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Background: The gut microbiome plays a crucial role in the pathogenesis and progression of inflammatory bowel disease (IBD). Understanding the dynamics of the gut microbiome in relation to treatment can provide valuable insights into disease management and therapy strategies. The aim of this study is to investigate if diversity and composition of the gut microbiome correlate with time since treatment and disease activity during maintenance infliximab (IFX) therapy among children with IBD., Methods: Data was collected from IBD patients aged 10-17 participating in an IFX-eHealth study. IFX infusions were administered in 4-12-week intervals based on weekly faecal calprotectin (FC) combined with symptom scores. Excess stool samples underwent microbiome profiling using 16S rRNA gene sequencing. Microbiome features, including alpha diversity and single taxa, were analysed for three key variables: 1) weeks-since-treatment, 2) FC, and 3) symptom score., Results: From 25 patients (median age 14.4 years) diagnosed with Crohn´s Disease (n = 16) or ulcerative colitis (n = 9), microbiota were analysed in 671 faecal samples collected across 15 treatment intervals. A significant decrease over time in Shannon diversity, following the initial increase within four weeks of treatment, was found across patients. FC levels showed no association with alpha diversity (p>0.1), while symptom scores showed a negative association with Shannon and observed diversity in patients with UC. At the genus level, a lower abundance of the genera Anaerostipes and Fusicatenibacter (Firmicutes), and a greater abundance of the genus Parasutterella (Proteobacteria), were associated (p.adj<0.05) with the time elapsed since last infusion in UC specifically, while only Parasutterella was associated across the full cohort (p.adj = 1e-10)., Conclusions: We found a recurring reduction over time in alpha diversity following the initial increase in diversity after an IFX infusion. Changes in an individual's microbiome may be an early sign of increasing disease activity that precedes clinical symptoms and increased FC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Carlsen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives: Adult-onset immune-mediated inflammatory disease (IMID) increases the risk of several cancers. However, data on pediatric-onset IMID (pIMID) remains scarce. We estimated the long-term cancer risk in pIMID and the association between medical treatment and specific cancers., Methods: We used the nationwide Danish health registers to identify pIMID patients diagnosed from Jan 1, 1980 to Dec 31, 2018. Patients were matched with ten reference individuals based on age, sex, and residence. The primary exposure was pIMID, including autoimmune hepatitis, primary sclerosing cholangitis, Crohn's disease, ulcerative colitis, juvenile idiopathic arthritis, systemic lupus erythematosus, vasculitis, and connective tissue disease. Secondary exposures were immunomodulators and tumor necrosis factor-α antagonists (anti-TNFα). The primary outcome was cancer. Estimates are presented as hazard ratios adjusted for family income at diagnosis (AHR)., Results: We included 12,664 pIMID patients and 109,274 reference individuals. Median follow-up time was 10.6 (interquartile range: 5.4-17.7) years for patients and 10.2 (interquartile range: 5.2-17.3) years for reference individuals. Patients with pIMID had a twofold higher cancer risk (AHR 2.2 [95 % confidence interval (CI): 1.8-2.6]) compared with reference individuals. Thiopurine treatment was associated with a higher risk of lymphoma (AHR 6.1 [95%CI: 2.2-16.8]) and skin cancer (AHR 6.1 [95%CI: 2.4-15.4]). Anti-TNFα treatment was associated with a higher risk of lymphoma (AHR 4.9 [95%CI: 1.1-22.6])., Conclusions: We found an increased cancer risk in patients with pIMID followed into adulthood. Additionally, thiopurines and anti-TNFα were associated with increased lymphoma and skin cancer risks. This highlights the importance of individualized immunotherapy and cancer surveillance., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Thiopurine therapy is a cornerstone in the treatment of inflammatory bowel disease (IBD). We aimed to assess the effect of thiopurines on cancer risk in IBD according to drug exposure and