacteria. In this study, the development of the equine gut m...
Article
Aim: The aim was to examine associations between thymus size and anthropometric measurements, sex, age, breastfeeding status, presence of siblings, household pets, and infections and allergies since birth in 8-13-month-old healthy Danish infants. Methods: Data collected from 256 healthy infants enrolled in the ProbiComp study were used. Thymus s...
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Billions of bacteria inhabit the gastrointestinal tract. Immune-microbial cross talk is responsible for immunological homeostasis, and symbiotic microbial species induce regulatory immunity, which helps to control the inflammation levels. In this study we aimed to identify species within the equine intestinal microbiota with the potential to induce...
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Purpose: We explored the effect of winter cholecalciferol (vitamin D3) supplementation on innate immune markers in healthy Danish children (55°N). Methods: In the double-blind, placebo-controlled trial, ODIN Junior, 119 healthy, white, 4-8 year-olds were randomized to 0 (placebo), 10 or 20 µg/day of vitamin D3for 20 weeks (October-March). Cheek...
Article
Objective: Children with severe acute malnutrition (SAM) may have impaired intestinal function which can result in malabsorption, diarrhoea and poor growth. This study evaluated the gut function of children with SAM using fecal and blood biomarkers and assessed their correlates. Methods: A cross-sectional study, nested in a randomized trial (htt...
Article
We compared 6 frequently used mouse blood-sampling methods (lateral tail incision; tail-tip amputation; sublingual, submandibular, and saphenous vein puncture; and retrobulbar sinus puncture during isoflurane anesthesia) with regard to induction of local and systemic inflammation, stomach contents, weight changes, and corticosterone levels at 6 h t...
Article
Beneficial microbes may positively affect host physiology at various levels, e.g., by participating in immune system maturation and modulation, boosting defenses and dampening reactions, thus affecting the whole homeostasis. As a consequence, the use of probiotics is increasingly regarded as suitable for more extended applications for health mainte...
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Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders...
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Intergenerational transmission of bacteria during birth initiates the natural successional development of the intestinal microbiota in mammals. This process can be disrupted by antibiotic exposure, potentially affecting early-life microbiota-dependent metabolic programming. In the present study, we specifically investigate the metabolic consequence...
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Previous studies demonstrated that oral antibiotic (ABX) treatment prior to and during influenza A virus (IAV) infection of adult mice profoundly altered gut microbiota (GM) and was associated with increased susceptibility and impaired immunity to IAV. We examined the impact of ABX during critical times relevant to the establishment of GM in early...
Article
Scope This study addressed whether administration of Lactobacillus rhamnosus HN001 could mitigate the effects of a compromised gut microbiota on the composition of mature leukocytes and granulocyte‐macrophage progenitor cells (GMPs) in newborn mice. Methods and results Pregnant dams received oral broad‐spectrum antibiotics, which dramatically decr...
Article
Objectives: To examine the effect of a combination of probiotics on the antibody response to pneumococcal and pertussis vaccination in Danish healthy children, aged 8-14 months, at the time of starting day care. Moreover, the cytokine response to LPS of whole blood was assessed. Methods: A total of 290 children were randomly allocated to receive...
Article
Background: Low serum 25-hydroxyvitamin D [25(OH)D] has been associated with unfavorable cardiometabolic risk profiles in many observational studies in children, but very few randomized controlled trials have investigated this. Objective: We explored the effect of winter-time cholecalciferol (vitamin D3) supplementation on cardiometabolic risk m...
Article
Background: Low-grade systemic inflammation (LGSI) is often characterized by elevated levels of interleukin (IL)6, tumor necrosis factor (TNF)α, and C-reactive protein (CRP). Other serum proteins, ex vivo-stimulated cytokine production, and leukocyte count have, however, also been suggested LGSI-markers, but their associations with the metabolic s...
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Faecalibacterium prausnitzii is a highly abundant human gut microbe in healthy individuals, but it is present at reduced levels in individuals with gastrointestinal inflammatory diseases. It has therefore been suggested to constitute a marker of a healthy gut and is associated with anti-inflammatory properties. However, factors affecting the coloni...
