| 1. |
- Girdhar, Khyati, et al.
(författare)
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Dynamics of the gut microbiome, IgA response, and plasma metabolome in the development of pediatric celiac disease
- 2023
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Ingår i: Microbiome. - : BMC. - 2049-2618. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Celiac disease (CD) is an autoimmune disorder triggered by gluten consumption. Almost all CD patients possess human leukocyte antigen (HLA) DQ2/DQ8 haplotypes; however, only a small subset of individuals carrying these alleles develop CD, indicating the role of environmental factors in CD pathogenesis. The main objective of this study was to determine the contributory role of gut microbiota and microbial metabolites in CD onset. To this end, we obtained fecal samples from a prospective cohort study (ABIS) at ages 2.5 and 5 years. Samples were collected from children who developed CD after the final sample collection (CD progressors) and healthy children matched by age, HLA genotype, breastfeeding duration, and gluten-exposure time (n=15-16). We first used 16S sequencing and immunoglobulin-A sequencing (IgA-seq) using fecal samples obtained from the same children (i) 16 controls and 15 CD progressors at age 2.5 and (ii) 13 controls and 9 CD progressors at age 5. We completed the cytokine profiling, and plasma metabolomics using plasma samples obtained at age 5 (n=7-9). We also determined the effects of one microbiota-derived metabolite, taurodeoxycholic acid (TDCA), on the small intestines and immune cell composition in vivo.Results CD progressors have a distinct gut microbiota composition, an increased IgA response, and unique IgA targets compared to healthy subjects. Notably, 26 plasma metabolites, five cytokines, and one chemokine were significantly altered in CD progressors at age 5. Among 26 metabolites, we identified a 2-fold increase in TDCA. TDCA treatment alone caused villous atrophy, increased CD4+ T cells, Natural Killer cells, and two important immunoregulatory proteins, Qa-1 and NKG2D expression on T cells while decreasing T-regulatory cells in intraepithelial lymphocytes (IELs) in C57BL/6J mice.Conclusions Pediatric CD progressors have a distinct gut microbiota composition, plasma metabolome, and cytokine profile before diagnosis. Furthermore, CD progressors have more IgA-coated bacteria and unique targets of IgA in their gut microbiota. TDCA feeding alone stimulates an inflammatory immune response in the small intestines of C57BJ/6 mice and causes villous atrophy, the hallmark of CD. Thus, a microbiota-derived metabolite, TDCA, enriched in CD progressors plasma, has the potential to drive inflammation in the small intestines and enhance CD pathogenesis.
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| 2. |
- Brekke, Hilde Kristin, 1972, et al.
(författare)
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Breastfeeding and introduction of solid foods in Swedish infants: the All Babies in Southeast Sweden study.
- 2005
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Ingår i: The British journal of nutrition. - 0007-1145 .- 1475-2662. ; 94:3, s. 377-82
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this report is to describe breastfeeding duration and introduction of foods in Swedish infants born 1997-9, in relation to current recommendations. A secondary aim is to examine breastfeeding duration and introduction of certain allergenic foods in allergy-risk families (for whom allergy-preventive advice has been issued). Out of 21,700 invited infants, screening questionnaires were completed for 16,070 infants after delivery. Parents to 11,081 infants completed a follow-up questionnaire regarding breastfeeding and introduction of foods and 9849 handed in detailed food diaries at 1 year of age. The percentages of infants who were exclusively breast-fed at 3, 6 and >or=9 months of age were 78.4, 10.1 and 3.9, respectively. The corresponding percentages for partial breastfeeding were 87.8, 68.9 and 43.6. Gluten-containing foods were introduced to 66% of infants between 4 and 6 months, as recommended at the time of the study, and one-quarter had stopped breastfeeding when gluten was introduced. More than 90% of parents introduced the first sample of solid food during months 4-6, as recommended. Fish and eggs had been introduced during the first year in 43% and 29%, respectively, of infants with atopic heredity. Exclusive breastfeeding duration and time of introduction of solid foods, including gluten, seemed to have been in line with Swedish recommendations at the time, although gluten was often introduced late, and not during ongoing breastfeeding as recommended. The adherence to allergy-preventive advice was less than optimal in infants with atopic heredity.
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| 3. |
- Huus, Karina, et al.
