BACKGROUND:Mosaic genetic variation has been implicated in the pathogenesis of both malignant and nonmalignant immunologic diseases. OBJECTIVE:We sought to investigate a unique case of postnatal acquisition of a gain-of-function (GoF) KRAS variant, with an additional GoF STAT5B variant, in an 18-year-old woman with inflammatory bowel disease, splenomegaly, thrombocytopenia, bronchiectasis, monocytosis, and eosinophilia. METHODS:Diagnostic panel, whole-genome, and targeted amplicon sequencing were performed on longitudinal blood and tissue samples to reveal germline and mosaic variants and their allele frequencies across different cell populations. Short- and long-read single-cell RNA sequencing and flow cytometry were used to measure the effect of variants on RNA, protein, and leukocyte cell state. RESULTS:Both mosaic variants were present across multiple leukocyte subsets and historical blood and tissue samples, with the emergence of both variants coinciding with the clinical presentation. Both variants were expressed in a unique population of monocytes, associated with dysregulated cytokine signaling and the presence of a distinct population of highly granular CD24+ leukocytes. CONCLUSIONS:Taken together with the clinical presentation, these findings led to a diagnosis of combined Ras-associated autoimmune leukoproliferative disorder and nonclonal STAT5B GoF disease. To our knowledge, this is the first reported combination of 2 distinct acquired errors of immunity causing a mixed clinical phenotype, and this highlights the importance of considering acquired monogenic diseases within a broader genomic context.

INTRODUCTION:The chronic immune mediated gastrointestinal disease, Inflammatory Bowel Disease (IBD), is increasing in prevalence. However, IBD pathogenesis remains unclear despite decades of research. Therefore, new methods and models of disease are required to gain further insights into IBD pathogenesis. Recent advances in stem cell culture technology now allows for the routine in vitro culture of stem cells derived from an individual. These in vitro stem cells can differentiate into cell-types and cell clusters that resemble the tissue origin of the stem cells. These cell clusters have been termed organoids. AREAS COVERED:Following review of recent available literature, the goal of this review was to specifically focus on intestinal organoids and provide basic methodology of organoid derivation. The review will also discuss the current and potential applications of intestinal organoid models in Gastroenterology research including IBD pathogenesis, host-microbiome interactions, therapeutic response and drug discovery, very-early onset IBD, organ-on-a-chip and bioprinted models. EXPERT OPINION:Organoids offer tangible benefits for improved patient outcomes, particularly with respect to personalized medicine approaches to IBD management.

Abstract Background Inflammatory Bowel Disease (IBD) activity as well as disease monitoring and management have a substantial impact on the health-related quality of life (HRQoL) of affected patients1. This study investigated the association between HRQoL and gut microbial composition in IBD patients using the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). Methods Paired faecal and oral samples alongside participant demographics, disease characteristics and the IBDQ-32 survey were collected at baseline from patients with Crohn’s disease (CD) or ulcerative colitis (UC) enrolled in the Australian IBD Microbiome (AIM) study2 from June 2019 to November 2023. IBDQ-32 scores range from 32 to 224, with a higher score indicating better HRQoL. Patients were divided into two groups: impaired HRQoL (cumulative score <170) and preserved HRQoL (>170). Faecal and oral samples were self-collected in DNA stabilising buffer, aliquoted and stored at -80oC until extraction. Samples underwent 16S rRNA sequencing with annotation of DNA sequences to operational taxonomic units at the genus level. Differences in alpha diversity (Chao1) between groups were assessed using Mann-Whitney U tests. Linear discriminant analysis was performed between groups to identify significantly enriched bacterial taxa. Beta diversity (weighted UniFrac dissimilarity) in bacterial communities were shown using Principal Coordinate Analysis (PCoA), and significance of variance was tested using ADONIS in R. Results 446 participants (232 CD, 214 UC) returned baseline faecal (n = 403) and/or oral samples (n = 436) and were included in the analysis, with patient and HRQoL characteristics in Table 1. Most CD and UC patients were in clinical remission at baseline (77.4% and 65.2% respectively, Table 1). Despite this, impaired HRQoL was common in both CD (42%) and UC (41%). Patients with impaired HRQoL had lower faecal microbial alpha and beta diversity (Fig 1A,B). There were no differences in alpha or beta diversity in oral samples. Linear discriminant analysis showed 9 and 36 significantly altered genera enrichment in impaired and preserved HRQoL faecal samples respectively (Fig 1C). Conclusion Despite a high proportion of clinical and biochemical remission, impaired HRQoL was common amongst UC and CD patients within the AIM study. Lower faecal but not oral alpha diversity was associated with impaired HRQoL, indicating reduced microbial richness in the gut. A high number of bacterial taxa had differential enrichment according to HRQoL status. Identification of a distinct microbial signature associated with impaired HRQoL may help to identify patients that require both optimisation of disease control and greater psychosocial support. References 1.Little RD, Jayawardana T, Koentgen S, et al. Pathogenesis and precision medicine for predicting response in inflammatory bowel disease: advances and future directions. eGastroenterology 2024;2:e100006. doi:10.1136/ egastro-2023-100006 2.Williams A, Paramsothy R, Wu N, et al. Australia IBD Microbiome (AIM) Study: protocol for a multicentre longitudinal prospective cohort study. BMJ Open 2021;11:e042493. doi: 10.1136/bmjopen-2020-042493

