Functional contribution of the intestinal microbiome in autism spectrum disorder, attention deficit hyperactivity disorder, and Rett syndrome: a systematic review of pediatric and adult studies.

Introduction: Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent studies have shown the presence of gut microbiota alterations in neurodevelopmental disorders. Here we performed a systematic review of alterations of the intestinal microbiota composition and function in pediatric and adult patients affected by autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Rett syndrome (RETT). Methods: We searched selected keywords in the online databases of PubMed, Cochrane, and OVID (January 1980 to December 2021) with secondary review of references of eligible articles. Two reviewers independently performed critical appraisals on the included articles using the Critical Appraisal Skills Program for each study design. Results: Our systematic review identified 18, 7, and 3 original articles describing intestinal microbiota profiles in ASD, ADHD, and RETT, respectively. Decreased Firmicutes and increased Bacteroidetes were observed in the gut microbiota of individuals affected by ASD and ADHD. Proinflammatory cytokines, short-chain fatty acids and neurotransmitter levels were altered in ASD and RETT. Constipation and visceral pain were related to changes in the gut microbiota in patients affected by ASD and RETT. Hyperactivity and impulsivity were negatively correlated with Faecalibacterium (phylum Firmicutes) and positively correlated with Bacteroides sp. (phylum Bacteroidetes) in ADHD subjects. Five studies explored microbiota-or diet-targeted interventions in ASD and ADHD. Probiotic treatments with Lactobacillus sp. and fecal microbiota transplantation from healthy donors reduced constipation and ameliorated ASD symptoms in affected children. Perinatal administration of Lactobacillus sp. prevented the onset of Asperger and ADHD symptoms in adolescence. Micronutrient supplementation improved disease symptomatology in ADHD without causing significant changes in microbiota communities' composition. Discussion: Several discrepancies were found among the included studies, primarily due to sample size, variations in dietary practices, and a high prevalence of functional gastrointestinal symptoms. Further studies employing longitudinal study designs, larger sample sizes and multi-omics technologies are warranted to identify the functional contribution of the intestinal microbiota in developmental trajectories of the human brain and neurobehavior. Systematic review registration: https://clinicaltrials.gov/, CRD42020158734.

Development of the Pediatric Integrated Nutrition Pathway for Acute Care (P-INPAC) using a modified Delphi technique.

One in three hospitalized children have disease-related malnutrition (DRM) upon admission to hospital, and all children are at risk for further nutritional deterioration during hospital stay; however, systematic approaches to detect DRM in Canada are lacking. To standardise and improve hospital care, the multidisciplinary pediatric working group of the Canadian Malnutrition Taskforce aimed to develop a pediatric, inpatient nutritional care pathway based on available evidence, feasibility of resources, and expert consensus. The working group (n = 13) undertook a total of four meetings: an in-person meeting to draft the pathway based on existing literature and modelled after the Integrated Nutrition Pathway for Acute Care (INPAC) in adults, followed by three online surveys and three rounds of online Delphi consensus meetings to achieve agreement on the draft pathway. In the first Delphi survey, 32 questions were asked, whereas in the second and third rounds 27 and 8 questions were asked, respectively. Consensus was defined as any question/issue in which at least 80% agreed. The modified Delphi process allowed the development of an evidence-informed, consensus-based pathway for inpatients, the Pediatric Integrated Nutrition Pathway for Acute Care (P-INPAC). It includes screening <24 h of admission, assessment with use of Subjective Global Nutritional Assessment (SGNA) <48 h of admission, as well as prevention, and treatment of DRM divided into standard, advanced, and specialized nutrition care plans. Research is necessary to explore feasibility of implementation and evaluate the effectiveness by integrating P-INPAC into clinical practice.

Malnutrition care in hospitalized pediatric inpatients: comparison of perceptions and experiences across two pediatric academic health sciences centres.

