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Lindsey G Albenberg, Petar Mamula, Judith R KelsenDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USAAbstract: Ulcerative colitis (UC) is a chronic, inflammatory disease of the large intestine. In pediatric patients, UC is associated with significant morbidity including persistent symptoms affecting quality of life, hospitalizations, and surgery, and therapeutic strategies are limited. The advent of biologics, specifically anti-tumor necrosis factor- α medications, has been very beneficial for pediatric patients suffering from UC. Since the introduction of these therapies, there has been improvement in the rates of both remission as well as colectomy-free survival. However, there has been concern regarding the adverse events associated with these medications including the risk of infection and malignancy. The efficacy and safety of infliximab, the most frequently used biologic medication in pediatric patients with UC, will be the focus of this review.Keywords: ulcerative colitis, biologics, anti-TNF-α, infliximab, adalimumab

Objectives: The PRASCO trial reported the short-term superiority of an antibiotic cocktail plus intravenous corticosteroids (IVCS) over IVCS alone in children with acute severe colitis (ASC). Here, we report the extension of the PRASCO trial and the long-term outcomes of the antibiotic cocktail in ASC., Methods: This prospective follow-up of the PRASCO trial documented disease outcomes and treatments annually through 5 years. The primary outcome was colectomy, and the secondary outcome was escalation to biologics, analyzed descriptively., Results: A total of 26 children were included (12 receiving IVCS and 14 receiving IVCS + antibiotics), 19% of whom underwent colectomy during the follow-up period. The estimated probability of colectomy at 3, 6, and 12 months from admission were 7.1%, 7.1%, and 21% with IVCS + antibiotics and 0%, 8.3%, and 17% with IVCS. No children required colectomy after the first year of follow-up. The estimated probability of escalating to biologics were 66%, 77%, and 77% after 1, 2, and 3 years with IVCS + antibiotics and 42%, 51%, and 76% with IVCS. Clinical remission was higher in the IVCS + antibiotics group at each timepoint (e.g., 30% vs. 11% at 5-years). Delta of Pediatric Ulcerative Colitis Activity Index (PUCAI) score from baseline to day three of admission predicted future escalation to biologics (area under curves (AUC) 0.84 [95%CI 0.59-1.0])., Conclusion: While adding antibiotics to IVCS may provide better short-term outcomes, the long-term benefits were comparable to IVCS alone. At 5 years, about one-fifth of children had undergone colectomy, and almost four-fifths had escalated to biologics, particularly during the first year after admission., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background and Aims: Epidemiological studies have suggested an association between the inflammatory potential of dietary patterns and Crohn's disease (CD). However, the relationships of these inflammatory dietary determinants with the microbiome remain largely unknown. In this cross-sectional study, we evaluate the association between the inflammatory potential of habitual diet, as assessed by the modified Children-Dietary Inflammatory Index (mC-DII), and the fecal microbiome and metabolome of children with CD in comparison to healthy children., Methods: A cross-sectional study including 51 children with CD between 6 and 18 years of age and 50 healthy controls was conducted. Dietary inflammatory potential was measured using the mC-DII, and diet quality was assessed by the Healthy Eating Index (HEI)-2015 and alternate Mediterranean Eating Index (aMed). The microbiome was analyzed using shotgun metagenomic sequencing and untargeted metabolomic analysis., Results: A poor-quality, pro-inflammatory diet, with similar mC-DII, HEI-2015, and aMed scores, was found across healthy children and children with CD. In children with active disease, a pro-inflammatory diet was associated with decreased diversity, increased virulence potential, and expansion of the Proteobacteria phylum dominated by Escherichia coli (E. coli) spp. A positive correlation between E. coli relative abundance and mC-DII was associated with a low intake of a cluster composed of fibers, vitamins, and minerals with anti-inflammatory potential. A negative association between metabolites of fatty acid metabolism and HEI was found., Conclusions: In total, our results suggest that a pro-inflammatory diet may potentiate hallmarks of the inflammation-associated dysbiosis in CD and highlight the need for microbiome-targeted dietary interventions optimizing the anti-inflammatory potential of habitual diet in the management of pediatric CD., (© The Author(s) 2025. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. 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.)

Objectives: Real-world data on ustekinumab for the treatment of pediatric Crohn's disease (CD) are limited. This study sought to evaluate the effectiveness, long-term durability, and safety of ustekinumab in the treatment of children with CD., Methods: A retrospective longitudinal cohort study of children with CD treated with ustekinumab from two large centers between 2015 and 2020 was performed. The primary outcome was frequency of steroid-free clinical remission at 1 year. Secondary outcomes included time to steroid-free clinical remission, frequency of clinical and biochemical remission, drug escalation and discontinuation, serum level data, and adverse events. Standard descriptive and comparative statistics were performed. Logistic regression was used to identify factors associated with steroid-free remission at 1 year. Kaplan-Meier curves were used to visualize time-to-event relationships for outcomes., Results: A total of 101 patients were included. Median follow-up time on ustekinumab was 16.6 months (interquartile range [IQR]: 8.71-31.2) with drug failure in 28% at 1 year. Fifty-nine patients were in steroid-free clinical remission at 1 year. Higher baseline disease activity (odds ratio [OR]: 0.91 (95% confidence interval [CI]: 0.84-0.97), p = 0.01) and stricturing/penetrating disease phenotype (OR: 0.14 (95% CI: 0.03-0.65), p = 0.02) were associated with decreased likelihood of steroid-free clinical remission at 1-year. Ustekinumab drug escalation occurred in 70% of patients, and after escalation, 50 (70%) achieved clinical remission, and 49 (69%) achieved steroid-free remission at the last follow-up. Adverse events were rare and did not require therapy discontinuation., Conclusions: Ustekinumab is effective and safe in the treatment of children with CD. Escalation of therapy occurs frequently but results in sustained durability., (© 2025 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Research suggests a link between autoimmune illnesses (AI) and eating disorders (ED). We retrospectively reviewed charts of adolescent patients presenting for eating disorder treatment. We compared the presentation and treatment course for those with an ED and comorbid AI [with (GI-AI, N  = 59) or without (non-GI, N  = 21) gastrointestinal inflammation] with matched ED-only cases. The sample was overwhelmingly female, with an average age of 15.40. Weight gain trajectories differed across groups, with similar rates of weight gain between controls and non GI-AI cases and with a lower rate of weight gain for individuals with comorbid GI-AI. Over half (56%) of patients reported an AI diagnosis prior to ED; 38% reported an AI diagnosis following ED, and 6% reported ED and AI simultaneous diagnosis. On presentation, ED-only controls had higher rates of comorbid anxiety than cases in either AI group, while those with non-GI AI were more likely to report depression. Mean total GI symptoms, % goal weight at presentation, vital sign instability, and markers of refeeding syndrome did not differ across groups. Health care professionals treating patients with either condition should have a low threshold for asking additional questions to identify the presence of the other condition.