Abstract Background Diet has been considered as one driving factor in the onset and course of Inflammatory Bowel Disease (IBD[DT1] ) (1). However, the mechanisms of interplay between diet and disease activity are unclear. Given people living with IBD perceive diet to be an important modifiable factor in their disease management, ongoing research is needed to provide specific dietary recommendations (2). We explored dietary adequacy in people with IBD compared to healthy controls, and the association between dietary intake and disease activity. Methods We analysed cross-sectional baseline dietary and clinical data from the Australian IBD Microbiome (AIM) study, the largest longitudinal microbial cohort study in the Southern Hemisphere on people with Crohn’s disease (CD), Ulcerative colitis (UC), first-degree relatives and population healthy controls (both considered in the HC cohort). Nutrient intake, food groups, and the Dietary Inflammatory Index (DII) were calculated. Associations between dietary intake, clinical disease activity (remission or active) measured via the CDAI for CD participants or Partial Mayo for UC participants, and faecal calprotectin (FCP) were explored in adult participants. Results The analysis included 542 adults (CD = 155, UC = 144, HC = 243), with a median age of 46 years, and 58% female. Median partial Mayo (1 [0 – 2]) and CDAI (59 [29 – 146]) scores indicated clinical remission. Median FCP was higher in IBD (32.7 [0.0-179.0] μg/g) vs. HC (0.0 [0.0-0.0] μg/g), with no significant difference between UC and CD. Intake of grains, vegetable, dairy, and fruit was 25–50% below Australian Dietary Guideline recommended serves across all cohorts (3). Intake of dietary fibre, iodine and calcium was 25-40% lower than recommended intakes (4). There were no differences in intake of nutrients or food groups between IBD vs. HC or CD vs. UC cohorts. Within the UC cohort, kilojoule, iodine, iron, zinc, and grain intake were significantly lower in clinically active disease vs. remission. There was no difference in dietary intake based on clinical disease activity status in the CD cohort. The mean dietary inflammatory score was 0.17 ± 2.29, indicating a pro-inflammatory diet, with no differences between IBD and HC. No relationship was observed between dietary intake or DII score and FCP in IBD. Conclusion Dietary intake did not differ between the IBD cohort and HC cohorts. Both cohorts consumed pro-inflammatory diets with low adherence to Australian dietary guidelines. Further longitudinal studies will be beneficial to examine associations between baseline dietary intake and future disease activity. References 1.Bischoff SC, Bager P, Escher J, Forbes A, Hébuterne X, Hvas CL, Joly F, Klek S, Krznaric Z, Ockenga J, Schneider S. ESPEN guideline on Clinical Nutrition in inflammatory bowel disease. Clinical Nutrition. 2023 Mar 1;42(3):352-79. 2.Limdi JK, Aggarwal D and McLaughlin JT. Dietary practices and beliefs in patients with inflammatory bowel disease. Inflammatory bowel diseases 2016; 22: 164-170. 3.National Health and Medical Research Council. Australian Dietary Guidelines Summary. Canberra: National Health and Medical Research Council [online],. 2013. 4.National Health and Medical Research Council, Australian Government Department of Health and Ageing, New Zealand Ministry of Health. Nutrient Reference Values for Australia and New Zealand. Canberra: National Health and Medical Research Council; 2006.