Malnutrition affects up to one in three Canadian children admitted to hospital. Awareness among pediatric healthcare providers (HCPs) of the prevalence and impacts of hospitalized malnutrition is critical for optimal management. The purpose of this study was to determine perceptions of malnutrition among pediatric HCP across two major academic health sciences centres, and to determine how the use of a standardized pediatric nutritional screening tool at one institution affects responses. Between 2020 and 2022, 192 HCPs representing nursing, dietetics, medicine, and other allied health were surveyed across McMaster Children's Hospital and The Hospital for Sick Children. 38% of respondents from both centres perceived rates of malnutrition between approximately one in three patients. Perceptions of the need for nutritional screening, assessment, and management were similar between centres. All respondents identified the need for better communication of hospitalized malnutrition status to community providers at discharge, and resource limitations affecting nutritional management of pediatric inpatients. This study represents the largest and most diverse survey of inpatient pediatric HCPs to date. We demonstrate high rates of baseline knowledge of hospital malnutrition, ongoing resource challenges, and the need for a systematic approach to pediatric nutritional management.

Physical Activity in Pediatric Inflammatory Bowel Disease: A Scoping Review.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, systemic condition affecting the gastrointestinal tract. IBD can be severe and are associated with impairment in growth, school absences, abdominal pain, and fatigue. Physical activity (PA) could have an anti-inflammatory effect in addition to other benefits. It is important to address the possible risks, physiological effects of PA, and potential barriers, and facilitators for PA participation in pediatric IBD. However, potential barriers and facilitators to PA have yet to be adequately described. METHODS: We conducted a scoping review to map and describe the current literature on PA in pediatric IBD populations between 1980 and April 2022 using Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines for Scoping reviews. RESULTS: Nineteen articles were identified including 10 descriptive, 6 interventional, and 3 physiological responses to PA studies. Patients and healthy controls demonstrated similar responses to exercise. Barriers to participation were low self-esteem, body image, and active IBD symptoms. Facilitators included personal interest, activity with friends, and support from family. CONCLUSION: This review highlighted that PA participation may reduce in children with IBD-related symptoms. Short- and medium-term impacts of PA on immune modulation require further study; it is possible that regular PA does not negatively affect biomarkers of disease activity.

Significant vomiting and weight loss in a pediatric epilepsy patient secondary to vagus nerve stimulation: A case report and review of the literature.

Vagus nerve stimulation is a neuromodulatory treatment option for individuals with drug resistant epilepsy who are not resective surgical candidates. As the vagus nerve has widespread neural connections, stimulation can lead to an array of adverse effects. While vomiting and weight loss are known side effects of vagus nerve stimulation, these are typically transient, mild, and do not limit the ability to continue treatment. We describe a 17-year-old female with drug resistant focal epilepsy secondary to tuberous sclerosis complex, who began to experience daily emesis and significant weight loss approximately 2.5 years after VNS device insertion. Her body mass index progressively fell from between the 75th-85th percentiles to less than the first percentile. She underwent extensive workup by neurology, gastroenterology, and adolescent medicine services with no obvious cause identified. Prior to the insertion of an enteral tube for feeding support and urgent weight restoration, her vagus nerve stimulator was switched off, resulting in immediate cessation of her vomiting and a dramatically rapid recovery of weight over the ensuing few months. This case emphasizes the need to consider adverse effects of vagus nerve stimulation in the differential diagnosis of patients with otherwise unexplained new medical sequelae, and provides evidence potentially linking vagal stimulation to significant malnutrition-related complications. Outside of GI-related effects, few studies have shown late-onset adverse effects from VNS, including laryngeal and facial pain as well as bradyarrhythmia. Further research is needed to elucidate the exact mechanisms of vagus nerve stimulation to better anticipate and mitigate adverse effects, and to understand the pathophysiology of late-onset adverse effects in previously tolerant VNS patients.

Intestinal microbiome in short bowel syndrome: diagnostic and therapeutic opportunities.

