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.

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

Modern precision sequencing techniques have established humans as a holobiont that live in symbiosis with the microbiome. Microbes play an active role throughout the life of a human ranging from metabolism and immunity to disease tolerance. Hence, it is of utmost significance to study the eukaryotic host in conjunction with the microbial antigens to obtain a complete picture of the host-microbiome crosstalk. Previous attempts at profiling host-microbiome interactions have been either superficial or been attempted to catalogue eukaryotic transcriptomic profile and microbial communities in isolation. Additionally, the nature of such immune-microbial interactions is not random but spatially organised. Hence, for a holistic clinical understanding of the interplay between hosts and microbiota, it's imperative to concurrently analyze both microbial and host genetic information, ensuring the preservation of their spatial integrity. Capturing these interactions as a snapshot in time at their site of action has the potential to transform our understanding of how microbes impact human health. In examining early-life microbial impacts, the limited presence of communities compels analysis within reduced biomass frameworks. However, with the advent of spatial transcriptomics we can address this challenge and expand our horizons of understanding these interactions in detail. In the long run, simultaneous spatial profiling of host-microbiome dialogues can have enormous clinical implications especially in gaining mechanistic insights into the disease prognosis of localised infections and inflammation. This review addresses the lacunae in host-microbiome research and highlights the importance of profiling them together to map their interactions while preserving their spatial context.

The objective of this Special Issue entitled ‘Role of Probiotics and Prebiotics in Gut Symbiosis’ is to publish reviews, clinical trials and experimental studies that focus on probiotics and prebiotics that have a role in influencing disease and promoting gastrointestinal and overall health [...]

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.

OBJECTIVE:To determine whether proton pump inhibitor (PPI) exposure is associated with an increased risk of developing eosinophilic esophagitis (EoE) in children with esophageal atresia (EA). STUDY DESIGN:A retrospective chart review of children with EA from January 1, 2005 to December 31, 2020 was undertaken at Sydney Children's Hospital Randwick. Children with EA and EoE (cases) were matched (1:2) to children with only EA (controls) to compare PPI exposure. Other early-life factors such as infantile antibiotic exposure and personal or family history of atopy were also analyzed using simple and multivariable logistic regression. RESULTS:Of 184 children with EA, 46 (25%) developed EoE during this period. Thirty-eight EoE participants were matched to 76 controls. Children with EoE and EA received PPI for significantly higher durations (p = .018) and at significantly higher cumulative doses (p = .017) than controls. Food allergy (adjusted odds ratio [aOR], 7.317; 95% confidence interval [CI], 2.244-23.742), family history of atopy (aOR, 3.504; 95% CI, 1.268-9.682), and infantile antibiotic exposure (aOR, 1.040; 95% CI, 1.006-1.075) were also significantly associated with an increased risk of developing EoE in the EA cohort. CONCLUSIONS:Prolonged duration and high cumulative dose of PPI exposure were significantly associated with subsequent EoE development in children with EA. Food allergy, family history of atopy, and infantile antibiotic exposure in EA were also significantly associated with an increased risk of EoE development.

Background Emulsifiers are implicated in the pathogenesis of inflammatory bowel disease (IBD). Few studies have examined emulsifier intake in people with existing IBD. We aimed to describe the frequency of exposure to 6 selected emulsifiers in a contemporary cohort of people with IBD and compare intake with healthy controls (HCs).Methods Baseline food records from participants in an Australian prospective cohort study examining the microbiome of IBD patients and HCs were analyzed. Exposure to inflammatory emulsifiers polysorbate-80 (P80); carboxymethylcellulose (CMC); carrageenan; xanthan gum (XG); lecithin (soy and sunflower) and mono- and diglycerides of fatty acids (MDGs) were determined by examining ingredient lists. Frequency of emulsifier exposure between groups (IBD vs HC, Crohn's disease [CD] vs ulcerative colitis [UC], IBD children vs adults, active disease vs remission) was examined after controlling for confounders.Results Records from 367 participants were analyzed (n = 176 IBD, of which there were 101 CD, 75 UC, and 191 HC patients). In total, 5022 unique food items were examined, with 18% containing 1 or more emulsifier of interest. Inflammatory bowel disease participants had significantly higher total daily emulsifier exposure compared with HCs (2.7 +/- 1.8 vs 2.3 +/- 1.6, P = .02). In IBD participants, emulsifiers with the highest daily exposure were MDGs (1.2 +/- 0.93), lecithin (0.85 +/- 0.93), and XG (0.38 +/- 0.42). There were no recorded exposures to P80.Conclusions Inflammatory bowel disease participants were exposed to more emulsifiers than HCs. Intake of inflammatory emulsifiers were low or nonexistent, suggesting their presence in the food supply are not as common as frequently stated. Graphical Abstract