Abstract Background Gut microbiota are associated with both disease course and treatment outcomes in inflammatory bowel disease (IBD)1. This study aimed to characterise differences in gut microbial signatures according to medication use in the Australian IBD Microbiome (AIM) study2. Methods Faecal and oral samples alongside participant characteristics were collected at baseline from all patients with IBD enrolled in the AIM study from June 2019 to November 2023. Faecal and oral microbial samples were collected in DNA stabilising buffer, aliquoted and stored at -80oC. Samples underwent 16S rRNA sequencing with annotation of DNA sequences to operational taxonomic units at the genus level. Differences in alpha diversity (Shannon index) and relative abundance of observed genera between medication groups were assessed using Mann-Whitney U and Kruskal-Wallis tests. Beta diversity (Bray-Curtis dissimilarity) between bacterial communities were shown using the Principal Coordinate Analysis (PCoA), and significance of variance tested using ADONIS within R. Results 446 participants (232 CD, 214 UC) returned baseline faecal (n = 403) and/or oral samples (n = 436) with patient and disease characteristics presented in Table 1. No differences in faecal calprotectin were observed between patients on advanced therapy vs. patients who were not, nor between each advanced therapy class. Patients on advanced therapy had lower alpha diversity (p = 0.003) and distinct beta diversity (R2 0.64, p = 0.002) than those not on advanced therapy. Patients on anti-TNF therapy had lower alpha (p < 0.001) and distinct beta diversity (R2 1.75, p = 0.008) compared to patients on no advanced therapy (Figure 1AB). Alpha diversity remained lower when comparing those on either infliximab (p = 0.008) or adalimumab (p = 0.012) to patients on no therapy. There were no differences in alpha or beta diversity between other advanced therapy classes, between types of immunomodulator and between patients on 5-ASA compared to patients who were not. Pairwise comparisons between patients on no therapy and each class of advanced therapy demonstrated significantly different relative abundances of multiple genera observed in faecal samples (Figure 1C). No differences were observed in oral samples. Conclusion Distinct differences in both community structure and the relative abundance of multiple genera were observed in IBD patients according to type of advanced therapy despite no significant difference in biochemical activity. No microbiota differences were observed according to conventional 5-ASA or immunomodulator use. Future analysis including longitudinal samples and treatment outcomes may allow identification of unique microbial signatures predictive of treatment response. References 1.Little RD, Jayawardana T, Koentgen S, et al. Pathogenesis and precision medicine for predicting response in inflammatory bowel disease: advances and future directions. eGastroenterology 2024;2:e100006. doi:10.1136/ egastro-2023-100006 2.Williams A, Paramsothy R, Wu N, et al. Australia IBD Microbiome (AIM) Study: protocol for a multicentre longitudinal prospective cohort study. BMJ Open 2021;11:e042493. doi: 10.1136/bmjopen-2020-042493

