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  • 1. Candy, David C. A.
    et al.
    Van Ampting, Marleen T. J.
    Nijhuis, Manon M. Oude
    Wopereis, Harm
    Butt, Assad M.
    Peroni, Diego G.
    Vandenplas, Yvan
    Fox, Adam T.
    Shah, Neil
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Garssen, Johan
    Harthoorn, Lucien F.
    Knol, Jan
    Michaelis, Louise J.
    A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants2018In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 83, no 3, p. 677-686Article in journal (Refereed)
    Abstract [en]

    Background: Prebiotics and probiotics (synbiotics) can modify gut microbiota and have potential in allergy management when combined with amino-acid-based formula (AAF) for infants with cow’s milk allergy (CMA).

    Methods: This multicenter, double-blind, randomized controlled trial investigated the effects of an AAF-including synbiotic blend on percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) in feces from infants with suspected non-IgE-mediated CMA. Feces from age-matched healthy breastfed infants were used as reference (healthy breastfed reference (HBR)) for primary outcomes. The CMA subjects were randomized and received test or control formula for 8 weeks. Test formula was a hypoallergenic, nutritionally complete AAF including a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V. Control formula was AAF without synbiotics.

    Results: A total of 35 (test) and 36 (control) subjects were randomized; HBR included 51 infants. At week 8, the median percentage of bifidobacteria was higher in the test group than in the control group (35.4% vs. 9.7%, respectively; P<0.001), whereas ER/CC was lower (9.5% vs. 24.2%, respectively; P<0.001). HBR levels of bifidobacteria and ER/CC were 55% and 6.5%, respectively.

    Conclusion: AAF including specific synbiotics, which results in levels of bifidobacteria and ER/CC approximating levels in the HBR group, improves the fecal microbiota of infants with suspected non-IgE-mediated CMA.

  • 2.
    Chorell, Elin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Karlsson, Frida
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The impact of feeding Lactobacillus F19 during weaning: a study of the plasma metabolomeManuscript (preprint) (Other academic)
  • 3.
    Chorell, Elin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Videhult, Frida Karlsson
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    West, Christina E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Impact of probiotic feeding during weaning on the serum lipid profile and plasma metabolome in infants2013In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 110, no 1, p. 116-126Article in journal (Refereed)
    Abstract [en]

    The gut microbiome interacts with the host in the metabolic response to diet, and early microbial aberrancies may be linked to the development of obesity and metabolic disorders later in life. Probiotics have been proposed to affect metabolic programming and blood lipid levels, although studies are lacking in infants. Here, we report on the lipid profile and global metabolic response following daily feeding of probiotics during weaning. A total of 179 healthy, term infants were randomised to daily intake of cereals with (n 89) or without (n 90) the addition of Lactobacillus paracasei ssp. paracasei F19 (LF19) 108 colony-forming units per serving from 4 to 13 months of age. Weight, length and skinfold thickness were monitored. Venous blood was drawn at 5·5 and 13 months of age for analysis of the serum lipid profile. In a subsample, randomly selected from each group, GC-time-of-flight/MS was used to metabolically characterise plasma samples from thirty-seven infants. A combination of multi- and univariate analysis was applied to reveal differences related to LF19 treatment based on 228 putative metabolites, of which ninety-nine were identified or classified. We observed no effects of probiotic feeding on anthropometrics or the serum lipid profile. However, we detected significantly lower levels of palmitoleic acid (16 : 1) (P < 0·05) and significantly higher levels of putrescine (P < 0·01) in LF19-treated infants. Palmitoleic acid is a major MUFA strongly linked to visceral obesity, while putrescine is a polyamine with importance for gut integrity. Whether the observed differences will have long-term health consequences are being followed.

  • 4.
    Domellöf, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Processed infant cereals as vehicles of functional components.2007In: Nestle Nutr Workshop Ser Pediatr Program., Vol. 60, p. 107-21Article in journal (Other academic)
    Abstract [en]

    Cereals are the most common complementary foods all over the world and there is now a novel possibility to add functional components to target health problems that are not caused by a simple nutritional deficiency. So far there have been very few published trials on the addition of functional components to infant cereals. A single trial has suggested that infant cereals containing a combination of probiotics, prebiotics and zinc are an effective adjunct to oral rehydration solution in the treatment of acute gastroenteritis. Up to now there has been no evidence that infant cereals supplemented with probiotics or prebiotics have a preventive effect on diarrhea but a recent study has suggested that a milk fat globule membrane (MFGM) protein fraction added to an infant cereal reduces the risk of diarrhea in a developing country. There are some promising results suggesting that infant cereals supplemented with probiotics or prebiotics may prevent atopic eczema. The addition of prebiotic oligosaccharides to infant cereals may lead to softer stools, likely to benefit those infants who are suffering from constipation. More studies are needed to verify these results and to assess the effects of other functional components - especially probiotics, prebiotics, nucleotides, novel protein fractions and recombinant human milk proteins - added to infant cereals.

  • 5. Dunstan, JA
    et al.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. School of Paediatrics and Child Health, Centre for Child Health Research, University of Western Australia, Perth .
    McCarthy, S
    Metcalfe, J
    Meldrum, S
    Oddy, WH
    Tulic, MK
    D'Vaz, N
    Prescott, SL
    The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood2012In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 67, no 1, p. 50-57Article in journal (Refereed)
    Abstract [en]

    Background: Dietary changes may epigenetically modify fetal gene expression during critical periods of development to potentially influence disease susceptibility. This study examined whether maternal and/or fetal folate status in pregnancy is associated with infant allergic outcomes.

    Methods: Pregnant women (n = 628) were recruited in the last trimester of pregnancy. Folate status determined by both food frequency questionnaires and folate levels in maternal and cord blood serum was examined in relation to infant allergic outcomes at 1 year of age (n = 484).

    Results: Infants who developed allergic disease (namely eczema) did not show any differences in cord blood or maternal folate levels compared with children without disease. Although maternal folate intake from foods was also not different, folate derived from supplements was higher (= 0.017) in children with subsequent eczema. Furthermore, infants exposed to >500 μg folic acid/day as a supplement in utero were more likely to develop eczema than those taking <200 μg/day (OR [odds ratio] = 1.85; 95% CI 1.14–3.02;= 0.013), remaining significant after adjustment for maternal allergy and other confounders. There was a nonlinear relationship between cord blood folate and sensitization, with folate levels <50 nmol/l (OR = 3.02; 95% CI 1.16–7.87; = 0.024) and >75 nmol/l (OR = 3.59; 95% CI 1.40–9.20; = 0.008) associated with greater sensitization risk than levels between 50 and 75 nmol/l.

    Conclusion: Fetal levels between 50 and 75 nmol/l appeared optimal for minimizing sensitization. While folate taken as a supplement in higher doses during the third trimester was associated with eczema, there was no effect on other allergic outcomes including sensitization. Further studies are needed to determine the significance of this.

  • 6. Forsberg, A.
    et al.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. International Inflammation (in-FLAME) network of the World Universities Network, Umeå, Sweden.
    Prescott, S. L.
    Jenmalm, M. C.
    Pre- and probiotics for allergy prevention: time to revisit recommendations?2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 12, p. 1506-1521Article, review/survey (Refereed)
    Abstract [en]

    Reduced intensity and diversity of microbial exposure is considered a major factor driving abnormal postnatal immune maturation and increasing allergy prevalence, particularly in more affluent regions. Quantitatively, the largest important source of early immunemicrobial interaction, the gut microbiota, is of particular interest in this context, with variations in composition and diversity in the first months of life associated with subsequent allergy development. Attempting to restore the health consequences of the ` dysbiotic drift' in modern society, interventions modulating gut microbiota for allergy prevention have been evaluated in several randomized placebo-controlled trials. In this review, we provide an overview of these trials and discuss recommendations from international expert bodies regarding prebiotic, probiotic and synbiotic interventions. Recent guidelines from the World Allergy Organization recommend the use of probiotics for the primary prevention of eczema in pregnant and breastfeeding mothers of infants at high risk for developing allergy and in high-risk infants. It is however stressed that these recommendations are conditional, based on very low-quality evidence and great heterogeneity between studies, which also impedes specific and practical advice to consumers on the most effective regimens. We discuss how the choice of probiotic strains, timing and duration of administration can critically influence the outcome due to different effects on immune modulation and gut microbiota composition. Furthermore, we propose strategies to potentially improve allergy-preventive effects and enable future evidence-based implementation.

