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1.	Zhang, C., et al. (författare) The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease 2020 Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:4 Tidskriftsartikel (refereegranskat)abstract The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
2.	Gustavsson, A., et al. (författare) Colectomy after rescue therapy for intravenous-steroid resistant acute ulcerative colitis : a 3-year follow-up study of the Swedish-Danish infliximab/placebo trial 2008 Ingår i: Gut. - 0017-5749 .- 1468-3288. ; 57(Suppl 1), s. A79-A79 Tidskriftsartikel (refereegranskat)
3.	Mardinoglu, Adil, et al. (författare) The Potential Use of Metabolic Cofactors in Treatment of NAFLD 2019 Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 11:7 Forskningsöversikt (refereegranskat)abstract Non-alcoholic fatty liver disease (NAFLD) is caused by the imbalance between lipid deposition and lipid removal from the liver, and its global prevalence continues to increase dramatically. NAFLD encompasses a spectrum of pathological conditions including simple steatosis and non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and liver cancer. Even though there is a multi-disciplinary effort for development of a treatment strategy for NAFLD, there is not an approved effective medication available. Single or combined metabolic cofactors can be supplemented to boost the metabolic processes altered in NAFLD. Here, we review the dosage and usage of metabolic cofactors including l-carnitine, Nicotinamide riboside (NR), l-serine, and N-acetyl-l-cysteine (NAC) in human clinical studies to improve the altered biological functions associated with different human diseases. We also discuss the potential use of these substances in treatment of NAFLD and other metabolic diseases including neurodegenerative and cardiovascular diseases of which pathogenesis is linked to mitochondrial dysfunction.
4.	Einarsdottir, Sigrun, et al. (författare) Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity. 2022 Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 6:9, s. 2723-2730 Tidskriftsartikel (refereegranskat)abstract Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlapS1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P = .009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P = .02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/mL) of anti-RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P = .007, Fisher's exact test). We conclude that although allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses.
5.	Altay, Özlem, et al. (författare) Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19 2021 Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; 8:17 Tidskriftsartikel (refereegranskat)abstract COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.
6.	Bergquist, Annika, et al. (författare) Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis 2008 Ingår i: Clinical Gastroenterology and Hepatology. - New York : Elsevier. - 1542-3565 .- 1542-7714. ; 6:8, s. 939-943 Tidskriftsartikel (refereegranskat)abstract Background & Aims: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. Methods: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. Results: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6–84.4), 11.1 (3.3–37.8), and 2.3 (0.9–6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3–4.9) and for Crohn's disease 1.4 (0.8–2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9–18.9). Conclusions: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.
7.	Bergquist, Annika, et al. (författare) Perinatal events and the risk of developing primary sclerosing cholangitis 2006 Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 12:37, s. 6037-6040 Tidskriftsartikel (refereegranskat)abstract AIM: To investigate whether perinatal events, intrauterine or postpartum, are associated with the development of primary sclerosing cholangitis (PSC) later in life.METHODS: Birth records from 97 patients with adult PSC in Sweden were reviewed. Information on perinatal events including medications and complications during pregnancy, gestation length, birth weight and length were collected. Two control children of the same sex were selected for each subject. Conditional multiple logistic regression was used to assess associations of the perinatal measures with development of PSC.RESULTS: No significant associations were found between gestational age, birth length, breastfeeding, and the majority of medical complications including infections or medication during pregnancy for the mothers or postpartum for the children. Vaginal bleeding and peripheral oedema showed associations with PSC, with matched odds ratios of 5.70 (95% CI, 1.13-28.83) and 2.28 (95% CI, 1.04-5.03), respectively. CONCLUSION: The associations of vaginal bleeding and oedema with subsequent PSC cannot readily be explained, so our findings do not strongly support the hypothesis of a significant role of perinatal events as a risk for the development of PSC later in life.
8.	van Ampting, Marleen T. J., et al. (författare) Intestinal barrier function in response to abundant or depleted mucosal glutathione in Salmonella-infected rats 2009 Ingår i: BMC Physiology. - London : BioMed Central. - 1472-6793. ; 9, s. 6- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Glutathione, the main antioxidant of intestinal epithelial cells, is suggested to play an important role in gut barrier function and prevention of inflammation-related oxidative damage as induced by acute bacterial infection. Most studies on intestinal glutathione focus on oxidative stress reduction without considering functional disease outcome. Our aim was to determine whether depletion or maintenance of intestinal glutathione changes susceptibility of rats to Salmonella infection and associated inflammation.Rats were fed a control diet or the same diet supplemented with buthionine sulfoximine (BSO; glutathione depletion) or cystine (glutathione maintenance). Inert chromium ethylenediamine-tetraacetic acid (CrEDTA) was added to the diets to quantify intestinal permeability. At day 4 after oral gavage with Salmonella enteritidis (or saline for non-infected controls), Salmonella translocation was determined by culturing extra-intestinal organs. Liver and ileal mucosa were collected for analyses of glutathione, inflammation markers and oxidative damage. Faeces was collected to quantify diarrhoea. RESULTS: Glutathione depletion aggravated ileal inflammation after infection as indicated by increased levels of mucosal myeloperoxidase and interleukin-1beta. Remarkably, intestinal permeability and Salmonella translocation were not increased. Cystine supplementation maintained glutathione in the intestinal mucosa but inflammation and oxidative damage were not diminished. Nevertheless, cystine reduced intestinal permeability and Salmonella translocation. CONCLUSION: Despite increased infection-induced mucosal inflammation upon glutathione depletion, this tripeptide does not play a role in intestinal permeability, bacterial translocation and diarrhoea. On the other hand, cystine enhances gut barrier function by a mechanism unlikely to be related to glutathione.
9.	van Baarlen, Peter, et al. (författare) Differential NF-κB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance 2009 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Washington, DC : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:7, s. 2371-2376 Tidskriftsartikel (refereegranskat)abstract How do we acquire immune tolerance against food microorganisms and commensal bacteria that constitute the intestinal microbiota? We investigated this by stimulating the immune system of adults with commensal Lactobacillus plantarum bacteria. We studied the in vivo human responses to L. plantarum in a randomized double-blind placebo-controlled cross-over study. Healthy adults ingested preparations of living and heat-killed L. plantarum bacteria. Biopsies were taken from the intestinal duodenal mucosa and altered expression profiles were analyzed using whole-genome microarrays and by biological pathway reconstructions. Expression profiles of human mucosa displayed striking differences in modulation of NF-kappaB-dependent pathways, notably after consumption of living L. plantarum bacteria in different growth phases. Our in vivo study identified mucosal gene expression patterns and cellular pathways that correlated with the establishment of immune tolerance in healthy adults.
