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1.	Nowrouzian, Forough, 1957, et al. (author) Superantigens and adhesins of infant gut commensal Staphylococcus aureus strains and association with subsequent development of atopic eczema. 2017 In: The British journal of dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 176:2, s. 439-445 Journal article (peer-reviewed)abstract According to the hygiene hypothesis, insufficient immune activation by microbes increases the risk of allergy development. Staphylococcus aureus, which is part of the skin and gut microbiota of infants in Western countries, produces a variety of T-cell-activating enterotoxins, called superantigens.To investigate whether early (0-2 months of age) gut colonization by S. aureus strains that carry specific superantigens and adhesins was related to subsequent development of atopic eczema in a Swedish birth cohort.Staphylococcus aureus was isolated from rectal swabs and cultured quantitatively from faecal samples, with individual strains being tested for carriage of genes for superantigens and adhesins. Atopic eczema was diagnosed at onset of symptoms and at 18 months of age.Although the frequency of early gut colonization by S. aureus was not related to subsequent eczema development, the S. aureus strains that were found to colonize those infants who developed atopic eczema were less likely to carry the gene encoding the superantigen SElM (P = 0·008) and the gene for elastin-binding protein (P = 0·03), compared with strains that were isolated from infants who had not developed atopic eczema by 18 months of age.Gut colonization by S. aureus strains carrying a certain combination of superantigen and adhesin genes was negatively associated with subsequent development of atopic eczema. Such strains may provide stimulation and promote maturation of the infant immune system.
2.	Adlerberth, Ingegerd, 1959, et al. (author) Gut microbiota and development of atopic eczema in 3 European birth cohorts. 2007 In: The Journal of allergy and clinical immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 120:2, s. 343-50 Journal article (peer-reviewed)abstract BACKGROUND: Stimulation of the immune system by gut microbes might prevent allergy development. OBJECTIVE: The present study examined the hypothesis that sensitization to food allergens and atopic eczema are influenced by the infantile intestinal colonization pattern. METHODS: Infants were recruited perinatally in Göteborg (n = 116), London (n = 108), and Rome (n = 100). Commensal bacteria were identified to the genus or species level in rectal (3 days) and quantitative stool cultures (7, 14, and 28 days and 2, 6, and 12 months of age). At 18 months of age, atopic eczema and total and food-specific IgE levels were assessed. These outcomes were modeled in relation to time to colonization with 11 bacterial groups and to ratios of strict anaerobic to facultative anaerobic bacteria and gram-positive to gram-negative bacteria at certain time points. Study center, mode of delivery, parity, and infant diet were included as covariates. RESULTS: Neither atopic eczema nor food-specific IgE by 18 months of age were associated with time of acquisition of any particular bacterial group. Cesarean section delayed colonization by Escherichia coli and Bacteroides and Bifidobacterium species, giving way to, for example, Clostridium species. Lack of older siblings was associated with earlier colonization by Clostridium species and lower strict anaerobic/facultative anaerobic ratio at 12 months. CONCLUSIONS: This study does not support the hypothesis that sensitization to foods or atopic eczema in European infants in early life is associated with lack of any particular culturable intestinal commensal bacteria. CLINICAL IMPLICATIONS: The nature of the microbial stimulus required for protection from allergy remains to be identified.
3.	Adlerberth, Ingegerd, 1959, et al. (author) Reduced enterobacterial and increased staphylococcal colonization of the infantile bowel: an effect of hygienic lifestyle? 2006 In: Pediatric research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 59:1, s. 96-101 Journal article (peer-reviewed)abstract The modern Western lifestyle may have altered the composition of the commensal microflora. Here, we investigated the first year's intestinal colonization pattern in 99 vaginally delivered Swedish infants and 17 delivered by cesarean section. Rectal swabs obtained at 3 d of age were cultured for aerobic bacteria and fecal samples obtained at 1, 2, 4, and 8 wk and at 6 and 12 mo of age were cultivated quantitatively for aerobic and anaerobic bacteria. Vaginally delivered infants more often had Escherichia coli compared with cesarean section-delivered infants, whereas the latter more frequently carried other enterobacteria, such as Klebsiella and Enterobacter. Independent of delivery mode, it took 2 mo until most infants were colonized by enterobacteria, traditionally the first colonizers. In contrast, coagulase-negative staphylococci colonized 99% of the infants from d 3 onwards. The poor adaptation of staphylococci to the gut was shown by declining population sizes after some weeks. Dominating anaerobes were initially bifidobacteria and clostridia, whereas Bacteroides initially colonized only 30% of vaginally delivered infants and increased very slowly in prevalence. Bacteroides colonization was delayed up to 1 y in cesarean section-delivered compared with vaginally delivered infants. Our results show that some "traditional" fecal bacteria are acquired late today especially in cesarean section-delivered infants, probably due to limited environmental circulation. In their absence, skin bacteria like staphylococci have become the first gut colonizers.
4.	Adlerberth, Ingegerd, 1959, et al. (author) Toxin-producing Clostridium difficile strains as long-term gut colonizers of healthy infants. 2014 In: Journal of clinical microbiology. - 1098-660X. ; 52:1, s. 173-179 Journal article (peer-reviewed)abstract Clostridium difficile is a colonizer of the human gut, and toxin-producing strains may cause diarrhea if infectious burden is heavy. Infants are more frequently colonized than adults, but rarely develop C. difficile disease. It is not known whether strains of C. difficile differ in capacity to colonize and persist in the human gut microbiota. Here, we strain-typed isolates of C. difficile colonizing 42 healthy infants followed from birth to ≥12 months of age, using PCR ribotyping of the 16S-23S rRNA intergenic spacer region. The isolates were also characterized regarding carriage of the toxin genes tcdA, tcdB and cdtA/B, and capacity to produce toxin B in vitro. Most strains (71%) were toxin-producers, and 51% belonged to the 001 or 014 ribotypes, that often cause disease in adults. These ribotypes were significantly more likely than other ones to persist for ≥6 months in the infant micobiota, and were isolated from 13/15 children carrying such long-term colonizing strains. Ribotype 001 strains were often acquired in the first week of life and attained higher population counts than other C. difficile ribotypes in newborn infants' faeces. Several toxin-negative ribotypes were identified, two of which (GI and GIII) were long-term colonizers, each in one infant. Our results suggest that the toxin-producing C. difficile ribotypes 001 and 014 have special fitness in the infantile gut microbiota. Toxin-producing strains colonizing young children for long time periods may represent a reservoir for strains causing disease in adults.
5.	Ahrné, Siv, et al. (author) Lactobacilli in the intestinal microbiota of Swedish infants 2005 In: Microbes and Infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 7:11-12, s. 1256-62 Journal article (peer-reviewed)abstract Lactobacillus colonisation was examined in 112 Swedish infants. Faecal samples obtained at 1, 2, 4 and 8 weeks and at 6, 12 and 18 months of age were cultivated quantitatively on Rogosa agar. Lactobacilli were speciated by PCR and typed to the strain level by randomly amplified polymorphic DNA (RAPD). Lactobacilli reached a peak at 6 months when 45% of the infants were colonised. L. rhamnosus and L. gasseri were the most common species in this period. Colonisation by lactobacilli in general (P < 0.01) and L. rhamnosus in particular (P < 0.05) was more common in breast-fed than in weaned infants at 6 months of age. Lactobacillus isolation reached a nadir of 17% by 12 months (P < 0.0001), but increased to 31% by 18 months of age P < 0.05). The food-related species L. paracasei, L. plantarum, L. acidophilus and L. delbrueckii dominated in this second phase. A single strain persisted for at least 3 weeks in 17% of the infants during the first 6 months, most commonly L. rhamnosus. Lactobacillus population counts in colonised infants increased from 10(6.4) cfu/g at 1 week to 10(8.8) cfu/g at 6 months, and then dropped to 10(5.4) cfu/g faeces at 12 months of age. Lactobacillus colonisation was not significantly related to delivery mode, or to presence of siblings or pets in the household. Our results suggest that certain Lactobacillus species, especially L. rhamnosus, thrive in the intestinal flora of breast-fed infants. After weaning they are replaced by other Lactobacillus species of types found in food.
6.	Barman, Malin, 1983, et al. (author) Cord Blood Levels of EPA, a Marker of Fish Intake, Correlate with Infants' T- and B-Lymphocyte Phenotypes and Risk for Allergic Disease 2020 In: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 12:10, s. 1-18 Journal article (peer-reviewed)abstract Maternal fish intake during pregnancy has been associated with reduced allergy development in the offspring and here, we hypothesized that components of fish stimulate fetal immune maturation. The aim of this study was to investigate how maternal fish intake during pregnancy and levels of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in the infant's cord serum correlated with different subsets of B- and T-cells in cord blood and B-cell activating factor (BAFF) in cord plasma, and with doctor-diagnosed allergy at 3 and 8 years of age in the FARMFLORA birth-cohort consisting of 65 families. Principal component analysis showed that infant allergies at 3 or 8 years of age were negatively associated with the proportions of n-3 LCPUFAs (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) in infant cord serum, which, in turn correlated positively with maternal fish intake during pregnancy. Both maternal fish intake and cord serum n-3 LCPUFAs correlated negatively to CD5(+) B cells and the FOXP3(+)CD25(high) of the CD4(+) T cell subsets in cord blood, but not to BAFF in cord plasma. Our observational study suggests that fish might contain components that promote maturation of the infant's immune system in a manner that protects against allergy development.