PURPOSE OF REVIEW: The intestinal microbiome plays a strong, complementary role in the development and integrity of the intestinal epithelium. This biology is crucial for intestinal adaptation, particularly after the mucosal insults that lead to short bowel syndrome (SBS). The purpose of this review is to discuss relationships between the intestinal microbiota and the physiology of intestinal adaptation. RECENT FINDINGS: We will address interactions between the intestinal microbiome and nutritional metabolism, factors leading to dysbiosis in SBS, and common compositional differences of the gut microbiome in SBS patients as compared to healthy controls. We will also discuss novel opportunities to expand diagnostic and therapeutic interventions in this population, by using our knowledge of the microbiome to manipulate luminal bacteria and study their resultant metabolites. As microbial therapeutics advance across so many fields of medicine, this review is timely in its advocacy for ongoing research that focuses on the SBS population.Our review will discuss 4 key areas: 1) physiology of the intestinal microbiome in SBS, 2) clinical and therapeutic insults that lead to a state of dysbiosis, 3) currently available evidence on microbiome-based approaches to SBS management, and 4) opportunities and innovations to inspire future research. SUMMARY: The clinical implications of this review are both current, and potential. Understanding how the microbiome impacts intestinal adaptation and host physiology may enhance our understanding of why we experience such clinical variability in SBS patients' outcomes. This review may also expand clinicians' understanding of what 'personalized medicine' can mean for this patient population, and how we may someday consider our nutritional, therapeutic, and prognostic recommendations based on our patients' host, and microbial physiology.

Generic Health-Related Quality of Life Utility Measure for Preschool Children (Health Utilities Preschool): Design, Development, and Properties.

OBJECTIVES: Health Utilities Preschool (HuPS) was developed to fill the need for a generic preference-based measure (GPM) applicable in early childhood. A GPM has all the properties for higher-order summary measures, such as quality-adjusted life-years, required to inform important policy decisions regarding health and healthcare services. METHODS: Development was in accordance with published standards for a GPM, statistical procedures, and modeling. HuPS incorporates key components of 2 existing measurement systems: Health Status Classification System for Preschool Children and Health Utilities Index Mark 3 (HUI3). The study included a series of 4 measurement surveys: definitional, adaptational, quantificational, and evaluational health-related quality of life (HRQL). HuPS measurements were evaluated for reliability, validity, interpretability, and acceptability. RESULTS: Definitional measurements identified 8 Health Status Classification System for Preschool Children attributes in common with HUI3 (vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain and discomfort), making the HUI3 scoring equation commensurate with HuPS health states. Adaptational measurements informed the content of attribute-level descriptions (n = 35). Quantificational measurements determined level scoring coefficients. HRQL scoring inter-rater reliability (intraclass correlation coefficient = 0.79) was excellent. Continuity of HRQL scoring with HUI3 was reliable (intraclass correlation coefficient = 0.80, P < .001) and valid (mean absolute difference = 0.016, P = .396). CONCLUSIONS: HuPS is an acceptable, reliable, and valid GPM. HRQL scoring is continuous with HUI3. Continuity expands the applicability of GPM (HUI3) scoring to include subjects as young as 2 years of age. Widespread applications of HuPS would inform important health policy and management decisions as HUI3 does for older subjects.

Characteristics of Pediatric Patients With Celiac Disease Identified Due to an Affected First-Degree Family Member.

The incidence of celiac disease in first-degree relatives of affected individuals is higher than in the general population, yet the clinical characteristics of this unique subset of patients has not been well described. Through a retrospective review of patients seen in a tertiary care pediatric celiac disease clinic, we identified 49 patients diagnosed with celiac disease following screening due to an affected first-degree relative. Although 51% of patients screened due to an affected first-degree relative were asymptomatic, their disease histology was as severe as those screened for symptoms suggestive of celiac disease. These findings support current recommendations to screen all first-degree relatives of patients with celiac disease regardless of clinical symptoms.

Evaluation of Hepatitis in Pediatric Patients With Presumed Nonalcoholic Fatty Liver Disease.

In 2017, the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition published clinical practice guidelines for the assessment and diagnosis of nonalcoholic fatty liver disease (NAFLD). We determined how frequently these investigations suggest an alternate etiology for chronic hepatitis in 8- to 17-year-old patients with body mass index >85%, elevated alanine aminotransferase and radiographic steatosis, and rates of adherence to 2017 guidelines. Methods: We conducted a retrospective chart review of patients presenting to McMaster Children's Hospital from 2017-2020 for evaluation of suspected NAFLD. Bloodwork was reviewed. Results: Ninety-five patients met inclusion criteria. Abnormal bloodwork that required further testing was found in 28.4%; a different chronic liver disease was ultimately diagnosed in 11.6%. Only 9.5% received comprehensive, additional bloodwork for other causes of liver disease. Conclusion: A high proportion of patients evaluated for suspected NAFLD had bloodwork possibly suggesting an alternate diagnosis. Comprehensive testing was infrequently performed. These results reinforce the importance of maintaining a differential diagnosis among children presumed to have NAFLD.