  • 7. Fox, A. T.
    et al.
    Wopereis, H.
    Van Ampting, M. T.
    Oude, Nijhuis M. M.
    Butt, A. M.
    Peroni, D. G.
    Vandenplas, Y.
    Candy, Dc
    Shah, N.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Garssen, J.
    Harhoorn, L. F.
    Knol, J.
    Michaelis, L. J.
    Amino acid-based formula including specific synbiotics modifies the gut microbiota and reduces clinical symptoms in non-IgE mediated cow's milk allergic infants2017In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 72, p. 102-103Article in journal (Other academic)
  • 8. Fox, A.
    et al.
    van Ampting, M.
    Nijhuis, M. O.
    Wopereis, H.
    Butt, A.
    Peroni, D.
    Vandenplas, Y.
    Candy, D.
    Shah, N.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Garssen, J.
    Knol, J.
    Harthoorn, L.
    Michaelis, L.
    Acid-based formula with synbiotics modifies gut microbiota in non-ige mediated cow's milk allergic infants2017In: Internal medicine journal (Print), ISSN 1444-0903, E-ISSN 1445-5994, Vol. 47, p. 15-15Article in journal (Other academic)
  • 9. Fox, Adam T.
    et al.
    Wopereis, Harm
    Van Ampting, Marleen T. J.
    Nijhuis, Manon M. Oude
    Butt, Assad M.
    Peroni, Diego G.
    Vandenplas, Yvan
    Candy, David C. A.
    Shah, Neil
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Garssen, Johan
    Harthoorn, Lucien F.
    Knol, Jan
    Michaelis, Louise J.
    Smets, Francoise
    Mullier, Sandra
    Noimark, Lee
    Muraro, Antonella
    A specific synbiotic-containing amino acid-based formula in dietary management of cow's milk allergy: a randomized controlled trial2019In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 9, article id 5Article in journal (Refereed)
    Abstract [en]

    Background: Here we report follow-up data from a double-blind, randomized, controlled multicenter trial, which investigated fecal microbiota changes with a new amino acid-based formula (AAF) including synbiotics in infants with non-immunoglobulin E (IgE)-mediated cow’s milk allergy (CMA).

    Methods: Subjects were randomized to receive test product (AAF including fructo-oligosaccharides and Bifidobacterium breve M-16V) or control product (AAF) for 8 weeks, after which infants could continue study product until 26 weeks. Fecal percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoidesgroup (ER/CC) were assessed at 0, 8, 12, and 26 weeks. Additional endpoints included stool markers of gut immune status, clinical symptoms, and safety assessments including adverse events and medication use.

    Results: The trial included 35 test subjects, 36 controls, and 51 in the healthy reference group. Study product was continued by 86% and 92% of test and control subjects between week 8–12, and by 71% and 80%, respectively until week 26. At week 26 median percentages of bifidobacteria were significantly higher in test than control [47.0% vs. 11.8% (p < 0.001)], whereas percentages of ER/CC were significantly lower [(13.7% vs. 23.6% (p = 0.003)]. Safety parameters were similar between groups. Interestingly use of dermatological medication and reported ear infections were lower in test versus control, p = 0.019 and 0.011, respectively. Baseline clinical symptoms and stool markers were mild (but persistent) and low, respectively. Symptoms reduced towards lowest score in both groups.

    Conclusion: Beneficial effects of this AAF including specific synbiotics on microbiota composition were observed over 26 weeks, and shown suitable for dietary management of infants with non-IgE-mediated CMA.

  • 10. Gustafsson, Anna
    et al.
    Granström, Elisabeth
    Umeå University, Faculty of Medicine, Department of Odontology.
    Stecksén-Blicks, Christina
    Umeå University, Faculty of Medicine, Department of Odontology.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The antisecretory factor in plasma and breast milk in breastfeeding mothers: a prospective cohort study in Sweden2018In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, no 9, article id 1227Article in journal (Refereed)
    Abstract [en]

    Inflammation and infection postpartum threaten the mother and her infant. Human milk provides a defense for the infant, but inflammatory complications like mastitis may lead to the cessation of breastfeeding. Antisecretory factor (AF) has a role in the regulation of secretory processes and inflammation. The objective of the study was to describe AF-levels in plasma and breast milk, and in relation to breast complications. Breastfeeding mothers (n = 95) were consecutively recruited at a Well Baby Clinic in Umeå, Sweden. At inclusion four weeks postpartum, samples of venous blood (10 mL) and breast milk (10 mL) were collected. Active AF was analyzed with ELISA using a monoclonal antibody mAb43, and was detected in all samples of plasma and breast milk with a positive correlation (Spearman coefficient = 0.40, p < 0.001; Pearson correlation = 0.34, p < 0.01). High AF-levels in plasma correlated with high AF-levels in breast milk. The results suggest a co-regulation between active AF in plasma and breastmilk, and/or a local regulation of AF in the breast. Further studies are needed to determine the pathways for the activation of AF-levels in breast milk and plasma.

  • 11.
    Hasslöf, Pamela
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Karlsson Videhult, Frida
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Silfverdal, Sven Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stecksén-Blicks, Christina
    Umeå University, Faculty of Medicine, Department of Odontology.
    Vitamin D Insufficiency among Women Post-Partum in Northern Sweden: A Public Health Concern2017In: Food and Nutrition Sciences, ISSN 2157-944X, E-ISSN 2157-9458, no 8, p. 99-109Article in journal (Refereed)
    Abstract [en]

    Pregnancy and post-partum represent a period of susceptibility for vitamin D insufficiency. This study investigated S-25 [OH] D levels in women in northern Sweden 4 weeks post-partum and its association with selected background factors. Blood from 100 healthy women were analyzed for iron status and serum levels of S-25[OH] D using ionization-mass spectrometry (HPLC-APCI-MS). <50 nmol/L was categorized as insufficiency and <25 nmol/L as deficiency. Maternal BMI, dietary habits, fungal infections during pregnancy, and infant birth characteristics were collected using questionnaires and medical charts. 58% were vitamin D insufficient whereas 10% had deficiency. Insufficiency was most common during winter (OR = 2.77; 95% CI = 1.1-6.96) and women with deficiency reported lower milk consumption; 11.3 ± 22.8 intakes per months vs. 34.0 ± 28.9 for those above 25 nmol/L (p < 0.05). Vitamin D-insufficient women had lower serum ferritin levels (p < 0.01) and higher serum transferrin levels (p < 0.05). A history of vaginal fungal infection during pregnancy was associated with insufficiency (OR = 5.10; 95% CI = 1.01-25.73), however, the confidence interval of the estimate was wide, resulting in uncertainty. It is concluded that vitamin D insufficiency 4 weeks post-partum was common in women living at 63°49'N. The odds of being insufficient were increased during winter whereas milk consumption was negatively associated with deficiency. The low vitamin D-levels particularly during winter is a public health concern. From a public health perspective it has to be considered whether dietary advices alone should be modified or if supplementation with vitamin D during pregnancy and the post-partum period also is needed.

  • 12.
    Hasslöf, Pamela
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Karlsson Videhult, Frida
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Brandelius, Charlotte
    Umeå University, Faculty of Medicine, Department of Odontology.
    Stecksén-Blicks, Christina
    Umeå University, Faculty of Medicine, Department of Odontology.
    Early intervention with probiotic Lactobacillus paracasei F19 has no long-term effect on caries experience2013In: Caries Research, ISSN 0008-6568, E-ISSN 1421-976X, Vol. 47, no 6, p. 559-565Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to evaluate possible long-term effects of a cereal diet supplemented with Lactobacillus paracasei F19 (LF19) during weaning on caries experience, mutans streptococci (MS) and lactobacilli (LBC) in a group of 9-year-old children. A secondary aim was to evaluate if the intervention resulted in the permanent integration of LF19 as part of the oral microbiota. The study followed up on a double-blind placebo-controlled randomised trial. Among 179 infants that were randomised to a daily diet that included cereals with or without LF19 from 4 to 13 months of age, 56 from the probiotic group and 62 from the placebo group participated in the follow-up at 9 years. Data were collected by oral clinical examination and questionnaires. MS and LBC levels were assessed with conventional cultivation; LF19 was detected by using randomly amplified polymerase chain reactions (RAPD-PCR). At the follow-up, neither decayed, missing and filled surfaces for primary teeth (dmfs) nor decayed, missing and filled surfaces for permanent teeth (DMFS) differed significantly between the probiotic and placebo groups (p > 0.05). MS and LBC levels were similar in both groups (p > 0.05). RAPD-PCR showed no evidence of oral colonisation with LF19 in the study group. It is concluded that an early intervention with LF19 did not affect the frequency of dental caries, MS or LBC. LF19 did not establish itself as a permanent facet of the oral microbiota in any of the subjects included in this study.