Introduction: There are limited data characterizing eating habits among pediatric patients with eosinophilic esophagitis (EoE). We compared eating behaviors in pediatric patients with EoE with healthy controls and assessed the degree of correlation with symptomatology, endoscopic and histologic findings, and esophageal distensibility., Methods: We conducted a prospective, observational study where subjects consumed 4 food textures (puree, soft solid, chewable, and hard solid) and were scored for eating behaviors including number of chews per bite, sips of fluid per food, and consumption time. Symptomatic, endoscopic, histologic, and esophageal distensibility data were collected for case subjects., Results: Twenty-seven case subjects and 25 healthy controls were enrolled in our study (mean age 11.0 years, 63.5% male). Compared with healthy controls, pediatric patients with EoE demonstrated more chews per bite with soft solid (13.6 vs 9.1, P = 0.031), chewable (14.7 vs 10.7, P = 0.047), and hard solid foods (19.0 vs 12.8, P = 0.037). Patients with EoE also demonstrated increased consumption time with soft solid (94.7 vs 58.3 seconds, P = 0.002), chewable (90.0 vs 65.1 seconds, P = 0.005), and hard solid foods (114.1 vs 76.4 seconds, P = 0.034) when compared with healthy controls. Subgroup analysis based on disease status showed no statistically significant differences in eating behaviors between active and inactive EoE. Total endoscopic reference score positively correlated with consumption time ( r = 0.53, P = 0.008) and number of chews ( r = 0.45, P = 0.027) for chewable foods and with number of chews ( r = 0.44, P = 0.043) for hard solid foods. Increased consumption time correlated with increased eosinophil count ( r = 0.42, P = 0.050) and decreased esophageal distensibility ( r = -0.82, P < 0.0001)., Discussion: Altered eating behaviors including increased chewing and increased consumption time can be seen in pediatric patients with EoE, can persist despite histologic remission, and may be driven by changes in esophageal distensibility., (Copyright © 2024 by The American College of Gastroenterology.)

Aim: To investigate whether a structured yoga program improves health-related quality of life (HRQOL) and self-efficacy in pediatric patients receiving care for inflammatory bowel disease (IBD)., Methods: IBD patients who were 10-17 years old participated in a 12 week, in-person yoga intervention at two clinical sites. Outcomes were measured at time of consent (T0), start of yoga (T1), and completion of yoga (T2) and 3 months after yoga completion (T3) using the IMPACT-III, Pediatric Quality of Life Inventory (PedsQL), and General Self Efficacy (GSE) scales., Results: Seventy-eight patients were enrolled. Fifty-six patients completed nine or more classes. 73.2% had Crohn's disease and 26.8% ulcerative colitis or IBD-unclassified. A significant increase in IMPACT-III was seen from T1 to T3 (mean change of 5.22, SD = 14.33, p = 0.010), in the PedsQL (mean change = 2.3, SD = 10.24, p = 0.050), and GSE (mean change = 1, SD = 3.60, p = 0.046). 85.2% of patients reported yoga helped them to control stress. Long-term data was available for 47 subjects with 31.9% (n = 15) continuing to practice yoga one to 3 years after study completion., Conclusion: This structured 12-week yoga program showed significant improvements in HRQOL and general self-efficacy, particularly 3 months after classes were concluded suggesting that yoga's benefits may persist. Yoga is a safe and effective adjunct to standard medical care to improve QOL and self-efficacy in youth with IBD., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: There is increasing recognition that children with Crohn's Disease (CD) can develop obesity., Methods: Using the RISK Study, an inception cohort of pediatric CD participants, and Bone Mineral Density in Childhood Study (BMDCS), a longitudinal cohort of healthy children, multivariable linear mixed effects, generalized linear mixed effects, and logistic regression models were used to evaluate factors associated with change in body mass index z-score (BMIZ), obesity, and excessive weight gain, respectively., Results: 1029 CD participants (625 exposed to antitumor necrosis factor (anti-TNF) therapy) and 1880 healthy children were included. Change in BMIZ was higher in CD exposed to anti-TNF as compared to CD unexposed to anti-TNF and the healthy reference group. Sex, age, baseline BMIZ, C-reactive protein, anti-TNF, and steroids were associated with changes in BMIZ in CD. CD exposed (odds ratio [OR] 4.81, confidence interval [CI] 4.00-5.78) and unexposed (OR 3.14, CI 2.62-3.76) had a greater likelihood of becoming obese versus the healthy reference group. While the prevalence of obesity was higher at baseline in the healthy reference group (21.3%) versus CD participants (8.5% exposed vs. 11.1% unexposed), rates of obesity were similar by the end of follow-up (21.4% healthy vs. 20.3% exposed vs. 22.5% unexposed). Anti-TNF therapy was an independent risk factor for the development of obesity and excessive weight gain in CD participants., Conclusions: Patients with CD have dynamic changes in BMIZ over time, and while for most, this is restorative, for some, this can lead to obesity and excessive weight gain. It is important to understand the factors that may lead to these changes, including anti-TNF therapy. Counseling of patients and early lifestyle intervention may be necessary., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Anastomotic ulceration (AU) is a rare but life-threatening complication of pediatric short bowel syndrome (SBS). AUs may be challenging to detect and refractory to treatment. This study aimed to identify features associated with symptomatic bleeding AUs in children with SBS and factors that may impact resolution of bleeding. The relationship between dietary changes and symptomatic anastomotic hemorrhage was also explored., Methods: We conducted a retrospective chart review of 381 patients cared for in the Intestinal Rehabilitation Program at our center from 2013 to 2022. Patients with symptomatic AUs were identified based on at least 1 endoscopic procedure showing AUs and evidence of clinically significant gastrointestinal bleeding. We collected patient demographics, clinical characteristics, dietary history, radiologic imaging, and histopathology. We used descriptive statistics to identify patterns of presentation., Results: AUs were identified in 22 patients who were followed for a median duration of 2.9 years after anastomotic ulcer identification. AUs uniformly evolved years after the initial anastomosis (median 3.2 years). Characteristics included bowel stricture (4/22), small bowel-colon anastomosis (19/22), partial colectomy (17/22), and an increase in whole foods fraction (12/18). Bleeding resolved with operative intervention in the majority with anastomotic stricture (3/4). Recurrent bleeding was common in those without stricture (13/18). In a subset of patients without stricture, whole food reduction was associated with improvement or resolution of bleeding (5/6)., Conclusions: We observed a higher proportion of patients with AUs who responded to surgical intervention in the subset of children with definitive anastomotic strictures versus those without, suggesting that careful characterization of intestinal anatomy may be critical to predicting response to therapy. We also observed that bleeding from AU typically first manifested within 1 year of a shift from elemental or hydrolyzed enteral formula to a whole food-based diet (including commercial blenderized feeds), which may indicate that components of the enteral diet play a role in the pathogenesis of AU. Further studies are needed to validate these hypotheses., 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.)