Microbiota-Immune Interactions in Ulcerative Colitis and Colitis Associated Cancer and Emerging Microbiota-Based Therapies.

Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn's disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.

Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease.

Rates of pediatric Crohn's disease (CD) and ulcerative colitis (UC) are increasing globally. Differentiation of these inflammatory bowel disease (IBD) subtypes however can be challenging when relying on invasive endoscopic approaches. We sought to identify urinary metabolic signatures of pediatric IBD at diagnosis, and during induction treatment. Nontargeted metabolite profiling of urine samples from CD (n = 18) and UC (n = 8) in a pediatric retrospective cohort study was performed using multisegment injection-capillary electrophoresis-mass spectrometry. Over 122 urinary metabolites were reliably measured from pediatric IBD patients, and unknown metabolites were identified by tandem mass spectrometry. Dynamic changes in sum-normalized urinary metabolites were also monitored following exclusive enteral nutrition (EEN) or corticosteroid therapy (CS) in repeat urine samples collected over 8 weeks. Higher urinary excretion of indoxyl sulfate, hydroxyindoxyl sulfate, phenylacetylglutamine, and sialic acid were measured in CD as compared to UC patients, but lower threonine, serine, kynurenine, and hypoxanthine (p < 0.05). Excellent discrimination of CD from UC was achieved based on the urinary serine:indoxylsulfate ratio (AUC = 0.972; p = 3.21 × 10-5). Urinary octanoyl glucuronide, pantothenic acid, and pyridoxic acid were also identified as specific dietary biomarkers of EEN in pediatric IBD patients who achieved clinical remission. This work may complement or replace existing strategies in the diagnosis and early management of children with IBD.

Protocol for a systematic review on the role of the gut microbiome in paediatric neurological disorders.

INTRODUCTION: The gut-brain axis refers to the bidirectional communication that occurs between the intestinal tract and central nervous system (CNS). Through a series of neural, immune, endocrine, and metabolic signalling pathways, commensal microbiota are able to influence CNS development and neurological function. Alterations in gut microbiota have been implicated in various neuropathologies. The purpose of this review is to evaluate and summarise existing literature assessing the role of specific bacterial taxa on the development of neurodevelopmental, neuropsychiatric, and neurodegenerative pathologies of childhood. We will also discuss microbiota-based therapies dietary interventions and their efficacy. METHODS AND ANALYSIS: We will search PubMed, Cochrane Library, and OVID electronic databases for articles published between January 1980 and February 2021. A search method involving two rounds of reviewing the literature using a three-step method in each round will be performed. Two researchers will be selected, and screen titles and abstracts independently. The full text of selected articles will be assessed against inclusion criteria. Data will be extracted and evaluated using the appropriate Critical Appraisal Skills Programme (CASP) checklist. ETHICS AND DISSEMINATION: Findings from this study will be shared across relevant paediatric neurology and gastroenterology societies and submitted for peer review. This study did not require institutional ethics approval.

Nutritional Therapies and Their Influence on the Intestinal Microbiome in Pediatric Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic, autoimmune disorder of the gastrointestinal tract with numerous genetic and environmental risk factors. Patients with Crohn's disease (CD) or ulcerative colitis (UC) often demonstrate marked disruptions of their gut microbiome. The intestinal microbiota is strongly influenced by diet. The association between the increasing incidence of IBD worldwide and increased consumption of a westernized diet suggests host nutrition may influence the progression or treatment of IBD via the microbiome. Several nutritional therapies have been studied for the treatment of CD and UC. While their mechanisms of action are only partially understood, existing studies do suggest that diet-driven changes in microbial composition and function underlie the diverse mechanisms of nutritional therapy. Despite existing therapies for IBD focusing heavily on immune suppression, nutrition is an important treatment option due to its superior safety profile, potentially low cost, and benefits for growth and development. These benefits are increasingly important to patients. In this review, we will describe the clinical efficacy of the different nutritional therapies that have been described for the treatment of CD and UC. We will also describe the effects of each nutritional therapy on the gut microbiome and summarize the strength of the literature with recommendations for the practicing clinician.