10.	Veldhorst, Margriet A. B., et al. (författare) Comparison of the effects of a high- and normal-casein breakfast on satiety, 'satiety' hormones, plasma amino acids and subsequent energy intake 2009 Ingår i: British Journal of Nutrition. - Cambridge : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 101:2, s. 295-303 Tidskriftsartikel (refereegranskat)abstract The present study compared the effects of a high- and normal-casein-protein breakfast on satiety, 'satiety' hormones, plasma amino acid responses and subsequent energy intake. Twenty-five healthy subjects (BMI 23.9 (SEM 0.3) kg/m2; age 22 (SEM 1) years) received a subject-specific standardised breakfast (20% of daily energy requirements): a custard with casein as the single protein source with either 10, 55 and 35 (normal-casein breakfast) or 25, 55 and 20 (high-casein breakfast) % of energy (En%) from protein, carbohydrate and fat respectively in a randomised, single-blind design. Appetite profile (visual analogue scale; VAS), plasma glucose, insulin, glucagon-like peptide 1, ghrelin and amino acid concentrations were determined for 4 h; here the sensitive moment in time for lunch was determined. Subjects came for a second set of experiments and received the same custards for breakfast, and an ad libitum lunch was offered at 180 min after breakfast; energy intake was assessed. There were increased scores of fullness and satiety after the 25 En% casein-custard compared with the 10 En% casein-custard, particularly at 180 min (26 (SEM 4) v. 11 (SEM 5) mm VAS; P<0.01) and 240 min (13 (SEM 5) v. -1 (SEM 5) mm VAS; P<0.01). This coincided with prolonged elevated plasma amino acid concentrations; total amino acids and branched-chain amino acids were higher after the 25 En% casein-custard compared with the 10 En% casein-custard at 180 and 240 min (P<0.001). There was no difference in energy intake (3080 (SEM 229) v. 3133 (SEM 226) kJ for 25 En% and 10 En% respectively; NS) from the ad libitum lunch. In conclusion, a breakfast with 25% of energy from casein is rated as being more satiating than a breakfast with 10% of energy from casein at 3 and 4 h after breakfast, coinciding with prolonged elevated concentrations of plasma amino acids, but does not reduce subsequent energy intake.
11.	Veldhorst, Margriet A. B., et al. (författare) Dose-dependent satiating effect of whey relative to casein or soy 2009 Ingår i: Physiology and Behavior. - Amsterdam : Elsevier. - 0031-9384 .- 1873-507X. ; 96:4-5, s. 675-682 Tidskriftsartikel (refereegranskat)abstract Dietary protein plays a role in body weight regulation, partly because of its effects on appetite. The objective was to compare the effects of high or normal casein-, soy-, or whey-protein breakfasts on appetite, specific hormones, amino acid responses and subsequent energy intake. Twenty-five healthy subjects (mean+/-SEMBMI:23.9+/-0.3 kg/m2; age:22+/-1 years) received standardized breakfasts: custards with either casein-, soy, or whey-protein with either 10/55/35 (normal) or 25/55/20 (high)En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite profile (Visual Analogue Scales) and amino acid concentrations were determined for 4 h whereas plasma glucose, insulin, active Glucagon-like Peptide 1 (GLP-1), and active ghrelin concentrations were determined for 3 h; the sensitive moment for lunch was determined. Subjects returned for a second set of experiments and received the same breakfasts, ad lib lunch was offered 180 min later; energy intake (EI) was assessed. At 10En%, whey decreased hunger more than casein or soy (p <0.05), coinciding with higher leucine, lysine, tryptophan, isoleucine, and threonine responses (p<0.05). At 25En% there were no differences in appetite ratings. Whey triggered the strongest responses in concentrations of active GLP-1 (p<0.05) and insulin (p<0.05) compared with casein and/or soy. There were no differences in EI. In conclusion, differences in appetite ratings between different proteins appeared at a normal concentration; at 10En% whey-protein decreased hunger more than casein- or soy-protein. At 25En% whey-protein triggered stronger responses in hormone concentrations than casein- or soy-protein. The results suggest that a difference in appetite ratings between types of protein appears when certain amino acids are above and below particular threshold values.
12.	Willing, Ben, et al. (författare) Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease 2009 Ingår i: Inflammatory Bowel Diseases. - New York : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 15:5, s. 653-660 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Large interindividual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease (CD).METHODS: To reduce variations in exposure during establishment of the gut flora and the influence of genotype, we studied the mucosa-associated microbiota of monozygotic twin pairs that were discordant (n = 6) or concordant (n = 4) for CD. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing, and quantitative real-time polymerase chain reaction (PCR).RESULTS: The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal CD had a dramatically lower abundance (P < 0.001) of Faecalibacterium prausnitzii and increased abundance (P < 0.03) of Escherichia coli compared to healthy co-twins and those with CD localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype.CONCLUSIONS: The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal CD phenotype, distinct from colonic CD, and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of CD and eventually customized treatment.
13.	Rydén, Petra, 1972-, et al. (författare) What happens with the healthiness of the diet among Swedish adolescent boys and girls when a gluten-free diet is required? Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Objectives To explore how diagnosis of celiac disease (CD) in early adolescence affects overall food intake and healthiness of the diet in comparison with age- and sex matched controls and children with CD diagnosed in early childhood. Methods This is a longitudinal dietary sub-study of a school-based CD-screening of 12-year-olds (ETICS - Exploring the Iceberg of Coeliacs in Sweden), a part of the PreventCD project. The dietary study was conducted in 2005-2008 and included the following groups resulting from the screening: I) screening-detected CD cases (n=80), II) previously diagnosed CD cases (n=28), and III) two samples of age- and sex matched non-CD children (admission, n=619; follow-up, n=447). All CD cases completed two food-frequency-and-amount-questionnaires (FFQ), covering the previous four weeks; one at admission and one at a follow-up 18-24 months later. The screening-detected CD cases completed the first FFQ before a gluten free diet was initiated. The non-CD children consisted of a cross-sectional sample at each time point, and thus only completed one FFQ each (i.e. either at admission or follow-up). The Goldberg cut-off method was used to validate reported energy intake. The food choices at admission and follow-up were compared among the three groups, and the healthiness of the diet evaluated using two Swedish dietary indexes. Results and Conclusion Intakes of most food groups were similar at baseline. The adolescents diagnosed with CD did only minor changes in their overall food choices. Visible changes were reductions within food groups where gluten-free alternatives are not readily available, such as pastries and pizza. In contrast, total intake of bread and pasta did not change. All three groups scored fairly low on the dietary indexes at both time points, and there is an obvious need to improve the healthiness of the adolescent diet, whether CD is present or not.
14.	Stråvik, Mia, 1994, et al. (författare) Maternal Intake of Cow's Milk during Lactation Is Associated with Lower Prevalence of Food Allergy in Offspring 2020 Ingår i: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 12:12, s. 1-19 Tidskriftsartikel (refereegranskat)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.
15.	Ludvigsson, Jonas F., et al. (författare) A population-based study of coeliac disease, neurodegenerative and neuroinflammatory diseases 2007 Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 25:11, s. 1317-1327 Tidskriftsartikel (refereegranskat)abstract BackgroundIt has been suggested that coeliac disease (CD) is associated with several neurological diseases. However, the evidence of such an association is inconclusive as earlier research has often been based on small numbers with retrospective data collection.AimTo use Cox regression to examine the risk of neurological disease in individuals with CD.MethodsThrough Swedish national registers we identified some 14 000 individuals with a diagnosis of CD (1964–2003) and 70 000 reference individuals matched for age, sex, calendar year and county.ResultsCoeliac disease was associated with later polyneuropathy [hazard ratio (HR) = 3.4; 95% CI = 2.3–5.1]. We found no statistically significant association between CD and subsequent multiple sclerosis (HR = 0.9; 95% CI = 0.3–2.3), Parkinson’s disease (HR = 1.2; 95% CI = 0.8–1.9), Alzheimer’s disease (HR = 1.5; 95% CI = 0.9–2.6), hereditary ataxia (HR = 1.3; 95% CI = 0.5–3.6), the symptom ataxia (HR = 1.9; 95% CI = 0.6–6.2), Huntington’s disease (HR = 1.7; 95% CI = 0.3–8.6), myasthenia gravis (HR = 0.8; 95% CI = 0.2–3.8) or spinal muscular atrophy (HR = 0.5; 95% CI = 0.1–3.8). Prior polyneuropathy was associated with subsequent CD (odds ratio = 5.4; 95% CI = 3.6–8.2).ConclusionsThe association between CD and polyneuropathy indicates shared risks. We suggest that individuals with polyneuropathy routinely undergo screening for CD. There is no notable association between CD and other neurological outcomes investigated in this study.