7.	Barman, Malin, 1983, et al. (author) High Levels of Both n-3 and n-6 Long-Chain Polyunsaturated Fatty Acids in Cord Serum Phospholipids Predict Allergy Development 2013 In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7 Journal article (peer-reviewed)abstract Background Long-chain polyunsaturated fatty acids (LCPUFAs) reduce T-cell activation and dampen inflammation. They might thereby counteract the neonatal immune activation and hamper normal tolerance development to harmless environmental antigens. We investigated whether fatty acid composition of cord serum phospholipids affects allergy development up to age 13 years. Methods From a population-based birth-cohort born in 1996/7 and followed until 13 years of age (n = 794), we selected cases with atopic eczema (n = 37) or respiratory allergy (n = 44), as well as non-allergic non-sensitized controls (n = 48) based on diagnosis at 13 years of age. Cord and maternal sera obtained at delivery from cases and controls were analysed for proportions of saturated, monounsaturated and polyunsaturated fatty acids among serum phospholipids. Results The cord serum phospholipids from subject who later developed either respiratory allergy or atopic eczema had significantly higher proportions of 5/8 LCPUFA species, as well as total n-3 LCPUFA, total n-6 LCPUFA and total LCPUFA compared to cord serum phospholipids from controls who did not develop allergy (P<0.001 for all comparisons). Conversely, individuals later developing allergy had lower proportion of the monounsaturated fatty acid 18:1n-9 as well as total MUFA (p<0.001) among cord serum phospholipids. The risk of respiratory allergy at age 13 increased linearly with the proportion of n-3 LCPUFA (Ptrend<0.001), n-6 LCPUFA (Ptrend = 0.001), and total LCPUFA (Ptrend<0.001) and decreased linearly with the proportions of total MUFA (Ptrend = 0.025) in cord serum phospholipids. Furthermore, Kaplan-Meier estimates of allergy development demonstrated that total LCPUFA proportion in cord serum phospholipids was significantly associated with respiratory allergy (P = 0.008) and sensitization (P = 0.002), after control for sex and parental allergy. Conclusion A high proportion of long-chain PUFAs among cord serum phospholipids may predispose to allergy development. The mechanism is unknown, but may involve dampening of the physiologic immune activation in infancy needed for proper maturation of the infant's immune system.
8.	Barman, Malin, 1983, et al. (author) No association between allergy and current 25-hydroxy vitamin D in serum or vitamin D intake 2015 In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 104:4, s. 405-413 Journal article (peer-reviewed)abstract Aim Vitamin D may be involved in allergy development, but there is conflicting evidence. We investigated if dietary intake of vitamin D and levels of 25OHD in serum differed between allergic and nonallergic adolescents and if serum 25OHD correlated with dietary intake of vitamin D or season of blood sampling. Methods Serum 25-hydroxy vitamin D (25OHD) levels were analysed in 13-year-old subjects with atopic eczema (n = 55), respiratory allergy (n = 55) or no allergy (n = 55). Intake of fat-containing foods was assessed by food-frequency questionnaires, and total daily vitamin D intake was calculated. Logistic regression was used to adjust for gender, parental allergy and time of blood sampling. Results Subjects with atopic eczema or respiratory allergy did not differ from nonallergic controls regarding serum 25OHD levels or calculated vitamin D intake. Subjects sampled in the autumn had significantly higher levels of serum 25OHD than subjects sampled in the winter or spring. Serum 25OHD levels correlated to consumption of vitamin D-fortified lean milk (p = 0.001). Conclusion The findings suggest no association between allergy and 25OHD levels in serum or vitamin D intake in adolescents. Serum 25OHD levels correlated to intake of vitamin D-fortified lean milk.
9.	Barman, Malin, 1983, et al. (author) Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE): a prospective birth cohort in northern Sweden 2018 In: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 8:10 Journal article (peer-reviewed)abstract © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: Prenatal and neonatal environmental factors, such as nutrition, microbes and toxicants, may affect health throughout life. Many diseases, such as allergy and impaired child development, may be programmed already in utero or during early infancy. Birth cohorts are important tools to study associations between early life exposure and disease risk. Here, we describe the study protocol of the prospective birth cohort, 'Nutritional impact on Immunological maturation during Childhood in relation to the Environment' (NICE). The primary aim of the NICE cohort is to clarify the effect of key environmental exposures-diet, microbes and environmental toxicants-during pregnancy and early childhood, on the maturation of the infant's immune system, including initiation of sensitisation and allergy as well as some secondary outcomes: infant growth, obesity, neurological development and oral health.METHODS AND ANALYSIS: The NICE cohort will recruit about 650 families during mid-pregnancy. The principal inclusion criterion will be planned birth at the Sunderby Hospital in the north of Sweden, during 2015-2018. Questionnaires data and biological samples will be collected at 10 time-points, from pregnancy until the children reach 4 years of age. Samples will be collected primarily from mothers and children, and from fathers. Biological samples include blood, urine, placenta, breast milk, meconium, faeces, saliva and hair. Information regarding allergic heredity, diet, socioeconomic status, lifestyle including smoking, siblings, pet ownership, etc will be collected using questionnaires. Sensitisation to common allergens will be assessed by skin prick testing and allergic disease will be diagnosed by a paediatrician at 1 and 4 years of age. At 4 years of age, the children will also be examined regarding growth, neurobehavioural and neurophysiological status and oral health.ETHICS AND DISSEMINATION: The NICE cohort has been approved by the Regional Ethical Review Board in Umeå, Sweden (2013/18-31M). Results will be disseminated through peer-reviewed journals and communicated on scientific conferences.
10.	Gio-Batta, Monica, et al. (author) Fecal short chain fatty acids in children living on farms and a link between valeric acid and protection from eczema. 2020 In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1 Journal article (peer-reviewed)abstract Children growing up on farms have low rates of allergy, but the mechanism for this protective effect has not been fully elucidated. Short chain fatty acids (SCFAs) produced by the gut microbiota may play a role in protection from allergy. We measured fecal SCFA levels in samples collected from 28 farming and 37 control children over the first 3years of life using gas chromatography. Data on diet and other host factors were recorded and allergy was diagnosed at 8years of age. Among all children, median propionic and butyric acid concentration increased over the first 3years, and longer SCFAs typically appeared by 1year of age. Farm children had higher levels of iso-butyric, iso-valeric and valeric acid at 3years of age than rural controls. In addition, children with elder siblings had higher levels of valeric acid at 3years of age, and dietary factors also affected SCFA pattern. High levels of valeric acid at 3years of age were associated with low rate of eczema at 8years of age. The fecal SCFA pattern in farm children suggests a more rapid maturation of the gut microbiota. Valeric acid or associated microbes may have protective potential against eczema.
11.	Hesselmar, Bill, 1955, et al. (author) An index to predict asthma in wheezing young children produced promising initial results. 2017 In: Acta Paediatrica. - : Wiley. - 0803-5253. ; 106:9, s. 1532-1533 Journal article (peer-reviewed)abstract Diagnosing asthma is difficult in infants and preschool children because wheezing is common in this age group and it is not synonymous with asthma. Some children outgrow the tendency to wheeze during colds in a few years' time, whereas other develop asthma. Efforts have been made to find ways to identify the subgroup of preschool children with wheeze who are most likely to develop asthma (1,2). However, the different asthma predictive indexes mainly aim to predict children who will have a persistent wheeze or asthma, not necessarily the subgroup who will outgrow their symptoms. This article is protected by copyright. All rights reserved.
12.	Hesselmar, Bill, 1955, et al. (author) Early fish introduction is associated with less eczema, but not sensitization, in infants. 2010 In: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 99:12, s. 1861-7 Journal article (peer-reviewed)abstract To investigate if the development of allergic diseases during the child's first 18 months of life is influenced by the time at which different food items were introduced into the child's diet.