  • 13.
    Hernell, Olle
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Do we need personalized recommendations for infants at risk of developing disease?2008In: Nestle Nutr Workshop Ser Pediatr Program, ISSN 1661-6677, Vol. 62, p. 239-52Article in journal (Other academic)
  • 14.
    Hernell, Olle
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Clinical effects of probiotics: scientific evidence from a paediatric perspective2013In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 109, no Suppplement 2, p. S70-S75Article in journal (Refereed)
    Abstract [en]

    Probiotics are live micro-organisms that when given in adequate amounts can cause health benefits. The safety and efficacy of probiotics in the prevention and treatment of various clinical conditions have been evaluated in randomised controlled clinical trials, systematic reviews and meta-analyses. Generally, their safety has been documented. As a supplement to standard rehydration therapy, probiotics have been demonstrated to shorten the duration of diarrhoea resulting from acute viral gastroenteritis and in preventing antibiotic-associated diarrhoea in healthy children. Preliminary evidence suggests that probiotics might prevent necrotising enterocolitis in very-low-birth-weight infants, but further studies are needed before definite conclusions can be drawn. Probiotics have also been assessed in the treatment and prevention of allergic disease but the results, although promising, need further confirmation. Targeting a paediatric population, probiotics have been evaluated in the treatment of irritable bowel syndrome, ulcerative colitis, Helicobacter pylori gastritis and infantile colic, but at this stage, there is no evidence to support their routine use for these indications. There is a great need for studies aiming at disentangling the mechanisms by which probiotics mediate their clinical effects and for comparative studies between various probiotic bacteria. We still need to know which probiotic(s) to use and for which indications. A clearer message on dosages, optimal timing and duration of administration is needed. For this purpose, more carefully designed and sufficiently powered, randomised controlled trials with predefined outcomes are needed.

  • 15.
    Karlsson Videhult, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Yvonne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Impact of probiotics during weaning on the metabolic and inflammatory profile: follow-up at school age2015In: International Journal of Food Sciences and Nutrition, ISSN 0963-7486, E-ISSN 1465-3478, Vol. 66, no 6, p. 686-691Article in journal (Refereed)
    Abstract [en]

    We hypothesised that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) (dep. nr LMG P-17806) during weaning would program the metabolic and inflammatory profile and studied its association with previously assessed body composition. In a double-blind, placebo-controlled trial, 179 infants were randomised to daily feeding of cereals with or without LF19 10 8 CFU from 4 to 13 months of age. At age 8-9 years, 120 children were reassessed. Using high-sensitivity multiplex immunoassay technology and ELISA, we found that overweight/obese children had increased plasma C-peptide, plasminogen activator inhibitor-1, leptin and serum high-sensitivity C-reactive protein (hsCRP) after overnight fasting compared with normal weight children, independently of LF19. After excluding the obese, leptin and hsCRP were still increased, revealing an aberrant metabolic and inflammatory state already in overweight, pre-pubertal children. Higher body mass index z-score, sagittal abdominal diameter, truncal and total body fat % were associated with an aberrant metabolic and inflammatory profile, emphasising the need for early prevention strategies although no programming effect of LF19 was observed.

  • 16.
    Karlsson Videhult, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nutrition, gut microbiota and child health outcomes2016In: Current opinion in clinical nutrition and metabolic care, ISSN 1363-1950, E-ISSN 1473-6519, Vol. 19, no 3, p. 208-213Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review Diet is one of the main drivers of the composition and function of the gut microbiota. The scope of this review is to summarize recent studies assessing the role of gut microbiota in clinical pediatric conditions and to review studies using nutritional approaches to favorably modify the gut microbiota to improve health outcomes in children. Recent findings New studies underscore that breastfeeding and infant diet impact the gut microbiome and metagenome. A comprehensive study using metagenomic shotgun sequencing, suggests that the cessation of breastfeeding rather than the introduction of solid foods, drives the functional maturation of the infant gut microbiome toward an adult-like state. There is further support for the view that a disturbed early gut microbiota is implicated in allergic and autoimmune diseases. New studies using prebiotics, probiotics, and synbiotics in various pediatric disorders have yielded promising results, yet the evidence for specific guidelines on their use is still low. Summary Intestinal dysbiosis is associated with several pediatric disorders but a cause-effect relationship remains to be clearly demonstrated in most conditions. Future studies using new systems biology approaches are anticipated to provide further insight into the functional capacities of the gut microbiome and its establishment in childhood. This may then lay the ground for improved treatment and prevention strategies targeting the gut microbiota.

  • 17.
    Karlsson Videhult, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Probiotics during weaning: a follow-up study on effects on body composition and metabolic markers at school age2015In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 54, no 3, p. 355-363Article in journal (Refereed)
    Abstract [en]

    PURPOSE: An aberrant gut microbiome has been suggested to contribute to the worldwide epidemic of obesity. In animal models, the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) induced upregulation of genes involved in energy homoeostasis, reduced body fat and altered the serum (S) lipoprotein profile. In our previous report, feeding LF19 to infants during weaning impacted the global plasma metabolome. LF19 lowered palmitoleic acid, a monounsaturated fatty acid associated with hypertriglyceridemia and increased visceral adiposity. Therefore, we assessed if feeding LF19 from 4 to 13 months of age would have long-term effects on body composition, growth and metabolic markers.

    METHODS: Of 179 children included in our baseline study, 120 entered the follow-up at 8-9 years of age, n = 58 in the probiotic and n = 62 in the placebo group. Body composition was measured using dual energy X-ray absorptiometry. Anthropometrics of the child and accompanying parent(s) were assessed. S-lipids, insulin, glucose and transaminases were determined after overnight fasting.

    RESULTS: LF19 did not affect body mass index z-score, sagittal abdominal diameter, fat-free mass, fat mass index, truncal fat %, android or gynoid fat % and had no long-term impact on any of the assessed metabolic markers (p > 0.05).

    CONCLUSION: Feeding LF19 during infancy did not modulate body composition, growth or any of the assessed metabolic markers at school age. The steady increase in probiotic products targeting infants and children calls for long-term follow-up of initiated probiotic intervention studies.

  • 18. Metcalfe, J. R.
    et al.
    D'Vaz, N.
    Makrides, M.
    Gold, M. S.
    Quinn, P.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. School of Paediatrics and Child Health, The University of Western Australia, Perth.
    Loh, R.
    Prescott, S. L.
    Palmer, D. J.
    Elevated IL-5 and IL-13 responses to egg proteins predate the introduction of egg in solid foods in infants with eczema2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 2, p. 308-316Article in journal (Refereed)
    Abstract [en]

    Background

    Egg allergy is a leading cause of food allergy in young infants; however, little is known about early allergen-specific T-cell responses which predate the presentation of egg allergy, and if these are altered by early egg exposure.

    Objective

    To investigate the early T-cell responses to multiple egg proteins in relation to patterns of egg exposure and subsequent IgE-mediated egg allergy.

    Methods

    Egg-specific T-cell cytokine responses (IL-5, IL-13, IL-10, IFNγ and TNFα) to ovomucoid (OM), ovalbumin (OVA), conalbumin (CON) and lysozyme (LYS) were measured in infants with eczema at 4 months of age (n = 40), before randomization to receive ‘early egg’ or a placebo as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry number 12609000415202) and at 12 months of age (n = 58), when IgE-mediated egg allergy was assessed by skin prick test and food challenge.

    Results

    In 4–month-old infants, who had not directly ingested egg, those who subsequently developed egg allergy already had significantly higher Th2 cytokine responses to multiple egg allergens, particularly elevated IL-13 responses to OVA (P = 0.004), OM (P = 0.012) and LYS (P = 0.003) and elevated IL-5 to the same antigens (P = 0.031, 0.04 and 0.003, respectively). IL-13 responses (to OVA and LYS) and IL-5 responses (to LYS) at 4 months significantly predicted egg allergy at 12 months. All responses significantly declined with age in the egg-allergic infants, and this did not appear to be modified by ‘early’ introduction of egg.

    Conclusions & Clinical Relevance

    Elevated egg-specific Th2 cytokine responses were established prior to egg ingestion at 4 months and were not significantly altered by introduction of egg. Th2 responses at 4 months of age predicted egg allergy at 12 months, suggesting that this could be used as a biomarker to select infants for early prevention and management strategies.