16.	Elfström, Peter, 1974-, et al. (författare) Hematopoietic cancer including lymphoma in celiac disease according to Marsh criteria 0-3 Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Background: Celiac disease (CD) is associated with an increased risk of lymphoma, but it is unknown if borderline mucosal damage and latent CD are risk factors for lymphoma.Methods: We examined the risk of hematopoietic cancer in a nationwide population–based cohort of 28,800 individuals with biopsy-verified CD (villous atrophy, Marsh 3), 12,663 individuals with small intestinal inflammation (Marsh 1+2), and 3,551 with latent CD (positive antiendomysial, tissue transglutaminase or antigliadin test but normal mucosa on biopsy). The study participants were identified through all pathology departments (n=28) in Sweden and were biopsied in 1969-2006 (median: 1998). Cox regression estimated the hazard ratio (HR) for hematopoietic malignancies.Results: While biopsy-verified CD and intestinal inflammation were both statistically significantly associated with lymphoma (CD: HR = 3.18; 95% CI = 2.63-3.83; inflammation: 1.66; 1.28-2.17), latent CD was not (1.04; 0.44-2.43). CD was associated with both non-Hodgkin’s (NHL) and Hodgkin’s lymphoma (HL) (4.81; 3.81-6.07 and 4.39; 2.59-7.45 respectively). Risk estimates for NHL and HL were lower in inflammation (1.65; 1.15-2.38 and 1.48; 0.60-3.62 respectively) and latent CD (1.79; 0.74-4.34 and 1.08; 0.13-9.00 respectively). No increased risk of lymphoma was seen in children with a small intestinal biopsy. This study found no association between leukemia and small intestinal pathology.Conclusion: CD is associated with an increased risk of lymphoma. This risk increase was also seen in individuals with small intestinal inflammation. Latent CD is not associated with lymphoma of any kind, and positive CD serology alone cannot be used to predict future risk of lymphoma.
17.	Ludvigsson, Jonas F., et al. (författare) Effect of HLA DQ2, dietary exposure and coeliac disease on the development of antibody response to gliadin in children 2006 Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:8, s. 919-928 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.
18.	Kahn, Robin, et al. (författare) Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms 2022 Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:2, s. 354-62 Tidskriftsartikel (refereegranskat)abstract Aim: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Methods: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively collected between 1 December 2020 and 31 May 2021. All patients met the World Health Organization criteria for MIS-C. The outcomes 2 and 8weeks after diagnosis are presented, and follow-up protocols are suggested. Results: We identified 152 cases, and 133 (87%) participated. When followed up 2weeks after MIS-C was diagnosed, 43% of the 119 patients had abnormal results, including complete blood cell counts, platelet counts, albumin levels, electrocardiograms and echocardiograms. After 8weeks, 36% of 89 had an abnormal patient history, but clinical findings were uncommon. Echocardiogram results were abnormal in 5% of 67, and the most common complaint was fatigue. Older children and those who received intensive care were more likely to report symptoms and have abnormal cardiac results. Conclusion: More than a third (36%) of the patients had persistent symptoms 8weeks after MIS-C, and 5% had abnormal echocardiograms. Older age and higher levels of initial care appeared to be risk factors. Structured follow-up visits are important after MIS-C.
19.	Block, T, et al. (författare) Diagnostic accuracy of plasma biomarkers for intestinal ischaemia 2008 Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 68:3, s. 242-248 Tidskriftsartikel (refereegranskat)abstract Objective. Intestinal ischaemia is a life‐threatening condition with high mortality, and the lack of accurate and readily available diagnostic methods often results in delay in diagnosis and treatment. The aim of this study was to investigate the accuracy of different plasma biomarkers in diagnosing intestinal ischaemia. Material and methods. Prospective inclusion of patients older than 50 years with acute abdomen admitted to hospital in Karlskrona, Sweden, between 2001 and 2003. Venous blood was sampled prior to any surgery and within 24h from onset of pain. D‐lactate, alpha glutathione S‐transferase, intestinal fatty acid binding protein, creatine kinase B, isoenzymes of lactate dehydrogenase (LD) and alkaline liver phosphatase (ALP) were analysed. D‐dimer was analysed using four different commercially available test kits. Results. In‐hospital mortalities among patients with (n = 10) and without (n = 61) intestinal ischaemia were 40% and 3%, respectively (p = 0.003). D‐dimer was associated with intestinal ischaemia (p = 0.001) independently of which assay was used. No patient presenting with a normal D‐dimer had intestinal ischaemia. D‐dimer >0.9mg/L had a specificity, sensitivity and accuracy of 82%, 60% and 79%, respectively. Total LD, isoenzymes of LD 1–4 and liver isoenzyme of ALP (ALP liver) were significantly higher in patients with intestinal ischaemia, and accuracies for LD 2 (cut‐off 2.3µkat/L) and ALP liver (cut‐off 0.7µkat/L) were 69% and 66%, respectively. Conclusions. D‐dimer may be used as an exclusion test for intestinal ischaemia, but lacks specificity. The other plasma biomarkers studied had insufficient accuracy for this group of patients. Further studies are needed.
20.	Olén, Ola, et al. (författare) Increased risk of immune thrombocytopenic purpura among inpatients with coeliac disease 2008 Ingår i: Scandinavian Journal of Gastroenterology. - Oslo : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 43:4, s. 416-422 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Case reports have indicated a link between coeliac disease (CD) and immune thrombocytopenic purpura (ITP). Two national, register-based studies were carried out to investigate a possible association between CD and ITP and vice versa. MATERIAL AND METHODS: In a cohort study of 14,347 individuals with inpatient diagnoses of CD and 69,967 reference individuals matched for age, gender, calendar year and county, the Cox regression was used to estimate the risk of subsequent inpatient diagnoses of ITP (of any type or chronic). In a case control design, conditional logistic regression was used to assess the risk of exposure (diagnosis of ITP prior to CD) in 15,382 cases (individuals with diagnoses of CD) and 76,824 matched controls. Diagnoses of CD and ITP were identified through the Swedish National Inpatient Register. RESULTS: Individuals with CD were at increased risk of both subsequent ITP of any type (hazard ratio (HR)=1.91; 95% CI=1.19-3.11; p=0.008) and subsequent chronic ITP (HR 2.77; 95% CI=1.09-7.04; p=0.033). Risk estimates were similar when reference individuals were restricted to inpatients. There was also a positive association between CD and prior ITP of any type (odds ratio (OR)=2.96; 95% CI=1.60-5.50; p=0.001) or with prior chronic ITP (OR=6.00; 95% CI=1.83-19.66; p=0.003). CONCLUSIONS: We found a positive association between CD and both ITP of any type and chronic ITP, irrespective of which disease came first, and suggest there should be increased awareness of CD in patients with ITP
21.	Vaga, S., et al. (författare) Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals 2020 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1 Tidskriftsartikel (refereegranskat)abstract Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities' compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.