13.	Hesselmar, Bill, 1955, et al. (author) Pacifier Cleaning Practices and Risk of Allergy Development. 2013 In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 131:6 Journal article (peer-reviewed)abstract OBJECTIVE:Immune stimulation through exposure to commensal microbes may protect against allergy development. Oral microbes may be transferred from parents to infants via pacifiers. We investigated whether pacifier cleaning practices affected the risk of allergy development.METHODS:A birth-cohort of 184 infants was examined for clinical allergy and sensitization to airborne and food allergens at 18 and 36 months of age and, in addition, promptly on occurrence of symptoms. Pacifier use and pacifier cleaning practices were recorded during interviews with the parents when the children were 6 months old. The oral microbiota of the infants was characterized by analysis of saliva samples collected at 4 months of age.RESULTS:Children whose parents "cleaned" their pacifier by sucking it (n = 65) were less likely to have asthma (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.01-0.99), eczema (OR 0.37; 95% CI 0.15-0.91), and sensitization (OR 0.37; 95% CI 0.10-1.27) at 18 months of age than children whose parents did not use this cleaning technique (n = 58). Protection against eczema remained at age 36 months (hazard ratio 0.51; P = .04). Vaginal delivery and parental pacifier sucking yielded independent and additive protective effects against eczema development. The salivary microbiota differed between children whose parents cleaned their pacifier by sucking it and children whose parents did not use this practice.CONCLUSIONS:Parental sucking of their infant's pacifier may reduce the risk of allergy development, possibly via immune stimulation by microbes transferred to the infant via the parent's saliva.
14.	Hesselmar, Bill, 1955, et al. (author) Pet-keeping in early life reduces the risk of allergy in a dose-dependent fashion. 2018 In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12 Journal article (peer-reviewed)abstract Several studies have indicated that early pet keeping could protect the infant from later allergy development. Here, we investigate if there is a dose-dependent association between cat- and dog-keeping during the first year of life and subsequent allergy development.Two cohorts were investigated: a cross-sectional questionnaire-based study of 7- to 8-year-old children (N = 1029) from Mölndal and Kiruna, and a birth-cohort of children from the Västra Götaland county clinically evaluated for asthma and allergy by paediatricians up to the age of 8-9 years (N = 249). The cross-sectional study asked validated questions on asthma and allergy that had been used in two previous studies of children from the same areas. In the birth-cohort study, a diagnosis of asthma and allergy was based on predefined clinical criteria, and laboratory evaluation included blood eosinophils, skin-prick tests and specific immunoglobulin E analyses. Information on pets during first year of life was collected retrospectively in the Cross-Sectional Cohort and prospectively in the Birth Cohort.A dose-response association was seen, with less allergic manifestations (any of asthma, allergic rhinoconjunctivitis, or eczema) with increasing number of household cats and dogs during the first year of life. In the Cross-Sectional Cohort, allergy ever decreased from 49% in those with no pets to zero in those with five or more pets (P-value for trend 0.038), and from 32% to zero for allergy last year (P-value for trend 0.006). The same pattern was seen in Birth Cohort. Sensitization to animals, as well as pollens, also decreased with increasing number of animals in the household.The prevalence of allergic disease in children aged 7-9 years is reduced in a dose-dependent fashion with the number of household pets living with the child during their first year of life, suggesting a "mini-farm" effect, whereby cats and dogs protect against allergy development.
15.	Jonsson, Karin, 1982, et al. (author) Fat intake and breast milk fatty acid composition in farming and nonfarming women and allergy development in the offspring. 2016 In: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 79, s. 114-123 Journal article (peer-reviewed)abstract Children growing up on small family farms are at much lower risk of developing allergy than other children. We hypothesized that low intake of margarine and polyunsaturated fats among farming families could contribute to this protection.
16.	Jonsson, Karin, 1982, et al. (author) High proportions of eicosapentaenoic acid (EPA) in infants' serum may decrease allergy risk: results from the FARMFLORA birth-cohort 2015 In: Allergy. - 0105-4538 .- 1398-9995. ; 70:Special issue 101, s. 402-402 Conference paper (other academic/artistic)
17.	Jonsson, Karin, 1982, et al. (author) Late introduction of fish and eggs is associated with increased risk of allergy development - results from the FARMFLORA birth cohort 2017 In: Food and Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 61:1 Journal article (peer-reviewed)abstract The prevalence of allergy is markedly low in children growing up on farms. An increasing number of studies indicate that the timing of food introduction may affect allergy development. We aimed to investigate if protection against allergy in farm environments may be mediated through differences in food-introduction practices between farm and non-farm families, using an explorative approach. Twenty-eight farm and 37 non-farm children were included in the FARMFLORA birth cohort. Practices of breastfeeding and introduction of formulas and complementary foods were collected by questionnaires at 6, 12, and 18 months of age. Allergy was diagnosed by pediatricians at 3 years of age. The only difference in food-introduction practices observed between farm and non-farm children was an earlier introduction of nuts in farmers (median month: 11 [IQR: 8-6] in farmers, 15 [12-19] in non-farmers). One farm child (4%) and 10 non-farm children (27%) were allergic at 3 years of age. Lower risk of allergy development was associated with early exclusive breastfeeding (continuous variable; OR = 0.59, 95% CI: 0.39-0.89), but also having received eggs (OR = 0.08, 95% CI: 0.13-0.54) and fish (logistic regression not applicable, P = 0.01 in likelihood ratio testing [chi(2)]) at 10 months of age or earlier compared to later. Our results were not affected by reverse causation, as judged by a questionnaire sent to the families in retrospect. Timing of introduction of complementary foods is unlikely to contribute to the lower risk of allergy among farm children. Although early exclusive breastfeeding was associated with a lower rate of allergy development, postponed introduction of complementary foods might increase the risk of developing allergy. Owing to the limited sample size, our results are only indicative, but support prior findings.
18.	Jonsson, Karin, 1982, et al. (author) Serum fatty acids in infants, reflecting family fish consumption, were inversely associated with allergy development but not related to farm residence. : Serum fatty acids and allergy in farm and control children 2016 In: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 105:12, s. 1462-1471 Journal article (peer-reviewed)abstract AIM: In this study, differences in serum fatty acid patterns between farm and non-farm infants were investigated and related to subsequent allergy development. We also related allergy-related serum fatty acids to maternal diet and breast milk fatty acids. METHODS: The FARMFLORA birth cohort included 28 farm and 37 non-farm infants. Serum was obtained from 21 farm infants and 29 controls at four months postpartum and analysed for phospholipid fatty acids. Allergy was diagnosed by paediatricians at three years of age. RESULTS: Serum fatty acid patterns were similar in farm and control infants, although farm infants had lower 18:1 omega-7 proportions. Serum proportions of eicosapentaenoic acid (EPA) were unrelated to farming status, but lower in children who subsequently developed allergy, with an odds ratio of 0.47 and 95% confidence interval of 0.27-0.83 (p=0.01) for every 0.1% EPA increase. The infants' serum EPA proportions correlated with breast milk EPA proportions, which, in turn, correlated with maternal oily fish intake during lactation. CONCLUSION: The allergy protective effect of farming was not linked to infant serum fatty acid composition. However, healthy infants had higher proportions of EPA in their sera, probably reflecting a family diet rich in fish, compared to subsequently allergic children.
19.	Jonsson, Karin, 1982, et al. (author) Serum fatty acids in infants, reflecting family fish consumption, were inversely associated with allergy development but not related to farm residence. 2016 In: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 105:12, s. 1462-1471 Journal article (peer-reviewed)abstract AIM:In this study, differences in serum fatty acid patterns between farm and non-farm infants were investigated and related to subsequent allergy development. We also related allergy-related serum fatty acids to maternal diet and breast milk fatty acids.METHODS:The FARMFLORA birth cohort included 28 farm and 37 non-farm infants. Serum was obtained from 21 farm infants and 29 controls at four months postpartum and analysed for phospholipid fatty acids. Allergy was diagnosed by paediatricians at three years of age.RESULTS:Serum fatty acid patterns were similar in farm and control infants, although farm infants had lower 18:1 omega-7 proportions. Serum proportions of eicosapentaenoic acid (EPA) were unrelated to farming status, but lower in children who subsequently developed allergy, with an odds ratio of 0.47 and 95% confidence interval of 0.27-0.83 (p=0.01) for every 0.1% EPA increase. The infants' serum EPA proportions correlated with breast milk EPA proportions, which, in turn, correlated with maternal oily fish intake during lactation.CONCLUSION:The allergy protective effect of farming was not linked to infant serum fatty acid composition. However, healthy infants had higher proportions of EPA in their sera, probably reflecting a family diet rich in fish, compared to subsequently allergic children.
20.	Jönsson, Bodil, 1959, et al. (author) Molecular epidemiology of Mycobacterium abscessus, with focus on cystic fibrosis. 2007 In: Journal of clinical microbiology. - 0095-1137. ; 45:5, s. 1497-504 Journal article (peer-reviewed)abstract Mycobacterium abscessus has been isolated increasingly often from the respiratory tracts of cystic fibrosis (CF) patients. It is not known whether these organisms are transmitted from person to person or acquired from environmental sources. Here, colony morphology and pulsed-field gel electrophoresis (PFGE) pattern were examined for 71 isolates of M. abscessus derived from 14 CF patients, three non-CF patients with chronic respiratory M. abscessus infection or colonization, one patient with mastoiditis, and four patients with infected wounds, as well as for six isolates identified as environmental contaminants in various clinical specimens. Contaminants and wound isolates mainly exhibited smooth colony morphology, while a rough colony phenotype was significantly associated with chronic airway colonization (P=0.014). Rough strains may exhibit increased airway-colonizing capacity, the cause of which remains to be determined. Examination by PFGE of consecutive isolates from the same patient showed that they all represented a single strain, even in cases where both smooth and rough isolates were present. When PFGE patterns were compared, it was shown that 24 patients had unique strains, while four patients harbored strains indistinguishable by PFGE. Two of these were siblings with CF. The other two patients, one of whom had CF, had not had contact with each other or with the siblings. Our results show that most patients colonized by M. abscessus in the airways have unique strains, indicating that these strains derive from the environment and that patient-to-patient transmission rarely occurs.
