Crohn's disease (CD) has an unclear etiology, but there is growing evidence of a direct link with a dysbiotic microbiome. Many gut microbes have previously been associated with CD, but these have ...mainly been confounded with patients' ongoing treatments. Additionally, most analyses of CD patients' microbiomes have focused on microbes in stool samples, which yield different insights than profiling biopsy samples.
We sequenced the 16S rRNA gene (16S) and carried out shotgun metagenomics (MGS) from the intestinal biopsies of 20 treatment-naïve CD and 20 control pediatric patients. We identified the abundances of microbial taxa and inferred functional categories within each dataset. We also identified known human genetic variants from the MGS data. We then used a machine learning approach to determine the classification accuracy when these datasets, collapsed to different hierarchical groupings, were used independently to classify patients by disease state and by CD patients' response to treatment. We found that 16S-identified microbes could classify patients with higher accuracy in both cases. Based on follow-ups with these patients, we identified which microbes and functions were best for predicting disease state and response to treatment, including several previously identified markers. By combining the top features from all significant models into a single model, we could compare the relative importance of these predictive features. We found that 16S-identified microbes are the best predictors of CD state whereas MGS-identified markers perform best for classifying treatment response.
We demonstrate for the first time that useful predictors of CD treatment response can be produced from shotgun MGS sequencing of biopsy samples despite the complications related to large proportions of host DNA. The top predictive features that we identified in this study could be useful for building an improved classifier for CD and treatment response based on sufferers' microbiome in the future. The BISCUIT project is funded by a Clinical Academic Fellowship from the Chief Scientist Office (Scotland)-CAF/08/01.
The anti-inflammatory effect of exclusive enteral nutrition on the gut of children with Crohn's disease is rapidly lost after food reintroduction. This study assessed disease dietary triggers ...following successful treatment with exclusive enteral nutrition.
Nutrient intake, dietary patterns and dietary biomarkers in faeces (gluten immunogenic peptides, undigestible starch, short chain fatty acids) were assessed in 14 children with Crohn's disease during early food reintroduction, following exclusive enteral nutrition. Groups above (Group A) and below (Group B) the median levels of faecal calprotectin after food reintroduction were assigned for comparative analysis.
Intakes of fibre, gluten-containing cereals and red and processed meat were significantly higher in Group A than Group B; (median Q1, Q3, g/day; Fibre: 12.1 11.2, 19.9 vs. 9.9 7.6, 12.1, p = 0.03; Red and processed meat: 151 66.7, 190 vs. 63.3 21.7, 67, p = 0.02; gluten-containing cereals: 289 207, 402 vs. 203 61, 232, p = 0.035). A diet consisting of cereals and meat products was predictive (92% accuracy) of higher faecal calprotectin levels after food reintroduction. In faeces, butyrate levels, expressed as absolute concentration and relative abundance, were higher in Group A than Group B by 28.4 µmol/g (p = 0.015) and 6.4% (p = 0.008), respectively. Levels of gluten immunogenic peptide and starch in faeces did not differ between the two groups.
This pilot study identified potential dietary triggers of gut inflammation in children with Crohn's disease after food reintroduction following treatment with exclusive enteral nutrition.
Clinical trials.gov registration number: NCT02341248; Clinical trials.gov URL: https://clinicaltrials.gov/ct2/show/NCT02341248 (retrospectively registered).
