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- Berntson, Lillemor, 1957-, et al.
(författare)
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A Pilot Study Investigating Faecal Microbiota After Two Dietary Interventions in Children with Juvenile Idiopathic Arthritis
- 2022
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Ingår i: Current Microbiology. - : Springer Science and Business Media LLC. - 0343-8651 .- 1432-0991. ; 79:7
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence for an impact of the gut microbiota on the immune system, which has consequences for inflammatory diseases. Exclusive enteral nutrition (EEN) and the specific carbohydrate diet (SCD) have been demonstrated as effective anti-inflammatory treatments for children with Crohn’s disease. We have previously shown an anti-inflammatory effect from these nutritional treatments in children with juvenile idiopathic arthritis (JIA). The aim of this study was to investigate if improved clinical symptoms after EEN or SCD treatment in children with JIA could be linked to changes in faecal microbiota. We included sixteen patients with JIA (age 7–17 years), six for treatment with EEN and ten with SCD. EEN was given for 3–5 weeks and SCD for 4–5 weeks, with clinical and laboratory status assessed before and after treatment. Faecal samples were analysed for microbiota diversity and composition using 16S rRNA gene sequencing. Analyses of the faecal microbiota showed an effect on the overall composition with both interventions; the most striking result was a decreased relative abundance of the genus Faecalibacterium from EEN and of Bifidobacterium from SCD. The α-diversity decreased significantly from SCD (P = 0.04), but not from EEN (P = 0.22). Despite the study cohorts being small, both EEN and SCD were shown to impact the faecal microbiota. Future larger studies with a focus on metagenomics or metabolomics could possibly reveal a link and clarify the clinical effects of those nutritional regimens.
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| 2. |
- Berntson, Lillemor, 1957-, et al.
(författare)
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Blood brain barrier permeability and astrocyte-derived extracellular vesicles in children with juvenile idiopathic arthritis : a cross-sectional study
- 2024
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Ingår i: Pediatric Rheumatology. - : Springer Nature. - 1546-0096. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Juvenile idiopathic arthritis (JIA) is the most prevalent rheumatic disease in children, and the inflammatory process is widely studied, primarily characterized by its impact on joint health. Emerging evidence suggests that JIA may also affect the central nervous system (CNS). This study investigates the potential CNS involvement in JIA by analyzing the presence of astrocyte-derived extracellular vesicles (EVs) and the S100B protein in plasma, both of which are indicative of astrocyte activity and blood-brain barrier (BBB) integrity.Methods: EDTA plasma from 90 children diagnosed with JIA and 10 healthy controls, matched by age and gender, was analyzed for extracellular vesicles by flow cytometric measurement. Astrocyte-derived EVs were identified using flow cytometry with markers for aquaporin 4 (AQP-4) and glial fibrillary acidic protein (GFAP). Levels of the S100B protein were measured using a commercial ELISA. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score (JADAS27, 0-57), and pain levels were measured using a visual analogue scale (VAS, 0-10 cm).Results: Our analyses revealed a significantly higher concentration of astrocyte-derived EVs in the plasma of children with JIA compared with healthy controls. Furthermore, children with JADAS27 scores of 1 or higher exhibited notably higher levels of these EVs. The S100B protein was detectable exclusively in the JIA group.Conclusion: The elevated levels of astrocyte-derived EVs and the presence of S100B in children with JIA provide evidence of BBB disruption and CNS involvement, particularly in those with higher disease activity. These findings underscore the importance of considering CNS health in the comprehensive management of JIA. Further research is required to elucidate the mechanisms behind CNS engagement in JIA and to develop treatments that address both joint and CNS manifestations of the disease.
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| 3. |
- Öman, Anders, 1975-, et al.
(författare)
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Fecal microbiota in children with juvenile idiopathic arthritis treated with methotrexate or etanercept
- 2021
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Ingår i: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlterations in the composition of the fecal microbiota in children with juvenile idiopathic arthritis (JIA) have been observed in several studies, but it has not been determined whether the standard treatment for JIA changes the composition or function of the microbiota.The first-line disease-modifying anti-rheumatic drug for treatment of JIA is usually methotrexate, followed or supplemented by anti-tumor necrosis factor alpha drugs, such as etanercept. The aim of this study was to investigate the effects of methotrexate and etanercept treatments on the fecal microbiota and the fecal short-chain fatty acids (SCFAs) in children with JIA.MethodsIn this multicenter study, the composition of fecal microbiota from 45 treatment-naïve children with JIA was compared with that from 29 children treated with methotrexate and 12 children treated with etanercept. We also made pairwise comparisons of 15 children sampled before and during methotrexate treatment and 7 children sampled before and during etanercept treatment.The microbiota was determined using sequencing amplicons from the V3 and V4 regions of the 16S rRNA gene. Alpha-diversity, community composition, and relative abundances of bacterial taxa were analyzed in all comparisons. Analyses of fecal SCFAs, using a high-performance liquid chromatograph, were performed for the pairwise comparisons.ResultsWe did not find any significant differences in α-diversity or community composition of microbiota. However, principal coordinate analysis indicated a change in community composition in 7 of the 15 paired samples before and during methotrexate and 2 of the 7 paired samples before and during etanercept.Comparisons of the relative abundance of taxa revealed minor differences before and during treatment with methotrexate or etanercept, but they were not significant after correction for multiple analyses, and the unpaired and paired analyses did not show similar changes.There were no significant differences in levels of fecal SCFAs before and during treatment with methotrexate or etanercept.ConclusionsTreatment with methotrexate or etanercept had minor, but no significant or consistent changes either on composition of microbiota or on levels of SCFAs, suggesting that these changes are not related to the therapeutic effects of methotrexate or etanercept.