Reduction of Central Line-Associated Bloodstream Infections and Line Occlusions in Pediatric Intestinal Failure Patients Receiving Long-Term Parenteral Nutrition Using an Alternative Locking Solution, 4% Tetrasodium Ethylenediaminetetraacetic Acid.

BACKGROUND: Patients with intestinal failure (IF) are dependent on parenteral nutrition (PN), however, they are at risk of central line-associated bloodstream infections (CLABSIs) and line complications. Four-percent tetrasodium ethylenediaminetetraacetic acid (EDTA) solution is an effective nonantibiotic, antimicrobial, antibiofilm, and anticoagulant agent. Our objective was to determine 4% tetrasodium EDTA efficacy in preventing CLABSIs and reducing line occlusions in pediatric IF patients. METHODS: We conducted a retrospective cohort study of patients managed at 2 tertiary Canadian pediatric centers between April 2016 and December 2018 who received 4% tetrasodium EDTA solution under the brand name Kitelock. Data were collected for 12 months pre and post-Kitelock. CLABSIs and alteplase administration were compared using a Wilcoxon matched-pairs signed-rank test. Data were reported as medians and frequencies. RESULTS: Twenty patients were included (10 boys; median age, 83 months [range, 8-232 months]). The rate of CLABSIs before 4% tetrasodium EDTA was 2.7+4 per 1000 catheter days. Patients received 4% tetrasodium EDTA for a median of 365 (278-365) days, with no infections in the 12 months post-therapy (P = .002). Median rates of occlusive episodes for the entire cohort before 4% tetrasodium EDTA were 0 (0-5.0) and 0 (0-2.0) after starting therapy (P = .018). In patients with previous occlusions (n = 9), the median episodes of alteplase use previously was 5.5 (2.7-19.2) compared with 2.7 (0-2.7) (P = .018). CONCLUSIONS: Our preliminary findings suggest 4% tetrasodium EDTA solution is effective in reducing CLABSIs and catheter occlusions in pediatric patients with long-term central-access.

Lyophilized fecal short-chain fatty acid and electrolyte determination by capillary electrophoresis with indirect UV detection for assessment of pediatric inflammatory bowel disease.

Short-chain fatty acids (SCFAs) and electrolytes are major constituents of human feces involved in maintaining gastrointestinal homeostasis that underlie complex diet, host and microbiome interactions. Reliable quantification of SCFAs and electrolytes is challenging given the heterogeneity of stool specimens from pediatric patients with diarrhea-predominate inflammatory bowel disease (IBD). Herein, we introduce two validated methods for determination of 3 SCFAs and 5 electrolytes consistently quantified from fecal extracts when using capillary electrophoresis with indirect UV detection (CE-iUV), where concentrations are normalized to total dried weight (mmol/kg d.w.). Lyophilization facilitates sample handling and extraction of heterogeneous stool specimens (∼ 15 mg) from a cohort of children with Crohn's disease (CD, n = 12) and ulcerative colitis (UC, n = 10) treated with exclusive enteral nutrition (EEN) or corticosteroid (CS) therapy to induce remission, respectively. Good technical precision (mean CV = 13 %, n = 14) and accuracy (recovery from 84 to 116%) is demonstrated for SCFAs and electrolytes from freeze dried stool extracts using a modified Bligh-Dyer protocol with low micromolar detection limits (∼ 2-15 µM). Fecal butyrate is 2.6-fold higher in CD as compared to UC patients (effect size = 1.51; p = 0.00291), and there is a strong co-linearity between fecal butyrate and acetate (r = 0.835) unlike propionate, which is correlated with fecal calprotectin (r = 0.517), a protein biomarker of intestinal inflammation. Also, a longitudinal study of matching stool samples collected from a sub-set of IBD patients revealed about a 7-fold enrichment in magnesium and calcium following 4 weeks of EEN as compared to baseline (F > 4.1 ; p < 0.05) unlike the CS treatment arm with no changes in other fecal SCFAs and electrolytes, including sodium, potassium, and ammonium. CE-iUV enables rapid fecal SCFA and electrolyte determination as required for new insights into the role of gut dysbiosis in IBD, as well as treatment monitoring of nutritional interventions that stabilize the disease course in affected children.