ObjectivesFollowing the disruption of normal paediatric inflammatory bowel disease (IBD) services during the peak of the COVID-19 pandemic, we prospectively audited the first-time use of home faecal ...calprotectin testing. We aimed to provide an alternative to laboratory tests and to assess the value of home testing as part of our regular services going forward.MethodsHome test kits as well as accompanying user instructions were made available to our patients with paediatric IBD that required faecal calprotectin test between 17 April and 12 August 2020. Once the user completed the test, results were automatically uploaded to the result portal and clinical staff were alerted. A user feedback questionnaire was sent to users that had completed the home test.ResultsOf the 54 patients, 41 (76%) aged between 4.7 and 18.1 years used the home test. A total of 45 home tests were done, one of which produced an invalid result. The decision to modify management was made in 12 (29%) of the patients, while 14 (34%) had no changes made and 15 (37%) required further assessment. Twenty (48.8%) responded to the questionnaire and 85% stated that they preferred the home test to the laboratory testing method.ConclusionsHome calprotectin tests were useful in guiding clinical management during a time when laboratory testing was less available. They may offer benefits as part of routine paediatric IBD monitoring to help target appointments and reduce unnecessary hospital attendances in the future.
Exposure to traumatic life events (TLE) is a risk factor for psychosis. Yet, a dearth of studies examines factors linking TLE to psychosis, while considering differences in TLE frequency. This study ...investigated dissociation and aberrant salience as mediators and moderators of the relation between three TLE groups (none, 1-3 TLE and 4+ TLE) and psychotic-like experiences (PLE) in a multi-ethnic sample of 816 emerging adults. The participants completed self-report inventories of PLE (Prodromal Questionnaire), TLE (Life Events Checklist), dissociative experiences (Dissociative Symptoms Scale), and aberrant salience (Aberrant Salience Inventory). As expected, groups with higher TLE frequency endorsed higher PLE. Parallel mediation models indicated that, while aberrant salience mediated the relation between both levels of cumulative traumatic experiences (1-3 TLE and 4+ TLE) and PLE, dissociation only mediated the relation between exposure to at least four different traumatic experiences and PLE. The moderation results showed that risk of PLE was highest among individuals with 1-3 TLE who endorsed dissociation. Our results suggest that, while aberrant salience processing explains why TLE may relate to higher psychosis risk, dissociation's role in this relation is dependent on the number of different TLE exposures.
On 31 March 2022, Public Health Scotland was alerted to five children aged 3-5 years admitted to hospital with severe hepatitis of unknown aetiology. Retrospective investigation identified eight ...additional cases aged 10 years and younger since 1 January 2022. Two pairs of cases have epidemiological links. Common viral hepatitis causes were excluded in those with available results. Five children were adenovirus PCR-positive. Other childhood viruses, including SARS-CoV-2, have been isolated. Investigations are ongoing, with new cases still presenting.
Exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn's disease (CD), but its acceptability is limited. There is a need for novel dietary treatments for CD.
We ...evaluated the effects of an individualized food-based diet (CD-TREAT), with similar composition to EEN, on the gut microbiome, inflammation, and clinical response in a rat model, healthy adults, and children with relapsing CD. Twenty-five healthy adults randomly received EEN or CD-TREAT for 7 days, followed by a 14-day washout period, followed by the alternate diet. Fecal microbiome and metabolome were assessed before and after each diet. HLA-B7 and HLA-B27 transgenic rats with gut inflammation received EEN, CD-TREAT, or standard chow for 4 weeks. Fecal, luminal, and tissue microbiome, fecal metabolites, and gut inflammation were assessed. Five children with active CD activity received CD-TREAT and their clinical activity and calprotectin were evaluated after 8 weeks of treatment.
For healthy adults, CD-TREAT was easier to comply with and more acceptable than EEN. CD-TREAT induced similar effects to EEN (EEN vs CD-TREAT) on fecal microbiome composition, metabolome, mean total sulfide (increase 133.0 ± 80.5 vs 54.3 ± 47.0 nmol/g), pH (increase 1.3 ± 0.5 vs 0.9 ± 0.6), and the short-chain fatty acids (μmol/g) acetate (decrease 27.4 ± 22.6 vs 21.6 ± 20.4), propionate (decrease 5.7 ± 7.8 vs 5.2 ± 7.9), and butyrate (decrease 7.0 ± 7.4 vs 10.2 ± 8.5). In the rat model, CD-TREAT and EEN produced similar changes in bacterial load (decrease 0.3 ± 0.3 log10 16S rRNA gene copies per gram), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score decreases of 1.25 for EEN P = .015 and 1.0 for CD-TREAT P = .044 vs chow). In children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent decreases in fecal calprotectin (mean decrease 918 ± 555 mg/kg; P = .002).