The pathogenesis of inflammatory bowel disease (IBD) involves a complex interaction between genetics, immune response, and the environment. Epidemiologic associations between diet and development of IBD plus the ability of diet to modify the microbiota and modulate immune function have led to the hypothesis that diet can prevent and/or treat IBD. It is well established that the induction of remission and healing of the mucosa in Crohn's disease can be accomplished with exclusive enteral nutrition. Whole food-based alternatives such as the Crohn's disease exclusion diet have shown promising results., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: While there are many epidemiologic studies of Asian immigrants to the West and risk of inflammatory bowel disease (IBD), the phenotype and lifestyle of Asian patients, particularly children, with IBD are not well described. In this study, we describe lifestyle practices, such as dietary pattern, as well as disease phenotype in Asian American children with IBD., Methods: We reviewed the records of children with IBD, ages 0 to 21 years old, and race identified as Asian, Indian, or Pacific Islander. Patients who received outpatient IBD care at our center between January 2013 and January 2020 were included. We excluded patients who were international second opinions, who did not have a definitive diagnosis of IBD, and in whom a diagnosis of IBD was made after 18 years of age. A survey, including a food frequency questionnaire adapted from NHANES DSQ with modifications to include culturally appropriate food elements, was designed and conducted within this cohort to assess for dietary patterns., Results: Asian patients in our cohort have similar phenotypes as non-Asians with few distinctive differences. There was a Crohn's disease and male predominance similar with non-Asians. However, there was a high rate of proctitis in ulcerative colitis in Asian patients. Asian patients reported a typical dietary pattern that reflects a Westernized pattern rather than a traditional pattern. Despite a similar dietary pattern, there was a high rate of 25-OH Vitamin D deficiency (44%) and insufficiency (40%)., Conclusions: This single center study showed that the phenotype of Asian children with IBD in the U.S. is similar with that of non-Asian with a few distinct differences. The Asian children in our cohort reported following a Westernized dietary pattern and lifestyle. However, there was a high rate of Vitamin D deficiency surrounding diagnosis, suggesting a need for vigilant monitoring., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zong 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: Internally penetrating Crohn's Disease complications, including abscesses and phlegmon, represent a high-risk Crohn's Disease phenotype. Anti-tumor-necrosis-factor-α (Anti-TNF) therapies are effective in treating penetrating Crohn's Disease and early initiation has shown unique benefits. However, timing of anti-TNF initiation in the setting of internally penetrating Crohn's Disease complications is typically heterogenous due to concern over precipitating serious infections. Recent studies demonstrate such an association may not exist., Aims: We aimed to describe the multidisciplinary management of pediatric patients with internally penetrating Crohn's Disease complications, focusing on the utilization and timing of anti-TNF therapy relative to complication resolution and adverse events., Methods: We performed a single-center retrospective cohort study of pediatric patients with internally penetrating Crohn's Disease complications from 2007 to 2021. The safety and effectiveness of anti-TNF therapy initiation prior to complication resolution was assessed by comparing rates of infectious and Crohn's Disease-related adverse events between those who received anti-TNF therapy prior to complication resolution, versus those who did not., Results: Twenty-one patients with internally penetrating Crohn's Disease complications were identified. 7/21 received anti-TNF therapy prior to complication resolution. Infectious adverse events within 90 days of complication occurred in 0/7 patients initiating anti-TNF therapy prior to complication resolution and 10/14 patients who did not (p = 0.004). Crohn's Disease-related surgeries and hospitalizations within 1 year of complication occurred in 12/20 patients, with similar frequency between groups., Conclusions: Initiating anti-TNF therapy prior to internally penetrating Crohn's Disease complication resolution may be a safe and effective strategy to improve clinical outcomes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Colectomy rates following acute severe ulcerative colitis have plateaued around 20% despite intravenous corticosteroid and intensified anti-tumor necrosis factor (TNF) biologic dosing. Recent studies have shown tofacitinib to provide additional benefit in further decreasing colectomy rates among hospitalized adult patients with corticosteroid- and anti-TNF-nonresponsive ulcerative colitis. Pediatric data describing the effectiveness of tofacitinib for this indication does not yet exist. We aimed to describe the treatment courses and colectomy-free survival among pediatric patients treated with tofacitinib while hospitalized for refractory ulcerative colitis., Methods: We performed a retrospective single-center cohort study of consecutive hospitalized pediatric patients initiating tofacitinib for refractory ulcerative colitis from 2018 to 2021. The primary outcome was 90-day colectomy-free survival. Secondary outcomes included colectomy-free clinical remission, corticosteroid independence, colectomy-free tofacitinib drug-persistence, tofacitinib-related adverse events, and postoperative complications. Baseline characteristics and details of the timing and positioning of therapies utilized during hospitalization were described. Outcomes were described using counts, percentages, and Kaplan-Meier curves., Results: Eleven patients met inclusion criteria. All patients demonstrated nonresponse to both intravenous corticosteroids and anti-TNF therapy prior to tofacitinib initiation. Median hospitalization length was 22 days and mean maximum pediatric ulcerative colitis activity index during hospitalization was 68. Eight of 11 patients remained colectomy-free at 90 days following hospital admission and 6 remained colectomy-free over median 182-day follow-up, including 4 of whom remained on tofacitinib., Conclusions: Tofacitinib may represent a new treatment option for hospitalized pediatric patients with corticosteroid- and anti-TNF-nonresponsive ulcerative colitis. Future research is essential in determining the optimal positioning of these therapies., Competing Interests: B.D.C. has received Advanced Inflammatory Bowel Disease Fellowship training funding from Pfizer Inc, unrelated to this research. R.B. is a consultant for Pfizer, unrelated to this research. R.S. has received research funding from Janssen Research & Development LLC and Pfizer, unrelated to this research. L.A. has received research funding from Seres Therapeutics and speaker fees from Nestle Health Sciences, unrelated to this research. The remaining authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background and Aims: Perianal fistulising disease can affect up to 25% of patients with Crohn's disease [CD] and lead to significant morbidity. Although the role of the gut microbiota in inflammatory bowel disease [IBD] has been increasingly recognised, its role in fistula development has scarcely been studied. Here, we aimed to define the microbial signature associated with perianal fistulising CD in children., Methods: A prospective observational study including children age 6-18 years with a diagnosis of perianal fistulising CD was conducted. Stool samples and rectal and perianal fistula swabs were collected. Stool samples and rectal swabs from children with CD without perianal disease and healthy children were included as comparison. Whole shotgun metagenomic sequencing was performed., Results: A total of 31 children [mean age 15.5 ± 3.5 years] with perianal CD were prospectively enrolled. The fistula-associated microbiome showed an increase in alpha diversity and alteration in the abundance of several taxa compared with the rectal- and faecal-associated microbiome with key taxa belonging to the Proteobacteria phylum. Genes conferring resistance to the clinically used antibiotic regimen ciprofloxacin and metronidazole were found in the three sample types. In comparison with children without the perianal phenotype [N = 36] and healthy controls [N = 41], the mucosally-associated microbiome of children with perianal CD harboured a reduced butyrogenic potential. Linear discriminant analysis identified key taxa distinguishing the rectal mucosally-associated microbiome of children with perianal CD from children without this phenotype., Conclusions: The microbial community within CD-related anorectal fistula is compositionally and functionally unique. Taken together, these findings emphasise the need to better understand the ecosystem of the fistula milieu to guide development of novel microbiome-based strategies in this CD phenotype., (© 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 & Aims: Epidemiologic and murine studies suggest that dietary emulsifiers promote development of diseases associated with microbiota dysbiosis. Although the detrimental impact of these compounds on the intestinal microbiota and intestinal health have been demonstrated in animal and in vitro models, impact of these food additives in healthy humans remains poorly characterized., Methods: To examine this notion in humans, we performed a double-blind controlled-feeding study of the ubiquitous synthetic emulsifier carboxymethylcellulose (CMC) in which healthy adults consumed only emulsifier-free diets (n = 9) or an identical diet enriched with 15 g per day of CMC (n = 7) for 11 days., Results: Relative to control subjects, CMC consumption modestly increased postprandial abdominal discomfort and perturbed gut microbiota composition in a way that reduced its diversity. Moreover, CMC-fed subjects exhibited changes in the fecal metabolome, particularly reductions in short-chain fatty acids and free amino acids. Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition., Conclusions: These results support the notion that the broad use of CMC in processed foods may be contributing to increased prevalence of an array of chronic inflammatory diseases by altering the gut microbiome and metabolome (ClinicalTrials.gov, number NCT03440229)., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The human gut microbiota is highly heterogenous between individuals and also exhibits considerable day-to-day variation within individuals. We hypothesized that diet contributed to such inter- and/or intra-individual variance. Hence, we investigated the extent to which diet normalization impacted microbiota heterogeneity. We leveraged the control arm of our recently reported controlled-feeding study in which nine healthy individuals consumed a standardized additive-free diet for 10 days. Diet normalization did not impact inter-individual differences but reduced the extent of intra-individual day-to-day variation in fecal microbiota composition. Such decreased heterogeneity reflected individual-specific enrichment and depletion of an array of taxa microbiota members and was paralleled by a trend toward reduced intra-individual variance in fecal LPS and flagellin, which, collectively, reflect microbiota's pro-inflammatory potential. Yet, the microbiota of some subjects did not change significantly over the course of the study, suggesting heterogeneity in microbiota resilience to dietary stress or that baseline diets of some subjects were perhaps similar to our study's standardized diet. Collectively, our results indicate that short-term diet heterogeneity contributes to day-to-day intra-individual microbiota composition variance.