  • 19.
    Nordstrom, Lisbet
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Strinnholm, Åsa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nylander, Annica
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Jonsell, A.
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Rönnmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Validation of new recipes for double-blind placebo-controlled food challenges in children2012In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 67, no Suppl. 1, p. 371-371Article in journal (Other academic)
  • 20. Palmer, D. J.
    et al.
    Metcalfe, J.
    Makrides, M.
    Gold, M. S.
    Quinn, P.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Loh, R.
    Prescott, S. L.
    Early regular egg exposure in infants with eczema: a randomised controlled trial2013In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, no Special issue, supplement 97, p. 17-17Article in journal (Other academic)
  • 21. Palmer, Debra J.
    et al.
    Metcalfe, Jessica
    Makrides, Maria
    Gold, Michael S.
    Quinn, Patrick
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Loh, Richard
    Prescott, Susan L.
    Early regular egg exposure in infants with eczema: a randomized controlled trial2013In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 132, no 2, p. 387-392Article in journal (Refereed)
    Abstract [en]

    Background: Observational studies suggest that early regular ingestion of allergenic foods might reduce the risk of food allergy. Objective: We sought to determine whether early regular oral egg exposure will reduce subsequent IgE-mediated egg allergy in infants with moderate-to-severe eczema. Methods: In a double-blind, randomized controlled trial infants were allocated to 1 teaspoon of pasteurized raw whole egg powder (n = 49) or rice powder (n = 37) daily from 4 to 8 months of age. Cooked egg was introduced to both groups after an observed feed at 8 months. The primary outcome was IgE-mediated egg allergy at 12 months, as defined based on the results of an observed pasteurized raw egg challenge and skin prick tests. Results: A high proportion (31% [15/49]) of infants randomized to receive egg had an allergic reaction to the egg powder and did not continue powder ingestion. At 4 months of age, before any known egg ingestion, 36% (24/67) of infants already had eggspecific IgE levels of greater than 0.35 kilounits of antibody (kUA)/L. At 12 months, a lower (but not significant) proportion of infants in the egg group (33%) were given a diagnosis of IgE-mediated egg allergy compared with the control group (51%; relative risk, 0.65; 95% CI, 0.38-1.11; P 5.11). Egg-specific IgG4 levels were significantly (P <.001) greater in the egg group at both 8 and 12 months. Conclusion: Induction of immune tolerance pathways and reduction in egg allergy incidence can be achieved by early regular oral egg exposure in infants with eczema. Caution needs to be taken when these high-risk infants are first exposed to egg because many have sensitization already by 4 months of age.

  • 22.
    Persson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nordström, Lisbeth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Vitamin D deficiency at the Arctic Circle a study in food-allergic adolescents and controls2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 6, p. 644-649Article in journal (Refereed)
    Abstract [en]

    Aim At the extremes of latitude, UVB intensity is insufficient for adequate vitamin D synthesis in winter. Fatty fish, vitamin D enriched milk, margarine and eggs are main dietary sources of vitamin D. Their elimination may increase the risk of vitamin D deficiency. The aim was to assess vitamin D status in food-allergic adolescents eliminating milk, egg and/or fish compared with adolescents on normal diets. Methods In winter, vitamin D intake was assessed by a food frequency questionnaire in 20 food-allergic adolescents and 42 controls in the population-based Obstructive Lung Disease In Northern Sweden (OLIN) cohort studies. Vitamin D supplementation was queried. Serum 25-hydroxyvitamin D [S-25(OH)D] and S-parathormone (S-PTH) levels were determined. Results Mean (SD) dietary vitamin D intake was 7.9 (3.6) g/day in allergic adolescents and 7.8 (3.4) in controls (p>0.05). Mean (SD) S-25(OH)D levels in supplement consumers were 44 (18) nmol/L compared with 35 (10) in non-consumers (p=0.03). S-25(OH)D and S-PTH levels were similar in food-allergic adolescents and controls (p>0.05). Eighty-two percentage had deficient S-25(OH)D levels <50nmol/L, and none reached levels >75nmol/L. Conclusion Vitamin D deficiency was as common in food-allergic adolescents as in controls although the vitamin D intake met national recommendations. Large-scale studies on the prevalence of vitamin D deficiency in this region are needed.

  • 23. Prescott, Susan L.
    et al.
    Larcombe, Danica-Lea
    Logan, Alan C.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. World Univ Network, In FLAME Global Network, West New York, NJ USA.
    Burks, Wesley
    Caraballo, Luis
    Levin, Michael
    Van Etten, Eddie
    Horwitz, Pierre
    Kozyrskyj, Anita
    Campbell, Dianne E.
    The skin microbiome: impact of modern environments on skin ecology, barrier integrity, and systemic immune programming2017In: World Allergy Organization Journal, ISSN 1731-3317, E-ISSN 1939-4551, Vol. 10, article id 29Article, review/survey (Refereed)
    Abstract [en]

    Skin barrier structure and function is essential to human health. Hitherto unrecognized functions of epidermal keratinocytes show that the skin plays an important role in adapting whole-body physiology to changing environments, including the capacity to produce a wide variety of hormones, neurotransmitters and cytokine that can potentially influence whole-body states, and quite possibly, even emotions. Skin microbiota play an integral role in the maturation and homeostatic regulation of keratinocytes and host immune networks with systemic implications. As our primary interface with the external environment, the biodiversity of skin habitats is heavily influenced by the biodiversity of the ecosystems in which we reside. Thus, factors which alter the establishment and health of the skin microbiome have the potential to predispose to not only cutaneous disease, but also other inflammatory non-communicable diseases (NCDs). Indeed, disturbances of the stratum corneum have been noted in allergic diseases (eczema and food allergy), psoriasis, rosacea, acne vulgaris and with the skin aging process. The built environment, global biodiversity losses and declining nature relatedness are contributing to erosion of diversity at a micro-ecological level, including our own microbial habitats. This emphasises the importance of ecological perspectives in overcoming the factors that drive dysbiosis and the risk of inflammatory diseases across the life course.

  • 24. Prescott, Susan
    et al.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Prebiotics and probiotics for treatment of allergic disease2011In: UpToDateArticle in journal (Refereed)
  • 25.
    Simonyté Sjödin, Kotryna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Sjödin, A.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Engstrand, L.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Temporal and long-term gut microbiota variation in allergic disease: a prospective study from infancy to school age2019In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 74, no 1, p. 176-185Article in journal (Refereed)
    Abstract [en]

    Background: Compositional changes in the early‐life gut microbiota have been implicated in IgE‐associated allergic diseases, but there is lack of longitudinal studies. We examined gut microbiota development from infancy to school age in relation to onset of IgE‐associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T‐cell regulation, estimated as responses to polyclonal T‐cell activation.

    Methods: Stool samples were collected from 93 children at 4, 6, 13 months, and 8 years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children, and mononuclear cells were polyclonally activated. Levels of IL‐10 and FOXP3 mRNA copies were determined using real‐time quantitative reverse transcriptase‐PCR.

    Results: At 8 years of age, 21 children were diagnosed with IgE‐associated allergic disease and 90% displayed allergic comorbidity. Seventy‐two children were nonallergic and nonsensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. The gut microbiota of the allergic 8‐year‐olds was enriched in Bifidobacteriumand depleted of Lactobacillus, Enterococcus, and Lachnospira. In allergic 8‐year-olds, Faecalibacterium correlated with IL‐10 mRNA levels (rs = 0.49, Padj = 0.02) with the same trend for FOXP3 (rs = 0.39, Padj = 0.08).

    Conclusions: We identified both temporal and long‐term variation in the differential abundance of specific bacterial genera in children developing IgE‐associated allergic disease. Improved dietary interventions aiming at expanding immune‐modulatory taxa could be studied for prevention of allergic disease.

  • 26.
    Sjödin, Kotryna Simonyte
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Vidman, Linda
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Emerging evidence of the role of gut microbiota in the development of allergic diseases2016In: Current Opinion in Allergy and Clinical Immunology, ISSN 1528-4050, E-ISSN 1473-6322, Vol. 16, no 4, p. 390-395Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review The purpose is to review recent studies examining the role of gut microbiota in allergic diseases and asthma.

    Recent findings Work in experimental models gives further evidence that a disturbed gut microbiota influences the propensity to develop allergic manifestations, and that changing the gut microbiota by dietary means (high fiber/acetate or prebiotics) in pregnancy may reduce the risk of allergic airways disease and food allergy in the offspring, respectively. The gut microbiome in established allergic disease and prior to disease onset has also been assessed in clinical trials. One study demonstrated a strong association between high abundance of Faecalibacterium prausnitzii and decreased levels of butyrate and propionate, and established eczema. Lower relative abundance of Ruminococcaceae appears to be implicated in food sensitization and to precede the development of atopic eczema. Decreased relative abundance of Lachnospira, Veillonella, Faecalibacterium, and Rothia in early infancy was reported to be associated with increased asthma risk. Inoculation of germ-free mice with these genera decreased airway inflammation in their offspring thereby proposing a causal role of bacteria in preventing allergic airways disease.

    Summary Gut microbiome research is an actively developing field. Although candidate bacterial taxa have been reported it still remains unclear which bacteria (or other microbes), in which numbers and combinations, and when during the gut colonization process may prevent allergic diseases and asthma. There is still a call for standardized approaches that will enable direct comparison of different studies.

  • 27. Slupsky, Carolyn M.
    et al.
    He, Xuan
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Yvonne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rudolph, Colin
    Lönnerdal, Bo
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Postprandial metabolic response of breast-fed infants and infants fed lactose-free vs regular infant formula: a randomized controlled trial2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 3640Article in journal (Refereed)
    Abstract [en]

    Lactose intolerance is a major concern driving the growth of lactose-free foods including lactose-free infant formula. It is unknown what the metabolic consequence is of consumption of a formula where lactose has been replaced with corn syrup solids (CSS). Here, a randomized double-blinded intervention study was conducted where exclusively formula-fed infants were fed formula containing either lactose or CSS-based infant formula and compared with an equal number of exclusively breast-fed infants. Plasma metabolites and insulin were measured at baseline, 15, 30, 60, 90 and 120 min after feeding. Differences in plasma metabolite profiles for formula-fed infants included a rapid increase in circulating amino acids, creatinine and urea compared with breast-fed infants. At 120 min post-feeding, insulin was significantly elevated in formula-fed compared with breast-fed infants. Infants fed lactose-based formula had the highest levels of glucose at 120 min, and leucine, isoleucine, valine and proline at 90 and 120 min, whereas infants fed CSS-based formula had the lowest levels of non-esterified fatty acids at all time points, and glucose at 120 min. Overall, these differences highlight that changes in infant formula composition impact infant metabolism, and show that metabolomics is a powerful tool to help with development of improved infant formulas.