21.	Kondori, Nahid, 1967, et al. (author) Candida species as commensal gut colonizers: A study of 133 longitudinally followed Swedish infants. 2020 In: Medical mycology. - 1460-2709. ; 58:4, s. 485-92 Journal article (peer-reviewed)abstract The gut microbiota harbor a wide range of bacterial species, but also yeasts may be part of this ecosystem. Infants who are being treated in intensive care units are often colonized by Candida species. However, little is known regarding commensal yeast colonization of healthy infants and young children. Here the acquisition of yeast species was studied in a birth-cohort including 133 healthy Swedish infants. A rectal swab sample was obtained on day 3 of life, and fresh fecal samples were obtained at regular intervals up to 3 years of age; the samples were cultured quantitatively for yeasts. Colonization with yeasts increased rapidly in the first months of life, with 73/133 infants (55%) colonized at 6 months of age. The yeast numbers in positive samples decreased from an average of 105 cfu/g in infants aged 0-2 months to 103.5 cfu/g at 3 years of age. Candida albicans was the most frequently isolated species and reached higher population counts than the other species in culture-positive infants. The yeast colonization rate did not differ between infants who were delivered vaginally and those birthed via Caesarean section, whereas breastfed infants showed a lower colonization rate (p < 0.05 for 1 year of age compared to the other infants). The results demonstrate that yeasts, particularly C. albicans and C. parapsilosis (sensu lato), are common commensals in the gut microbiota of healthy infants and young children.
22.	Käppi, Timo, 1975, et al. (author) High frequency of concomitant food allergy development and autoantibody formation in children who have undergone liver transplantation 2019 In: Transplantation. - 1534-6080. ; 103:11, s. 2338-2346 Journal article (peer-reviewed)abstract Allergy and other immune-mediated diseases are more frequently reported in children who have undergone liver transplantation. Furthermore, autoantibodies are also prevalent, suggesting a state of immune dysregulation in these patients. Whether or not these processes occur simultaneously in the same individual has not been studied previously.A cohort of 43 children who had undergone liver transplantation for nonautoimmune liver disease at median age of 1.3 years was investigated for allergy and autoimmune disease. Sensitization to food and inhalant allergens was assessed and autoantibodies were measured.The prevalence of food allergy was 26% and that of respiratory allergy was 23%, while 33% and 26% of the subjects were sensitized to food and inhalant allergens, respectively. Autoimmune disease (i.e., autoimmune hepatitis) occurred in a single individual (2%), whereas autoantibodies were present in 44% of the children. Food allergy and autoantibodies occurred concomitantly in 19% of the children, which was almost twice the frequency expected by chance (11%, p=0.04). Respiratory allergy and the presence of autoantibodies were unrelated (12% concurrence vs the expected 10%, p = 0.73). In the logistic regression analysis, autoantibody formation was associated with discontinued immunosuppression and food allergy, with odds ratios of 13 (p=0.01) and 7.1 (p=0.03), respectively.In contrast to respiratory allergy, food allergy and autoantibody formation occurred together in the same children who underwent liver transplantation at a frequency higher than would be expected by chance. This may reflect an underlying immune dysregulation that impairs immune tolerance to both food allergens and autoantigens.
23.	Lindberg, Erika, 1976, et al. (author) Effect of lifestyle factors on Staphylococcus aureus gut colonization in Swedish and Italian infants. 2011 In: Clinical microbiology and infection. - : Elsevier BV. - 1469-0691 .- 1198-743X. ; 17:8, s. 1209-1215 Journal article (peer-reviewed)abstract Clin Microbiol Infect ABSTRACT: In recent years, Staphylococcus aureus has become a common bowel colonizer in Swedish infants. We aimed to identify host factors that determine such colonization. Stool samples from 100 Italian and 100 Swedish infants were obtained on seven occasions during the first year of life and cultured quantitatively for S.aureus. In a subgroup of infants in each cohort, individual strains were identified by random amplified polymorphic DNA analysis. Colonization at each time-point was related to delivery mode, siblings in family and antibiotic treatment. In total, 66% of the Italian and 78% of the Swedish infants had S.aureus in their stools on at least one time-point (p 0.08) and 4% of Italian and 27% of Swedish infants were positive on at least six of the seven time-points investigated (p0.0001). Most infants analysed regarding strain carriage harboured a single strain in their microbiota for several months. The S.aureus stool populations in colonized infants decreased from 10(7) to 10(4) colony-forming units/g between 1week and 1year of age in both cohorts. In multivariate analysis, the strongest predictor for S.aureus colonization was being born in Sweden (OR 3.4 at 1week of age, p0.002). Having (an) elder sibling(s) increased colonization at peak phase (OR 1.8 at 6months, p0.047). Antibiotic treatment was more prevalent among Italian infants and correlated negatively with S.aureus colonization at 6months of age (OR 0.3, p0.01). To conclude, S.aureus is a more common gut colonizer in Swedish than Italian infants, a fact that could not be attributed to feeding or delivery mode.
24.	Lindberg, Erika, 1976, et al. (author) High rate of transfer of Staphylococcus aureus from parental skin to infant gut flora. 2004 In: Journal of clinical microbiology. - 0095-1137. ; 42:2, s. 530-4 Journal article (peer-reviewed)abstract Many Swedish infants carry Staphylococcus aureus in their intestinal microflora. The source of this colonization was investigated in 50 families. Infantile S. aureus strains were isolated from rectal swabs and stool samples at 3 days and at 1, 2, 4, and 8 weeks of age. The strains were identified by using the random amplified polymorphic DNA method and compared to strains from swab cultures of the mothers' hands, nipples, and nares and from the fathers' hands and nares. Maternal stool samples were also obtained at a later stage to compare infant and adult intestinal S. aureus colonization. Although 60% of 1-month-old children had S. aureus in the stools, this was true of only 24% of the mothers. The median population numbers in colonized individuals also differed: 10(6.8) CFU/g of feces among infants at 2 weeks of age versus 10(3.2) CFU/g of feces in the mothers. Of S. aureus strains in the stools of 3-day-old infants, 90% were identical to a parental skin strain. A total of 96% of infants whose parents were S. aureus skin carriers had S. aureus in their feces and 91% had the same strain as at least one of the parents. In comparison, only 37% of infants to S. aureus-negative parents had S. aureus in the stool samples. Thus, infantile intestinal S. aureus colonization was strongly associated with parental skin S. aureus carriage (P = 0.0001). These results suggest that S. aureus on parental skin establish readily in the infantile gut, perhaps due to poor competition from other gut bacteria.
25.	Lundell, Anna-Carin, 1976, et al. (author) High circulating immunoglobulin A levels in infants are associated with intestinal toxigenic Staphylococcus aureus and a lower frequency of eczema. 2009 In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222. ; 39:5, s. 662-70 Journal article (peer-reviewed)abstract BACKGROUND: Intestinal bacteria trigger IgA production and delayed maturation of mucosal IgA response is linked to allergy development. OBJECTIVE: Our aim was to investigate if plasma levels of IgA or APRIL (a proliferation inducing ligand), an important factor for IgA class switch recombination, in infancy correlates with intestinal colonization by any specific bacteria or yeast. We also examined if plasma IgA or APRIL levels are related to sensitization and the development of eczema. METHODS: IgA was quantified in plasma obtained from infants at birth and at 4 and 18 months of age and APRIL was measured at 4 months of age. Colonization by major bacterial groups and yeast was followed in the first 8 weeks of life by quantitative culture of stool samples. A clinical evaluation regarding the presence of allergen-specific IgE or eczema and eosinophil counts in blood was performed at 18 months of age. RESULTS: In multiple linear regression analysis, only colonization by Staphylococcus aureus strains producing toxins with superantigen function (SEA-D or TSST-1) made an independent contribution to plasma IgA levels at 4 months of age. Further, increased levels of APRIL in plasma at 4 months were negatively associated with sensitization while IgA plasma levels were inversely correlated to eczema development and blood eosinophil counts at 18 months of age. CONCLUSION: Early intestinal colonization by toxigenic S. aureus strains seems to promote systemic IgA responses. Furthermore, high levels of APRIL and IgA in the circulation at 4 months of age seem to correlate negatively with allergy development.