Complications of short bowel syndrome (SBS) include malabsorption and bacterial overgrowth, requiring prolonged dependence on parenteral nutrition (PN). We hypothesized that the intolerance of whole food in some SBS patients might be due to the effect of dietary fiber on the gut microbiome. Shotgun metagenomic sequencing and targeted metabolomics were performed using biospecimens collected from 55 children with SBS and a murine dietary fiber model. Bioinformatic analyses were performed on these datasets as well as from a healthy human dietary intervention study. Compared to healthy controls, the gut microbiota in SBS had lower diversity and increased Proteobacteria, a pattern most pronounced in children on PN and inversely correlated with whole food consumption. Whole food intake correlated with increased glycoside hydrolases (GH) and bile salt hydrolases (BSH) with reduced fecal conjugated bile acids suggesting that dietary fiber regulates BSH activity via GHs. Mechanistic evidence supporting this notion was generated via fecal and plasma bile acid profiling in a healthy human fiber-free dietary intervention study as well as in a dietary fiber mouse experiment. Gaussian mixture modeling of fecal bile acids was used to identify three clinically relevant SBS phenotypes. Dietary fiber is associated with bile acid deconjugation likely via an interaction between gut microbiota BSHs and GHs in the small intestine, which may lead to whole food intolerance in patients with SBS. This mechanism not only has potential utility in clinical phenotyping and targeted therapeutics in SBS based on bile acid metabolism but may have relevance to other intestinal disease states.

Competing Interests: The authors report no conflicts of interest.