22.	Mardinoglu, Adil, 1982, et al. (författare) Systems biology in hepatology: approaches and applications 2018 Ingår i: Nature Reviews Gastroenterology & Hepatology. - : Springer Science and Business Media LLC. - 1759-5045 .- 1759-5053. ; 15:6, s. 365-377 Tidskriftsartikel (refereegranskat)abstract Detailed insights into the biological functions of the liver and an understanding of its crosstalk with other human tissues and the gut microbiota can be used to develop novel strategies for the prevention and treatment of liver-associated diseases, including fatty liver disease, cirrhosis, hepatocellular carcinoma and type 2 diabetes mellitus. Biological network models, including metabolic, transcriptional regulatory, protein-protein interaction, signalling and co-expression networks, can provide a scaffold for studying the biological pathways operating in the liver in connection with disease development in a systematic manner. Here, we review studies in which biological network models were used to integrate multiomics data to advance our understanding of the pathophysiological responses of complex liver diseases. We also discuss how this mechanistic approach can contribute to the discovery of potential biomarkers and novel drug targets, which might lead to the design of targeted and improved treatment strategies. Finally, we present a roadmap for the successful integration of models of the liver and other human tissues with the gut microbiota to simulate whole-body metabolic functions in health and disease.
23.	Belda, E., et al. (författare) Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism 2022 Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 71:12 Tidskriftsartikel (refereegranskat)abstract Objectives Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. Design We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. Results Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. Conclusion Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.
24.	Hjortswang, Henrik, et al. (författare) The Short Health Scale : a valid measure of subjective health in ulcerative colitis 2006 Ingår i: Scandinavian Journal of Gastroenterology. - Oslo : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:10, s. 1196-1203 Tidskriftsartikel (refereegranskat)abstract Objective. Assessment of health-related quality of life (HRQOL) is important in both clinical practice and clinical trials, and several multi-item questionnaires are currently in use. We have devised and evaluated a simplified four-item questionnaire, the Short Health Scale (SHS), representing each of four health dimensions: (a) symptom burden, (b) social function, (c) disease-related worry and (d) general well-being.Material and methods. Three hundred patients with ulcerative colitis completed the SHS and three other HRQOL questionnaires (IBDQ, RFIPC and PGWB). Half of the patients repeated the questionnaires after 6 months – or earlier if disease activity changed. Test–retest reliability was derived from measurements of the SHS questions, 2 weeks apart, on 18 patients in remission.Results. Patients in relapse scored higher on each of the four SHS questions than patients in remission (p < 0.001). Each of the four SHS scores were associated with results of their corresponding health dimension obtained with the other three questionnaires (rs=0.57–0.78, p < 0.001) (validity). The results of the SHS proved stable on repeated measurement with a 2-week interval in patients in remission (rs=0.71–0.91, p < 0.01) (test–retest reliability). Patients with a change in disease activity had a significant change in their SHS scores (p < 0.05) (responsiveness).Conclusions. The SHS is a valid, reliable and responsive measure of subjective health in patients with ulcerative colitis. It is simple to administer, quickly completed and the results do not need further calculations. The SHS can be used in clinical trials and in clinical practice to identify the patient's main problems affecting health.
25.	Elfström, Peter, 1974-, et al. (författare) Risk of primary adrenal insufficiency in patients with celiac disease 2007 Ingår i: Journal of Clinical Endocrinology and Metabolism. - Chevy Chase, Md. : Endocrine Society. - 0021-972X .- 1945-7197. ; 92:9, s. 3595-3598 Tidskriftsartikel (refereegranskat)abstract Objectives: Earlier research has suggested a positive association between Addison’s disease (AD) and celiac disease (CD).Wehave here investigated the risk of AD in individuals with CD from a general population cohort.Methods: Through the Swedish national registers we identified 14,366 individuals with a diagnosis of CD (1964–2003) and 70,095 reference individuals matched for age, sex, calendar year, and county of residence. We used Cox regression to estimate hazard ratios (HRs) for subsequent AD. Analyses were restricted to individuals with more than 1 yr of follow-up and without AD prior to study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for CD in individuals with prior AD.Results: There was a statistically significantly positive association between CD and subsequent AD [HR _ 11.4; 95% confidence interval (CI) _ 4.4 –29.6]. This risk increase was seen in both children and adults and did not change with adjustment for diabetes mellitus or socioeconomic status. When we restricted reference individuals to inpatients, the adjusted HR for AD was 4.6 (95% CI _ 1.9 –11.4). Individuals with prior AD were at increased risk of CD (odds ratio _ 8.6; 95% CI _ 3.4 –21.8).Conclusions: This study found a highly increased risk of AD in individuals with CD. This relationship was independent of temporal sequence. We therefore recommend that individuals with AD should be screened for CD. We also suggest an increased awareness of AD in individuals with CD.
26.	Elfström, Peter, 1974-, et al. (författare) Risk of Thyroid Disease in Individuals with Celiac Disease 2008 Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:10, s. 3915-3921 Tidskriftsartikel (refereegranskat)abstract Background: It has been suggested that celiac disease is associated with thyroid disease. Earlier studies, however, have been predominately cross-sectional and have often lacked controls. There is hence a need for further research. In this study, we estimated the risk of thyroid disease in individuals with celiac disease from a general population cohort.Methods: A total of 14,021 individuals with celiac disease (1964–2003) and a matched reference population of 68,068 individuals were identified through the Swedish national registers. Cox regression estimated the risk of thyroid disease in subjects with celiac disease. Analyses were restricted to individuals with a follow-up ofmorethan 1 yr and withnothyroid disease before study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for subsequent celiac disease in individuals with thyroid disease.Results: Celiac disease was positively associated with hypothyroidism [hazard ratio (HR)_4.4;95% confidence interval (CI) _ 3.4 –5.6; P _ 0.001], thyroiditis (HR _ 3.6; 95% CI _1.9–6.7; P _ 0.001) and hyperthyroidism (HR_2.9;95%CI_2.0–4.2; P_0.001). The highest risk estimates were found in children (hypothyroidism, HR _ 6.0 and 95% CI _ 3.4 –10.6; thyroiditis, HR _ 4.7 and 95% CI _ 2.1–10.5; hyperthyroidism, HR _ 4.8 and 95% CI _ 2.5–9.4). In post hoc analyses, where the reference population was restricted to inpatients, the adjusted HR was 3.4 for hypothyroidism (95% CI_2.7– 4.4; P_0.001), 3.3 for thyroiditis(95%CI_1.5–7.7; P_0.001), and 3.1 for hyperthyroidism (95% CI _ 2.0–4.8; P _ 0.001).Conclusion: Celiac disease is associated with thyroid disease, and these associations were seen regardless of temporal sequence. This indicates shared etiology and that these individuals are more susceptible to autoimmune disease.