26.	Lundell, Anna-Carin, 1976, et al. (author) High Proportion of CD5(+) B Cells in Infants Predicts Development of Allergic Disease 2014 In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 193:2, s. 510-518 Journal article (peer-reviewed)abstract Delayed maturation of the immune system has been proposed to be a risk factor for development of allergy, but B cell maturation in relation to allergic disease has not been examined. B cells lose CD5 and acquire CD27 during maturation from immature via mature/naive to Ig-secreting cells and memory cells. We sought to investigate B cell maturation in relation to development of allergic disease and sensitization in the FARMFLORA birth cohort including 65 Swedish children. Total B cell numbers, proportions of CD5(+) and CD27(+) B cells, and levels of IgM, IgG, IgA, and IgE were measured in blood on repeated occasions from birth to 36 mo of age, and related to allergic disease and sensitization at 18 and 36 mo of age with multivariate discriminant analysis. We also compared the expression of CD24 and CD38 within CD5(+) and CD5(neg) B cells in children and in adults. We found that infants with a high proportion of CD5(+) B cells at birth and at 1 mo of age had an increased risk for having allergic disease at 18 and 36 mo of life. Further, the proportions of CD5(+) B cells at 1 mo of age were inversely correlated with total IgG levels at 18 and 36 mo of age. The majority of the CD5(+) B cells were of a CD24(hi/+)CD38(hi/+) immature/naive phenotype at birth (97%), 7 y of age (95%), and in adults (86%). These results suggest that development of allergic disease is preceded by an immaturity in neonatal B cell phenotype.
27.	Lundell, Anna-Carin, 1976, et al. (author) Higher B-cell activating factor levels at birth are positively associated with maternal dairy farm exposure and negatively related to allergy development 2015 In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749. ; 136:4, s. 1074- Journal article (peer-reviewed)abstract A high proportion of circulating immature/naive CD5(+) B cells during early infancy is a risk factor for allergy development. B-cell activating factor (BAFF) is an important cytokine for B-cell maturation.
28.	Lundell, Anna-Carin, 1976, et al. (author) Increased levels of circulating soluble CD14 but not CD83 in infants are associated with early intestinal colonization with Staphylococcus aureus 2007 In: Clin Exp Allergy. ; 37:1, s. 62-71 Journal article (peer-reviewed)abstract BACKGROUND: Soluble forms of the monocyte marker CD14 and the mature dendritic cell marker CD83 are plasma proteins with immunoregulatory functions. The physiological stimulus for their production is unclear and their possible role in allergy development is unknown. METHODS: We measured the plasma levels of soluble CD14 (sCD14) and soluble CD83 (sCD83) in 64 Swedish children in relation to intestinal bacterial colonization pattern in a prospective birth cohort. Soluble CD14 and sCD83 levels were quantified by enzyme linked immunosorbent assay in plasma obtained at birth and at 4, 18 and 36 months of age. All major aerobic and anaerobic bacteria were quantified in faecal samples obtained regularly over the first 8 weeks of life. Clinical allergy and IgE levels were evaluated at 18 months of age. RESULTS: Soluble CD14 in plasma increased during the first 18 months of life while sCD83 peaked at 4 months of age. Children who were perinatally colonized with Staphylococcus aureus had significantly higher levels of sCD14 in plasma at 4 months of age relative to non-colonized children. The levels of sCD14 were unrelated to colonization with Escherichia coli, other enterobacteria, enterococci, clostridia, Bacteroides, bifidobacteria or lactobacilli. Further, children with food allergy by 18 months tended to have lower levels of sCD14 than healthy children. Plasma levels of sCD83 were not related to either bacterial colonization pattern or allergy development. CONCLUSIONS: Perinatal colonization with S. aureus may trigger the occurrence of sCD14 in plasma, which may influence development of the infantile immune system and risk of allergy development.
29.	Malmquist, Marianne, 1961, et al. (author) Frequent Occurrence of Perianal Disease and Granuloma Formation in Patients with Crohn's Disease and Coexistent Orofacial Granulomatosis 2023 In: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 68:7, s. 3129-3138 Journal article (peer-reviewed)abstract BackgroundOrofacial granulomatosis (OFG) is an inflammatory disorder of the perioral region and oral cavity. Crohn's disease (CD) in conjunction with OFG (CD-OFG), has been suggested to constitute a phenotype of CD with distinct features at diagnosis.AimsThe aim of this project was to investigate whether the distinct phenotypic features of CD-OFG persist in the years following the initial diagnosis of CD.MethodsClinical data were extracted from medical records covering the first 5 years post-diagnosis for a cohort of patients with CD-OFG, and were compared to those of references with CD without OFG.ResultsThe clinical characteristics of our cohort of patients with CD-OFG (N = 25) were evaluated in comparison to references with CD without OFG (ratio 1:2). Five years post-diagnosis, more patients with CD-OFG had a phenotype with perianal disease (cumulative incidence: 16/25, 64% vs 13/50, 26%, P = 0.002) and intestinal granulomas (cumulative incidence: 22/25, 88% vs 24/50, 48%, P = 0.0009) than patients in the CD reference group. The patients with CD-OFG were also more likely to have undergone perianal surgery (12/25, 48% vs 4/50, 8%, P = 0.0002). At the end of the observation period, more of the patients with CD-OFG were receiving combination therapy, i.e., immunomodulators and tumor necrosis factor antagonists, than those in the CD reference group (9/25, 36% vs 5/50, 10%, P = 0.01).ConclusionThe results support the notion that CD in conjunction with OFG represents a specific phenotype of CD that is characterized by frequent perianal disease, pronounced intestinal granuloma formation and a need for extensive therapy.
30.	Nordström, Inger, 1958, et al. (author) Infection of infants with human herpesvirus type 6 may be associated with reduced allergic sensitization and T-helper type 2 development. 2010 In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222. ; 40:6, s. 882-90 Journal article (peer-reviewed)abstract Epidemiological studies point to an inverse relationship between microbial exposure and the prevalence of allergic diseases. The underlying mechanism for this observation remains largely unknown, as well as the nature of the microbes involved.
31.	Nowrouzian, Forough, 1957, et al. (author) Adhesin and superantigen genes and the capacity of Staphylococcus aureus to colonize the infantile gut. 2011 In: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 204:5, s. 714-21 Journal article (peer-reviewed)abstract Staphylococcus aureus is a pathogen and a skin commensal that is today also common in the infant gut flora. We examine the role of S. aureus virulence factors for gut colonization. S. aureus isolated from quantitative stool cultures of 49 Swedish infants followed from birth to 12 months of age were assessed for 30 virulence-associated genes, spa type, and agr allele by serial polymerase chain reaction (PCR) assays. Strains carrying genes encoding collagen-binding protein, and the superantigens S. aureus enterotoxin O/M (SEO/SEM) had higher stool counts than strains lacking these genes, whereas genes for S. aureus enterotoxin A (SEA) were associated with low counts. A cluster of strains belonging to agr allele I and the spa clonal cluster 630 (spa-CC 630) that carried genes encoding SEO/SEM, SEC, collagen-binding protein, and elastin-binding protein were all long-time colonizers. Thus, certain S. aureus virulence factors might promote gut colonization.
32.	Nowrouzian, Forough, 1957, et al. (author) Bacterial Carriage of Genes Encoding Fibronectin-Binding Proteins Is Associated with Long-Term Persistence of Staphylococcus aureus in the Nasal and Gut Microbiota of Infants 2021 In: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 87:15 Journal article (peer-reviewed)abstract Staphylococcus aureus can colonize both the anterior nares and the gastrointestinal tract. However, colonization at these sites in the same individuals has not been studied, and the traits that facilitate colonization and persistence at these sites have not been compared. Samples from the nostrils and feces collected on 9 occasions from 3 days to 3 years of age in 65 infants were cultured; 54 samples yielded S. aureus. The numbers of nasal and fecal S. aureus strains increased rapidly during the first weeks and were similar at 1 month of age (>40% of infants colonized). Thereafter, nasal carriage declined, while fecal carriage remained high during the first year of life. Individual strains were identified, and their colonization patterns were related to their carriage of genes encoding adhesins and superantigenic toxins. Strains retrieved from both the nose and gut (n =44) of an infant were 4.5 times more likely to colonize long term (>= 3 weeks at both sites) than strains found only in the rectum/feces (n = 56) or only in the nose (n = 32) (P <= 0.001). Gut colonization was significantly associated with carriage of the fnbA gene, and long-term colonization at either site was associated with carriage of fnbA and fnbB. In summary, gut colonization by S. aureus was more common than nasal carnage by S. aureus in the studied infants. Gut strains may provide a reservoir for invasive disease in vulnerable individuals. Fibronectin-binding adhesins and other virulence factors may facilitate commensal colonization and confer pathogenic potential. IMPORTANCE S. aureus may cause severe infections and frequently colonizes the nose. Nasal carriage of S. aureus increases 3-fold the risk of invasive S. aureus infection. S. aureus is also commonly found in the gut microbiota of infants and young children. However, the relationships between the adhesins and other virulence factors of S. aureus strains and its abilities to colonize the nostrils and gut of infants are not well understood. Our study explores the simultaneous colonization by S. aureus of the nasal and intestinal tracts of newborn infants through 3 years of follow-up. We identify bacterial virulence traits that appear to facilitate persistent colonization of the nose and gut by S. aureus. This expands our current knowledge of the interplay between bacterial commensalism and pathogenicity. Moreover, it may contribute to the development of targeted strategies for combating S. aureus infection.