OBJECTIVES:This study aims to compare the intestinal microbiota and intestinal inflammation of children with esophageal atresia (EA) to matched healthy controls, and to investigate the relationship between these factors and clinical outcomes. METHODS:A cross-sectional study of 35 children with EA and 35 matched healthy controls (HC) from a single tertiary pediatric hospital in Australia was conducted. Demographic and dietary data were collected using surveys. Stool samples were analyzed using 16S rRNA sequencing, and fecal calprotectin measurements were used to measure intestinal inflammation. Comparisons were made between the groups, and correlations between the microbiota and clinical factors were investigated in the EA cohort. RESULTS:Compared to HC, children with EA had similar alpha diversity, but beta diversity analysis revealed clustering of EA and HC cohorts. Children with EA had a significantly higher relative abundance of the order Lactobacillales, and a lower abundance of the genus uncultured Bacteroidales S24-7. Fecal calprotectin was significantly higher in children with EA compared to HC. In the EA cohort, children taking proton pump inhibitors (PPI's) had lower alpha diversity and higher calprotectin levels compared to those not taking PPI's. There was a negative correlation between calprotectin and length/height-for-age z scores, and children with higher calprotectin levels had a greater burden of gastrointestinal symptoms. CONCLUSIONS:Children with EA have an altered intestinal microbiota compared to HC, which is likely related to PPI use, and may be impacting on growth and quality of life. It is important to rationalize PPI use in this cohort.

Background: The role of gastrointestinal microbiome in health and disease is increasingly appreciated. A significant amount of evidence clearly points to a dysbiosis manifest in inflammatory bowel disease (IBD) when compared to healthy controls. Less understood is the microbiome profile in autoimmune liver disease (AILD). Both adult and paediatric data indicate a distinct microbial signature in patients with IBD and co-existent primary sclerosing cholangitis (PSC), which is unique and different compared to the microbial signature that exists in patients with IBD alone. However, there is limited information on the microbiome make-up of patients with parenchymal liver disease, with or without IBD. Methods: The present study sought to compare the microbiome of children with IBD, to those with IBD-AILD, those with AILD alone and those of healthy controls. Results: Results from this work indicate that children with AILD have a microbiome profile that mirrors healthy controls. Conclusion: Those with IBD-AILD and IBD have similar microbiome profiles which are distinct from AILD alone and healthy controls. This suggests that the dysbiosis in these groups is primarily due to IBD rather than AILD.

The process of microbiome development arguably begins before birth. Vertical transmission of bacteria from the mother to the infant is a keystone event in microbiome development. Subsequent to birth, the developing microbiome is vulnerable to influence from a wide range of factors. Additionally, the microbiome can influence the health and development of the host infant. This intricate interaction of the gastrointestinal microbiome and the host has been described as both symbiotic and dysbiotic. Defining these terms, a symbiotic microbiome is where the microbiome and host provide mutual benefit to each other. A pathogenic microbiome, or more precisely a gastrointestinal microbiome associated with disease, is increasing described as dysbiotic. This review seeks to investigate the factors that contribute to evolving a disease-causing or 'dysbiotic' microbiome. This review covers the development of the gastrointestinal microbiome in infants, the interaction of the microbiome with the host, and its contribution to host immunity and investigates specific features of the gastrointestinal microbiome that are associated with disease.