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Objective To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain d...
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Preterm neonates are highly sensitive to systemic infections in early life but little is known about systemic immune development following preterm birth. We hypothesized that preterm neonates have immature systemic immunity with distinct developmental trajectory for the first several weeks of life, relative to those born at near-term or term. Using...
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Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate from another much used mouse strain, C57BL/6, with res...
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Immature immunity may predispose preterm neonates to infections and necrotizing enterocolitis (NEC). Intravenous antibiotics are frequently given to prevent and treat sepsis while oral antibiotics are seldom used. We hypothesized that oral antibiotics promote maturation of systemic immunity and delay gut bacterial colonization and thereby protect p...
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A high energy supply and appropriate amount of polyunsaturated fatty acids is crucial for proper growth and development in neonates. The capacity for fatty acid absorption in newborns is however hampered due to an undeveloped pancreatic function combined with a low bile output. This seems in particular to limit fatty acid absorption in babies given...
Data
: Perinatal CD11b+Gr-1+ spleen cells comprise three distinct subpopulations differing in size and brightness of markers CD11b and Gr-1.
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To assess the microbial influence on postnatal hematopoiesis, we examined the role of early life microbial colonization on the composition of leukocyte subsets in the neonatal spleen. A high number of CD11b+Gr-1+ splenocytes present perinatally was sustained for a longer period in conventionally colonized (CONV) mice than in mono-colonized (MC) and...
Article
In large clinical trials, where RNA cannot be extracted immediately after sampling, preserving RNA in whole blood is a crucial initial step in obtaining robust qPCR data. The current golden standard for RNA preservation is costly and designed for time-consuming column-based RNA-extraction. We investigated the use of lysis buffer for long-term stora...
Chapter
Composed of nearly a thousand different types of micro-organisms, some beneficial, others not, the human gut microbiota plays an important role in health and disease. This is due to the presence of probiotic or beneficial microbes, or due to the feeding of prebiotics that stimulate the endogenous beneficial microbes: these promote health by stimula...
Article
We investigated whether n-3LCPUFA affected immune function in late infancy and explored effect-modification by single nucleotide polymorphisms (SNPs) and links to intestinal microbiota. Infants (n=105) were randomized to fish oil (FO, 1.2 g/d n-3LCPUFA) or sunflower oil (SO)-supplements from age 9–18 months. Immune function was assessed by ex vivo...
Article
Scope: The relationship between the immune modulatory properties of different mixed linkage beta-glucans from plant and microbial origin and their physico-chemical properties is elusive. By the use of murine dendritic cells and multivariate data analysis, this study examines the importance of the physico-chemical characteristics of beta-glucans for...
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Early life interventions in the intestinal environment have previously been shown to influence diabetes incidence. We therefore hypothesized that a gluten-free (GF) diet, known to decrease type 1 diabetes incidence, only during pregnancy and lactation period would protect against development of diabetes. Pregnant non-obese diabetic (NOD) mice were...
Data
Top 20 induced genes by H. pylori 251 in murine BMDMs.
Data
Addition of VacA-containing supernatant abrogates induction of IFN-β. (A) BMDMs were stimulated with L. acidophilus NCFM, H. pylori 251, or supernatant (SN) from H. pylori 251 (1:10, 1:20, and 1:30 diluted) alone or with L. acidophilus NCFM for 1 h prior to addition of H. pylori 251 or supernatant from H. pylori 251 (1:10, 1:20, and 1:30 diluted)....
Data
Heat map of BMDMs stimulated with L. acidophilus and H. pylori. Murine BMDMs from three individual mice were stimulated for 5 h with either L. acidophilus NCFM or H. pylori 251 or prestimulated with L. acidophilus NCFM for 1 h prior to the addition of Helicobacter pylori 251. Heat map of differentially expressed genes (P < 0.01; fold change greater...
Data
Full-text available
Top 20 induced genes by L. acidophilus NCFM in murine BMDMs.