33.	Nowrouzian, Forough, 1957, et al. (author) Escherichia coli B2 Phylogenetic Subgroups in the Infant Gut Microbiota: Predominance of Uropathogenic Lineages in Swedish Infants and Enteropathogenic Lineages in Pakistani Infants 2019 In: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 85:24 Journal article (peer-reviewed)abstract Escherichia coli segregates into phylogenetic groups, with group B2 containing both extraintestinal pathogenic E. coli (ExPEC) and enteropathogenic E. coli (EPEC) strains. Ten main B2 subgroups (subgroups I to X)/sequence type complexes (STcs), as well as EPEC lineages, have been identified. In the current study, we characterized ExPEC and EPEC strains of E. coli B2 phylogenetic subgroups/STcs that colonize Swedish and Pakistani infants. Gut commensal E. coli B2 strains, 120 from Swedish infants (n = 87) and 19 from Pakistani infants (n = 12), were assigned to B2 subgroups. Carriage of the bundle-forming pili and intimin adhesin was examined in the EPEC lineages. The ExPEC virulence markers and the time of persistence of the strains in the microbiota were previously determined. In total, 84% of the Swedish strains and 47% of the Pakistani strains belonged to 1 of the 10 main B2 subgroups (P = 0.001). Among the Swedish strains, the most common B2 subgroups were IX/STc95 (19%), II/STc73 (17%), VI/STc12 (13%), and III/STc127 (11%), with each subgroup carrying distinctive sets of ExPEC virulence markers. EPEC lineages with few ExPEC features constituted 47% of the Pakistani B2 strains but only 7% of the Swedish B2 strains (P = 0.0001). The subgroup distribution within phylogenetic group B2 strains colonizing the gut differed between Swedish and Pakistani infants. B2 subgroups with uropathogenic characteristics dominated the gut microbiota of Swedish infants, while EPEC lineage 1 strains frequently colonized the intestines of Pakistani infants. Moreover, within the B2 subgroups, ExPEC virulence genes were more prevalent in Swedish strains than in Pakistani strains. Thus, ExPEC traits exemplify the intestinal B2 strains from Western populations. IMPORTANCE The intestinal microbiota is an important reservoir for bacteria that cause extraintestinal infections. Escherichia coli is found ubiquitously in the gut microbiota, and it also causes urinary tract infections, infantile septicemia, and meningitis. Urinary tract infections are usually caused by E. coli strains that originate in the intestinal microbiota. E. coli also causes gastrointestinal infections and is a major cause of diarrhea in infants worldwide. The abilities of certain E. coli strains to cause infections are attributed to their virulence factors, i.e., bacterial components that contribute to the development of different diseases. Our study shows that different subtypes of potentially pathogenic E. coli strains dominate in the gut microbiota of infants in different geographical areas and expands our knowledge of the interplay between bacterial commensalism and pathogenicity.
34.	Nowrouzian, Forough, 1957, et al. (author) Escherichia coli in infants' intestinal microflora: colonization rate, strain turnover, and virulence gene carriage. 2003 In: Pediatric research. - 0031-3998. ; 54:1, s. 8-14 Journal article (peer-reviewed)abstract Colonization by Escherichia. coli in infants might have decreased in the last decades, owing to changes in hospital routines and family lifestyle. In this study, the E. coli flora was characterized in 70 healthy Swedish infants followed for the first year of life. E. coli was isolated from rectal swabs obtained at 3 d of age and quantified in fecal samples collected at 1, 2, 4, and 8 wk of age and at 6 and 12 mo of age. Strains were typed using random amplified polymorphic DNA, and their virulence factor genes were identified by multiplex PCR. Colonization by E. coli occurred late; only 61% of the infants were positive by 2 mo of age. The turnover of individual strains in the microflora was slow (1.5 strains per infant during 6 mo, 2.1 during 1 y). Environmental factors, such as siblings, pets, or feeding mode, did not influence colonization kinetics or strain turnover rate. Genes encoding type 1 fimbriae, P fimbriae, and hemolysin were significantly more common in E. coli strains persisting for at least 3 wk in the microflora than in transient strains. The P-fimbrial class III adhesin gene was more common in E. coli from children who had a cat in their homes than in E. coli from children without pets (p = 0.01); this adhesin type is common in E. coli from cats. The late colonization and low E. coli strain turnover rate suggest limited exposure of Swedish infants to E. coli. Our results confirm that P fimbriae and other virulence factors facilitate persistence of E. coli in the human colonic microflora.
35.	Nowrouzian, Forough, 1957, et al. (author) Neonatal gut colonization by Staphylococcus aureus strains with certain adhesins and superantigens is negatively associated with subsequent development of atopic eczema 2019 In: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 180:6, s. 1481-1488 Journal article (peer-reviewed)abstract Background Insufficient early immune stimulation may predispose to atopic disease. Staphylococcus aureus, a skin and gut colonizer, produces the B-cell mitogen protein A and T-cell-activating superantigens. Early gut colonization by S. aureus strains that possess the superantigens encoded by the enterotoxin gene (egc) cluster and elastin-binding protein is negatively associated with development of atopic eczema. Objectives To investigate (i) whether these findings could be replicated in a second birth cohort, FARMFLORA, and (ii) whether nasal colonization by S. aureus also relates to subsequent atopic eczema development. Methods Faecal samples and nasal swabs from infants in the FARMFLORA birth cohort (n = 65) were cultured for S. aureus. Individual strains were distinguished by random amplified polymorphic DNA and assessed for adhesin and superantigen gene carriage by polymerase chain reaction. Atopic eczema at 18 months of age was related to nasal and gut S. aureus colonization patterns during the first 2 months of life (well before onset of eczema). Results Staphylococcus aureus colonization per se was unrelated to subsequent eczema development. However, gut S. aureus strains from the infants who subsequently developed atopic eczema less frequently carried the ebp gene, encoding elastin-binding protein, and superantigen genes encoded by egc, compared with strains from children who remained healthy. Nasal colonization by S. aureus was less clearly related to subsequent eczema development. Conclusions The results precisely replicate our previous observations and may suggest that mucosal colonization by certain S. aureus strains provides immune stimulation that strengthens the epithelial barrier and counteracts the development of atopic eczema.
36.	Nowrouzian, Forough, 1957, et al. (author) Phylogenetic group B2 Escherichia coli strains from the bowel microbiota of Pakistani infants carry few virulence genes and lack the capacity for long-term persistence. 2009 In: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. - : Elsevier BV. - 1469-0691. ; 15:5, s. 466-72 Journal article (peer-reviewed)abstract Escherichia coli strains of phylogenetic group B2 obtained from Western human hosts are enriched in virulence-associated genes and have a superior capacity to persist in the colonic microbiota. Here, E . coli strains from 22 infants born in Pakistan whose rectal flora was sampled regularly over the first 6 months of life were examined. B2 strains did not carry the virulence-associated genes sfaD/E, papC, neuB or hlyA more often than strains of other phylogenetic groups. B2 origin was not associated with persistence in the bowel microbiota. As compared with B2 strains from Swedish infants, Pakistani B2 strains carried significantly less often the virulence genes fimH (p 0.04), papC (p 0.02), papG class III (p 0.01), sfaD/E (p < or =0.0001), neuB (p < or =0.0001), and hlyA (p 0.005), and also the high-pathogenicity island (p < or =0.0001). A minority of Pakistani B2 strains belonged to recognized uropathogenic O-groups, which are common among 'Western' B2 strains. Thus, extra-intestinal pathogenicity may be the foremost characteristic of B2 strains colonizing Western populations.
37.	Ross, Alastair, 1976, et al. (author) Umbilical cord blood metabolome differs in relation to delivery mode, birth order and sex, maternal diet and possibly future allergy development in rural children 2021 In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:1 Journal article (peer-reviewed)abstract Allergy is one of the most common diseases among young children yet all factors that affect development of allergy remain unclear. In a small cohort of 65 children living in the same rural area of south-west Sweden, we have previously found that maternal factors, including prenatal diet, affect childhood allergy risk, suggesting that in utero conditions may be important for allergy development. Here, we studied if metabolites in the umbilical cord blood of newborns may be related to development of childhood allergy, accounting for key perinatal factors such as mode of delivery, birth order and sex. Available umbilical cord blood plasma samples from 44 of the participants were analysed using gas chromatography-mass spectrometry metabolomics; allergy was diagnosed by specialised paediatricians at ages 18 months, 3 years and 8 years and included eczema, asthma, food allergy and allergic rhinoconjunctivitis. Nineteen cord blood metabolites were related to future allergy diagnosis though there was no clear pattern of up- or downregulation of metabolic pathways. In contrast, perinatal factors birth order, sex and mode of delivery affected several energy and biosynthetic pathways, including glutamate and aspartic acid-histidine metabolism (p = 0.004) and the tricarboxylic acid cycle (p = 0.006) for birth order; branched chain amino acid metabolism (p = 0.0009) and vitamin B-6 metabolism (p = 0.01) for sex; and glyoxylate and dicarboxylic acid metabolism (p = 0.005) for mode of delivery. Maternal diet was also related to some of the metabolites associated with allergy. In conclusion, the cord blood metabolome includes individual metabolites that reflect lifestyle, microbial and other factors that may be associated with future allergy diagnosis, and also reflects temporally close events/factors. Larger studies are required to confirm these associations, and perinatal factors such as birth order or siblings must be considered in future cord-blood metabolome studies.