Abstract Background Western diets characterised by high intake of meat and processed food, are implicated in IBD development1. Dietary habits are often shared amongst family members however, where familial diets diverge a difference in IBD risk may arise, compounding in members adhering to western diets. In this study, we compared macronutrient intake and dietary patterns between unaffected first degree relatives (FDRs), their IBD relatives and healthy controls (HCs). Methods 70 FDRs were recruited within the Australian IBD Microbiome (AIM) study. FDRs were matched ~1:3 to healthy participants (HC; n=200), IBD relatives (adult; n=25 and paediatric; n=25; no other groups contained paediatric participants) were also included for comparison. Macronutrient intake was assessed from 3-day food records. Dietary patterns were computed using principal component analysis (PCA) of food frequency questionnaires (FFQ). Results There was no difference in mean daily energy (KJ), total fat or protein intake (g/day) between groups. Paediatric IBD patients matched FDRs in energy intake (8031KJ; □□□□=2788 and 8046KJ; □□□□= 2741 respectively, p>0.9999). Carbohydrate intake (g/day) was significantly higher in the paediatric IBD group than FDRs (p=0.0408), however variance in daily intake was high (paediatric IBD; 210g, □□□□=108g). FDRs had the lowest percentage of energy from carbohydrate intake compared to all other groups (36.4%, p<0.0004). Energy contribution from total fat was highest in FDRs (38.2%); significantly higher than HCs (35.1%, p=0.0063). Energy from protein consumption was consistent among groups (~20%). PCA of FFQs (all participants) produced 5 distinct dietary patterns from 27 food groups, explaining 47.6% of the total variance. These patterns were described as ‘Ultra-Processed’, ‘Balanced Whole Foods’, ‘Processed High Fat’, ‘Meat Centric’, and ‘Sweetened Beverages & Low Fibre’. Adherence to the ‘Processed High Fat’ dietary pattern was significantly higher in paediatric IBD patients and FDRs than HCs (p<0.0362). This dietary pattern was characterised by high consumption of butters/creams, processed meats, pizzas, savoury pastries, sauces/condiments and red meat. Conclusion FDRs have unique macronutrient intake and habitual dietary pattern adherence, diverging significantly from HCs. Similarity in adherence to the ‘Processed High Fat’ dietary pattern between paediatric IBD and FDR cohorts may reflect food decision-making by parental FDRs. Macronutrient and dietary pattern analysis indicate fat-rich dietary habits in FDRs; Increased IBD risk may in part be due to fat rich dietary habits. References 1.Kaplan GG, Ng SC. Understanding and Preventing the Global Increase of Inflammatory Bowel Disease. Gastroenterology. 2017;152(2):313-321. doi:10.1053/j.gastro.2016.10.020

Vitamin D deficiency is common in Paediatric Inflammatory Bowel Disease (PIBD) and has been implicated in disease pathogenesis and disease exacerbation. Current guidelines recommend oral vitamin D supplementation when 25OHD levels are below 50 nmol/L. Supplementation comes in two forms: either a daily supplement of a low dose of vitamin D3 (2000 IU) for several months or a single high dose of oral vitamin D3-termed ‘stoss’ therapy, with no consensus regarding optimum treatment. A randomised controlled trial was conducted in children with a prior diagnosis of PIBD with 25OHD deficiency (< 50 nmol/L), comparing 2000 IU oral D3 daily to a stoss protocol (oral D3 dosage 400,000 IU for 3–12 years of age or 800,000 IU for > 12 years). Children were followed for 12 months, with biochemistry (25OHD, calcium, magnesium, phosphate, parathyroid hormone, haemoglobin, haematocrit, platelets, albumin), stool markers (calprotectin, S100A12), anthropometrics (weight, height, body mass index) as well as clinical disease indices (Paediatric Crohn’s Disease Activity Index, Paediatric Ulcerative Colitis Activity Index) and medication use collected at 3, 6, 9 and 12 months. 74 children aged 5–18 years completed the study. Both 2000 IU daily and stoss protocol significantly increased 25OHD from baseline values at 3, 6, 9 and 12 months. One patient randomised to stoss protocol had a 25OHD level of 263 nmol/L with normal serum calcium. There was no difference in biochemical, stool or clinical markers between groups at any time point, nor was there any correlation between 25OHD level and calprotectin or 25OHD level and clinical disease activity scores. Stoss protocol was non-inferior to 2000 IU daily vitamin D3 in raising 25OHD levels at 12 months. There was also no difference between 25OHD levels at 3, 6 and 9 months between groups.

Background/Objectives: Children with inflammatory bowel disease (IBD) are managed with multi-modal treatment strategies, including non-clinical components such as the development of self-management skills. Assessment tools have been developed to quantify such traits, and parents may be asked to provide proxy reports on behalf of their child. The aim of this study was for child/parent dyads to complete a self-management skills assessment tool [IBD-STAR] to assess the agreement level between reports. Methods: Children aged ≥10 years with IBD, and one parent/caregiver, were recruited from three tertiary care centers in New Zealand, Australia, and Italy [translated version]. IBD-STAR is scored as completing skills independently [score = 2], with help [score = 1], or not at all [score = 0]. Individual agreement was assessed as a proportion of the maximum agreement on items, category agreement as inter-rater reliability using Gwets AC1 coefficient, and aggregate agreement as a Bland–Altman plot and correlations between child/parent percentage scores. Results: Fifty child/parent dyads participated; child mean age of 14.5 years (±2.4), 31 (62%) female, and 31 (62%) had Crohn’s disease and 19 (38%) ulcerative colitis. At the individual level, the mean proportional agreement was 0.70 (±0.15), equating to complete agreement on ≥12 IBD-STAR items. Category agreement was in the range of 44–94% for items, parents were more likely to underestimate self-management skills, and inter-rater reliability ranged from poor to very good for items, and ‘good’ overall. Aggregate agreement showed high correlation between child/parent % scores (R 0.77, p < 0.001, CI 0.63 to 0.87), and 47 (94%) of the pairs had % scores within two standard deviations of each other. No level of agreement was associated with any independent variable. Conclusions: Parental proxy reports of self-management skills using IBD-STAR had acceptable agreement. The trend towards parental underestimation should be considered when child self-report cannot be assessed.