age., Methods: Danish national registers were used to identify incident IBD patients, exposure to drugs, and status of cancers, in 1996 to 2018. Cox regressions were used to compare cancer risks in IBD and non-IBD individuals and to assess IBD patients' cumulative drug exposure and the association to first cancer, excluding non-melanoma skin cancer., Results: We followed 43,419 patients with IBD for a median of 8.2 years (interquartile range, 3.7-14.2 years) after IBD diagnosis. Cancer was reported in 3128 (7.2%) patients with IBD. The risk of cancer was increased in patients with IBD in all age categories compared with non-IBD individuals (<50 years: adjusted hazard ratio [aHR], 1.59; 95% confidence interval [CI], 1.43-1.77; 50-65 years: aHR, 1.31; 95% CI, 1.19-1.44; and >65 years: aHR, 1.14; 95% CI, 1.05-1.24). Monotherapy (aHR, 1.36; 95% CI, 1.17-1.57) and combination therapy (aHR, 2.49; 95% CI, 1.64-3.78) were associated with an increased risk of cancer compared to unexposed patients with IBD. Among elderly patients (>65 years), the aHR was 2.79 (95% CI, 1.24-6.28) in those receiving combination therapy. In patients discontinuing thiopurines, aHRs returned to the level of unexposed (aHR, 0.89; 95% CI, 0.78-1.01). The aHR was positively associated with cumulative thiopurine exposure and in patients with >5 years of exposure, reaching an aHR of 1.36 (95% CI, 1.15-1.61)., Conclusions: Thiopurines were associated with increased hazard of cancer, especially when used in combination therapy in the elderly. The hazard increased by 36% when patients were exposed to thiopurines for more than 5 years. Reassuringly, the hazard returned to baseline after discontinuation of thiopurines., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Pediatric-onset ulcerative colitis (pUC) represents a more aggressive disease phenotype compared with adult-onset UC. We hypothesized that this difference can, in part, be explained by the composition of the microbiota., Methods: In a prospective, longitudinal study, we included pediatric (N = 30) and adult (N = 30) patients with newly or previously (>1 year) diagnosed UC. We analyzed the microbiota composition in the mucosa-adherent microbiota at baseline, using 16S rRNA gene sequencing, and the fecal microbiota at baseline and at 3-month intervals, using shotgun metagenomics., Results: For fecal samples, the bacterial composition differed between pUC and aUC in newly diagnosed patients (β-diversity, Bray Curtis: R2 = 0.08, P = .02). In colon biopsies, microbial diversity was higher in aUC compared with pUC (α-diversity, Shannon: estimated difference 0.54, P = .006). In the mucosa-adherent microbiota, Alistipes finegoldii was negatively associated with disease activity in pUC while being positively associated in aUC (estimate: -0.255 and 0.098, P = .003 and P = .02 in pUC and aUC, respectively). Finally, we showed reduced stability of the fecal microbiota in pediatric patients, evidenced by a different composition of the fecal microbiota in newly and previously diagnosed pUC, a pattern not found in adults., Conclusions: Our results indicate that pediatric UC patients have a more unstable fecal microbiota and a lower α diversity than adult patients and that the microbiota composition differs between aUC and pUC patients. These findings offer some explanation for the observed differences between pUC and aUC and indicate that individualized approaches are needed if microbiota modifications are to be used in the future treatment of UC., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Paediatric-onset and elderly-onset inflammatory bowel disease (IBD) present unique treatment challenges., Aims: We investigated treatment patterns following a first and second course of systemic steroids in paediatric- and elderly-onset IBD and compared them to adult-onset IBD., Methods: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2000 and 2018 were identified through the Danish healthcare registries. Patients were divided into groups based on their age at diagnosis. Kaplan-Meier plots were prepared for medications and surgeries after diagnosis and after the first and second courses of systemic steroids. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariate Cox regression analysis for steroid-sparing medications., Results: 1851 CD (13%) and 1687 (6%) UC patients were paediatric-onset, while 2952 (20%) CD and 5812 (23%) UC patients were elderly-onset. Paediatric-onset more frequently received immunomodulators [CD: HR: 1.64, CI: 1.52-1.77, UC: HR: 2.29, CI: 2.02-2.61] and biologics [CD: HR: 1.43, CI: 1.25-1.65, UC: HR: 1.27, CI: 0.99-1.64], while elderly-onset less frequently received immunomodulators [CD: HR: 0.39, CI: 0.35-0.44, UC: HR: 0.58, CI: 0.50-0.67] and biologics [CD: HR: 0.19, CI: 0.14-0.25, UC: HR: 0.36, CI: 0.27-0.48] compared to adult-onset age groups. After two courses of systemic steroids, elderly-onset still received less steroid-sparing medications. High frailty was associated with lower usage of medications for elderly-onset., Conclusion: There are significant differences in the use of steroid-sparing medication between age of onset, even after two courses with systemic steroids. High frailty could account for some of these differences in elderly-onset IBD., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making., (© 2024. The Author(s).)

Background: Paediatric-onset immune-mediated inflammatory diseases (pIMID) show more aggressive phenotypes than when diagnosed in adults. However, data on mortality are often extrapolated from adult studies., Aim: To estimate the effect of pIMID on mortality., Methods: In a population-based cohort study using the nationwide Danish healthcare registers, we included all patients diagnosed with pIMID in Denmark from 1980 to 2018. PIMID were defined as ICD codes indicative of autoimmune hepatitis, primary sclerosing cholangitis, Crohn's disease, ulcerative colitis, juvenile idiopathic arthritis, lupus erythematosus, or vasculitis registered before age 18 years. All-cause mortality was the primary outcome; cause-specific mortality was the secondary outcome. We used Cox survival analysis to estimate hazard ratios (HR), and Aalen survival analysis to estimate rate differences., Results: We included 11,581 individuals diagnosed with pIMID and 99,665 reference individuals, accounting for 1,371,994 person-years of follow-up. Median and interquartile (IQR) age at diagnosis was 12.6 (7.9-15.9) years. During follow-up, 152 patients with pIMID and 316 reference individuals died; adjusted HR (aHR) was 3.8 (95% confidence interval [CI] 3.1-4.7). This corresponded to 6.9 (95% CI: 5.3-8.5) additional deaths per 10,000 person-years. The strongest associations were found for gastrointestinal diseases (aHR 22.8; 95% CI 9.6-64.1), gastrointestinal cancers (aHR 19.2; 95% CI 5.0-74.2) and lymphoproliferative disorders (aHR 6.8; 95% CI 2.8-16.8)., Conclusion: Patients diagnosed with pIMID have a fourfold higher risk of mortality when followed into early adulthood compared with reference individuals. This underlines the severe disease course of pIMID and highlights the need for multidisciplinary care., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background and Aims: Inflammatory bowel diseases [IBD] are heterogeneous in the frequency and severity of their flare-ups. We aimed to describe disease activity patterns in a Danish nationwide paediatric IBD cohort., Methods: Paediatric patients [<18 years at diagnosis] with Crohn's disease [pCD] or ulcerative colitis [pUC] in the study period from 1996 to 2018 were identified in national registers. Disease activity [severe, moderate-to-mild, remission] was assessed at diagnosis according to medications prescribed, hospitalizations, and surgeries., Results: In total, 1965 pCD and 1838 pUC incident patients were included in the cohort. At diagnosis, severe disease activity was found in 87%/80% of pCD/pUC and in addition 6.1% of pUC patients had undergone a colectomy during the first year after diagnosis. Five years after diagnosis, the annual proportions of pCD/pUC with no disease activity were 70%/61%, and 10 years after diagnosis the proportions were 72%/64%. Colectomy was required in 6.1, 12, and 16% of pUC patients after 1, 5 and 10 years. No improvement of disease activity was seen in the proportion of prevalent pCD [N = 2515] and pUC [N = 2428] in the study period 2000-2018 concomitant with the introduction of biological treatment. However, decreasing disease activity was the most common pattern in both pCD and pUC [43 and 47%], respectively., Conclusions: pIBD was characterized by a high proportion of patients with severe activity at diagnosis, followed