  • 28.
    Stecksén-Blicks, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Granström, Elisabeth
    Umeå University, Faculty of Medicine, Department of Odontology.
    Silfverdal, Sven Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Prevalence of oral Candida in the first year of life2015In: Mycoses (Berlin), ISSN 0933-7407, E-ISSN 1439-0507, Vol. 58, no 9, p. 550-556Article in journal (Refereed)
    Abstract [en]

    Colonisation of the gastrointestinal tract is influenced by primary microbial exposure and bioactive factors in breastmilk. The aim was to explore the prevalence of oral Candida in the first year of life in relation to selected exposures. Oral Candida was studied in 100 healthy infants at 4 and 8 weeks, 3, 6 and 12 months of age and related to delivery mode, birth weight, infant health and feeding, antibiotics, antimycotics, steroids and probiotics in mother and infant, living conditions, maternal smoking and infections The association between lactoferrin and antisecretory factor in breastmilk and maternal serum haemoglobin, transferrin, and ferritin levels in relation to oral Candida was also explored. About 11% to 15% of the infants had oral Candida at the respective age. Colonisation was fairly stable until 6 months of age. There was no conclusive impact of the investigated exposures at entry. Infants with a furry pet at home had a lower frequency of Candida at 3 months, (P < 0.05) whereas all but one colonised infant had older siblings at 12 months (P < 0.01). Lactoferrin in breastmilk was negatively associated with colonisation at 6 months of age. It is concluded that 11 to 15% had oral Candida. Exposure to furry pets and siblings impacted oral Candida.

  • 29. Stray-Pedersen, Asbjorg
    et al.
    Sorte, Hanne Sormo
    Samarakoon, Pubudu
    Gambin, Tomasz
    Chinn, Ivan K.
    Akdemir, Zeynep H. Coban
    Erichsen, Hans Christian
    Forbes, Lisa R.
    Gu, Shen
    Yuan, Bo
    Jhangiani, Shalini N.
    Muzny, Donna M.
    Rodningen, Olaug Kristin
    Sheng, Ying
    Nicholas, Sarah K.
    Noroski, Lenora M.
    Seeborg, Filiz O.
    Davis, Carla M.
    Canter, Debra L.
    Mace, Emily M.
    Vece, Timothy J.
    Allen, Carl E.
    Abhyankar, Harshal A.
    Boone, Philip M.
    Beck, Christine R.
    Wiszniewski, Wojciech
    Fevang, Borre
    Aukrust, Pal
    Tjonnfjord, Geir E.
    Gedde-Dahl, Tobias
    Hjorth-Hansen, Henrik
    Dybedal, Ingunn
    Nordoy, Ingvild
    Jorgensen, Silje F.
    Abrahamsen, Tore G.
    Overland, Torstein
    Bechensteen, Anne Grete
    Skogen, Vegard
    Osnes, Liv T. N.
    Kulseth, Mari Ann
    Prescott, Trine E.
    Rustad, Cecilie F.
    Heimdal, Ketil R.
    Belmont, John W.
    Rider, Nicholas L.
    Chinen, Javier
    Cao, Tram N.
    Smith, Eric A.
    Soledad Caldirola, Maria
    Bezrodnik, Liliana
    Lugo Reyes, Saul Oswaldo
    Espinosa Rosales, Francisco J.
    Guerrero-Cursaru, Nina Denisse
    Pedroza, Luis Alberto
    Poli, Cecilia M.
    Franco, Jose L.
    Trujillo Vargas, Claudia M.
    Aldave Becerra, Juan Carlos
    Wright, Nicola
    Issekutz, Thomas B.
    Issekutz, Andrew C.
    Abbott, Jordan
    Caldwell, Jason W.
    Bayer, Diana K.
    Chan, Alice Y.
    Aiuti, Alessandro
    Cancrini, Caterina
    Holmberg, Eva
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Burstedt, Magnus
    Karaca, Ender
    Yesil, Gozde
    Artac, Hasibe
    Bayram, Yavuz
    Atik, Mehmed Musa
    Eldomery, Mohammad K.
    Ehlayel, Mohammad S.
    Jolles, Stephen
    Flato, Berit
    Bertuch, Alison A.
    Hanson, I. Celine
    Zhang, Victor W.
    Wong, Lee-Jun
    Hu, Jianhong
    Walkiewicz, Magdalena
    Yang, Yaping
    Eng, Christine M.
    Boerwinkle, Eric
    Gibbs, Richard A.
    Shearer, William T.
    Lyle, Robert
    Orange, Jordan S.
    Lupski, James R.
    Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders2017In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 139, no 1, p. 232-245Article in journal (Refereed)
    Abstract [en]

    Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.

  • 30.
    Strinnholm, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Food hypersensitivity is common in Swedish schoolchildren, especially oral reactions to fruit and gastrointestinal reactions to milk2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 12, p. 1290-1296Article in journal (Refereed)
    Abstract [en]

    AIM: This study examined the prevalence, symptom expression and risk factors for food hypersensitivity among Swedish schoolchildren.

    METHODS: Parents of 2585 (96% of invited) children aged 7-8 years completed a questionnaire regarding food hypersensitivity and allergic diseases. A random sample of 1700 children (90% of invited) also participated in skin prick testing with ten airborne allergens.

    RESULTS: The overall prevalence of reported food hypersensitivity to milk, egg, fish, wheat, soya, fruits and, or, nuts was 21%, with symptoms caused by milk (9%) being the most common. The most frequently reported symptoms were oral symptoms (47.4%), mainly caused by fruit, and gastrointestinal symptoms (45.7%), mainly caused by milk. Factors associated with any food hypersensitivity were female sex, allergic heredity and a positive skin prick test. Eczema was consistently associated with symptoms caused by milk, egg, fish, wheat, soya, fruits and nuts. Rhinitis was associated to the same foods, except milk.

    CONCLUSION: Reported food hypersensitivity was common among Swedish schoolchildren. The most frequent symptom expressions were oral symptoms triggered by fruits and gastrointestinal symptoms triggered by milk. The high prevalence of reported symptoms should be validated by clinical examinations to provide a diagnosis.

  • 31. Szajewska, Hania
    et al.
    Ruszczynski, Marek
    Szymanski, Henryk
    Sadowska-Krawczenko, Iwona
    Piwowarczyk, Anna
    Rasmussen, Preben Bodstrup
    Kristensen, Mette Bach
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of infant formula supplemented with prebiotics compared with synbiotics on growth up to the age of 12 mo: a randomized controlled trial2017In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 81, no 5, p. 752-758Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Growth is an essential outcome measure for evaluating the safety of infant formulas (IF). We investigated the effects of consumption of IF supplemented with prebiotics (fructooligosaccharides, FOS, and galactooligosaccharides, GOS) compared with synbiotics (FOS/GOS and Lactobacillus paracasei ssp. paracasei strain F19) on the growth of healthy infants. METHODS: 182 full-term infants who were weaned completely from breast milk to IF at 28 d of age were randomly assigned to receive prebiotic- or synbiotic-supplemented, otherwise identical, IF until 6 mo of age (intervention period). RESULTS: A total of 146 (80%) infants were included in the intention-to-treat analysis at 6 mo. Anthropometric parameters were similar in the two groups during the intervention and follow-up period until 12 mo of age. Compared with the prebiotic group, a significant reduction in the cumulative incidence of lower respiratory tract infections was found in the synbiotic group; however, the confidence interval of the estimate was wide, resulting in uncertainty. CONCLUSION: The lack of a significant difference between the formula-fed groups in growth, or the occurrence of serious adverse events, supports the safety of using IF supplemented with synbiotics. Further studies are needed to evaluate the effects of such formula on lower-respiratory tract infections.

  • 32.
    Timby, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lonnerdal, Bo
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Oral Microbiota in Infants Fed a Formula Supplemented with Bovine Milk Fat Globule Membranes: A Randomized Controlled Trial2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0169831Article in journal (Refereed)
    Abstract [en]

    Background In a recent study, supplementation of infant formula with milk fat globule membranes (MFGM) decreased the incidence of otitis media in infants <6 months of age. Objectives The aim of the present study was to characterize the oral microbiota in infants fed MFGM-supplemented formula and compare it to that of infants fed standard formula or breast milk.