Data
Addition of H. pylori to L. acidophilus-stimulated BMDMs downregulates the expression of Cxcl10 and Tnf-α but upregulates IL-1β. BMDMs were stimulated with either L. acidophilus NCFM or H. pylori 251 alone or with L. acidophilus NCFM for 1 h prior to addition of H. pylori 251. RNA was extracted after 4 h, cDNA was synthesized, and the expression of...
Article
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Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been suggested to exert beneficial effects as a supplement during H. pylori eradication therapy. In the present study, we applied whole-genome microarray analysis to compare the immune...
Article
Dietary carbohydrates improve growth conditions for distinct populations of bacteria that may affect mucosal and systemic immunity. In this study, we fed in a parallel experiment a 10% xylooligosaccharide (XOS)-supplemented diet or a control diet to 2 groups of male C57BL/6NTac mice for 10 wk from weaning. We found that the XOS diet significantly i...
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Postnatal regulation of the small intestinal mucus layer is potentially important in the development of adult gut functionality. We hypothesized that the nature of bacterial colonization affects mucus gene regulation in early life.We thus analyzed the influence of the presence of a conventional microbiota as well as two selected monocolonizing bact...
Article
To describe biomarkers of inflammation and markers related to the metabolic syndrome (MS) in healthy obese Danish adolescent and compare to a normal-weight group. Fifty-one obese and 30 normal-weight adolescents (12-15 years) were included. Anthropometry and blood pressure were measured, and blood was sampled. Obese adolescents had significantly hi...
Article
To improve our understanding of the interaction of food allergens with cells of the immune system, the endocytosis by human monocytes of bovine β-lactoglobulin (BLG) and ovomucoid (OM)--two major food allergens--and human serum albumin (HSA) was studied. BLG was covalently conjugated to dextran-coated magnetic nanoparticles (MNPs) without affecting...
Article
Bovine β-casein and its C-terminal sequence (191–209) were previously shown to possess immunomodulatory properties in studies on partially purified peptides from hydrolysates, where minor amounts of contaminants may affect the cellular response. The inhibitory effect of β-casein and of eight C-terminus synthetic β-casein peptides on mitogen-induced...
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Intricate regulation of tolerance to the intestinal commensal microbiota acquired at birth is critical. We hypothesized that epithelial cell tolerance toward early gram-positive and gram-negative colonizing bacteria is established immediately after birth, as has previously been shown for endotoxin. Gene expression in the intestine of mouse pups bor...
Article
The health promoting effects of probiotics are well-documented; however, current knowledge on immunostimulatory effects is based on data from a single strain or a limited selection of strains or species. Here, we compared the capacity of 27 lactobacilli and 16 bifidobacteria strains to stimulate bone marrow-derived dendritic cells (DC). Most lactob...
Article
Structural-based recognition of foreign molecules is essential for activation of dendritic cells (DCs) that play a key role in regulation of gut mucosal immunity. Orally ingested non-starch polysaccharides (NSP) are ascribed many health-promoting properties, but currently we lack insight into the impact of structure and size for their capacity to a...
Article
Dietary levels of n-3 PUFA are believed to influence the immune system. The importance of the source of n-3 PUFA is debated. This study addressed how the content and source of n-3 PUFA in the maternal diet influenced tissue FA composition and the immune response to ovalbumin (OVA) in mice pups. From the day of conception and throughout lactation, d...
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Milk contains immunomodulatory compounds that may be important to protect the immature intestine in preterm neonates from harmful inflammatory reactions involved in disorders like necrotising enterocolitis (NEC). We hypothesised that bovine colostrum and milk formulas enriched with sialic acids (SL), gangliosides (Gang) or osteopontin (OPN) would i...
Article
Lactobacilli are probiotics that, among other health-promoting effects, have been ascribed immunostimulating and virus-preventive properties. Certain Lactobacillus spp. have been shown to possess strong interleukin-12 (IL-12) -inducing properties. As IL-12 production depends on the up-regulation of type I interferons (IFNs), we hypothesized that th...