(författare)
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Exclusive breastfeeding of Swedish children and its possible influence on the development of obesity : a prospective cohort study
- 2008
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Ingår i: BMC Pediatrics. - London : BioMed Central. - 1471-2431. ; 8, s. 42-
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Tidskriftsartikel (refereegranskat)abstract
- Background Overweight and obesity are increasing among children all over the world. Socio-economic factors may influence the development of overweight and obesity in childhood, and it has been proposed that breastfeeding may protect against obesity. The aim of our study was to examine the relationship between exclusive breastfeeding and obesity when potential confounders, such as socioeconomic factors, are considered.Methods The data analyzed was from ABIS (All Babies in Southeast Sweden), a prospective cohort study. All parents with children born between October 1, 1997 and October 1, 1999 in Southeast Sweden (n = 21,700) were asked to participate. Parents were asked to answer periodic questionnaires from the time of the child's birth (n = 16,058) until he/she was five years of age (n = 7,356). Cutoffs for overweight and obesity were defined according to Cole et al, age and gender adjusted. Short-term exclusive breastfeeding was defined as < 4 months of exclusive breastfeeding. Multiple logistic regressions were used to identify variables that predict the child's BMI (Body Mass Index) at five years of age.Results At five years of age, 12.9% of the children in the study wereoverweight and 4.3% were obese. At the age of three months, 78.4% of the children were being breastfed exclusively. The median exclusive breastfeeding duration was four months. High maternal BMI > 30 (AOR = 1.07; CI = 1.05–1.09; P < 0.001), maternal smoking (AOR = 1.43; CI = 1.05–1.95; P = 0.023) and being a single parent (AOR = 2.10; CI = 1.43–3.09; P < 0.001) were associated with short-term exclusive breastfeeding (less than 4 months). Short-term exclusive breastfeeding was less common if one of the parents had a university degree (Mother: AOR = 0.74; CI = 0.61–0.90; P = 0.003 Father: AOR = 0.73; CI = 0.58–0.92; P = 0.008) or if the father was more than 37 years old (AOR = 0.74; CI = 0.55–0.99; P = 0.045). Short-term exclusive breastfeeding was associated with obesity in five-year-old children (simple logistic regression: OR = 1.44; CI = 1.00–2.07; P = 0.050), but when including other independent factors in the analysis, short-term exclusive breastfeeding did not attain statistical significance.Conclusion We cannot exclude the possibility that exclusive breastfeeding influences weight development, but it does not seem to protect against obesity at five years of age.
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| 4. |
- Huus, Karina, 1968-, et al.
(författare)
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Relationship of food frequencies as reported by parents to overweight and obesity at 5 years
- 2009
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 98:1, s. 139-143
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate if food frequencies are related to overweight/obesity in 5-year-old children.METHODS: During 1997-1999, 21 700 infants were invited to participate in ABIS (All Babies in Southeast Sweden), a prospective, cohort study. Participants were followed from birth (n = 16 058) to 5 years (n = 7356). Food frequencies reported by parents at 2.5 and 5 years were studied in the relation to overweight/obesity at 5 years using multiple logistic regressions. A p-value < 0.01 was considered statistically significant.RESULTS: At 2.5 years frequencies of intake of cheese were positively associated with overweight/obesity at 5 years while porridge, fried potatoes/french fries and cream/crème fraiche showed a negative association. When adjusting for known risk factors, porridge and fried potatoes/french fries remained negatively associated with overweight/obesity. At 5 years, chocolate and lemonade were positively associated with overweight/obesity whereas cream/crème fraiche, pastries and candy were negatively associated. Candy remained negatively associated to overweight/obesity after adjustment for potential confounders.CONCLUSION: Food frequencies do not offer any simple explanation for overweight/obesity. Porridge at 2.5 years may protect against overweight/obesity at 5 years, while lemonade may contribute to overweight. Our finding that fried potatoes/french fries may protect against overweight/obesity is unexpected and must be interpreted with caution. These findings should be confirmed by prospective studies using objective recordings.
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| 5. |
- Huus, Karina, et al.