Dysbiosis of the microbiome has been extensively studied in inflammatory bowel diseases (IBD). The roles of bacteria and fungi have been studied in detail, but viral communities, an important component of the microbiome, have been less thoroughly investigated. Metagenomics provided a way to fill this gap by using DNA sequencing to enumerate all viruses in a sample, termed the 'virome'. Such methods have now been employed in several studies to assess associations between viral communities and IBD, yielding several commonly seen properties, including an increase in tailed bacteriophage (Caudovirales) and a decrease in the spherical Microviridae. Numerous studies of single human viruses have been carried out, but no one virus has emerged as tightly associated, focusing attention on whole virome communities and further factors. This review provides an overview of research on the human virome in IBD, with emphasis on (1) dynamics of the gut virome, (2) candidate mechanisms of virome alterations with disease, (3) methods for studying the virome, and (4) potentially actionable implications of virome data., (Copyright © 2021. Published by Elsevier B.V.)

Background: As the microbiome plays an important role in instigating inflammation in ulcerative colitis (UC), strategies targeting the microbiome may offer an alternative therapeutic approach. The goal of the pilot trial was to evaluate the potential efficacy and feasibility of a novel UC exclusion diet (UCED) for clinical remission, as well as the potential of sequential antibiotics for diet-refractory patients to achieve remission without steroids., Methods: This was a prospective, single-arm, multicenter, open-label pilot study in patients aged 8-19, with pediatric UC activity index (PUCAI) scores >10 on stable maintenance therapy. Patients failing to enter remission (PUCAI < 10) on the diet could receive a 14-day course of amoxycillin, metronidazole and doxycycline (AMD), and were re-assessed on day 21. The primary endpoint was intention-to-treat (ITT) remission at week 6, with UCED as the only intervention., Results: Twenty-four UCED treatment courses were given to 23 eligible children (mean age: 15.3 ± 2.9 years). The median PUCAI decreased from 35 (30-40) at baseline to 12.5 (5-30) at week 6 ( p = 0.001). Clinical remission with UCED alone was achieved in 9/24 (37.5%). The median fecal calprotectin declined from 818 (630.0-1880.0) μg/g at baseline to 592.0 (140.7-1555.0) μg/g at week 6 ( p > 0.05). Eight patients received treatment with antibiotics after failing on the diet; 4/8 (50.0%) subsequently entered remission 3 weeks later., Conclusion: The UCED appears to be effective and feasible for the induction of remission in children with mild to moderate UC. The sequential use of UCED followed by antibiotic therapy needs to be evaluated as a microbiome-targeted, steroid-sparing strategy.

Background & Aims: This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms., Methods: Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC <250 μg/g and reduction by >50% among those with baseline FC >250 μg/g) and C-reactive protein (CRP) response (high-sensitivity CRP <5 mg/L and >50% reduction from baseline among those with high-sensitivity CRP >5 mg/L)., Results: The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68)., Conclusions: The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Inflammatory bowel disease (IBD) is associated with increased risk of venous thromboembolism (VTE). Despite this recognized risk, there are limited data and no anticoagulation guidelines for hospitalized pediatric IBD patients. The objectives of this study were to characterize pediatric IBD patients with VTE and determine risk factors., Methods: This was a nested case-control study comparing hospitalized children with IBD diagnosed with VTE to those without VTE over a decade at a large referral center. Standard descriptive statistics were used to describe the VTE group. Multivariable conditional logistic regression was used to assess risk factors., Results: Twenty-three cases were identified. Central venous catheter (CVC) presence (odds ratio [OR] 77.9; 95% confidence interval [CI]: 6.9--880.6; P < 0.001) and steroid use (OR 12.7; 95% CI: 1.3--126.4; P = 0.012) were independent risk factors. Median age at VTE was 17 years (interquartile range [IQR] 13.5--18.2), and in 48%, VTE was the indication for admission. Median duration of anticoagulation was 3.8 months (IQR 2.3--7.6), and there were no major bleeding events for patients on anticoagulation. There were no patients with known sequelae from VTE, though 22% had severe VTE that required interventions., Conclusions: Pediatric patients with IBD are at risk for VTE, although the absolute risk remains relatively low. The safety and efficacy of pharmacologic thromboprophylaxis needs to be further evaluated in this population with attention to risk factors, such as steroid use and presence of CVC., Competing Interests: The authors report no conflict of interests., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Alterations in the microbiome have been postulated to drive inflammation in IBD. In this pilot randomized controlled trial, we evaluated the effectiveness of quadruple antibiotic cocktail in addition to intravenous-corticosteroids (IVCSs) in acute severe colitis (ASC)., Methods: Hospitalized children with ASC (pediatric ulcerative colitis activity index [PUCAI] ≥65) were randomized into 2 arms: the first received antibiotics in addition to IVCS (amoxicillin, vancomycin, metronidazole, doxycycline/ciprofloxacin [IVCS+AB]), whereas the other received only IVCS for 14 days. The primary outcome was disease activity (PUCAI) at day 5. Microbiome was analyzed using 16S rRNA gene and metagenome., Results: Twenty-eight children were included: 16 in the AB + IVCS arm and 12 in the IVCS arm (mean age 13.9 ± 4.1 years and 23 [82%] with extensive colitis). The mean day-5 PUCAI was 25 ± 16.7 vs 40.4 ± 20.4, respectively (P = 0.037). Only 3 and 2 children, respectively, required colectomy during 1-year follow-up (P = 0.89). Microbiome data at time of admission were analyzed for 25 children, of whom 17 (68%) had a predominant bacterial species (>33% abundance); response was not associated with the specific species, whereas decreased microbiome diversity at admission was associated with day-5 response in the IVCS arm., Conclusion: Patients with ASC have alterations in the microbiome characterized by loss of diversity and presence of predominant bacterial species. Quadruple therapy in addition to IVCS improved disease activity on day 5, but larger studies are needed to determine whether this is associated with improved long-term outcomes (clinicaltrials.gov NCT02033408)., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hospitalizations are a time when providers often have uncertainty about what to feed patients with inflammatory bowel disease (IBD). While there are many trials evaluating the role of diet in the management of IBD, the role of diet for the hospitalized patient is less clear. The hospitalization may serve as an opportunity to educate patients about the role of diet, try different diets, and develop dietary recommendations for after discharge. Here, we review the literature for dietary considerations during hospitalizations and acute settings, as well as upon discharge. Patients with IBD benefit from screening and nutritional support for malnutrition and nutritional deficiencies. Enteral nutrition and exclusion diets are promising as induction and maintenance therapies, but no specific recommendations during hospitalization for adult patients are available currently. There are very few reasons to enforce bowel rest or clear liquids other than bowel obstruction, uncontrolled sepsis, or need for urgent or emergent surgery; most patients - including many with penetrating or stricturing disease - benefit from feeding in whichever capacity is tolerated, with enteral and parenteral nutrition used as needed to reach nutritional goals. Future studies are needed to define how the use of different diets can influence the outcomes of patients hospitalized for IBD., Competing Interests: Financial disclosures and conflicts of interest: none