CD-TREAT replicates EEN changes in the microbiome, decreases gut inflammation, is well tolerated, and is potentially effective in patients with active CD. ClinicalTrials.gov, numbers NCT02426567 and NCT03171246
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Prior studies have shown cannabis use is correlated with psychotic symptoms, but few have explored potential underlying mechanisms. The present study examined whether aberrant salience explains the ...association between cannabis use frequency and psychotic experiences (PE) while accounting for the mediating role of anxiety in this association. A US urban undergraduate sample of 816 racial and ethnic minorities contributed data used in linear regression models to determine associations between recent (3 months) cannabis use frequency, aberrant salience, anxiety, positive subscale Prodromal Questionnaire (PQ) items, and distressing positive PQ items. Results from hierarchical linear regression and mediation models using Hayes PROCESS application indicated the association between cannabis use frequency and PE was significantly explained by higher aberrant salience and anxiety. Furthermore, anxiety's indirect association with cannabis use frequency and PE significantly occurred through aberrant salience's indirect association with cannabis use frequency and PE (i.e., serial mediation). A similar pattern emerged for distressing PE. We also found earlier age of cannabis use onset (age 12–14) was associated with a higher number of PE and distressing PE and that this was partially explained by higher aberrant salience. Anxiety's indirect association between earlier age of onset and PE/distressing PE only occurred through aberrant salience (i.e., serial mediation). Aberrant salience may be the part of psychosis proneness most directly connected to why earlier initiation of cannabis use is a risk factor for psychotic disorders. This should be explored further in future longitudinal work with clinical high-risk populations and among minoritized youth.
Abstract
Background
Early onset cannabis use is associated with psychosis risk in a dose response fashion. Aberrant salience is a cognitive approach to perception and information integration believed ...to be involved in the development of psychosis. Recent studies suggest aberrant salience explains severity of cannabis-induced psychotic symptoms, but does not significantly distinguish cannabis users from non-users (e.g., Bloomfield et al., 2016), while other studies show cannabis users exhibit higher aberrant salience than non-users (e.g., Bernardini et al., 2018). The aim of the present study was to examine the degree to which aberrant salience explains any association between cannabis use and psychotic-like experiences (PLEs) in a diverse non-treatment-seeking population.
Methods
A Northeastern U.S. urban undergraduate sample of 816 racial minority or first/second-generation immigrant emerging adults completed a battery of self-report inventories on a computer in a research lab. Data from the Prodromal Questionnaire (PQ), Aberrant Salience Inventory (ASI), and cannabis use items from a Substance Use Questionnaire were used in multiple linear regression models to determine associations between frequency of recent (past 3-months) cannabis use, aberrant salience, positive subscale PQ items, and positive PQ items endorsed as distressing. Among users, associations were examined between age of onset of cannabis use (<15, >14), PLEs, and aberrant salience. The Hayes PROCESS application was employed to quantify the significance of indirect associations between ASI scores and the association between cannabis use frequency and PLEs. Trait anxiety was controlled for in the regression models.
Results
Recent cannabis use was endorsed by 25% of the sample, and lifetime use, 33%. The average age of onset was 16.6 (SD=2.22) with a range from 12 to 26. The mean number of PLEs and distressing PLEs were significantly higher among participants who used cannabis frequently (Mean PLE= 15.51(10.55) compared to those who never used or only experimented (Mean PLE= 14.01(SD=9.08). Mean total ASI scores were also significantly higher for users (Mean diff=1.8794, p=.025). Results from multiple linear regression models and mediation analyses indicated the association between recent cannabis use frequency and PLEs was significantly explained by higher levels of ASI among users. In the model for distressing PLEs, we found that recent cannabis use and aberrant salience interacted synergistically to increase distressing PLEs. Specifically, the gradient of the regression line slope relating cannabis use to PLEs for those with higher ASI scores was steeper (.360) than the slope for those with lower ASI scores (.169). We also found that earlier age of onset (age 12–14) was associated with a higher number of distressing PLEs (6.81 (SD=6.37) vs. 4.76 (SD=5.41); p=.002 and that this was partially explained by higher ASI scores among this group.