Abstract Background Microbial dysbiosis is associated with Crohn’s disease (CD) and ulcerative colitis (UC) onset and disease activity, however, large-scale data pertaining to Australian patients are limited1. This study aimed to describe the differences in gut microbiota composition between patients with IBD and healthy controls within the Australian IBD Microbiome (AIM) study2. Methods Paired faecal and oral samples alongside participant demographics and disease characteristics were collected at baseline from all healthy controls (HC) and IBD patients enrolled in the Australian IBD Microbiome (AIM) study from June 2019 to November 2023. Faecal and oral samples were self-collected in DNA stabilising buffer, aliquoted and stored at -80oC until extraction. Samples underwent 16S rRNA sequencing with annotation of DNA sequences to operational taxonomic units at the genus level. Differences in alpha diversity (Chao1) between groups were assessed using Mann-Whitney U tests. Beta diversity (weighted UniFrac dissimilarity) in bacterial communities were shown using Principal Coordinate Analysis (PCoA), and significance of variance was tested using ADONIS in R. Results 751 participants (305 HC, 232 CD, 214 UC) returned baseline faecal (n = 697) and/or oral samples (n = 737) and were included in the analysis, with patient group characteristics presented in Table 1. Most IBD patients were in clinical remission (Table 1). However, CD and UC patients had comparably lower faecal alpha diversity than the HC group (Figure 1A). Faecal beta diversity differed between CD, UC, and HC groups (Figure 1B). Five phyla were significantly different between the three groups in faecal samples (Figure 1C). No significant inter-group differences were seen with oral microbial analysis. Conclusion Compared to healthy adults, patients with IBD in Australia have distinct gut microbial profiles. Faecal rather than oral microbial sampling demonstrated a difference in community structure between IBD and healthy groups. Incorporating longitudinal microbial sampling and increasing sequencing resolution may elucidate a pathogenic relationship between gut microbiota and IBD. References 1.Little RD, Jayawardana T, Koentgen S, et al. Pathogenesis and precision medicine for predicting response in inflammatory bowel disease: advances and future directions. eGastroenterology 2024;2:e100006. doi:10.1136/ egastro-2023-100006 2.Williams A, Paramsothy R, Wu N, et al. Australia IBD Microbiome (AIM) Study: protocol for a multicentre longitudinal prospective cohort study. BMJ Open 2021;11:e042493. doi: 10.1136/bmjopen-2020-042493