by an improvement after 5 and 10 years of follow-up. Notably, the proportion of patients with no disease activity was unchanged when biological treatment was introduced and the number of colectomies in pUC remained high., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate the frequency of psychiatric disorders before and after onset of paediatric-onset immune-mediated inflammatory diseases (pIMID)., Study Design: In a nationwide study from 1996 to 2018, we investigated psychiatric disorders in patients with paediatric-onset inflammatory bowel diseases, autoimmune liver diseases and rheumatic diseases, using Danish national healthcare and population registers. Each case was matched with up to 10 controls from the background population. The cumulative incidence for psychiatric disorders prior to pIMID onset in patients was compared with controls. Cox proportional regression was used to estimate adjusted HRs (aHR) with a 95% CI between cases and controls after the index date., Results: We included 11 208 cases (57% female) and 98 387 controls. The median age at disease onset was 12.5 years (IQR 8-15) and follow-up time 9.8 years (IQR 5-15). We found an association between psychiatric disorders before index date and a diagnosis of subsequent pIMID (OR 1.3, 95% CI 1.2 to 1.4). Notably, after index date, cases also had an increased risk (aHR 1.6, 95% CI 1.5 to 1.7) of psychiatric disorders compared with controls. This risk was increased for all groups of psychiatric disorders. Female patients had an increased risk of suicide attempt after index date (aHR 1.4, 95% CI 1.1 to 1.8)., Conclusion: Patients with pIMID are at increased risk for a broad spectrum of psychiatric disorders both before and after onset of pIMID. The results support the need for awareness of psychiatric morbidity in this young patient group and the need for coordinated healthcare for those with comorbid states., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Early-life environmental triggers are thought to play a larger role in pediatric-onset inflammatory bowel disease (pIBD) compared to adult-onset IBD. We aimed to assess the risk of developing pIBD after exposure to oral antibiotics during the first 5 years of life., Methods: In a nation-wide cohort study, we identified all patients diagnosed with pIBD (<18 years at diagnosis) in Denmark between 1995 and 2018 from the National Patient Registry and matched them with up to 10 reference individuals. Antibiotic exposure was defined as being prescribed antibiotics during first 5 years of life. Data were retrieved from the National Prescription Register. Outcome was developing pIBD. Risk estimates are presented by hazard ratios (HR) with 95% confidence intervals (CI)., Results: We identified 1927 pIBD patients and 18,318 reference individuals. Oral antibiotic exposure during the first 5 years of life was associated with a higher risk of developing pIBD (HR = 1.33 [95% CI: 1.2-1.5], P <0.0001). The risk was also increased if patients had ≥4 antibiotic prescriptions compared to no antibiotics (HR = 1.33 [95% CI: 1.2-1.5], P <0.0001). Broad-spectrum antibiotics increased the risk of pIBD compared to narrow-spectrum antibiotics (HR = 1.29 [95% CI: 1.2-1.4], P < 0.0001). When stratified by IBD subtypes, only Crohn disease was significantly associated with exposure to antibiotics (HR = 1.37 [95% CI: 1.1-1.7], P = 0.002)., Conclusions: In this nationwide registry-based study, we found that oral antibiotic exposure during first 5 years of life was associated with an increased risk of pIBD. Repeated antibiotic exposures increased risk estimates., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Pediatric-onset inflammatory bowel disease (pIBD) increases the risk of developing several different cancer forms. In this case-control study, we aimed to assess the impact of medical treatment and disease activity on the risk of developing disease-associated cancer (DAC) and treatment-associated cancer (TAC)., Methods: In a previous study, we identified 27 cases of DAC (colorectal cancer, small bowel cancer, and cholangiocarcinoma) and 28 TAC (lymphoma and skin cancer) in 6689 patients with pIBD in Denmark and Finland during the period 1992-2015. In this study, the patient charts were reviewed manually. Cancer-free patients from another population-based pIBD cohort