Microbial orchestra in juvenile idiopathic arthritis: Sounds of disarray?

Arvonen, Miika; Vänni, Petri; Sarangi, Aditya Narayan; Tejesvi, Mysore V.; Vähäsalo, Paula; Aggarwal, Amita; Stoll, Matthew L.

doi:10.1111/imr.12826

Cited by 23 publications

(17 citation statements)

References 168 publications

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“…In addition, in JIA patients suffering from gastrointestinal symptoms, signs of altered mucosal immunity have been observed, such as inflammatory lesions in the intestine [44], ileal lymphonodular hyperplasia [45,46], and expression of HLA-DR in abnormal sites of the intestinal mucosa [45].Enthesitis-related arthritis (ERA) has been associated with certain intestinal microbial populations in a case-control study [47]. But other categories of JIA have also shown indications of alterations in the microbiota, as described by Arvonen et al [48]. The intestinal microbiota develops dramatically during the first years Table 3 Exposure to antibiotics in the uterus and during the early childhood of those children who later developed JIA, compared to controls from the general population…”

Section: Discussionmentioning

confidence: 99%

Infections and antibiotics during fetal life and childhood and their relationship to juvenile idiopathic arthritis: a prospective cohort study

Kindgren

Ludvigsson

2021

Pediatr Rheumatol

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Background The aetiology of juvenile idiopathic arthritis (JIA) is poorly understood. It has been shown that use of antibiotics is associated with JIA. However, whether the association is due to increased occurrence of infection in these individuals is unknown. The purpose of this investigation was to measure the association between number of infections and use of antibiotics during childhood with development of JIA. Methods In ABIS (All Babies in Southeast Sweden) a population-based prospective birth cohort of 17,055 children, data were collected on infections and antibiotic exposure during pregnancy and childhood. 102 individuals with JIA were identified. Multivariable logistic regression analyses were performed, adjusting for confounding factors. Results Exposure to antibiotics during the periods 1–12 months, 1–3 years and 5–8 years was significantly associated with increased risk for JIA. The odds of developing JIA were three times higher in those exposed to antibiotics during the first 3 years of life compared with those not exposed (aOR 3.17; 95% CI 1.11–9.03, p = 0.031), and more than twice as high in those exposed to antibiotics during the first 5 years of life compared with those not exposed (aOR 2.18; 95% CI 1.36–3.50, p = 0.001). The odds of developing JIA were 78% higher in those exposed to antibiotics during the first 8 years of life compared with those not exposed (aOR 1.78; 95% CI 1.15–2.73, p = 0.009). Occurrence of infection during fetal life or childhood showed no significant association with the risk of developing JIA, after confounder adjustment. The cumulative number of courses of antibiotics was significantly higher during childhood for the individuals who developed JIA (p < 0.001). Penicillins were more frequently used than non-penicillins, but both had an equal effect on the risk of developing JIA. Conclusions Exposure to antibiotics early in life is associated with later onset of JIA in a large birth cohort from the general population. The relationship was dose dependent. These results suggest that further, more restrictive, antibiotic policies during the first years of life would be advisable.

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Section: Discussionmentioning

confidence: 99%

Infections and antibiotics during fetal life and childhood and their relationship to juvenile idiopathic arthritis: a prospective cohort study

Kindgren

Ludvigsson

2021

Pediatr Rheumatol

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“…In addition, Faecalibacterium is involved in processes such as amino acid biosynthesis and starch and sugar degradation [48]. Studies have shown that increases in feces butyrate were found when the relative abundances of Lachnospiraceae, a family of digestive tract-associated bacteria [49], were increased [20]. In particular, the microbiota pro le appears to favor butyrate production, a common indicator of gut health, potentially through increases in the members of Lachnospiraceae, Faecalibacterium and Ruminococcaceae [20,45].…”

Section: Discussionmentioning

confidence: 99%

Specific Time Determinism: Circadian Rhythm of Microbial Community Assembly Patterns Under Common Light in Feces of Laying Hens