Abstract Background Identifying microbial changes associated with active inflammation and inflammatory bowel disease (IBD) phenotype may improve understanding of drivers of disease activity1. This study aimed to characterise differences in gut microbial signatures according to inflammatory activity amongst patients enrolled in the Australian IBD Microbiome (AIM) study2. Methods Paired faecal and oral samples alongside participant and disease characteristics were collected at baseline from all patients with Crohn’s disease (CD) and ulcerative colitis (UC) enrolled in the AIM study from June 2019 to November 2023. Clinically active disease was defined as Crohn’s disease activity index (CDAI) score >150 or partial Mayo score >1. Biochemical activity was defined as faecal calprotectin (FCP) ≥150 μg/g. Faecal and oral microbial samples were collected in DNA stabilising buffer and stored at -80oC. Samples underwent 16S rRNA sequencing with annotation of DNA sequences to operational taxonomic units at the genus level. Differences in alpha diversity (Shannon index) and relative abundance of identified genera between the groups were assessed using Mann-Whitney U tests. Beta diversity (Bray-Curtis dissimilarity) between bacterial communities were shown using the Principal Coordinate Analysis (PCoA), and significance of variance tested using ADONIS within R. Results 446 participants (232 CD, 214 UC) returned baseline faecal (n = 403) and/or oral samples (n = 436). The majority of patients were in clinical and biochemical remission with patient and disease characteristics presented in Table 1. Oral and faecal microbial analyses showed no statistical differences in alpha or beta diversity between CD and UC patients with clinical or biochemical activity vs. those in remission. In CD, lower faecal alpha diversity was observed in patients with a stricturing phenotype (p = 0.017) and isolated ileal disease (p = 0.043) in comparison to an inflammatory phenotype and colonic CD, respectively. No differences were observed according to UC extent. There were 17 and 39 genera with significantly different relative abundances between FCP activity vs. FCP remission in CD and UC patients, respectively (Figure 1). Conclusion There were no differences in broad measures of oral or faecal microbial community structure between IBD patients in clinical or biochemical remission compared to those with active disease. However, relative abundances at the genus-level distinguished IBD patients according to biochemical activity. Increasing the sequencing depth, as well as analysing serial biological sampling and their relationship to longitudinal changes in disease activity may allow identification of microbial signatures associated with both flare and pre-flare states. References 1. Little RD, Jayawardana T, Koentgen S, et al. Pathogenesis and precision medicine for predicting response in inflammatory bowel disease: advances and future directions. eGastroenterology 2024;2:e100006. doi:10.1136/ egastro-2023-100006 2. Williams A, Paramsothy R, Wu N, et al. Australia IBD Microbiome (AIM) Study: protocol for a multicentre longitudinal prospective cohort study. BMJ Open 2021;11:e042493. doi: 10.1136/bmjopen-2020-042493

INTRODUCTION:Inflammatory bowel disease (IBD) affects health-related quality of life (HRQoL). Gut dysbiosis in IBD is common and may contribute to this observation. The aims of this study were to measure HRQoL and its association with clinical and microbial features in patients with IBD and healthy controls (HCs). METHODS:Fecal and oral samples, demographics, 36-item Short-Form Health Survey (SF-36), and 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32) surveys were collected at baseline from patients with Crohn's disease (CD), ulcerative colitis (UC) and HCs enrolled in The Australian IBD Microbiome Study. Samples underwent 16S rRNA sequencing. Associations between HRQoL variables and alpha diversity, beta diversity, and microbial taxa abundance were measured using R. RESULTS:A total of 751 participants (305 HCs, 232 CD, 214 UC) were included. HRQoL was lower in IBD participants compared with HCs using the SF-36 (physical component summary 51.6 vs 55.7, P < 0.0001 and mental component summary score 45.1 vs 52.2, P < 0.001). Despite high rates of remission, impaired IBD-HRQoL (IBDQ-32 score <170) was common in patients with CD (42%) and UC (41%). Patients with impaired IBDQ-32 scores demonstrated lower alpha diversity (Chao1 155.2 vs 172.4, P = 0.015) and distinct beta diversity ( R2 = 0.003, P = 0.019) compared with those with preserved IBD-HRQoL. Sixty-two genera were associated with at least one HRQoL measure in both patients with UC and patients with CD. The number and strength of associations between genera and HRQoL measures outweighed microbial associations with clinical and biochemical activity. DISCUSSION:Alterations in gut microbiota are associated with HRQoL outcomes in patients with IBD and HCs.

Irritable bowel syndrome (IBS) is a chronic disorder of gut–brain interaction (DGBI) characterized by recurrent abdominal pain and altered bowel habits. Treatment typically focuses on symptom management without addressing underlying causes. This systematic review and meta-analysis aimed to explore the association between inflammatory markers and gut microbiome changes in individuals with IBS. A systematic search of PubMed, Scopus, EMBASE, and CINAHL databases was conducted in June 2024, identifying 41 studies that compared inflammatory markers and gut microbial composition in patients with IBS versus healthy controls. Meta-analysis was performed using a random-effects model, reporting standard mean differences (SMD) for inflammatory markers and mean differences (MD) for microbiome data, with 95