were included as controls. We recorded data on phenotype, medical treatment, surgery, and relapses. Logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) to estimate the relative risk., Results: We included 16 cases with DAC, 21 with TAC, and 331 controls. For DAC, lower frequencies of IBD-relapses were associated with an increased risk of cancer (OR 0.2 [95% CI: 0.04-0.8]). For TAC, we found an increased risk in patients receiving thiopurines at any point during the follow-up period (aOR: 11.7 [95% CI: 2.1-116.2]) and an association with proportion of follow-up time being exposed to thiopurines (aOR 5.6 [95% CI: 1.1-31.5])., Conclusions: In this nation-wide study, covering all pIBD patients from Denmark and Finland, we found that pIBD patients treated with thiopurines had an increased risk of TAC., Competing Interests: O.O. has been PI for projects (unrelated to the present paper) at Karolinska Institutet financed by grants from Janssen, Takeda, AbbVie, Ferring, and Pfizer. Karolinska Institutet has received fees for lectures (OO) and participation on advisory boards (OO) from Janssen, Ferring, Bristol Myers Squibb, Galapagos and Takeda. The remaining authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: We aimed to identify pre- and perinatal risk factors for developing pediatric-onset immune-mediated inflammatory (pIMID)., Methods: This nation-wide, cohort study included all children born in Denmark from 1994 to 2014 identified from the Danish Medical Birth registry. Individuals were followed through 2014 and cross-linked to the continuously updated national socioeconomic and healthcare registers to obtain data on pre- and perinatal exposures (maternal age, educational level, smoking, maternal IMID, parity, mode of conception and delivery, plurality, child's sex, and birth season). The primary outcome was a pIMID diagnosis (inflammatory bowel disease, autoimmune hepatitis, primary sclerosing cholangitis, juvenile idiopathic arthritis, or systemic lupus erythematosus) before 18 years of age. Risk estimates were calculated using Cox proportional hazards model and presented by hazard ratios (HR) with 95% confidence intervals (95%CI)., Results: We included 1,350,353 children with a follow-up time of 14,158,433 person-years. Among these, 2,728 were diagnosed with a pIMID. We found a higher risk of pIMID in children born to women with a preconception IMID diagnosis (HR: 3.5 [95%CI: 2.7-4.6]), children born by Caesarean section (HR: 1.2 [95%CI: 1.0-1.3]), and among females (1.5 [95%CI: 1.4-1.6]) than among children without these characteristics. Plural pregnancies were associated with a lower risk of pIMID than single pregnancies (HR: 0.7 [95%CI: 0.6-0.9])., Conclusions: Our results indicate a high genetic burden in pIMID but also identifies intervenable risk factors, such as Cesarean section. Physicians should, keep this in mind when caring for high-risk populations and pregnant women previously diagnosed with an IMID., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Incidence rates of inflammatory bowel disease [IBD] reported from developed countries are rising, with some levelling out. The aim of this study was to assess the disease burden of IBD by estimating the incidence and prevalence across age groups and projecting these to 2030 in a high-incidence country., Methods: Using an algorithm [incorporating ICD codes, medications and histopathology], patients [n = 69 862] diagnosed with Crohn's disease [CD] or ulcerative colitis [UC] between 1980 and 2017 were identified in the Danish National Patient Registry and included in a nationwide cohort., Results: From 1980 to 2017 the overall incidence of CD increased from 5.1 [95% CI: 4.5-5.8] to 15.6 [95% CI: 14.6-16.6] per 100 000, while the incidence of UC increased from 6.2 [95% CI: 5.5-6.9] to 27.2 [95% CI: 25.9-28.6] per 100 000. For paediatric-onset CD [pCD], the incidence increased from 1.9 [95% CI: 1.2-2.8] to 9.9 [95% CI: 8.1-11.8] per 100 000 and from 1.8 [95% CI: 1.2-2.8] to 8.7 [95% CI: 7.1- 10.5] per 100 000 for paediatric-onset UC [pUC]. In 2017, the prevalence of CD and UC was 293 [95% CI: 288-297] and 523 [95% CI: 517-528] per 100 000. For pCD and pUC, the prevalence was 35 [95% CI: 31-38] and 28 [95% CI: 26-32] per 100 000., Conclusions: The incidence of paediatric- and adult-onset IBD in Denmark