(författare)
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Risk factors in childhood obesity : findings from the All Babies In Southeast Sweden (ABIS) cohort
- 2007
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 96:9, s. 1321-1325
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Our objective was to investigate whether overweight at a very young age predicts overweight at 5 years and to identify risk factors for overweight/obesity at 5 years, thereby making it easier for Child Health Services to focus their prevention strategies on risk groups.Methods: We analysed data from the ABIS study (All Babies In Southeast Sweden), a prospective cohort study. Parents answered questionnaires between childbirth (n = 16,058) and 5 years (n = 7356).Results: High body mass index (BMI; >95th percentile) at 1 year (adjusted odds ratio [AOR]= 6.57; 95% CI = 4.63–9.33; p < 0.001) and age-adjusted BMI > 25 at 2.5 years (AOR = 14.24; 95% CI = 10.52–19.29; p < 0.001) were associated with increased risk of obesity (age-adjusted BMI > 30) at 5 years. Heredity for type 2 diabetes (p = 0.022), high parental BMI and the child's own BMI at birth and at 1 year predicted higher BMI of the child at 5 years (p < 0.001). High parental education was inversely associated with child overweight (p = 0.054 respective p < 0.005).Conclusion: Obesity at age 1 and at 2.5 years predicts obesity at 5 years. Obese parents, especially in families with heredity for type 2 diabetes and low education, should be targeted in early obesity prevention strategies by the Child Health Service.
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| 6. |
- Ludvigsson, Jonas F., et al.
(författare)
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Celiac disease and risk of subsequent type 1 diabetes : a general population cohort study of children and adolescents
- 2006
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 29:11, s. 2483-2488
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Earlier studies suggest that children with type 1 diabetes are more likely to have a subsequent diagnosis of celiac disease. However, research is sparse on the risk of subsequent type 1 diabetes in individuals with celiac disease. We sought to determine the risk of subsequent type 1 diabetes diagnosed before the age of 20 years in children and adolescents with celiac disease in a national, general population-based cohort.RESEARCH DESIGN AND METHODS:We identified 9,243 children with a diagnosis of celiac disease in the Swedish national inpatient register between 1964 and 2003. We then identified five reference individuals matched at time of diagnosis for age, calendar year, sex, and county (n = 45,680). Only individuals with >1 year of follow-up after study entry (diagnosis of celiac disease) were included in the analyses.RESULTS:Celiac disease was associated with a statistically significantly increased risk of subsequent type 1 diabetes before age 20 years (hazard ratio 2.4 [95% CI 1.9-3.0], P < 0.001). This risk increase was seen regardless of whether celiac disease was first diagnosed between 0 and 2 (2.2 [1.7-2.9], P < 0.001) or 3 and 20 (3.4 [1.9-6.1], P < 0.001) years of age. Individuals with prior celiac disease were also at increased risk of ketoacidosis or diabetic coma before the age of 20 years (2.3 [1.4-3.9], P = 0.001).CONCLUSIONS:Children with celiac disease are at increased risk of subsequent type 1 diabetes. This risk increase is low considering that 95% of individuals with celiac disease are HLA-DQ2 positive.
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| 7. |
- Ludvigsson, Jonas F., et al.
(författare)
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Coeliac disease and risk of renal disease : a general population cohort study
- 2006
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 21:7, s. 1809-1815
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Coeliac disease (CD) may be a risk factor for renal disease.METHODS:We investigated the risk of any form of glomerulonephritis (GN) (acute, chronic and non-specified), chronic glomerulonephritis (CGN) and renal replacement therapy including dialysis treatment and kidney transplantation (KT) in patients with CD in a general population-based cohort study. We used Cox regression to assess the risk of renal disease in 14,336 patients who had received a diagnosis of CD (1964-2003) and 69,875 reference individuals matched for age, calendar year, sex and county. Patients were identified using the Swedish Hospital Discharge Registry. Follow-up began 1 year after study entry.RESULTS:CD was associated with an increased risk of any form of GN (hazard ratio (HR) = 1.64; 95% confidence intervals (CI) = 1.01-2.66; P = 0.046; 89 events), CGN (HR = 2.65; 95% CI = 1.34-5.24; P = 0.005; 39 events), dialysis (HR = 3.48; 95% CI = 2.26-5.37; P < 0.001; 102 positive events) and KT (HR = 3.15; 95% CI = 1.29-7.71; P = 0.012; 22 events).CONCLUSION:We suggest that immune characteristics associated with CD increase the risk of chronic renal disease. Individuals with CD may also be at a moderately increased risk of any form of GN.
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| 8. |
- Ludvigsson, Jonas F., et al.