Background: Recent studies have shown that oral combination antibiotics may improve disease course in refractory inflammatory bowel disease (IBD). Here, we describe the use of combination oral antibiotics as salvage therapy in refractory ulcerative colitis (UC), Crohn's colitis, and IBD-unclassified (IBD-U) at a large pediatric IBD center., Methods: Clinical response, disease activity indices, adverse events, and clinical outcomes were measured up to 1 year after antibiotic treatment in this retrospective cohort study of children with medically refractory IBD colitis., Results: Sixty-three patients with refractory UC, Crohn's colitis, and IBD-U (median age [interquartile range {IQR}], 15.3 [11.2-16.5] years; median disease duration [IQR], 1.2 [0.41-4.6] years) received a combination of 3 or 4 oral antibiotics (most commonly amoxicillin, metronidazole, and either doxycycline or ciprofloxacin) for a median (IQR) of 29 (21-58) days. Thirty-four patients (54%) were deemed corticosteroid-refractory or -dependent, with the majority (62/63) having a previous or present loss of response or primary nonresponse to anti-tumor necrosis factor alpha (anti-TNFα) therapy. Use of combination antibiotics led to a significant decrease in median Pediatric Ulcerative Colitis Activity Index (PUCAI) score (IQR) from 55 (40-65) to 10 (0-40; P < 0.0001) over 3 ± 1 weeks, with 25/63 (39.7%) patients achieving clinical remission (PUCAI <10 points). The clinical benefits of oral antibiotics were independent of anti-TNFα therapy optimization. Among children entering clinical remission (n = 25), only 1 patient required surgery at 1-year follow-up, vs 10 patients in the nonresponder group. Negative predictors of response to combination antibiotics were exposure to doxycycline (odds ratio [OR], 0.25; 95% CI, 0.08-0.76) and PUCAI ≥65 at baseline (OR, 0.2; 95% CI, 0.05-0.74)., Conclusions: Oral combination antibiotics appears to be an effective rescue and steroid-sparing therapy to induce remission in the short term in patients failing a biologic., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Aims: Diet may be an important factor in the progression of Crohn's disease (CD). We performed a randomized controlled trial to determine whether reduced consumption of red and processed meats decreases the risk of symptomatic relapse of CD, analyzing results from the Food and Crohn's Disease Exacerbation Study (FACES) trial., Methods: Adults with CD were recruited into the FACES trial from IBD Partners, an Internet-based cohort of patients with inflammatory bowel disease, from November 2013 through June 2015. Individuals who were in remission (CD activity index [sCDAI] scores of ≤150), had completed a biannual survey, and reported consumption of red meat at least once weekly were randomly assigned to groups that consumed a minimum of 2 servings/week of red or processed meat (high meat, n = 118) or not more than 1 serving per month (low meat, n = 96) for 49 weeks. The primary outcome was relapse of CD, defined as increase in sCDAI score by ≥70 points and to >150 or a need for CD surgery or new CD medication. A secondary outcome, moderate or severe relapse, was based on an increase in sCDAI to >219., Results: During the trial, the high-meat groups reported consumption of 2 or more servings of red or processed meat during 98.5% of observed weeks compared with 18.8% of weeks for the low-meat group. Any and moderate to severe relapse occurred in 62% of participants in the high-meat group and 42% of participants in the low-meat group. There were no significant differences in time to any (P = .61) or moderate/severe (P = .50) relapse., Conclusions: In an analysis of data from the FACES trial, we found that among patients with CD in remission, level of red and processed meat consumption was not associated with time to symptomatic relapse. ClinicalTrials.gov, Number: NCT0192673., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In these studies, we evaluated the contribution of the NLRP3 inflammasome to Crohn's disease (CD) in a kindred containing individuals having a missense mutation in CARD8, a protein known to inhibit this inflammasome. Whole exome sequencing and PCR studies identified the affected individuals as having a V44I mutation in a single allele of the T60 isoform of CARD8. The serum levels of IL-1β in the affected individuals were increased compared with those in healthy controls, and their peripheral monocytes produced increased amounts of IL-1β when stimulated by NLRP3 activators. Immunoblot studies probing the basis of these findings showed that mutated T60 CARD8 failed to downregulate the NLRP3 inflammasome because it did not bind to NLRP3 and inhibit its oligomerization. In addition, these studies showed that mutated T60 CARD8 exerted a dominant-negative effect by its capacity to bind to and form oligomers with unmutated T60 or T48 CARD8 that impeded their binding to NLRP3. Finally, inflammasome activation studies revealed that intact but not mutated CARD8 prevented NLRP3 deubiquitination and serine dephosphorylation. CD due to a CARD8 mutation was not effectively treated by anti-TNF-α, but did respond to IL-1β inhibitors. Thus, patients with anti-TNF-α-resistant CD may respond to this treatment option.

Gut dysbiosis during inflammatory bowel disease involves alterations in the gut microbiota associated with inflammation of the host gut. We used a combination of shotgun metagenomic sequencing and metabolomics to analyze fecal samples from pediatric patients with Crohn's disease and found an association between disease severity, gut dysbiosis, and bacterial production of free amino acids. Nitrogen flux studies using 15 N in mice showed that activity of bacterial urease, an enzyme that releases ammonia by hydrolysis of host urea, led to the transfer of murine host-derived nitrogen to the gut microbiota where it was used for amino acid synthesis. Inoculation of a conventional murine host (pretreated with antibiotics and polyethylene glycol) with commensal Escherichia coli engineered to express urease led to dysbiosis of the gut microbiota, resulting in a predominance of Proteobacteria species. This was associated with a worsening of immune-mediated colitis in these animals. A potential role for altered urease expression and nitrogen flux in the development of gut dysbiosis suggests that bacterial urease may be a potential therapeutic target for inflammatory bowel diseases., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

A general consensus exists that IBD is associated with compositional and metabolic changes in the intestinal microbiota (dysbiosis). However, a direct causal relationship between dysbiosis and IBD has not been definitively established in humans. Findings from animal models have revealed diverse and context-specific roles of the gut microbiota in health and disease, ranging from protective to pro-inflammatory actions. Moreover, evidence from these experimental models suggest that although gut bacteria often drive immune activation, chronic inflammation in turn shapes the gut microbiota and contributes to dysbiosis. The purpose of this Review is to summarize current associations between IBD and dysbiosis, describe the role of the gut microbiota in the context of specific animal models of colitis, and discuss the potential role of microbiota-focused interventions in the treatment of human IBD. Ultimately, more studies will be needed to define host-microbial relationships relevant to human disease and amenable to therapeutic interventions.