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| 4. |
- Öman, Anders, 1975-, et al.
(författare)
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Fecal microbiota in untreated children with Juvenile Idiopathic Arthritis : a comparison with healthy children and healthy siblings
- 2021
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:10, s. 1589-1595
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Tidskriftsartikel (refereegranskat)abstract
- Objective Changes in the composition of gut microbiota has been suggested to be associated with Juvenile idiopathic arthritis (JIA). The objective in this study was to investigate if the diversity and composition of the fecal microbiota differed between children with JIA and healthy controls, and if the microbiota differed between children with JIA and their healthy siblings. MethodsIn this multicenter, case-control study, fecal samples were collected from 75 children with JIA and 32 healthy controls. Eight of the healthy controls were siblings to eight children with JIA and they were compared only pairwise with their siblings.The microbiota was determined using sequencing amplicons from the V3 and V4 regions of the 16S rRNA gene.Alpha diversity, community composition of microbiota and relative abundances of taxa were compared between children with JIA and healthy unrelated controls as well as between children with JIA and healthy siblings. ResultsOur data revealed no significant differences in α-diversity or community composition of microbiota between children with JIA, healthy unrelated controls or healthy siblings.Analyses of relative abundances of phyla, families and genera identified trends of differing abundances of some taxa in children with JIA, in comparison with both healthy controls and healthy siblings, but none of these findings were significant after adjustment for multiple comparisons. ConclusionThere were no significant differences in the composition of fecal microbiota in children with JIA compared with healthy controls. The composition of microbiota in children with JIA did not differ significantly from that in their healthy siblings.
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| 5. |
- Öman, Anders, 1975-
(författare)
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Studies of the Role of the Gastrointestinal Tract in Children with Juvenile Idiopathic Arthritis (JIA)
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children, but its cause is not fully established. Changes in the intestinal canal and an unfavourable composition of gut bacteria have been suggested as factors that can increase the risk of developing JIA and influence the disease course.This thesis investigated the possible association between JIA and changes in the intestinal canal.In a population-based study, 213 children diagnosed with JIA were screened for coeliac disease using immunoglobulin antibodies against tissue transglutaminase 2. Three children had a diagnosis of coeliac disease prior to screening and three previously undiagnosed cases were found through screening. The point prevalence for coeliac disease among children with JIA was 2.8%.In order to investigate if the composition of gut microbiotas in children with JIA differed from in healthy children and healthy siblings, 75 children with JIA were compared with 24 healthy controls, and eight children with JIA were compared pairwise with healthy siblings. Comparisons of microbiotas revealed trends towards altered relative abundances of taxa in children with JIA, but these were not significant when corrected for multiple comparisons.To examine the effects on gut microbiotas of treatment with methotrexate (MTX) or etanercept (ETN), faecal samples from 46 treatment-naïve children with JIA were compared with samples from children during treatment with MTX (n=29) or ETN (n=12). Paired comparisons were also made of children sampled both as treatment-naïve and during treatment with MTX (n=15) or ETN (n=7), including analyses of levels of faecal short-chain fatty acids. No significant differences were found after correction for multiple analyses.A pilot study investigated if improved clinical symptoms after interventions with exclusive enteral nutrition (EEN; n=6) or specific carbohydrate diet (SCD; n=10) in children with JIA were linked to changes in the gut microbiota. Faecal samples collected before the interventions were compared pairwise with samples collected after 3–5 weeks on the interventions. Both interventions altered microbiota composition, with a significant decrease in alpha-diversity and relative abundance of Actinobacteria during SCD.In conclusion, children with JIA most likely have an increased risk of coeliac disease and screening should be recommended. Faecal microbiota in children with JIA do not seem to differ compared with in healthy children or siblings. Treatment with MTX or ETN has no, or very limited, effect on the microbiota in faecal samples, but dietary interventions with EEN or SCD showed some changes in a pilot study.
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