38.	Schwab, U E, et al. (author) Increased adherence of Staphylococcus aureus from cystic fibrosis lungs to airway epithelial cells. 1993 In: The American review of respiratory disease. - 0003-0805. ; 148:2, s. 365-9 Journal article (peer-reviewed)abstract Airway colonization by Staphylococcus aureus is a frequent feature of cystic fibrosis (CF). To assess the pathogenesis of selective colonization with this organism, we compared the capacity of S. aureus isolated from the respiratory tract of CF and non-CF patients to adhere to epithelial cells from the upper and lower airways of CF and control subjects. Bacterial adherence to bronchial epithelial cell lines was significantly greater for CF than for non-CF isolates (p < 0.001). Of 17 CF S. aureus isolates 12 adhered at a level > 1 bacterium per cell; this was true for only 1 of 14 non-CF isolates. CF S. aureus isolates also bound more avidly than non-CF isolates to ciliated (p < 0.05) and squamous nasal cells (p < 0.02) and buccal epithelial cells (p < 0.005) freshly harvested by scraping. Each S. aureus isolate bound with equal avidity to epithelial cells from CF patients and healthy individuals. Adherence was not related to sex, age, severity of pulmonary disease, presence of other microorganisms in the airways, or genotype of the CF hosts. Binding of S. aureus was blocked by proteinase treatment of organisms, suggesting that adherence is mediated by one or more peptide adhesins. We propose that the high prevalence of adherent S. aureus is due either to selection of adherent strains by CF airways or to induction of an adherent phenotype by factors residing at the CF airways surface.
39.	Skovbjerg, Susann, 1973, et al. (author) Gram-positive and gram-negative bacteria induce different patterns of cytokine production in human mononuclear cells irrespective of taxonomic relatedness. 2010 In: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. - New York, USA : Mary Ann Liebert Inc. - 1557-7465 .- 1079-9907. ; 30:1, s. 23-32 Journal article (peer-reviewed)abstract Upon bacterial stimulation, tissue macrophages produce a variety of cytokines that orchestrate the immune response that clears the infection. We have shown that Gram-positives induce higher levels of interleukin-12 (IL-12), interferon-gamma (IFN-gamma), and tumor necrosis factor (TNF) from human peripheral blood mononuclear cells (PBMCs) than do Gram-negatives, which instead induce more of IL-6, IL-8, and IL-10. Here, we study whether these patterns follows or crosses taxonomic borders. PBMCs from blood donors were incubated with UV-inactivated bacteria representing 37 species from five phyla. IL-12, TNF, IL-1beta, IL-6, IL-8, and IL-10 were measured in the supernatants after 24 h and IFN-gamma after 5 days. Irrespective of phylogenetic position, Gram-positive bacteria induced much more IL-12 (nine times more on average) and IFN-gamma (seven times), more TNF (three times), and slightly more IL-1beta (1.5 times) than did Gram-negatives, which instead induced more IL-6 (1.5 times), IL-8 (1.9 times), and IL-10 (3.3 times) than did Gram-positives. A notable exception was the Gram-positive Listeria monocytogenes, which induced very little IL-12, IFN-gamma, and TNF. The results confirm the fundamental difference in innate immune responses to Gram-positive and Gram-negative bacteria, which crosses taxonomic borders and probably reflects differences in cell wall structure.
40.	Skovbjerg, Susann, 1973, et al. (author) Spray bacteriotherapy decreases middle ear fluid in children with secretory otitis media. 2008 In: Archives of disease in childhood. - : BMJ. - 1468-2044 .- 0003-9888. ; 94:2, s. 92-8 Journal article (peer-reviewed)abstract OBJECTIVE: Secretory otitis media (SOM) is characterized by persistent fluid in the middle ear cavity, but the cause is unknown. We investigated clinical, bacteriological and immunological effects of treatment with probiotic bacteria on SOM. DESIGN: In this double blind, pilot/premlininary study, 60 children with long-standing SOM (median 6 months) who were scheduled for insertion of tympanostomy tubes were randomized to nasal spray treatment with Streptococcus sanguinis, Lactobacillus rhamnosus or placebo for 10 days before surgery. Clinical evaluation was made after 10 days of treatment. Middle ear fluid (MEF) was collected during surgery for quantification of cytokines and detection of bacteria by culture and PCR. Nasopharyngeal swabs were obtained before treatment and at surgery. RESULTS: Complete or significant clinical recovery occurred in 7/19 patients treated with S. sanguinis compared to 1/17 patient in the placebo group (p<0.05). In the L. rhamnosus treatment group 3/18 patients were cured or much better (p=0.60 compared with placebo). Spray treatment did not alter the composition of the nasopharyngeal flora, or the cytokine pattern observed in the nasopharynx or MEF, except a higher level of IL-8 in nasopharynx of L. rhamnosus treated children. CONCLUSIONS: This study shows that spray treatment with S. sanguis may be effective against SOM. The mechanism for the effect remains to be investigated.
41.	Stockfelt, Marit, et al. (author) Circulating proteins associated with allergy development in infants-an exploratory analysis 2021 In: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 18:1 Journal article (peer-reviewed)abstract Background Protein profiles that can predict allergy development in children are lacking and the ideal sampling age is unknown. By applying an exploratory proteomics approach in the prospective FARMFLORA birth cohort, we sought to identify previously unknown circulating proteins in early life that associate to protection or risk for development of allergy up to 8 years of age. Methods We analyzed plasma prepared from umbilical cord blood (n = 38) and blood collected at 1 month (n = 42), 4 months (n = 39), 18 months (n = 42), 36 months (n = 42) and 8 years (n = 44) of age. We profiled 230 proteins with a multiplexed assay and evaluated the global structure of the data with principal component analysis (PCA). Protein profiles informative to allergic disease at 18 months, 36 months and/or 8 years were evaluated using Lasso logistic regression and random forest. Results Two clusters emerged in the PCA analysis that separated samples obtained at birth and at 1 month of age from samples obtained later. Differences between the clusters were mostly driven by abundant plasma proteins. For the prediction of allergy, both Lasso logistic regression and random forest were most informative with samples collected at 1 month of age. A Lasso model with 27 proteins together with farm environment differentiated children who remained healthy from those developing allergy. This protein panel was primarily composed of antigen-presenting MHC class I molecules, interleukins and chemokines. Conclusion Sampled at one month of age, circulating proteins that reflect processes of the immune system may predict the development of allergic disease later in childhood.
42.	Stråvik, Mia, 1994, et al. (author) Maternal Intake of Cow's Milk during Lactation Is Associated with Lower Prevalence of Food Allergy in Offspring 2020 In: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 12:12, s. 1-19 Journal article (peer-reviewed)abstract Maternal diet during pregnancy and lactation may affect the propensity of the child to develop an allergy. The aim was to assess and compare the dietary intake of pregnant and lactating women, validate it with biomarkers, and to relate these data to physician-diagnosed allergy in the offspring at 12 months of age. Maternal diet during pregnancy and lactation was assessed by repeated semi-quantitative food frequency questionnaires in a prospective Swedish birth cohort (n = 508). Fatty acid proportions were measured in maternal breast milk and erythrocytes. Allergy was diagnosed at 12 months of age by a pediatrician specialized in allergy. An increased maternal intake of cow's milk during lactation, confirmed with biomarkers (fatty acids C15:0 and C17:0) in the maternal blood and breast milk, was associated with a lower prevalence of physician-diagnosed food allergy by 12 months of age. Intake of fruit and berries during lactation was associated with a higher prevalence of atopic eczema at 12 months of age. Our results suggest that maternal diet modulates the infant's immune system, thereby influencing subsequent allergy development.