Objectives: Diverting ileostomy is used as a temporizing therapy in patients with perianal Crohn disease; however, little data exist regarding its use for colonic disease. The primary aim of the present study was to determine the role of diversion in severe refractory colonic inflammatory bowel disease (IBD) in a pediatric population., Methods: Retrospective study of patients who underwent diverting ileostomy at The Children's Hospital of Philadelphia from 2000 to 2014 for the management of severe, refractory colonic IBD. Clinical variables were compared in the 1 year before ileostomy and 1 year after diversion. Surgical and disease outcomes including changes in diagnosis were reviewed through 2015., Results: Twenty-four patients underwent diverting ileostomy for refractory colonic disease. Initial diagnoses were Crohn disease in 10 (42%), ulcerative colitis in 1 (4%), and IBD-unclassified in 13 patients (54%). Comparing data before and after surgery, there were statistically significant improvements in height and weight velocities, height velocity z score, blood transfusion requirement, hemoglobin, and hospitalization rates. Chronic steroid use decreased from 71% to 22%. At the conclusion of the study, 10 patients had undergone subsequent colectomy, 7 had successful bowel reanastomosis, and 7 remain diverted. Seven patients (29%) had a change in diagnosis. There were 13 surgical complications in 7 subjects, including prolapse reduction, stoma revision, and resection of ischemic bowel., Conclusions: In pediatric patients with refractory colonic IBD, diverting ileostomy can be a successful intervention to induce clinical stability. Importantly, diversion is a steroid-sparing therapy and allows additional time to clarify the diagnosis.

Inflammatory bowel disease is believed to be caused by a combination of genetic and environmental stimuli such as our diet. Diets high in meat and fats and low in fruits and vegetables have been associated with new-onset inflammatory bowel disease. This has triggered interest in using dietary modification as a treatment. The 3 principle models of dietary intervention are supplementation with selected dietary components, exclusion of selected dietary components, or use of dietary formulas in place of a normal diet. Despite the high level of interest in dietary interventions as a treatment for inflammatory bowel disease, few well-designed clinical trials have been conducted to firmly establish the optimal diet to induce or maintain remission. This may be in part related to the challenges of conducting dietary intervention trials. This review examines these challenges and potential approaches to be used in dietary intervention trials., Competing Interests: Potential Conflicts of Interest: Dr. Lewis has served as a consultant for and received research funding from Nestle Health Science. Dr. Kratz has received honoraria and compensation for travel as well as a research grant from dairy-related organizations. Dr. Reinisch has served as a consultant for Nestle Health Science. Drs. Gottlieb, Lee, and Albenberg report no potential conflicts of interest.

Background: Vedolizumab is effective for inducing and maintaining remission in adults with inflammatory bowel disease (IBD); however, there is limited pediatric data. This study aimed to describe the adverse events and clinical response to vedolizumab in refractory pediatric IBD., Methods: Disease activity indices, clinical response, concomitant medication use, and adverse events were measured over 22 weeks in an observational prospective cohort study of children with refractory IBD who had failed anti-tumor necrosis factor therapy and subsequently initiated vedolizumab therapy., Results: Twenty-one subjects, 16 with Crohn disease, received vedolizumab. Clinical response was observed in 6/19 (31.6%) of the evaluable subjects at week 6 and in 11/19 (57.9%) by week 22. Before induction, 15/21 (71.4%) participants were treated with systemic corticosteroids, as compared with 7/21 (33.3%) subjects at 22 weeks. Steroid-free remission was seen in 1/20 (5.0%) subjects at 6 weeks, 3/20 (15.0%) at 14 weeks, and 4/20 (20.0%) at 22 weeks. There was statistically significant improvement in serum albumin and hematocrit; however, C-reactive protein increased by week 22 (P < 0.05). There were no infusion reactions. Vedolizumab was discontinued in 2 patients because of severe colitis, requiring surgical intervention., Conclusions: There is limited experience with vedolizumab therapy in pediatric IBD. There seems to be a marked number of subjects with clinical response in the first 6 weeks that increases further by week 22 despite the severity of disease in this cohort. Adverse events may not be directly related to vedolizumab. This study is limited by small sample size, and larger prospective studies are warranted.