continues to increase and is among the highest in the world., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Inflammatory bowel diseases [IBD], which are associated with a high disease burden, are also reported to be accompanied by a high prevalence of psychiatric disorders. However, the literature on IBD and psychiatric disorders has not been reviewed., Methods: This systematic review followed the PRISMA guidelines, and its protocol was registered at PROSPERO [ID: CRD42020214359]. PubMed, Embase and PsycINFO were consulted for the literature search. Studies reporting on diagnosed psychiatric disorders in IBD were included. Pooled prevalence rates were calculated using random effects meta-analyses. Study quality was assessed using the Newcastle-Ottawa Scale [NOS]., Results: Sixty-nine studies were identified with an average cohort size of 60 114 patients. Pooled prevalence rates were: mood disorders, 10% (95% confidence interval [CI] = 7%; 15%); anxiety disorders, 12% [95% CI = 8%; 18%]; substance misuse, 3% [95% CI = 1%; 7%]; psychotic disorders, 2% [95% CI = 1%; 4%]; behavioural disorders, 1% [95% CI = 0%; 3%]; personality disorders, 3% [95% CI = 1%; 10%]; developmental disorders, 1% [95% CI = 0%; 3%]; and behavioural and emotional disorders with onset usually during childhood, 1% [95% CI = 1%; 3%]. All analyses had high statistical heterogeneity [I2 > 99%]. Seven studies reported an increased risk of suicide in IBD patients compared to controls., Conclusion: The prevalence of psychiatric comorbidities was high [11-82%] in patients with IBD and was higher than in the background population. Addressing mental health problems in patients with IBD can improve their adherence to treatment and the somatic disease course and, consequently, reduce morbidity and mortality., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: To estimate psychiatric comorbidity in childhood onset immune-mediated inflammatory diseases (IMID)., Methods: The PRISMA guidelines were followed, and the protocol was registered at Prospero (ID: CRD42021233890). Literature was searched in PubMed, PsycINFO and Embase. Original papers on prevalence rates of diagnosed psychiatric disorders and/or suicide in paediatric onset inflammatory bowel disease (pIBD), rheumatic diseases (RD) and autoimmune liver diseases were selected. Pooled prevalence rates of psychiatric disorders (grouped according to ICD-10 criteria) within the various IMID were calculated using random-effects meta-analysis. Risk of bias was evaluated by the Newcastle-Ottawa scale., Results: Twenty-three studies were included; 13 describing psychiatric disorders in pIBD and 10 in RD. Anxiety and mood disorders were mostly investigated with pooled prevalence rates in pIBD of 6% (95% confidence interval (CI): 4%-9%) and 4% (95%CI: 2%-8%), respectively, in register-based studies, and 33% (95%CI: 25%-41%) and 18% (95%CI: 12%-26%), respectively, in studies using psychiatric assessment. In RD, rates were 13% (95%CI: 12%-15%) for anxiety disorders and 20% (95%CI: 15%-26%) for mood disorders based on psychiatric assessment., Conclusion: Anxiety and depression are commonly reported in childhood onset IMID. Physicians should be attentive to mental health problems in these patients as they seem overlooked., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Terpenes are one of the largest classes of secondary metabolites that occur in all kingdoms of life and offer diverse valuable properties for food and pharma industry including pleasant odor or taste as well as antimicrobial or anticancer activities. A multitude of terpene biosynthesis pathways are known, but their efficient biotechnological exploitation requires an adequate microorganism as host which can ideally provide an optimal supply with biosynthetic isoprene precursors. Rhodobacter capsulatus, a Gram-negative, facultative anaerobic, photosynthetic non-sulfur purple bacterium belonging to the α-proteobacteria represents such a host particularly suitable for terpene production. Here, we describe methods for the expression of terpene biosynthetic enzymes in R. capsulatus and the extraction of products for analysis. At the same time, we summarize the current strategies to adjust the biosynthetic precursor supply via isoprenoid biosynthetic pathways., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)