    Methods In a prospective double-blinded randomized controlled trial, exclusively formula-fed infants <2 months of age were randomized to be fed experimental formula (EF, n = 80) with reduced energy and protein and supplemented with a bovine MFGM concentrate, or standard formula (SF, n = 80) until 6 months of age. A breast-fed reference (BFR, n = 80) group was also recruited. The oral microbiota was analyzed at 4 (n = 124) and 12 (n = 166) months of age using Illumina MiSeq multiplex sequencing and taxonomic resolution against the HOMD 16S rDNA database of oral bacteria.

    Results Species richness in the oral samples did not differ between the EF and SF groups, but partial least square modeling identified a few taxa that were significantly associated with being in either group, e.g. lower level of Moraxella catarrhalis in the EF group. Infants in the BFR group had significantly lower species richness at 4 months of age and their microbiota pattern differed markedly from the formula-fed groups.

    Conclusions Supplementation of infant formula with MFGM yielded moderate effects on the oral micro biome. Moraxella catarrhalis was less prevalent in infants fed EF than in those fed SF and may be associated with the decrease in otitis media seen in the same group.

  • 33.
    Videhult, Frida K.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Body mass but not vitamin D status is associated with bone mineral content and density in young school children in northern Sweden2016In: Food & Nutrition Research, ISSN 1654-6628, E-ISSN 1654-661X, Vol. 60, article id 30045Article in journal (Refereed)
    Abstract [en]

    Background: High latitude of residence where sun exposure is limited affects vitamin D status. Although vitamin D levels have been associated with poor bone health, cut-off values for optimising bone health are yet to be decided. Objective: To assess vitamin D intake and status among young school children living at latitude 63-64 degrees N, in northern Sweden and to examine the association between vitamin D status and bone mineral content (BMC) and bone mineral density (BMD). Design: In a cross-sectional study, diet was assessed by a 4-day food diary and a food frequency questionnaire in 8- to 9-year-old children (n = 120). Energy, vitamin D, and calcium intakes were calculated. Physical activity was assessed using a pedometer for 7 days. Serum 25-hydroxyvitamin D (S-25[OH]D) levels were analysed by high-pressure liquid chromatography-atmospheric pressure chemical ionisation-mass spectrometry (n = 113). BMC and BMD were assessed by dual energy X-ray absorptiometry scan. Height and weight were measured by standard procedures and BMI z-score was calculated using WHO AnthroPlus programme. Results: The majority of children, 91%, did not reach the recommended vitaminDintake of 7.5 mu g/day and 50% had insufficient S-25[OH]D levels defined as <50 nmol/l. The highest concentrations of S-25[OH]D were observed during the summer months (p = 0.01). Body mass (p < 0.01) but not S-25[OH]D was associated with measures of BMC and BMD. Furthermore, boys had higher total BMC (p = 0.01), total body less head BMC (p = 0.02), fat free mass (p < 0.01), and a higher degree of physical activity (p = 0.01) compared to girls. Conclusions: Body mass was related to BMC and BMD measures in a population of prepubertal school children living at high latitudes in Sweden. Despite insufficient S-25[OH]D levels and low vitamin D intake, this did not appear to affect bone parameters. Prospective studies with repeated assessment of vitamin D status are needed to examine cut-off values for optimising bone health.

  • 34.
    West, C E
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Videky, D J
    School of Paediatrics and Child Health Research (SPACH), University of Western Australia, Perth, WA, Australia.
    Prescott, S L
    School of Paediatrics and Child Health Research (SPACH), University of Western Australia, Perth, WA, Australia.
    Dietary polyunsaturated fatty acids in the prevention of allergic inflammatory conditions: progress and perspectives2010In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 40, no 8, p. 1113-1115Article in journal (Refereed)
  • 35.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Feeding Lactobacillus paracasei ssp. paracasei strain F19 to infants during weaning: effects on adaptive immunity and gut microbial function2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: Gut microbial composition has been associated with immune-mediated diseases. Breastfeeding yields a microbiota rich in bifidobacteria and promotes colonization by lactobacilli. Bifidobacteria and lactobacilli are considered health-promoting and are used as probiotics, i.e. live microbial food supplements which when ingested in adequate amounts confer a beneficial effect on the host. During weaning the developing gut immune system is exposed to an increasing variety of antigens from both foods and gut microbiota.

    Aims: We aimed to determine if daily feeding of 1x108 colony-forming units (CFU) of the probiotic Lactobacillus paracasei ssp. paracasei strain F19 (LF19) to healthy term infants from 4 to 13 months of age could maintain some of the beneficial effects conferred by breastfeeding on gut microbial composition, with possible effects on gut microbial function, T cell function, Th1/Th2 immune balance and eczema incidence.

    Study design: Infants were randomized to daily intake of cereals with (n=89) or without LF19 (n=90) from 4-13 months of age. Clinical outcome measures were monitored by diaries and a questionnaire. Stool and blood samples were obtained at 4, 6½, 9, 13 and 5½, 6½, 12 and 13 months of age, respectively. Stool samples were analyzed for lactobacilli counts by conventional culture methods and the presence of LF19 was verified by randomly amplified polymerase chain reaction (RAPD-PCR). Fecal short-chain fatty acid (SCFA) pattern, a proxy for gut microbial function, was determined by gas-liquid chromatography. After polyclonal or specific activation of T cells, the cytokine mRNA expression levels [interleukin 2 (IL2), IFN-, IL4 and IL10] were determined on isolated mRNA by quantitative real time reverse transcriptase-PCR. Serum concentrations of total and specific IgE antibodies, Haemophilus influenzae type b, diphtheria and tetanus toxoid specific IgG antibodies were analyzed by enzyme immunoassay.

    Results: Feeding LF19 maintained high fecal lactobacilli counts during weaning. Persistent colonization with LF19 induced differences in the fecal SCFA pattern. The cumulative incidence of eczema was lower in the probiotic group, in conjunction with a higher IFN-γ/IL4 mRNA ratio in polyclonally activated T cells. Even though there was an effect by LF19 on Th1/Th2 immune balance, there was no effect on IgE sensitization. Infants in both groups increased their capacity to express both Th1 and Th2 cytokines during the second half of infancy but the expression was still lower than that of adults. Infants in the probiotic group had lower IL2 levels after polyclonal T cell activation at 13 months of age compared with infants in the placebo group. Infants fed LF19 did not have fewer infections, but had fewer days with antibiotic prescription compared with infants fed placebo. In addition, compared to placebo, persistent colonization by LF19 enhanced specific vaccine responses to protein antigens during the course of vaccination.

    Conclusions: We conclude that feeding LF19 was safe, based on no observed adverse effects in our study. Infants in both groups demonstrated maturation of adaptive immune responses during weaning. Adding probiotics in complementary foods during weaning reduced the risk of eczema by 50%, with a concomitant shift towards an enhanced Th1/Th2 ratio. The reduction of eczema might be explained by probiotic effects on both T cell-mediated immune responses and reinforced gut microbial function.

  • 36.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Introduction of Complementary Foods to Infants2017In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 70, p. 47-54Article in journal (Refereed)
    Abstract [en]

    While earlier food allergy prevention strategies implemented avoidance of allergenic foods in infancy, the current paradigm is shifting from avoidance to controlled exposure. This review focuses on the outcome of recent randomized controlled trials, which have examined the early introduction of allergenic foods for allergy prevention, and discusses the implementation of results in clinical practice. In infants at high risk of allergic disease, there is now direct evidence that regular early peanut consumption will reduce the prevalence of peanut allergy, compared to avoidance. Many international infant feeding guidelines already recommend complementary foods, including allergenic foods, to be introduced from 4 to 6 months of age irrespective of family history risk. Interim guidelines from 10 International Pediatric Allergy Associations state that healthcare providers should recommend the introduction of peanut-containing products into the diets of infants at high risk of allergic disease in countries where peanut allergy is prevalent. Direct translation of the results obtained from a cohort of high-risk infants to the general population has proved difficult, and issues regarding feasibility, safety, and cost-effectiveness have been raised. Five randomized placebo-controlled trials have assessed the effects of early egg exposure in infancy with varying results. In a recent comprehensive meta-analysis, there was moderate-certainty evidence that early versus late introduction of egg was associated with a reduced egg allergy risk. Although promising, optimal timing, doses, and if the feeding regimen should be stratified according to infant allergy risk remain to be determined. The single study that assessed introduction of multiple foods from 3 months whilst breastfeeding compared with exclusive breastfeeding until 6 months of age showed no reduction in food allergy prevalence. Future research should aim at optimizing infant feeding regimens and support a tolerogenic gastrointestinal microenvironment during the period of food allergen introduction. 