Abnormal composition of intestinal bacteria--"dysbiosis"-is characteristic of Crohn's disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ancillary antibiotic therapy, but their effects on microbiota composition are undetermined. Using shotgun metagenomic sequencing, we analyzed fecal samples from a prospective cohort of pediatric Crohn's disease patients starting therapy with enteral nutrition or anti-TNFα antibodies and reveal the full complement and dynamics of bacteria, fungi, archaea, and viruses during treatment. Bacterial community membership was associated independently with intestinal inflammation, antibiotic use, and therapy. Antibiotic exposure was associated with increased dysbiosis, whereas dysbiosis decreased with reduced intestinal inflammation. Fungal proportions increased with disease and antibiotic use. Dietary therapy had independent and rapid effects on microbiota composition distinct from other stressor-induced changes and effectively reduced inflammation. These findings reveal that dysbiosis results from independent effects of inflammation, diet, and antibiotics and shed light on Crohn disease treatments., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Therapeutic targets in pediatric Crohn's disease include symptoms, quality of life (QOL), and mucosal healing. Although partial enteral nutrition (PEN), exclusive enteral nutritional (EEN), and anti-tumor necrosis factor alpha (anti-TNF) therapy all improve symptoms, the comparative effectiveness of these approaches to improve QOL and achieve mucosal healing has not been assessed prospectively., Methods: In a prospective study of children initiating PEN, EEN, or anti-TNF therapy for Crohn's disease, we compared clinical outcomes using the Pediatric Crohn's Disease Activity Index (PCDAI), QOL (IMPACT score), and mucosal healing as estimated by fecal calprotectin (FCP). PCDAI, IMPACT, FCP, and diet (prompted 24-h recall) were measured at baseline and after 8 weeks of therapy., Results: We enrolled 90 children with active Crohn's disease (PCDAI, 33.7 ± 13.7; and FCP, 976 ± 754), of whom 52 were treated with anti-TNF, 22 with EEN, and 16 with PEN plus ad lib diet. Clinical response (PCDAI reduction ≥15 or final PCDAI ≤10) was achieved by 64% on PEN, 88% EEN, and 84% anti-TNF (test for trend P = 0.08). FCP ≤250 μg/g was achieved with PEN in 14%, EEN 45%, and anti-TNF 62% (test for trend P = 0.001). Improvement in overall QOL was not statistically significantly different between the 3 groups (P = 0.86). However, QOL improvement was the greatest with EEN in the body image (P = 0.03) domain and with anti-TNF in the emotional domain (P = 0.04)., Conclusions: Although PEN improved clinical symptoms, EEN and anti-TNF were more effective for decreasing mucosal inflammation and improving specific aspects of QOL.

Increasing evidence indicates that the gut microbiota can be altered to ameliorate or prevent disease states, and engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research. In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease. Here, we engineered murine gut microbiota to reduce urease activity. Animals were depleted of their preexisting gut microbiota and then inoculated with altered Schaedler flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility.

Some of the most common symptoms of the inflammatory bowel diseases (IBD, which include ulcerative colitis and Crohn's disease) are abdominal pain, diarrhea, and weight loss. It is therefore not surprising that clinicians and patients have wondered whether dietary patterns influence the onset or course of IBD. The question of what to eat is among the most commonly asked by patients, and among the most difficult to answer for clinicians. There are substantial variations in dietary behaviors of patients and recommendations for them, although clinicians do not routinely endorse specific diets for patients with IBD. Dietary clinical trials have been limited by their inability to include a placebo control, contamination of study groups, and inclusion of patients receiving medical therapies. Additional challenges include accuracy of information on dietary intake, complex interactions between foods consumed, and differences in food metabolism among individuals. We review the roles of diet in the etiology and management of IBD based on plausible mechanisms and clinical evidence. Researchers have learned much about the effects of diet on the mucosal immune system, epithelial function, and the intestinal microbiome; these findings could have significant practical implications. Controlled studies of patients receiving enteral nutrition and observations made from patients on exclusion diets have shown that components of whole foods can have deleterious effects for patients with IBD. Additionally, studies in animal models suggested that certain nutrients can reduce intestinal inflammation. In the future, engineered diets that restrict deleterious components but supplement beneficial nutrients could be used to modify the luminal intestinal environment of patients with IBD; these might be used alone or in combination with immunosuppressive agents, or as salvage therapy for patients who do not respond or lose responsiveness to medical therapies. Stricter diets might be required to induce remission, and more sustainable exclusion diets could be used to maintain long-term remission., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The gut microbiota is a complex and densely populated community in a dynamic environment determined by host physiology. We investigated how intestinal oxygen levels affect the composition of the fecal and mucosally adherent microbiota., Methods: We used the phosphorescence quenching method and a specially designed intraluminal oxygen probe to dynamically quantify gut luminal oxygen levels in mice. 16S ribosomal RNA gene sequencing was used to characterize the microbiota in intestines of mice exposed to hyperbaric oxygen, human rectal biopsy and mucosal swab samples, and paired human stool samples., Results: Average Po2 values in the lumen of the cecum were extremely low (<1 mm Hg). In altering oxygenation of mouse intestines, we observed that oxygen diffused from intestinal tissue and established a radial gradient that extended from the tissue interface into the lumen. Increasing tissue oxygenation with hyperbaric oxygen altered the composition of the gut microbiota in mice. In human beings, 16S ribosomal RNA gene analyses showed an increased proportion of oxygen-tolerant organisms of the Proteobacteria and Actinobacteria phyla associated with rectal mucosa, compared with feces. A consortium of asaccharolytic bacteria of the Firmicute and Bacteroidetes phyla, which primarily metabolize peptones and amino acids, was associated primarily with mucus. This could be owing to the presence of proteinaceous substrates provided by mucus and the shedding of the intestinal epithelium., Conclusions: In an analysis of intestinal microbiota of mice and human beings, we observed a radial gradient of microbes linked to the distribution of oxygen and nutrients provided by host tissue., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Enteral nutritional therapy (EN) is an effective modality for inducing and maintaining remission in pediatric patients with Crohn's disease (CD). The standard protocol for EN provides patients with 100% of their caloric needs for induction of remission. The aim of this study was to determine the efficacy of delivering 80% to 90% of patient's caloric needs through EN, to induce remission in pediatric patients with CD. This approach allows patients to consume remaining calories from a normal diet., Methods: A retrospective review of charts from 1998 to 2010 was conducted at The Children's Hospital of Philadelphia. Remission (Pediatric Crohn's Disease Activity Index <10) and response (decrease in Pediatric Crohn's Disease Activity Index score of ≥12.5 points) were calculated before and after treatment with EN. Weight z scores and laboratory parameters were evaluated in all participants., Results: Forty-three charts were evaluated. Mean age of participants was 12.8 years (5.1-17.4), 67% were male and 33% female patients. Remission and response were evaluated in a group of 23 participants, with no missing data. There were reductions in erythrocyte sedimentation rate (P < 0.0001) and C-reactive protein (P < 0.02), and increases in albumin (P < 0.03). Mean Pediatric Crohn's Disease Activity Index score at baseline was 26.9 and was reduced to a score of 10.2 at follow-up (P < 0.0001). Induction of remission was achieved in 65% and response in 87% at a mean follow-up of 2 months (1-4 months)., Conclusions: This novel EN protocol seems to be effective for the induction of remission in pediatric patients with CD and contributes to increasing weight and improving laboratory markers. This protocol may result in improved EN acceptance and compliance and will be evaluated prospectively.