43.	Strömbeck, Anna, et al. (author) Allergic disease in 8-year old children is preceded by delayed B-cell maturation. 2017 In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222. ; 47:7, s. 918-928 Journal article (peer-reviewed)abstract We previously reported that exposure to a farming environment is allergy-protective, while high proportions of neonatal immature/naïve CD5(+) B cells and putative regulatory T cells (Tregs) are risk factors for development of allergic disease and sensitization up to 3 years of age.To examine if B- and T-cell maturation are associated with allergic disease and farming environment over the first 8 years in life.In the prospective FARMFLORA study, including both farming and non-farming families, 48 out of 65 children took part in the 8-year follow-up study. Various B- and T-cell maturation variables were examined in blood samples obtained at several occasions from birth to 8 years of age and related to doctors' diagnosed allergic disease and sensitization, and to farming environment.We found that the incidence of allergic disease was lower among farmers' compared to non-farmers' children during the 8-years follow-up period, and that farmers' children had higher proportions of memory B cells at 8 years of age. Moreover, a high proportion of neonatal CD5(+) B cells was a risk factor for and may predict development of allergic disease at 8 years of age. A high proportion of Tregs was not protective against development of these conditions.High proportions of neonatal naïve B cells remained as a risk factor for allergic disease in school-aged children. Thus, the accelerated B-cell maturation observed among farmers' children may be crucial for the allergy-protective effect of a farming environment. This article is protected by copyright. All rights reserved.
44.	Strömbeck, Anna, et al. (author) High proportions of FOXP3(+) CD25(high) T cells in neonates are positively associated with allergic sensitization later in childhood. 2014 In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222. ; 44:7, s. 940-952 Journal article (peer-reviewed)abstract The role of FOXP3(+) regulatory T cells in the prevention against sensitization and allergy development is controversial.
45.	Wang, Mei, et al. (author) Reduced diversity in the early fecal microbiota of infants developing atopic eczema 2008 In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 121:1, s. 129-134 Journal article (peer-reviewed)abstract Background It might be that early intestinal colonization by bacteria in westernized infants fails to give rise to sufficient immune stimulation to support maturation of regulatory immune mechanisms. Objective The purpose of the present study was to characterize the very early infantile microbiota by using a culture-independent approach and to relate the colonization pattern to development of atopic eczema in the first 18 months of life. Methods Fecal samples were collected from 35 infants at 1 week of age. Twenty infants were healthy, and 15 infants were given diagnoses of atopic eczema at the age of 18 months. The fecal microbiota of the infants was compared by means of terminal restriction fragment length polymorphism (T-RFLP) and temporal temperature gradient gel electrophoresis (TTGE) analysis of amplified 16S rRNA genes. Results By means of T-RFLP analysis, the median number of peaks, Shannon-Wiener index, and Simpson index of diversity were significantly less for infants with atopic eczema than for infants remaining healthy in the whole group and for the Swedish infants when AluI was used for digestion. The same was found when TTGE patterns were compared. In addition, TTGE analysis showed significantly less bands and lower diversity indices for the British atopic infants compared with those of the control subjects. Conclusion There is a reduced diversity in the early fecal microbiota of infants with atopic eczema during the first 18 months of life.
46.	Adlerberth, Ingegerd, 1959, et al. (author) A mannose-specific adherence mechanism in Lactobacillus plantarum conferring binding to the human colonic cell line HT-29. 1996 In: Applied and environmental microbiology. - 0099-2240. ; 62:7, s. 2244-51 Journal article (peer-reviewed)abstract Two Lactobacillus plantarum strains of human intestinal origin, strains 299 (= DSM 6595) and 299v (= DSM 9843), have proved to be efficient colonizers of the human intestine under experimental conditions. These strains and 17 other L. plantarum strains were tested for the ability to adhere to cells of the human colonic cell line HT-29.L.plantarum 299 and 299v and nine other L. plantarum strains, including all six strains that belong to the same genetic subgroup as L. plantarum 299 and 299v, adhered to HT-29 cells in a manner that could be inhibited by methyl-alpha-D-mannoside. The ability to adhere to HT-29 cells correlated with an ability to agglutinate cells of Saccharomyces cerevisiae and erythrocytes in a mannose-sensitive manner and with adherence to D-mannose-coated agarose beads. L. plantarum 299 and 299v adhered to freshly isolated human colonic and ileal enterocytes, but the binding was not significantly inhibited by methyl-alpha-D-mannoside. Periodate treatment of HT-29 cells abolished mannose-sensitive adherence, confirming that the cell-bound receptor was of carbohydrate nature. Proteinase K treatment of the bacteria also abolished adherence, indicating that the binding involved protein structures on the bacterial cell surface. Thus, a mannose-specific adhesin has been identified in L. plantarum; this adhesin could be involved in the ability to colonize the intestine.
47.	Adlerberth, Ingegerd, 1959, et al. (author) Adhesins of Escherichia coli associated with extra-intestinal pathogenicity confer binding to colonic epithelial cells. 1995 In: Microbial pathogenesis. - 0882-4010. ; 18:6, s. 373-85 Journal article (peer-reviewed)abstract Escherichia coli adhesins are virulence factors in intestinal and extra-intestinal infections, but their role in normal intestinal colonization has not been defined. We investigated the intestinal adherence of E. coli with Dr hemagglutinin, S fimbriae, CFA/I or CFA/II, using freshly isolated ileal or colonic enterocytes and cells from the human colonic cell line HT-29. E. coli with S-fimbrial adhesins (Sfa I or Sfa II), P or type 1 fimbriae, adhered in a non-polarized manner, and in similar numbers to colonic and ileal enterocytes. S fimbriae of the variety Sfa II (originating from a meningitis isolate), mediated a stronger binding than Sfa I (of uropathogenic origin). Strains expressing Dr hemagglutinin adhered preferentially to the brush borders, slightly better to colonic than ileal enterocytes. Strains expressing CFA/I or II adhered to colonic and ileal enterocytes, although brush border adherence was predominantly observed with ileal cells. Binding to HT-29 cells paralleled binding to colonic enterocytes for all adhesin specificities except CFA/I. The results suggest that Dr hemagglutinin, P-, type 1- and S-fimbrial adhesins mediate binding to both colonic and ileal enterocytes. These specificities may contribute to the establishment of E. coli in the intestinal microflora, which precedes their spread to extra-intestinal sites.
48.	Adlerberth, Ingegerd, 1959, et al. (author) Establishment of the gut microbiota in Western infants. 2009 In: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 98:2, s. 229-38 Research review (peer-reviewed)abstract In adult individuals, the intestinal microbiota comprises several hundred, mostly anaerobic, bacterial species. This complex ecosystem is formed through the successive establishment of different bacteria in infancy and early childhood. Facultative and aerotolerant bacteria establish first, followed by more and more strict anaerobes. The bacteria derive from different sources and the colonization pattern is influenced by delivery mode and environmental factors. Commensal microbes provide the major drive for maturation of the immune system. Increased hygiene appears to have changed the gut flora of Western infants, which may affect the risk of developing immune mediated diseases. CONCLUSION: It is clear that the process of infant colonization needs to be studied further, since composition of the microbiota may impact on child health.
49.	Adlerberth, Ingegerd, 1959, et al. (author) High turnover rate of Escherichia coli strains in the intestinal flora of infants in Pakistan. 1998 In: Epidemiology and infection. - 0950-2688. ; 121:3, s. 587-98 Journal article (peer-reviewed)abstract The Escherichia coli flora of infants in developed countries is dominated by one or a few strains which persist for prolonged periods of time, but no longitudinal studies have been performed in developing countries. To this end, we studied the rectal enterobacterial flora in 22 home-delivered Pakistani infants during their first 6 months of life. Three colonies were isolated and species typed on each of 11 sampling occasions. E. coli isolates were strain typed using electromorphic typing of cytoplasmic enzymes, and their O serogroups were determined. There was a very rapid turnover of enterobacterial strains in the rectal flora of individual infants. On average, 8.5 different E. coli strains were found per infant, and several biotypes of other enterobacteria. Less than 50% of the infants were colonized with E. coli from their mothers, but strains of maternal origin were four times more likely to persists in the infants' flora than other E. coli strains. Enterobacteria other than E. coli were always of non-maternal origin, and Enterobacter cloacae and Klebsiella pneumoniae biotypes recovered from contaminated feeds were later identified in the infants' rectal flora. An early colonization with klebsiella or enterobacter was significantly associated with diarrhoea during the neonatal period, although these bacteria were not likely to be the cause of the disease. The results suggest that poor hygienic conditions result in an unstable and diverse enterobacterial flora, which may influence infant health.
50.	Adlerberth, Ingegerd, 1959, et al. (author) Interaction of P-fimbriated Escherichia coli with human meconium. 1991 In: FEMS microbiology letters. - 0378-1097. ; 68:1, s. 57-62 Journal article (peer-reviewed)abstract The ability of Escherichia coli with different receptor specificities to interact with meconium was studied. E. coli strains expressing P-fimbriae, specific for Gal alpha 1-4Gal beta-containing receptors, were agglutinated by meconium at high titres. This reaction was inhibited by globotetraosylceramide. The attachment of P-fimbriated E. coli to human colonic epithelial cells of the HT-29 cell line was inhibited by meconium. Some type 1 fimbriated strains were agglutinated by meconium, but the agglutination was rarely blocked by methyl alpha-D-mannoside. The attachment by type 1 fimbriated strains to HT-29 cells was reduced by meconium only in some cases. These results suggest that meconium interacts with the P-fimbriae of E. coli, in a way that may influence bacterial colonization of the neonatal intestine.

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