  • 37.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kan prebiotika eller probiotika lindra eller förhindra allergi?2011In: Nordisk nutrition, ISSN 1654-8337, no 1, p. 18-20Article in journal (Other academic)
  • 38.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kan rätt kost förhindra insjuknande i allergier?2011In: Små & stora nyheter, ISSN 1400-4186, no MajArticle in journal (Other (popular science, discussion, etc.))
  • 39.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gut microbiota and allergic disease: new findings2014In: Current opinion in clinical nutrition and metabolic care, ISSN 1363-1950, E-ISSN 1473-6519, Vol. 17, no 3, p. 261-266Article, review/survey (Refereed)
    Abstract [en]

    Purpose of reviewDisturbed gut colonization patterns are proposed to be associated with the development of allergic disease.Recent findingsStudies using new systems biology methods confirm previous findings that early environmental exposures, for example cesarean delivery, are associated with disturbed gut colonization patterns and reduced microbial diversity. Low microbial diversity in infancy is also observed to precede onset of allergic disease. In a large population-based cohort study, probiotic consumption in pregnancy was associated with reduced risk of eczema and rhinoconjunctivitis in the child, but not asthma. The association between probiotics and rhinoconjunctivitis appeared stronger if both mother and child (from 6 months) consumed probiotics. Follow-up data from primary prevention studies with probiotics do not support a role for probiotics in asthma prevention. In meta-analyses, both prebiotics (high-risk infants only) and probiotics modestly reduce the eczema risk, but no other allergic manifestations. Their use is not generally recommended for prevention, or treatment, of allergic disease.SummaryGut microbial patterns are associated with susceptibility to allergic disease, but the incomplete understanding of what constitutes a healthy gut microbiota that promotes tolerance, remains a challenge. Further understanding of gut microbial functions may pave the way for more effective allergy prevention and treatment strategies.

  • 40.
    West, Christina E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Prebiotics in infancy and childhood; clinical research warranted2011In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 106, no 11, p. 1628-1629Article in journal (Refereed)
  • 41.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Probiotics for allergy prevention2016In: Beneficial Microbes, ISSN 1876-2883, E-ISSN 1876-2891, Vol. 7, no 2, p. 171-179Article, review/survey (Refereed)
    Abstract [en]

    Probiotics, given either as a supplement or in infant foods, have been evaluated in randomised controlled trials for allergy prevention. Here, the aim is to give an overview of the results from these primary prevention studies and to discuss current strategies. In most studies, single strains or a mixture of strains of lactic acid bacteria and bifidobacteria have been used - prenatally, postnatally or perinatally. Several meta-analyses have reported a moderate benefit of probiotics for eczema prevention, and the most consistent effect has been observed with a combined perinatal intervention in infants at high risk of allergic disease due to familial predisposition. In a recent meta-analysis, the use of multi-strain probiotics appeared to be most effective for eczema prevention. No preventive effect has been shown for other allergic manifestations. As long-term follow-up data on later onset allergic conditions (asthma and allergic rhinitis) are available only from a few of the initiated studies, reports from ongoing follow-up studies that are adequately powered to examine long-term outcomes are anticipated to provide more insight. Arguably, the differences in many aspects of study design and the use of different probiotic strains and combinations have made direct comparison difficult. To date, expert bodies do not generally recommend probiotics for allergy prevention, although the World Allergy Organization (WAO) in their recently developed guidelines suggests considering using probiotics in pregnant women, during breastfeeding and/or to the infant if at high risk of developing allergic disease (based on heredity). However, in concordance with other expert bodies, the WAO guideline panel stressed the low level of evidence and the need for adequately powered randomised controlled trials and a more standardised approach before clinical recommendations on specific strains, dosages and timing can be given.

  • 42.
    West, Christina E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The role of prebiotics in infectious and inflammatory conditions in infancy and childhood2010In: Infantil, Vol. 1, no 1Article in journal (Other academic)
  • 43.
    West, Christina E
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dunstan, Janet
    McCarthy, Suzi
    Metcalfe, Jessica
    D'Vaz, Nina
    Meldrum, Suzanne
    Oddy, Wendy H
    Tulic, Meri K
    Prescott, Susan L
    Associations between maternal antioxidant intakes in pregnancy and infant allergic outcomes2012In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 4, no 11, p. 1747-1758Article in journal (Refereed)
    Abstract [en]

    Antioxidant intakes in pregnancy may influence fetal immune programming and the risk of allergic disease. We investigated associations between maternal intakes of β-carotene, vitamin C, vitamin E, copper and zinc, and infant allergic outcomes. Antioxidant intakes of pregnant women (n = 420) assessed prospectively by a food frequency questionnaire, were examined in relation to allergic outcomes at 1 year of age (n = 300). The main relationships with allergic outcomes were seen with dietary vitamin C and copper. Specifically, higher maternal dietary vitamin C intake was associated with a reduced risk of any diagnosed infant allergic disease and wheeze. After adjustment for potential confounders the relationship with wheeze remained statistically significant. There was also an inverse linear relationship between vitamin C and food allergy. Higher dietary copper intake was associated with reduced risk of eczema, wheeze and any allergic disease. The relationship with wheeze and any allergic disease remained statistically significant in multivariate analysis, and there was also an inverse linear relationship between copper and food allergy. However, these relationships were only seen for nutrients present in food. There were no relationships between β-carotene, vitamin E or zinc and any allergic outcomes. In summary, this study suggests that maternal diet of fresh foods rich in vitamin C is associated with reduced risk of infant wheeze, and that copper intake is associated with reduced risk of several allergic outcomes.

  • 44.
    West, Christina E
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    D'Vaz, Nina
    Prescott, Susan L
    Dietary Immunomodulatory Factors in the Development of Immune Tolerance.2011In: Current Allergy and Asthma Reports, ISSN 1529-7322, E-ISSN 1534-6315, Vol. 11, no 4, p. 325-333Article in journal (Refereed)
    Abstract [en]

    Emerging evidence suggests that exposures during pregnancy and the early postnatal period can modify gene expression and disease propensity. Diet is a major environmental exposure, and dietary factors, including polyunsaturated fatty acids, probiotics, oligosaccharides, antioxidants, folate, and other vitamins, have effects on immune function. Some also have been implicated in reduced risk of allergy in observational studies. Intervention trials with polyunsaturated fatty acids, probiotics, and oligosaccharides suggest preliminary but as-of-yet-unconfirmed benefits. Food allergen avoidance during pregnancy, lactation, or infancy has provided no consistent evidence in allergy prevention and is no longer recommended. Rather, there is now a focus on food allergens in tolerance induction. Specific nutrients can induce changes in gene expression during early development and have been implicated in potentially heritable "epigenetic" changes in disease predisposition. Collectively, these observations emphasize that early exposures may modify tolerance development and that further research on these exposures should remain a priority.

  • 45.
    West, Christina E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. inFLAME Global Network (Worldwide Universities Network), West New York, NJ, USA.
    Dzidic, Majda
    Prescott, Susan L.
    Jenmalm, Maria C.
    Bugging allergy; role of pre-, pro- and synbiotics in allergy prevention2017In: Allergology International, ISSN 1323-8930, E-ISSN 1440-1592, Vol. 66, no 4, p. 529-538Article, review/survey (Refereed)
    Abstract [en]

    Large-scale biodiversity loss and complex changes in social behaviors are altering human microbial ecology. This is increasingly implicated in the global rise in inflammatory diseases, most notably the "allergy epidemic" in very early life. Colonization of human ecological niches, particularly the gastrointestinal tract, is critical for normal local and systemic immune development and regulation. Disturbances in composition, diversity and timing of microbial colonization have been associated with increased allergy risk, indicating the importance of strategies to restore a dysbiotic gut microbiota in the primary prevention of allergic diseases, including the administration of probiotics, prebiotics and synbiotics. Here, we summarize and discuss findings of randomized clinical trials that have examined the effects of these microbiome-related strategies on short and long-term allergy preventative effects - including new guidelines from the World Allergy Organization which now recommend probiotics and prebiotics for allergy prevention under certain conditions. The relatively low quality evidence, limited comparative studies and large heterogeneity between studies, have collectively hampered recommendations on specific probiotic strains, specific timing and specific conditions for the most effective preventive management. At the same time the risk of using available products is low. While further research is needed before specific practice guidelines on supplement probiotics and prebiotics, it is equally important that the underlying dietary and lifestyle factors of dysbiosis are addressed at both the individual and societal levels.