27.	Åkerman, Linda, 1983- (författare) Aspects of the Pre-Diabetic Period in Type 1 Diabetes 2016 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency, due to immune-mediated destruction of beta cells. Current knowledge regarding the period preceding disease onset comes, to a large extent, from studying risk cohorts based on relatives of T1D-patients, as they have an increased disease risk. Among T1D patients in general, however, few have the disease in their immediate family. It is therefore important to study risk cohorts from the general population as well. An ongoing autoimmune reaction can often be seen in the blood long before disease onset, by detection of autoantibodies directed towards beta cell antigens. By autoantibody screening among participants in the ABIS (All Babies in the South-east of Sweden) cohort, we could identify a group of children from the general population with increased risk for T1D, positive for multiple autoantibodies. They were enrolled in a 2-year prospective follow-up aiming to characterize the prediabetic period and to identify factors indicative of progression/non-progression to T1D. We assessed glucose homeostasis and autoantibody titers over time, and searched for risk-biomarkers by analyzing the expression of immune-related genes (Th1-Th2-Th3) in peripheral blood mononuclear cells (PBMC) from these children, in comparison to healthy children and newly diagnosed T1D patients. In the same groups we also compared serum micro RNA (miRNA) profiles, knowing that miRNA molecules have desirable biomarker properties. We found that two specific autoantibodies, IA2A and ZnT8A, were detected at higher concentrations in risk-individuals who progressed to overt T1D during or after the follow-up period, compared to those who still have not. We also observed disturbed glucose homeostasis long before onset in the progressors, but it was seen among those who remain symptom free as well. Further, we found support for the possible role of insulin resistance as an accelerator of the disease process. For gene expression and serum miRNA, few differences were observed between risk-individuals and healthy children overall. However, for PBMC gene expression and serum miRNA both, there were associations to beta cell function and glucose homeostasis, and for miRNA also to islet autoantibodies. Although specific profiles for prediction of disease onset or identification of risk-individuals could not be found, these results are interesting and deserve to be evaluated further. As part of another sub-study within ABIS, the effects of physical activity on glucose homeostasis were assessed in healthy schoolchildren. The level of physical activity, measured by pedometers, was related to insulin resistance and beta cell-stress, and decreased physical activity was associated with increased insulin resistance and load on the insulin-producing beta cells, already at school-age.
28.	Elfström, Peter, 1974-, et al. (författare) Cardiomyopathy, pericarditis and myocarditis in a population-based cohort of inpatients with coeliac disease 2007 Ingår i: Journal of Internal Medicine. - Oxford : Blackwell Publishing. - 0954-6820 .- 1365-2796. ; 262:5, s. 545-554 Tidskriftsartikel (refereegranskat)abstract Objectives: We investigated the risk of myocarditis, cardiomyopathy, and pericarditis in patients with celiac disease (CD) from a general population cohort.Subjects and methods: Through the Swedish national registers we identified 9363 children and 4969 adults with a diagnosis of CD (1964–2003). These individuals were matched with upto five reference individuals for age, sex, calendar year and county (n = 69 851). Cox regression estimated hazard ratios (HRs) for later heart disease. Main outcome measures: Myocarditis, cardiomyopathy (any or dilated), and pericarditis defined according torelevant international classification of disease codes in the Swedish national inpatient register.Results: Celiac disease diagnosed in childhood was not associated with later myocarditis (HR = 0.2; 95% CI = 0.0–1.5), cardiomyopathy of any type (HR = 0.8; 95% CI = 0.2–3.7), or pericarditis (HR = 0.4; 95% CI = 0.1–1.9). Restricting our analyses to adulthood CD and heart disease diagnosed from 1987 and onwards in departments of cardiology ⁄ internal medicine, we found no association between CD and later myocarditis (HR = 2.1; 95% CI = 0.4–11.7), dilated cardiomyopathy (HR = 1.7; 95% CI = 0.4– 6.5) or pericarditis (HR = 1.5; 95% CI = 0.5–4.0).Conclusion: This study found no association between CD, later myocarditis, cardiomyopathy or pericarditis
29.	Weinmayr, Gudrun, et al. (författare) Particulate matter air pollution components and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts of Air Pollution Effects (ESCAPE) 2018 Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 120, s. 163-171 Tidskriftsartikel (refereegranskat)abstract Introduction: Previous analysis from the large European multicentre ESCAPE study showed an association of ambient particulate matter < 2.5 mu m (PM2.5) air pollution exposure at residence with the incidence of gastric cancer. It is unclear which components of PM are most relevant for gastric and also upper aerodigestive tract (UADT) cancer and some of them may not be strongly correlated with PM mass. We evaluated the association between long-term exposure to elemental components of PM2.5 and PM10 and gastric and UADT cancer incidence in European adults.Methods: Baseline addresses of individuals were geocoded and exposure was assessed by land-use regression models for copper (Cu), iron (Fe) and zinc (Zn) representing non-tailpipe traffic emissions; sulphur (S) indicating long-range transport; nickel (Ni) and vanadium (V) for mixed oil-burning and industry; silicon (Si) for crustal material and potassium (K) for biomass burning. Cox regression models with adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined with random effects meta-analyses.Results: Ten cohorts in six countries contributed data on 227,044 individuals with an average follow-up of 14.9 years with 633 incident cases of gastric cancer and 763 of UADT cancer. The combined hazard ratio (HR) for an increase of 200 ng/m(3) of PM2.5_S was 1.92 (95%-confidence interval (95%-CI) 1.13; 3.27) for gastric cancer, with no indication of heterogeneity between cohorts (I-2= 0%), and 1.63 (95%-CI 0.88; 3.01) for PM2.5_Zn (I-2= 70%). For the other elements in PM2.5 and all elements in PM10 including PM10_S, non-significant HRs between 0.78 and 1.21 with mostly wide CIs were seen. No association was found between any of the elements and UADT cancer. The HR for PM2.5_S and gastric cancer was robust to adjustment for additional factors, including diet, and restriction to study participants with stable addresses over follow-up resulted in slightly higher effect estimates with a decrease in precision. In a two-pollutant model, the effect estimate for total PM2.5 decreased whereas that for PM2.5_S was robust.Conclusion: This large multicentre cohort study shows a robust association between gastric cancer and long-term exposure to PM2.5 S but not PM10 S, suggesting that S in PM2.5 or correlated air pollutants may contribute to the risk of gastric cancer.