Lan

Zhu

Zhang

et al. 2021

Preprint

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BackgroundAs an important part of biological rhythm, the circadian rhythm of the gut microbiota plays a crucial role in host health. However, few studies have determined the associations between the circadian rhythm and gut microbiota in laying hens. The purpose of this experiment was to investigate the circadian rhythm of the feces microbiota in laying hens.ResultsFeces samples were collected from ten laying hens at nine different time points (06:00-12:00-18:00-00:00-06:00-12:00-18:00-00:00-06:00) to demonstrate the diurnal oscillation of the feces microbiota. We described the phenomenon of circadian rhythmicity of the feces microbiota in laying hens based on 16S rRNA gene sequencing. According to the results, the α and β diversity of the feces microbiota fluctuated significantly at different time points. Beta Nearest Taxon Index analysis suggested that assembly strategies of the abundant and rare amplicon sequence variants (ASVs) sub-communities are different. Abundant ASVs preferred disperal limitation (weak selction), whereas rare ASVs randomly formed due to the “non-dominant” fractions. Highly robust circadian fluctuations were found, for instance, in Firmicutes and Proteobacteria, which fluctuated oppositely, and the total ratio remained in a dynamic balance over 48 h. We found that temporal dynamic changes had a significant effect on the relative abundance of the important bacteria in the feces microbiota community by using the random forest algorithm. Eight bacteria, Ruminococcus gnavus, Faecalibacterium, Ruminococcaceae, Enterococcus cecorum, Lachnospiraceae, Clostridium, Clostridiales, and Megamonas, gained rhythmicity. Interestingly, one unexpected finding was the fact that these eight bacteria all belong to Firmicutes. In particular, the microbiota profile appears to favor butyrate production, a common indicator of gut health, potentially through increases in the members of Lachnospiraceae, Faecalibacterium and Ruminococcaceae. The pathways were the functionalities that gained rhythmicity within the microbiota, which belonged to the most abundant functions, including xenobiotic biodegradation and metabolism, carbohydrate metabolism, and amino acid metabolism, which were consistent with the metabolic functions of amino acids and carbohydrates from feed.ConclusionThis study has shown that the defecation time could be among the important factors influencing the diversity, proportion, and functions of the feces microbiota community. We also note the potential application of beneficial microbial communities in livestock species, especially in the environment of raising antibiotic-free animals. These results provide references for further exploring the circadian rhythm of the gut microbiota in laying hens.

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“…Although conceptually attractive, some therapies targeting IL-17A are efficacious in the joint but not vice versa, and the targeting of adhesion molecules such as α4β7 in IBD can lead to onset or flares of SpA (67). Recent studies in ethnically different patient populations, and especially in patients with HLA-B27, have demonstrated dysbiosis in patients with SpA (68)(69)(70)(71)(72)(73)(74)(75)(76). Such dysbiosis is highly dependent on the host's genetic background and/or environment, implicating an "ecological model of dysbiosis", with the effects of a multitude of microbes contributing all to the aberrant immunopathogenesis (77).…”

Section: Subclinical Gut Inflammation (Gut-joint Axis)mentioning

confidence: 99%

Immunopathophysiology of Juvenile Spondyloarthritis (jSpA): The “Out of the Box” View on Epigenetics, Neuroendocrine Pathways and Role of the Macrophage Migration Inhibitory Factor (MIF)

Harjaček

2021

Front. Med.

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Juvenile spondyloarthritis (jSpA) is a an umbrella term for heterogeneous group of related seronegative inflammatory disorders sharing common symptoms. Although it mainly affects children and adolescents, it often remains active during adulthood. Genetic and environmental factors are involved in its occurrence, although the exact underlying immunopathophysiology remains incompletely elucidated. Accumulated evidence suggests that, in affected patients, subclinical gut inflammation caused by intestinal dysbiosis, is pivotal to the future development of synovial–entheseal complex inflammation. While the predominant role of IL17/23 axis, TNF-α, and IL-7 in the pathophysiology of SpA, including jSpA, is firmly established, the role of the cytokine macrophage migration inhibitory factor (MIF) is generally overlooked. The purpose of this review is to discuss and emphasize the role of epigenetics, neuroendocrine pathways and the hypothalamic-pituitary (HPA) axis, and to propose a novel hypothesis of the role of decreased NLRP3 gene expression and possibly MIF in the early phases of jSpA development. The decreased NLRP3 gene expression in the latter, due to hypomethylation of promotor site, is (one of) the cause for inflammasome malfunction leading to gut dysbiosis observed in patients with early jSpA. In addition, we highlight the role of MIF in the complex innate, adaptive cellular and main effector cytokine network, Finally, since treatment of advanced bone pathology in SpA remains an unmet clinical need, I suggest possible new drug targets with the aim to ultimately improve treatment efficacy and long-term outcome of jSpA patients.

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Microbial orchestra in juvenile idiopathic arthritis: Sounds of disarray?

Cited by 23 publications

References 168 publications

Infections and antibiotics during fetal life and childhood and their relationship to juvenile idiopathic arthritis: a prospective cohort study

Infections and antibiotics during fetal life and childhood and their relationship to juvenile idiopathic arthritis: a prospective cohort study

Specific Time Determinism: Circadian Rhythm of Microbial Community Assembly Patterns Under Common Light in Feces of Laying Hens

Immunopathophysiology of Juvenile Spondyloarthritis (jSpA): The “Out of the Box” View on Epigenetics, Neuroendocrine Pathways and Role of the Macrophage Migration Inhibitory Factor (MIF)

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