(författare)
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Coeliac disease in the father affects the newborn
- 2001
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 49:2, s. 169-175
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS Untreated coeliac disease in the mother is associated with lower birth weight. We examined the risk of adverse neonatal outcome when the infant's mother, father, or other relative suffered from known coeliac disease.METHODS Mothers answered a questionnaire a few days after the birth of their infant. Of a total of 10597 single birth infants from Southeast Sweden, 53 infants had a mother with coeliac disease (father 27, sibling 70, other close relative 442). Adjusted odds ratios and adjusted differences for neonatal outcome were calculated.RESULTS Infants whose father suffered from coeliac disease had a lower birth weight (95% adjusted confidence interval (CI) −459, −72 g), more often belonged to the low birth weight (LBW) category (LBW ⩽2499 g) (95% CI adjusted odds ratio (AOR) 1.48–17.18), and had a shorter pregnancy duration (95% adjusted CI −1.53, −0.08 weeks) than non-coeliac controls. They also weighed less than infants whose father suffered from other autoimmune diseases (95% CI −549, −93 g). Infants whose mother suffered from coeliac disease had a lower birth weight (95% adjusted CI −370, −74 g) and more often belonged to the LBW category (95% CI AOR 2.60–15.08) than non-coeliac controls. These infants were more often in the LBW category than infants whose mother suffered from non-diabetic autoimmune diseases (95% CI AOR 1.24–9.65). Coeliac disease in other relatives was not associated with any adverse effect on neonatal outcome.CONCLUSIONS This study suggests that even treated coeliac disease, in either of the parents, has a negative effect on pregnancy, resulting in lower birth weight and perhaps shorter duration of pregnancy.
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| 9. |
- Ludvigsson, Jonas F., et al.
(författare)
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Effect of HLA DQ2, dietary exposure and coeliac disease on the development of antibody response to gliadin in children
- 2006
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:8, s. 919-928
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the effect of HLA DQ2, dietary history and development of coeliac disease (CD) on the induction of antibody response to wheat gliadin and cow's milk, beta-lactoglobulin between 1 and 2.5 years of age in children who developed CD and in healthy children. MATERIAL AND METHODS: Infants participating in a birth cohort study (the ABIS study) in Sweden were studied. Thirty-nine children developed CD (=cases), confirmed through biopsy, during follow-up until 2.5-5 years of age. A total of 181 healthy control children were matched for duration of exclusive breast-feeding, birth-weight, gender, maternal smoking and season of birth. IgG and IgA antigliadin and anti-beta-lactoglobulin antibodies were measured using enzyme immunoassay (EIA). The effects of HLA-risk genotypes, DQ2 and DQ8, on CD were also considered. RESULTS: Children who developed CD had higher IgG and IgA antigliadin and anti-beta-lactoglobulin antibody levels at 1 year of age than controls (all comparisons: p<0.001). Similar differences were seen between cases with as yet undiagnosed CD by 1 year of age and controls, and also when cases were compared with HLA-matched controls. Higher levels of IgG and IgA antibodies to beta-lactoglobulin (p=0.003; p=0.001), but not to gliadin, were found in treated cases versus controls at 2.5 years of age. HLA-DQ2-positive healthy children had lower levels of IgG and IgA antigliadin antibodies than HLA-DQ2 negative controls at 1 year of age (p=0.004; p=0.012). CONCLUSIONS: Enhanced humoral response emerging not only to gliadin, but also to other food antigens seems to be primarily associated with CD. Poor induction of antibody response to wheat gliadin in healthy children with the HLA-DQ2 risk molecule could at least partly explain the genetic predisposition to gluten intolerance and CD.
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| 10. |
- Ludvigsson, Jonas F., et al.
(författare)
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Milk consumption during pregnancy and infant birth weight
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective To examine birth weight and risk of low birth weight (≤2 499g, LBW) in relation to milk intake.Design Questionnaire-based study.Setting Southeast SwedenPopulation Single birth infants within the ABIS project included during a two-year period (ABIS = All Babies In Southeast Sweden).Main outcome measures Birth weight and LBW.Results Low milk intake during pregnancy was associated with a decrease in infant birth weight (P<0,01l, Kruskal-Wallis) but did not correlate with LBW (P=0.434, Chi-2) (10 489 infants with complete data)When adjusting for confounders (regression analyses) low milk intake during pregnancy was associated with a decrease in infant birth weight (adjusted P for trend<0,001) and with an increased risk of LBW (adjusted P for trend= 0.028) (9 097 infants with complete data).Conclusion This study suggests that low milk intake in the pregnant mother is associated with lower birth weight of the newborn. Further research is needed to evaluate the relationship between low milk intake and the risk of LBW.
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