30.	Bohr, Johan, et al. (författare) Mikroskopisk kolit hos äkta makar 2008 Ingår i: Gastrokuriren. ; 13:30, s. PO-09 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
31.	Dicksved, Johan, et al. (författare) Molecular analysis of the gut microbiota of identical twins with Crohn's disease 2008 Ingår i: The ISME Journal. - : Nature Publishing Group. - 1751-7362 .- 1751-7370. ; 2:7, s. 716-727 Tidskriftsartikel (refereegranskat)abstract Increasing evidence suggests that a combination of host genetics and the composition of the gut microbiota are important for development of Crohn's disease (CD). Our aim was to study identical twins with CD to determine microbial factors independent of host genetics. Fecal samples were studied from 10 monozygotic twin pairs with CD (discordant n=6 and concordant n=4) and 8 healthy twin pairs. DNA was extracted, 16S rRNA genes were PCR amplified and T-RFLP fingerprints generated using general bacterial and Bacteroides group-specific primers. The microbial communities were also profiled based on their percentage G+C contents. Bacteroides 16S rRNA genes were cloned and sequenced from a subset of the samples. The bacterial diversity in each sample and similarity indices between samples were estimated based on the T-RFLP data using a combination of statistical approaches. Healthy individuals had a significantly higher bacterial diversity compared to individuals with CD. The fecal microbial communities were more similar between healthy twins than between twins with CD, especially when these were discordant for the disease. The microbial community profiles of individuals with ileal CD were significantly different from healthy individuals and those with colonic CD. Also, CD individuals had a lower relative abundance of B. uniformis and higher relative abundances of B. ovatus and B. vulgatus. Our results suggest that genetics and/or environmental exposure during childhood, in part, determine the gut microbial composition. However, CD is associated with dramatic changes in the gut microbiota and this was particularly evident for individuals with ileal CD.
32.	Hagstrom, H., et al. (författare) Morbidity, risk of cancer and mortality in 3645 HFE mutations carriers 2021 Ingår i: Liver International. - : Wiley. - 1478-3223 .- 1478-3231. ; 41:3, s. 545-553 Tidskriftsartikel (refereegranskat)abstract Background & Aims Mutations in the HFE gene can lead to hereditary haemochromatosis (HH) and have been suggested to increase the risk of extra-hepatic diseases, especially breast and colorectal cancer. Here we investigated long-term outcomes of Swedish patients with HFE mutations. Methods We identified 3645 patients with a homozygous p.C282Y (62%) or a compound heterozygous p.C282Y/p.H63D (38%) mutation from eight centres in Sweden between 1997 and 2017. These were matched 1:10 by age, sex and county of residence to reference individuals from the general population. We ascertained incident outcomes until the end of 2017 by linkage to national registers. Studied outcomes were HH, cirrhosis, hepatocellular carcinoma (HCC), breast cancer (in women), colorectal cancer, type 1 and 2 diabetes, hypothyroidism, Parkinson's disease and mortality. Cox proportional hazards regression was used to estimate hazard ratios for these outcomes. Results Median age at diagnosis was 52 years, 44% were females. During a mean follow-up of 7.9 years, we found an increased risk for HCC, HH, cirrhosis, type 2 diabetes, osteoarthritis and death. Excess mortality was only seen in men. No increased risk was seen for colorectal or breast cancer. Liver-related outcomes were rare, with a cumulative incidence of HFE mutation carriers in a university hospital setting had an increased risk for mortality in men, along with increased risks of cirrhosis, HCC, diabetes type 2, and osteoarthritis. In general, the absolute risk for adverse outcomes was low and no increased risk for colon or breast cancer was observed.
33.	Hamer, H. M., et al. (författare) Review article : the role of butyrate on colonic function 2008 Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 27:2, s. 104-119 Forskningsöversikt (refereegranskat)abstract BACKGROUND: Butyrate, a short-chain fatty acid, is a main end-product of intestinal microbial fermentation of mainly dietary fibre. Butyrate is an important energy source for intestinal epithelial cells and plays a role in the maintenance of colonic homeostasis. AIM: To provide an overview on the present knowledge of the bioactivity of butyrate, emphasizing effects and possible mechanisms of action in relation to human colonic function. METHODS: A PubMed search was performed to select relevant publications using the search terms: 'butyrate, short-chain fatty acid, fibre, colon, inflammation, carcinogenesis, barrier, oxidative stress, permeability and satiety'. RESULTS: Butyrate exerts potent effects on a variety of colonic mucosal functions such as inhibition of inflammation and carcinogenesis, reinforcing various components of the colonic defence barrier and decreasing oxidative stress. In addition, butyrate may promote satiety. Two important mechanisms include the inhibition of nuclear factor kappa B activation and histone deacetylation. However, the observed effects of butyrate largely depend on concentrations and models used and human data are still limited. CONCLUSION: Although most studies point towards beneficial effects of butyrate, more human in vivo studies are needed to contribute to our current understanding of butyrate-mediated effects on colonic function in health and disease.
34.	Järnerot, G., et al. (författare) Twin studies in inflammatory bowel disease : a review 2007 Ingår i: Austral - Asian Journal of Cancer. - 0972-2556. ; 6:1, s. 29-33 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
35.	Ludvigsson, Jonas F., et al. (författare) Coeliac disease in the father and risk of adverse pregnancy outcome : a population-based cohort study 2006 Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:2, s. 178-185 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE:The risk of adverse foetal outcomes was investigated in offspring to men with coeliac disease (CD) diagnosed prior to infant birth and in offspring to men who did not receive a diagnosis of CD until after the delivery.MATERIAL AND METHODS:A cohort study was based on national registry data restricted to women aged 15-44 years with singleton live-born infants, with linkage between the Swedish national birth registry (1973-2001) and the national inpatient registry (1964-2001). A total of 1059 offspring to men who had received a diagnosis of CD were included: 554 offspring to men diagnosed prior to birth and 505 offspring to men diagnosed after infant birth.RESULTS:Undiagnosed CD in the father was associated with an increased risk of caesarean section (adjusted odds ratio (AOR)=1.83; 95% confidence interval (CI) for AOR=1.13-2.95; p=0.014) but was otherwise not linked to adverse pregnancy outcome: (intrauterine growth retardation (OR=1.37; 95% CI=0.91-2.07), low birth-weight (OR=1.41; 95% CI=0.93-2.12), very low birth-weight (OR=1.21; 95% CI=0.39-3.77), preterm birth (OR=1.10; 95% CI=0.74-1.62), and very preterm (OR=0.62; 95% CI=0.09-4.40)). A paternal diagnosis of CD made before infant birth was not associated with adverse foetal outcome.CONCLUSIONS:CD in the father is not a risk factor for unfavourable foetal outcome. The increased risk for caesarean section in offspring to men with undiagnosed CD in this study may be due to multiple comparisons.
36.	Meijnikman, A. S., et al. (författare) Microbiome-derived ethanol in nonalcoholic fatty liver disease 2022 Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28:10, s. 2100-2106 Tidskriftsartikel (refereegranskat)abstract A new study examines microbiome-generated ethanol in individuals with and without nonalcoholic fatty liver disease (NAFLD), concluding that microbial ethanol might contribute to pathogenesis in some patients with NAFLD. To test the hypothesis that the gut microbiota of individuals with nonalcoholic fatty liver disease (NAFLD) produce enough ethanol to be a driving force in the development and progression of this complex disease, we performed one prospective clinical study and one intervention study. Ethanol was measured while fasting and 120 min after a mixed meal test (MMT) in 146 individuals. In a subset of 37 individuals and in an external validation cohort, ethanol was measured in portal vein blood. In an intervention study, ten individuals with NAFLD and ten overweight but otherwise healthy controls were infused with a selective alcohol dehydrogenase (ADH) inhibitor before an MMT. When compared to fasted peripheral blood, median portal vein ethanol concentrations were 187 (interquartile range (IQR), 17-516) times higher and increased with disease progression from 2.1 mM in individuals without steatosis to 8.0 mM in NAFL 21.0 mM in nonalcoholic steatohepatitis. Inhibition of ADH induced a 15-fold (IQR,1.6- to 20-fold) increase in peripheral blood ethanol concentrations in individuals with NAFLD, although this effect was abolished after antibiotic treatment. Specifically, Lactobacillaceae correlated with postprandial peripheral ethanol concentrations (Spearman's rho, 0.42; P < 10(-5)) in the prospective study. Our data show that the first-pass effect obscures the levels of endogenous ethanol production, suggesting that microbial ethanol could be considered in the pathogenesis of this highly prevalent liver disease.