Discussion
The association between cannabis use and early onset of such use and PLEs was explained by the cognitive tendency to misjudge the salience of stimuli. When cannabis use is combined with this aberrant salience, there may be greater risk for psychotic phenomena experienced as distressing and perhaps more clinically significant. While this should be examined further in a clinically high-risk sample, our findings highlight a potential cognitive area to assess and even target in clinical high-risk populations.
We describe the case of a patient with ongoing weight loss, low mood and previously undisclosed gastrointestinal (GI) symptoms initially diagnosed with an eating disorder and subsequently diagnosed ...with ulcerative colitis over a year following initial presentation. This patient exhibited disordered eating secondary to the worsening symptoms of undiagnosed inflammatory bowel disease (IBD) and had altered her eating habits to reduce the diarrhoea and rectal bleeding she was experiencing, contributing to significant weight loss.The implications of a delayed diagnosis of IBD or incorrect diagnosis of eating disorder are severe both physically and psychologically. We discuss factors in the assessment of patients which may raise suspicion of organic GI disease such as IBD-an important differential diagnosis in those with non-specific GI symptoms and suspected eating disorder-and highlight baseline investigations which should be performed to ensure a diagnosis of IBD is not missed in these patients.
Summary
Background
Faecal calprotectin decreases during exclusive enteral nutrition in children with active Crohn's disease. It is unknown how faecal calprotectin changes during food re‐introduction ...and the influence of maintenance enteral nutrition.
Aims
To study changes to faecal calprotectin during exclusive enteral nutrition and at food reintroduction, and explore associations with maintenance enteral nutrition.
Methods
Children with Crohn's disease were followed during exclusive enteral nutrition and during food‐reintroduction. Faecal calprotectin was measured before, at 33 and 54 days of exclusive enteral nutrition, and at 17, 52 and 72 days after food‐reintroduction. Maintenance enteral nutrition use was recorded with estimated weight food diaries. Data are presented with medians and Q1:Q3.
Results
Sixty‐six patients started exclusive enteral nutrition and 41 (62%) achieved clinical remission (weighted paediatric Crohn's disease activity index <12.5). Baseline faecal calprotectin (mg/kg) decreased after 4 and 8 weeks of exclusive enteral nutrition (Start: 1433 Q1: 946, Q3: 1820 vs 33 days: 844 314, 1438 vs 54 days: 453 165, 1100; P < .001). Within 17 days of food reintroduction, faecal calprotectin increased to 953 Q1: 519, Q3: 1611 and by 52 days to 1094 660, 1625 (both P < .02). Fifteen of 41 (37%) children in remission used maintenance enteral nutrition (333 kcal or 18% of energy intake). At 17 days of food reintroduction, faecal calprotectin was lower in maintenance enteral nutrition users than non‐users (651 Q1: 271, Q3: 1781 vs 1238 749, 2102, P = .049) and correlated inversely with maintenance enteral nutrition volume (rho: −0.573, P = .041), kcals (rho: −0.584, P = .036) and % energy intake (rho: −0.649, P = .016). Maintenance enteral nutrition use was not associated with longer periods of remission (P = .7). Faecal calprotectin at the end of exclusive enteral nutrition did not predict length of remission.
Conclusions
The effect of exclusive enteral nutrition on faecal calprotectin is diminished early during food reintroduction. Maintenance enteral nutrition at ~18% of energy intake is associated with a lower faecal calprotectin at the early phase of food reintroduction but is ineffective in maintaining longer term remission.
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