| 1. |
- Zhang, C., et al.
(author)
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The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease
- 2020
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In: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:4
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Journal article (peer-reviewed)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.
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| 2. |
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| 3. |
- Mardinoglu, Adil, et al.
(author)
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The Potential Use of Metabolic Cofactors in Treatment of NAFLD
- 2019
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In: Nutrients. - : MDPI. - 2072-6643. ; 11:7
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Research review (peer-reviewed)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.
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| 4. |
- Einarsdottir, Sigrun, et al.
(author)
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Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity.
- 2022
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In: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 6:9, s. 2723-2730
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Journal article (peer-reviewed)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.
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| 5. |
- Altay, Özlem, et al.
(author)
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Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19
- 2021
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In: Advanced Science. - : Wiley. - 2198-3844. ; 8:17
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Journal article (peer-reviewed)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.
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| 6. |
- Bergquist, Annika, et al.
(author)
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Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis
- 2008
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In: Clinical Gastroenterology and Hepatology. - New York : Elsevier. - 1542-3565 .- 1542-7714. ; 6:8, s. 939-943
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Journal article (peer-reviewed)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.
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| 7. |
- Bergquist, Annika, et al.
(author)
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Perinatal events and the risk of developing primary sclerosing cholangitis
- 2006
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In: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 12:37, s. 6037-6040
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Journal article (peer-reviewed)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.
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| 8. |
- van Ampting, Marleen T. J., et al.
(author)
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Intestinal barrier function in response to abundant or depleted mucosal glutathione in Salmonella-infected rats
- 2009
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In: BMC Physiology. - London : BioMed Central. - 1472-6793. ; 9, s. 6-
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Journal article (peer-reviewed)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.
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| 9. |
- van Baarlen, Peter, et al.
(author)
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Differential NF-κB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance
- 2009
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In: 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
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Journal article (peer-reviewed)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.
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| 10. |
- Veldhorst, Margriet A. B., et al.
(author)
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Comparison of the effects of a high- and normal-casein breakfast on satiety, 'satiety' hormones, plasma amino acids and subsequent energy intake
- 2009
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In: British Journal of Nutrition. - Cambridge : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 101:2, s. 295-303
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Journal article (peer-reviewed)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.
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| 11. |
- Veldhorst, Margriet A. B., et al.
(author)
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Dose-dependent satiating effect of whey relative to casein or soy
- 2009
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In: Physiology and Behavior. - Amsterdam : Elsevier. - 0031-9384 .- 1873-507X. ; 96:4-5, s. 675-682
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Journal article (peer-reviewed)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.
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| 12. |
- Willing, Ben, et al.
(author)
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Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease
- 2009
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In: Inflammatory Bowel Diseases. - New York : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 15:5, s. 653-660
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Journal article (peer-reviewed)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.
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| 13. |
- Rydén, Petra, 1972-, et al.
(author)
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What happens with the healthiness of the diet among Swedish adolescent boys and girls when a gluten-free diet is required?
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Other publication (other academic/artistic)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.
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| 14. |
- Stråvik, Mia, 1994, et al.
(author)
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Maternal Intake of Cow's Milk during Lactation Is Associated with Lower Prevalence of Food Allergy in Offspring
- 2020
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In: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 12:12, s. 1-19
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Journal article (peer-reviewed)abstract
- Maternal diet during pregnancy and lactation may affect the propensity of the child to develop an allergy. The aim was to assess and compare the dietary intake of pregnant and lactating women, validate it with biomarkers, and to relate these data to physician-diagnosed allergy in the offspring at 12 months of age. Maternal diet during pregnancy and lactation was assessed by repeated semi-quantitative food frequency questionnaires in a prospective Swedish birth cohort (n = 508). Fatty acid proportions were measured in maternal breast milk and erythrocytes. Allergy was diagnosed at 12 months of age by a pediatrician specialized in allergy. An increased maternal intake of cow's milk during lactation, confirmed with biomarkers (fatty acids C15:0 and C17:0) in the maternal blood and breast milk, was associated with a lower prevalence of physician-diagnosed food allergy by 12 months of age. Intake of fruit and berries during lactation was associated with a higher prevalence of atopic eczema at 12 months of age. Our results suggest that maternal diet modulates the infant's immune system, thereby influencing subsequent allergy development.
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| 15. |
- Ludvigsson, Jonas F., et al.
(author)
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A population-based study of coeliac disease, neurodegenerative and neuroinflammatory diseases
- 2007
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In: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 25:11, s. 1317-1327
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Journal article (peer-reviewed)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.
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| 16. |
- Elfström, Peter, 1974-, et al.
(author)
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Hematopoietic cancer including lymphoma in celiac disease according to Marsh criteria 0-3
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Other publication (other academic/artistic)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.
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| 17. |
- Ludvigsson, Jonas F., et al.
(author)
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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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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:8, s. 919-928
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Journal article (peer-reviewed)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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| 18. |
- Kahn, Robin, et al.
(author)
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Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms
- 2022
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In: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:2, s. 354-62
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Journal article (peer-reviewed)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.
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| 19. |
- Block, T, et al.
(author)
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Diagnostic accuracy of plasma biomarkers for intestinal ischaemia
- 2008
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In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 68:3, s. 242-248
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Journal article (peer-reviewed)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.
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| 20. |
- Olén, Ola, et al.
(author)
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Increased risk of immune thrombocytopenic purpura among inpatients with coeliac disease
- 2008
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In: Scandinavian Journal of Gastroenterology. - Oslo : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 43:4, s. 416-422
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Journal article (peer-reviewed)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
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| 21. |
- Vaga, S., et al.
(author)
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Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)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.
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| 22. |
- Mardinoglu, Adil, 1982, et al.
(author)
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Systems biology in hepatology: approaches and applications
- 2018
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In: Nature Reviews Gastroenterology & Hepatology. - : Springer Science and Business Media LLC. - 1759-5045 .- 1759-5053. ; 15:6, s. 365-377
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Journal article (peer-reviewed)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.
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| 23. |
- Belda, E., et al.
(author)
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Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism
- 2022
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 71:12
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Journal article (peer-reviewed)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.
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| 24. |
- Hjortswang, Henrik, et al.
(author)
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The Short Health Scale : a valid measure of subjective health in ulcerative colitis
- 2006
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In: Scandinavian Journal of Gastroenterology. - Oslo : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:10, s. 1196-1203
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Journal article (peer-reviewed)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.
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| 25. |
- Elfström, Peter, 1974-, et al.
(author)
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Risk of primary adrenal insufficiency in patients with celiac disease
- 2007
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In: Journal of Clinical Endocrinology and Metabolism. - Chevy Chase, Md. : Endocrine Society. - 0021-972X .- 1945-7197. ; 92:9, s. 3595-3598
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Journal article (peer-reviewed)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.
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