  • 46.
    West, Christina E
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Pediatrik.
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Pediatrik.
    Granström, Marta
    Käyhty, Helena
    Hammarström, Marie-Louise K C
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Pediatrik.
    Effects of feeding probiotics during weaning on infections and antibody responses to diphtheria, tetanus and Hib vaccines.2008In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 19, no 1, p. 53-60Article in journal (Other academic)
    Abstract [en]

    Microbial exposure is necessary for the development of normal immune function, which has driven the idea of using probiotics for treatment and prevention of immune-mediated diseases in infancy and childhood. Mounting evidence indicates that probiotics have immunomodulatory effects. However, the mechanisms are still poorly understood. Specific antibody response is a valuable proxy for immune system maturation status in infancy. We aimed at determining the impact of Lactobacillus F19 (LF19) during weaning on infections and IgG antibody responses to routine vaccines. In a double-blind, placebo-controlled randomized intervention trial, infants were fed cereals with (n = 89) or without LF19 (n = 90) from 4 to 13 months of age. Infants were immunized with DTaP (diphtheria and tetanus toxoid and acellular pertussis), polio and Hib-conjugate vaccines at (3), 5(1/2) and 12 months of age. We assessed the number of days with infections, antibiotic prescriptions and antibody concentrations to Hib capsular polysaccharide (HibPS), diphtheria toxin (D) and tetanus toxoid (T) before and after the second and third doses. Days with infectious symptoms did not differ between the groups. Days with antibiotic prescriptions were fewer in the LF19 group (p = 0.044). LF19 enhanced anti-D concentrations when adjusting for breastfeeding duration and colonization with LF19 (p = 0.024). There was an interaction of the intervention and colonization with LF19 on anti-T concentrations during the course of vaccination (p = 0.035). The anti-HibPS concentrations were higher after the first and second dose of Hib vaccine in infants breastfed <6 months compared with those breastfed > or =6 months (p < 0.05), with no effect by LF19. In conclusion, feeding LF19 did not prevent infections, but increased the capacity to raise immune responses to protein antigens, with more pronounced effects in infants breastfed <6 months.

  • 47.
    West, Christina E
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Probiotics during weaning reduce the incidence of eczema.2009In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, ISSN 1399-3038, Vol. 20, p. 430-7Article in journal (Refereed)
    Abstract [en]

    A reduced microbial load early in life has been suggested to be linked to the increasing prevalence of allergic diseases in the industrialized world. Some studies have indicated that probiotics may be effective in the prevention of eczema. In vitro studies indicate that probiotics have immunomodulatory effects. In the present study, we evaluated the effects of feeding Lactobacillus F19 during weaning on the incidence of eczema and Th1/Th2 balance. In a double-blind, placebo-controlled randomized intervention trial, infants were fed cereals with (n = 89) or without Lactobacillus F19 (n = 90) from 4 to 13 months of age. We assessed the cumulative incidence of eczema at 13 months of age. The ratio of interferon-gamma (IFN-gamma) to interleukin 4 (IL4) mRNA expression levels in polyclonally stimulated peripheral blood T cells was used as a proxy for immune balance. Total and specific IgE serum levels were also assessed. The cumulative incidence of eczema at 13 months was 11% (4-17%, 95% CI) and 22% (13-31%, 95% CI) in the probiotic and placebo groups, respectively (p < 0.05). The number needed to treat was 9 (6.5-11.5, 95% CI). At 13 months of age, the IFN-gamma/IL4 mRNA ratio was higher in the probiotic compared with the placebo group (p < 0.05). In contrast, there were no differences between groups in serum concentrations of IgE. In summary, feeding Lactobacillus F19 during weaning could be an effective tool in the prevention of early manifestation of allergy, e.g., eczema. The higher Th1/Th2 ratio in the probiotic compared with the placebo group suggests enhancing effects of Lactobacillus F19 on the T cell-mediated immune response.

  • 48.
    West, Christina E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Probiotics in primary prevention of allergic disease - follow-up at 8-9 years of age2013In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, no 8, p. 1015-1020Article in journal (Refereed)
    Abstract [en]

    Background: Long-term effects of probiotics in primary prevention of allergic disease need further evaluation. We previously reported a reduced cumulative incidence of infant eczema by feeding Lactobacillus paracasei ssp paracasei F19 (LF19) during weaning. Therefore, we assessed effects of LF19 on the prevalence of allergic disease at school age. Methods: In a double-blind placebo-controlled trial infants were randomized to daily intake of cereals with (n=89) or without LF19 10(8) CFU (n=90) from 4-13months of age. At age 8-9, we evaluated the prevalence of allergic disease (eczema, allergic rhinitis, asthma, and food allergy) by clinical examination and validated questionnaires. IgE sensitization was assessed by skin prick test (inhalant allergens) and specific IgE levels (food allergens). Lung function was evaluated by a spirometry reversibility test. Fractional exhaled nitric oxide (FENO) was measured. Results: Of 171 children that completed the intervention, 121 were assessed at age 8-9. In the probiotic group, 15/59 (25%) were diagnosed with any allergic disease vs 22/62 (35%) in the placebo group [OR (95% CI) 0.62 (0.28-1.36)]. Corresponding numbers for IgE-associated allergic disease were 9/53 (17%) vs 12/59 (20%) [0.80 (0.31-2.09)]. Median (25th-75th percentile) FENO was 9 (8-12) in the probiotic vs 8 (7-12) ppb in the placebo group (P>0.05). There was no effect of LF19 on lung function measures (P>0.05). Conclusions: There was no long-term effect of LF19 on any diagnosed allergic disease, airway inflammation or IgE sensitization. This suggests delayed eczema onset but to fully examine long-term benefits a larger study population had been needed.

  • 49.
    West, Christina E
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Yvonne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Sjöstedt, M
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Probiotic effects on T-cell maturation in infants during weaning.2012In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 42, no 4, p. 540-549Article in journal (Refereed)
    Abstract [en]

    Background: We previously reported that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) during weaning reduced the cumulative incidence of eczema.

    Objective: To investigate the impact of feeding LF19 on T-cell maturation.

    Methods: One hundred and seventy-nine healthy, term infants with no prior allergic manifestations were randomized to daily intake of cereals with (n = 89) or without (n = 90) the addition of LF19 10colony forming units per serving from 4 to 13 months of age. Venous blood was drawn at 5.5 and 13 months of age. We used the cytokine response to polyclonal T-cell stimulation by anti-CD3 plus anti-CD28 monoclonal antibodies, and in vitro stimulation with the vaccine tetanus toxoid (TT) as measures of global adaptive immunity and capacity to raise a specific T-cell response, respectively. Expression levels of IL-2, IFN-γ, IL-4, IL-17A and IL-10 messenger RNAs (mRNAs) were used as proxies for general T-cell stimulation and naive Th0 cells, Th1-, Th2-, Th17- and T regulatory lineages.

    Results: There was no difference between the two groups at 5.5 months of age. At 13 months, the polyclonal IL-2 response was higher in the placebo group (P < 0.05), whereas the IFN-γ/IL-2 (P < 0.01) and IL-17A/IL-2 (P < 0.05) ratios after polyclonal stimulation were higher in the probiotic group, as was the TT-specific IL17-A response (P < 0.001). In both groups, the IFN-γ and IL-4 responses increased from 5.5 to 13 months upon both polyclonal and specific stimulation (P < 0.01), whereas the IL-10 response remained low (P > 0.05).

    Conclusion and Clinical Relevance: Our findings suggest modest effects by probiotics on T-cell maturation following 9 months of probiotic intake. Future studies should address if specific probiotics may drive immune development with possible preventive effects on the development of allergic disease.

  • 50.
    West, Christina E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jenmalm, M. C.
    Prescott, S. L.
    The gut microbiota and its role in the development of allergic disease: a wider perspective2015In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, no 1, p. 43-53Article, review/survey (Refereed)
    Abstract [en]

    The gut microbiota are critical in the homoeostasis of multiple interconnected host metabolic and immune networks. If early microbial colonization is delayed, the gut-associated lymphoid tissues (GALT) fail to develop, leading to persistent immune dysregulation in mice. Microbial colonization has also been proposed as a major driver for the normal age-related maturation of both Th1 and T regulatory (Treg) pathways that appear important in suppressing early propensity for Th2 allergic responses. There is emerging evidence that resident symbionts induce tolerogenic gut-associated Treg cells and dendritic cells that ensure the preferential growth of symbionts; keeping pathogenic strains in check and constraining proinflammatory Th1, Th2, and Th17 clones. Some effects of symbionts are mediated by short-chain fatty acids, which play a critical role in mucosal integrity and local and systemic metabolic function and stimulate the regulatory immune responses. The homoeostatic IL-10/TGF- dominated tolerogenic response within the GALT also signals the production of secretory IgA, which have a regulating role in mucosal integrity. Contrary to the sterile womb' paradigm, recent studies suggest that maternal microbial transfer to the offspring begins during pregnancy, providing a pioneer microbiome. It is likely that appropriate microbial stimulation both pre- and postnatally is required for optimal Th1 and Treg development to avoid the pathophysiological processes leading to allergy. Disturbed gut colonization patterns have been associated with allergic disease, but whether microbial variation is the cause or effect of these diseases is still under investigation. We are far from understanding what constitutes a healthy gut microbiome' that promotes tolerance. This remains a major limitation and might explain some of the inconsistency in human intervention studies with prebiotics and probiotics. Multidisciplinary integrative approaches with researchers working in networks, using harmonized outcomes and methodologies, are needed to advance our understanding in this field.

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