Objectives: The ketogenic diet (KD) is a treatment for children with intractable epilepsy (IE), can cause gastrointestinal symptoms, and have an adverse effect on growth, nutrition and quality of life (QOL). This study investigated the extent of these side effects by comparing children with IE on KDs to their counterparts on normal diets. Methods: Patients with IE were categorized into patients with KD or control groups. Gastrointestinal side effects and QOL were assessed using the PedsQL Gastrointestinal Symptoms Module. Cross sectional growth, gut microbiome compositions, and inflammation levels were also analyzed. Results: Fourteen patients on the KD and 13 control patients were enrolled. Patients had been on KD for a median duration of 15 months (interquartile range: 9.8–60 months). The patients on the KD reported a trend to lower total gastrointestinal symptoms scores (more symptoms) compared to control patients, at 71.1 and 84.9, respectively ( P = 0.06, not significant). Patients on the KD had significantly lower QOL scores compared to control patients ( P = 0.01). Patients on the KD were found to have consistently lower median height/length, weight, and body mass index z scores compared to the controls although these were not statistically significant. Patients on the KD had a lower microbial diversity, Both groups had a normal level of S100A12, a marker of gut inflammation. Conclusions: Patients on the KD reported a trend to more gastrointestinal symptoms and more QOL concerns compared to controls. Although microbial differences were noted in patients on the KD, this did not result in detectable gut inflammation.

Blenderised tube feeds (BTF) have become a popular alternative to commercial formula (CF) for enterally fed children. This study sought to compare gastrointestinal (GI) symptoms, GI inflammation, and stool microbiome composition between children receiving BTF or CF. This prospective cohort study involved 41 gastrostomy-fed children, aged 2–18 years, receiving either BTF (n = 21) or CF (n = 20). The Paediatric Quality of Life Inventory Gastrointestinal Symptoms Scale (GI-PedsQL) was used to compare GI symptoms between the groups. Anthropometric data, nutritional intake, nutritional blood markers, faecal calprotectin levels, stool microbiota, and parental satisfaction with feeding regimen were also assessed. Caregivers of children on BTF reported greater GI-PedsQL scores indicating significantly fewer GI symptoms (74.7 vs. 50.125, p = 0.004). Faecal calprotectin levels were significantly lower for children receiving BTF compared to children on CF (33.3 mg/kg vs. 72.3 mg/kg, p = 0.043) and the BTF group had healthier, more diverse gut microbiota. Subgroup analysis found that 25% of caloric intake from BTF was sufficient to improve GI symptoms. The CF group had better body mass index (BMI) z-scores (−0.7 vs. 0.5, p = 0.040). Although growth was poorer in children receiving only BTF in comparison to the CF group, this was not seen in children receiving partial BTF. A combination of BTF and CF use may minimise symptoms of tube feeding whilst supporting growth.

Objectives: Children with esophageal atresia (EA) often have feeding difficulties and dysphagia, which may compromise their nutritional status. This study aimed to compare dietary intake between children with EA and matched healthy controls (HC) and to investigate the relationship between dietary factors, growth, dysphagia, and feeding difficulties in the EA cohort. Methods: This cross-sectional cohort study recruited children with EA and HC aged 2-17 years from a tertiary pediatric hospital in Australia. Growth parameters were measured. Dietary intake was assessed using the validated Australian Child and Adolescent Eating Survey. Dysphagia and feeding difficulties were assessed using objective questionnaires. Results: Twenty-one children with EA were matched for age and sex with 21 HC. Compared to HC, children with EA had lower mean z scores for height-for-age, but mean weight-for-age and body mass index-for-age z scores were similar. Energy intake was similar between the groups. The diet of children with EA consisted of a higher proportion of fats and lower proportion of carbohydrates compared to matched HC. Dysphagia severity in children with EA positively correlated with proportion of energy from fats and saturated fats. Conclusions: Children with EA have similar energy intake and growth parameters to HC, but their diet consists of a higher proportion of fats and lower proportion of carbohydrates compared to HC. Targeted dietary interventions and parental education are necessary.