37.	Nyhlin, Nils, et al. (författare) Abdominal pain is common in microscopic colitis despite remission : a long-term follow-up of 203 patients 2008 Ingår i: Gut. - 0017-5749 .- 1468-3288. ; 57:suppl I Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
38.	Olén, Ola, et al. (författare) Urinary tract infections in pregnant women with coeliac disease 2007 Ingår i: Scandinavian Journal of Gastroenterology. - Oslo : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 42:2, s. 186-193 Tidskriftsartikel (refereegranskat)abstract Objective. Previous research has indicated a link between coeliac disease (CD) and urinary tract infection (UTI). The objective of this study was to assess the risk of UTI and repeated episodes of UTI before the current pregnancy in women with diagnosed or undiagnosed CD. Material and methods. A national registry-based cohort study restricted to pregnant women was used in this investigation, with linkage between the Swedish National Medical Birth Registry and the National Inpatient Registry. We analysed the risk of UTI during pregnancy from 1973 to 1989 in 212 pregnancies to women who had received a diagnosis of CD prior to giving birth and in 786 pregnancies to women diagnosed after giving birth. We also assessed the risk of repeated episodes of UTI before the current pregnancy according to data in the national birth records of 1990-2001 in 617 women with CD diagnosed prior to giving birth and 109 women diagnosed after giving birth. Results. UTI during pregnancy: UTI occurred during 19,139/1,678,304 pregnancies to women who had never had a diagnosis of CD, compared with in 12/786 pregnancies to women with undiagnosed CD (adjusted odds ratio (AOR) =1.37; 95% CI =0.78-2.43; p=0.276) and in 0/212 pregnancies to women with diagnosed CD (AOR =0.06; 95% CI =0.00-8.94; p=0.277) (ORs adjusted for maternal age, parity, nationality and calendar period). Repeated episodes of UTI before the current pregnancy: among 692,991 women who had never had a diagnosis of CD, 74,776 reported repeated episodes of UTI, compared with 14/101 women with undiagnosed CD (AOR =1.39; 95% CI =0.79-2.45; p=0.255) and 69/566 women with diagnosed CD (AOR =1.02; 95% CI =0.79-1.32; p=0.864) (ORs adjusted for maternal age, parity, nationality, calendar period and civil status). Adjustment for smoking in a subset of patients with available data did not change the risk estimates. Conclusions. It cannot be ruled out that undiagnosed CD in pregnant women is associated with a small, increased risk of UTI. In pregnant women with diagnosed CD, there seems to be no increased risk of UTI.
39.	Stjernman, H. C. R., et al. (författare) Demographic and disease-related factors influencing assessment of disease activity in Crohn's disease 2008 Ingår i: Journal of Crohn's and Colitis Supplements. - 1873-9954. ; 2 (Suppl):1, s. 28-28 Tidskriftsartikel (refereegranskat)
40.	Stjernman, Henrik, et al. (författare) Evaluation of the inflammatory bowel disease questionnaire in Swedish patients with Crohn's disease 2006 Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:8, s. 934-943 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Health-related quality of life (HRQoL) is an important measure of inflammatory bowel disease (IBD) health outcome. The Inflammatory Bowel Disease Questionnaire (IBDQ) comprising 32 items grouped into four dimensions is a widely used IBD-specific HRQoL instrument. The purpose of this study was to evaluate the validity, reliability and responsiveness of the Swedish translation of the IBDQ in patients with Crohn's disease (CD). MATERIAL AND METHODS: Four hundred and forty-eight patients with CD completed the IBDQ and three other HRQoL questionnaires (Rating Form of IBD Patient Concerns; Short Form-36; and the Psychological General Well-Being Index) in connection with their regular visit at the outpatient clinic. Disease activity was assessed by the physician on a 4-point Likert scale. Thirty-two patients who were stable in remission completed the questionnaires a second time, 4 weeks later. A total of 418 patients repeated all measurements after 6 months. RESULTS: The dimensional scores were highly correlated with other measures of corresponding aspects of HRQoL and were significantly better in remission than in relapse. High test-retest correlations indicated good reliability. Responsiveness was confirmed in patients whose disease activity changed over time. However, high correlations between the dimensions, poor correlations between items within each dimension, and factor analysis all indicated that the original grouping of the items is not valid for Swedish CD patients. CONCLUSIONS: Although the Swedish IBDQ has good external validity, reliability and responsiveness for patients with CD, our results did not support the original grouping of the items.
41.	Stjernman, H., et al. (författare) Faktorer som påverkar bedömning av sjukdomsaktivitet vid Crohns sjukdom 2008 Ingår i: Gastrokuriren. ; 13:27 PO-04 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
42.	Stjernman, Henrik, et al. (författare) Short health scale : a valid, reliable, and responsive instrument for subjective health assessment in Crohn's disease. 2008 Ingår i: Inflammatory Bowel Diseases. - New York, NY : Raven Press. - 1078-0998 .- 1536-4844. ; 14:1, s. 47-52 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Health-related quality of life (HRQoL) is an essential part of inflammatory bowel disease (IBD) assessment. The Short Health Scale (SHS), an HRQoL questionnaire in which the patients rate the disease impact on 4 important aspects of subjective health (symptoms, function, worry, and general well-being) was demonstrated in a previous study to be valid, reliable, and responsive in patients with ulcerative colitis. The present study evaluates the SHS in patients with Crohn's disease (CD). METHODS: In all, 367 CD patients completed the SHS and 4 other HRQoL questionnaires (IBDQ, SF-36, RFIPC, and PGWB) at their regular outpatient visits. Then 330 patients completed the questionnaires at a second visit 6 months later. In addition, reliability data were obtained from repeat measurements 4 weeks after the first visit in 40 patients stable in remission. RESULTS: Patients in remission scored better on all 4 questions than those with active disease (P < 0.001). All 4 questions were strongly correlated with the corresponding dimensions of the other HRQoL questionnaires (r(s) = 0.74-0.83). Reliability was confirmed with strong test-retest correlations (r(s) = 0.69-0.82) and intraclass correlation coefficients (0.66-0.77). Patients who changed from remission to active disease or vice versa showed a significant change in all 4 SHS scores (P < 0.005). CONCLUSIONS: SHS is a valid, reliable and responsive HRQoL instrument also in patients with CD. It is easily completed by the patient and requires no further calculation by the investigator. SHS gives a comprehensive overview of the main aspects of the patient's subjective health perception and is a useful tool in both clinical practice and clinical studies.