BACKGROUND:The frequency of EoE has been increasing in Northern Hemisphere cohorts, yet there is a scarcity of data in our region. Regional climatic factors, and lifestyle habits may influence the presentation of EoE, and appropriate management is crucial to prevent complications. WIth this is mind we undertook the first comprehensive multisite study of EoE in Australasian children. AIM:To determine the incidence, prevalence, clinical characteristics and management of eosinophilic esophagitis (EoE) in Australasian children. METHODS:Retrospective audit of endoscopic records, histology reports and case notes (ICD code) over a 10-year period (1 January 2008 to 31 December 2018). Cases were defined as having >15 eosinophils per high-power field (HPF) at endoscopy and oesophageal biopsy, while treatment response was defined as <5 eosinophils per HPF. Included were patients aged 0-18 years presenting to tertiary paediatric hospitals in seven capital cities (Adelaide, Auckland, Brisbane, Christchurch, Melbourne, Perth and Sydney), while those with conditions that could cause eosinophilia (organ transplantation, hyper-eosinophilic syndrome) or taking medications that may influence tissue eosinophilia (systemic corticosteroids immunosuppressants) were excluded. Australian Bureau of Statistics and Stats NZ were used to define comparative population data. Demographics (age at diagnosis, gender, country of birth, race) comorbidities (atopic conditions, e.g. asthma, seasonal rhinitis, eczema) and treatment (diet, steroids, proton pump inhibitors) were noted. RESULTS:The prevalence of EoE ranged from 15 to 54 per 100 000 children, where cases were more common in Adelaide than other localities. Incidence increased significantly in all sites across the 10 years, with peak incidence in Adelaide of 6.4 per 100 000 children in 2017. EoE was most frequent in males (male:female ratio = 3:1) and >90% were white Caucasian. Polynesian racial background in Auckland (10%) and middle eastern racial background in Sydney (10%) were the next most frequent. Treatment choice varied across sites, and greater than 30% of patients did not undergo endoscopy to assess initial treatment success. CONCLUSION:The prevalence of EoE in Australasian children is comparable to that observed elsewhere, and the incidence is increasing significantly. Regional differences in disease frequency, management practices and access to endoscopy warrant further study.

Background: Few studies have explored the relationship between habitual dietary patterns and disease activity in people with Inflammatory Bowel Disease (IBD). This cross-sectional study explored the association between dietary patterns and clinical and objective markers of inflammation in adults from the Australian IBD Microbiome Study. Methods: Dietary patterns were derived using principal component analysis (PCA) of baseline food frequency questionnaire data. Food intake was quantified using 3-day food record data. Associations between dietary intake and both clinical disease activity index (CDAI) and faecal calprotectin (FCP) were analysed. Results: Participants included 412 adults (IBD = 223, Healthy controls (HC) = 189). Both cohorts consumed poor-quality diets with inadequate servings of most food groups compared to Australian reference standards. IBD participants without FCP inflammation had significantly higher fibre intake than those with moderate FCP. In the Crohn’s Disease group, high adherence to ‘High plant diversity’ and ‘Meat eaters’ dietary patterns were associated with increased CDAI and FCP, respectively. In the combined IBD cohort, high adherence to a ‘Vegan-style’ dietary pattern was associated with increased FCP. Conclusions: There is a need for dietary modifications among Australian adults, both with and without IBD, to improve dietary fibre intake and adherence to dietary guidelines. Dietary patterns characterised by a high intake of plant foods or meat products were both positively associated with indicators of active IBD. It is possible that some participants with active IBD were modifying their diet to try to manage their disease and reduce symptoms, contributing to the association between healthier dietary patterns and active disease. Further clinical and longitudinal studies are needed to expand upon the findings. This study offers a unique contribution by utilising FCP as an objective marker of intestinal inflammation and applying dietary pattern analysis to investigate the relationship between diet and inflammatory markers.

Management of ulcerative colitis and Crohn’s disease, the main subtypes of inflammatory bowel disease (IBD), focuses on the induction and maintenance of remission. Tacrolimus, a member of a group of drugs termed calcineurin inhibitors, may have a role in the medical management of IBD when given either systemically or topically. This review aimed to evaluate the available data focusing on the use of topical tacrolimus in the management of IBD. Reports of the use of topical tacrolimus in IBD were extracted from databases up to 31 May 2024. Topical tacrolimus therapy appears to have reasonable efficacy in the induction and maintenance of remission in patients with refractory IBD, with an acceptable safety profile. Overall, the available data are supportive of the use of topical tacrolimus in selected patients. Further comparative clinical studies are required to more fully delineate the role of this drug.