43.	Troost, Freddy J., et al. (författare) Identification of the transcriptional response of human intestinal mucosa to Lactobacillus plantarum WCFS1 in vivo 2008 Ingår i: BMC Genomics. - London : BioMed Central. - 1471-2164. ; 9, s. 374- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: There is limited knowledge on the extent and dynamics of the mucosal response to commensal and probiotic species in the human intestinal lumen. This study aimed to identify the acute, time-dependent responses of intestinal mucosa to commensal Lactobacillus plantarum WCFS1 in vivo in two placebo-controlled human intervention studies in healthy volunteers. Transcriptional changes in duodenal mucosa upon continuous intraduodenal infusion of L. plantarum WCFS1 for one- and six h, respectively, were studied using oro- and nasogastric intubations with dedicated orogastric catheters and tissue sampling by standard flexible gastroduodenoscopy. RESULTS: One- and six-h exposure of small intestinal mucosa to L. plantarum WCFS1 induced differential expression of 669 and 424 gene reporters, respectively. While short-term exposure to L. plantarum WCFS1 inhibited fatty acid metabolism and cell cycle progression, cells switched to a more proliferative phase after prolonged exposure with an overall expression profile characterized by upregulation of genes involved in lipid metabolism, cellular growth and development. Cell death and immune responses were triggered, but cell death-executing genes or inflammatory signals were not expressed. Proteome analysis showed differential expression of several proteins. Only the microsomal protein 'microsomal triglyceride transfer protein' was regulated on both the transcriptional and the protein level in all subjects. CONCLUSION: Overall, this study showed that intestinal exposure to L. plantarum WCFS1 induced consistent, time-dependent transcriptional responses in healthy intestinal mucosa. This extensive exploration of the human response to L. plantarum WCFS1 could eventually provide molecular support for specific or probiotic activity of this strain or species, and exemplifies the strength of the applied technology to identify the potential bio-activity of microbes in the human intestine.
44.	Tysk, Curt, et al. (författare) Diagnosis and management of microscopic colitis 2008 Ingår i: World Journal of Gastroenterology. - Beijing : WJG Press. - 1007-9327 .- 2219-2840. ; 14:48, s. 7280-7288 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Microscopic colitis, comprising collagenous and lymphocytic colitis, is characterized clinically by chronic watery diarrhea, and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4-6/100,000 inhabitants, with a peak incidence in 60-70-year-old individuals and a noticeable female predominance for collagenous colitis. The etiology is unknown. Chronic diarrhea, abdominal pain, weight loss, fatigue and fecal incontinence are common symptoms, which impair the health-related quality of life of the patient. There is an association with other autoimmune disorders such as celiac disease, diabetes mellitus, thyroid disorders and arthritis. Budesonide is the best-documented short-term treatment, but the optimal long-term strategy needs further study. The long-term prognosis is good and the risk of complications including colonic cancer is low.
45.	Tysk, Curt, et al. (författare) Nationella riktlinjer för handläggning av akut svårt skov av ulcerös kolit : utarbetat av arbetsgrupp fran SGF och SOIBD 2008 Ingår i: Gastrokuriren. - Lund : Svensk gastroenterologisk förening. - 1651-0453. ; 13:3, s. 35-36 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
46.	Walch, A., et al. (författare) Outcome of rescue therapy in steroid-resistant ulcerative colitis : a retrospective study comparing cyclosporine and infliximab 2008 Ingår i: Gut. - 0017-5749 .- 1468-3288. ; 57(Suppl II), s. A265- Tidskriftsartikel (refereegranskat)
47.	Willing, B., et al. (författare) Studying discordant monozygotic twins reveals differences in mucosa-associated microbiota depending on Crohn's disease phenotype 2008 Konferensbidrag (populärvet., debatt m.m.)
48.	Maasfeh, Lujain, et al. (författare) Impaired Luminal Control of Intestinal Macrophage Maturation in Patients With Ulcerative Colitis During Remission 2021 Ingår i: Cellular and Molecular Gastroenterology and Hepatology. - : Elsevier BV. - 2352-345X. ; 12:4, s. 1415-1432 Tidskriftsartikel (refereegranskat)abstract BACKGROUND & AIMS: Intestinal macrophages adopt a hyporesponsive phenotype through education by local signals. Lack of proper macrophage maturation in patients with ulcerative colitis (UC) in remission may initiate gut inflammation. The aim, therefore, was to determine the effects of fecal luminal factors derived from healthy donors and UC patients in remission on macrophage phenotype and function. METHODS: Fecal supernatants (FS) were extracted from fecal samples of healthy subjects and UC patients in remission. Monocytes were matured into macrophages in the presence of granulocyte-macrophage colony-stimulating factor without/with FS, stimulated with lipopolysaccharide, and macrophage phenotype and function were assessed. Fecal metabolomic profiles were analyzed by gas-chromatography/mass-spectrometry. RESULTS: Fecal luminal factors derived from healthy donors were effective in down-regulating Toll-like receptor signaling, cytokine signaling, and antigen presentation in macrophages. Fecal luminal factors derived from UC patients in remission were less potent in inducing lipopolysaccharide hyporesponsiveness and modulating expression of genes involved in macrophage cytokine and Toll-like receptor signaling pathways. Although phagocytic and bactericidal abilities of macrophages were not affected by FS treatment, healthy FS-treated macrophages showed a greater ability to suppress cluster of differentiation 4(+) T-cell activation and interferon gamma secretion compared with UC remission FS-treated counterparts. Furthermore, metabolomic analysis showed differential fecal metabolite composition for healthy donors and UC patients in remission. CONCLUSIONS: Our data indicate that UC patients in remission lack luminal signals able to condition macrophages toward a hyporesponsive and tolerogenic phenotype, which may contribute to their persistent vulnerability to relapse.
49.	Ludvigsson, Jonas F., et al. (författare) Coeliac disease and the risk of fractures : a general population-based cohort study 2007 Ingår i: Alimentary Pharmacology and Therapeutics. - Oxford : Blackwell Scientific. - 0269-2813 .- 1365-2036. ; 25:3, s. 273-285 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Background: Earlier studies have suggested that untreated coeliac disease may be associated with osteoporosis, but results are contradictory for the risk of long-term fractures.Aim: To study the association between coeliac disease and fractures.Methods: We used Cox regresson to examine the future risk of hip fracture and fracture of any type in more than 13 000 individuals with coeliac disease and 65 000 age- and sex-matched reference individuals in a general population-based cohort.Results: During follow-up, 1365 first hip fractures and 4847 fractures of any type occurred. Coeliac disease was positively associated with subsequent hip fracture (hazard ratio = 2.1; 95% CI = 1.8-2.4) (in children: hazard ratio = 2.6; 95% CI = 1.1-6.2) and fractures of any type (hazard ratio = 1.4; 95% CI = 1.3-1.5) (in children: hazard ratio = 1.1; 95% CI = 1.0-1.2). The absolute excess risk of hip fractures in children with coeliac disease was 4/100 000 person-years. Incidence ratios for hip fracture in individuals with CD were around two both prior to diagnosis of coeliac disease and afterwards; this risk increase remained 20 years after diagnosis of coeliac disease.Conclusions: Individuals with coeliac disease, including children with coeliac disease, may be at increased risk of hip fracture and fracture of any type. Coeliac disease may be positively associated with long-term hip fracture risk.
50.	Jansson, Janet, et al. (författare) Metabolomics reveals metabolic biomarkers of Crohn's disease 2009 Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:7, s. e6386- Tidskriftsartikel (refereegranskat)abstract The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

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