Pediatric Patient and Parent Perceptions of Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis.

BACKGROUND: Fecal microbiota transplantation (FMT) has gained attention for its role in the treatment of ulcerative colitis (UC). Acceptance of this treatment, particularly among children and their parents, is an important aspect of assessing its feasibility for pediatric inflammatory bowel disease care. To date, no studies have assessed FMT acceptance among pediatric patients who underwent FMT treatment. Here, we explored the perceptions and experiences of FMT in a population of pediatric UC patients who participated in a recent FMT pilot randomized controlled trial. METHODS: Children who received bi-weekly FMT treatments for 6 weeks through a clinical trial (NCT02606032) and their parents participated in face-to-face, semi-structured interviews led by study investigators. Interviews were audiotaped, transcribed, and analyzed using validated qualitative research methods. RESULTS: Eight patients and eight parents were interviewed, with qualitative data summarized across four themes and 11 subthemes. The majority of participants perceived FMT as a "natural treatment" and cited lack of response to conventional medications and fear of medication side-effects as motivators for pursuing FMT. Pre-treatment, patients and parents expressed concerns regarding physical discomfort with FMT administration; post-treatment, most patients reported feeling "completely normal." Both patients and parents uniformly expressed interest in pursuing FMT again in the future if available. Convenience of medication therapies, and perceived naturality and efficacy of FMT were all endorsed. CONCLUSIONS: This is the first study to describe pediatric and parent experiences receiving FMT. This information is valuable to develop and encourage future FMT trials involving children. Pre-treatment, concerns about FMT were common. Post-treatment, patients reported tolerance to FMT and a desire to continue receiving this therapy if available. Further trials of FMT in UC are needed. Investigators should include pediatric patients without concern of acceptance.

Influence of bacterial components on the developmental programming of enteric neurons.

BACKGROUND: Intestinal bacteria have been increasingly shown to be involved in early postnatal development. Previous work has shown that intestinal bacteria are necessary for the structural development and intrinsic function of the enteric nervous system in early postnatal life. Furthermore, colonization with a limited number of bacteria appears to be sufficient for the formation of a normal enteric nervous system. We tested the hypothesis that common bacterial components could influence the programming of developing enteric neurons. METHODS: The developmental programming of enteric neurons was studied by isolating enteric neural crest-derived cells from the fetal gut of C57Bl/6 mice at embryonic day 15.5. After the establishment of the cell line, cultured enteric neuronal precursors were exposed to increasing concentrations of a panel of bacterial components including lipopolysaccharide, flagellin, and components of peptidoglycan. KEY RESULT: Exposure to bacterial components consistently affected proportions of enteric neuronal precursors that developed into nitrergic neurons. Furthermore, flagellin and D-gamma-Glu-mDAP were found to promote the development of serotonergic neurons. Proportions of dopaminergic neurons remained unchanged. Proliferation of neuronal precursor cells was significantly increased upon exposure to lipopolysaccharide and flagellin, while no significant changes were observed in the proportion of apoptotic neuronal precursors compared to baseline with exposure to any bacterial component. CONCLUSIONS AND INTERFACES: These findings suggest that bacterial components may influence the development of enteric neurons.

Effect of Exclusive Enteral Nutrition and Corticosteroid Induction Therapy on the Gut Microbiota of Pediatric Patients with Inflammatory Bowel Disease.

INTRODUCTION: Exclusive enteral nutrition (EEN) and corticosteroids (CS) are effective induction therapies for pediatric Crohn's Disease (CD). CS are also therapy for ulcerative colitis (UC). Host-microbe interactions may be able to explain the effectiveness of these treatments. This is the first prospective study to longitudinally characterize compositional changes in the bacterial community structure of pediatric UC and CD patients receiving EEN or CS induction therapy. METHODS: Patients with diagnoses of CD or UC were recruited from McMaster Children's Hospital (Hamilton, Canada). Fecal samples were collected from participants aged 5-18 years old undergoing 8 weeks of induction therapy with EEN or CS. Fecal samples were submitted for 16S rRNA sequencing. The Shannon diversity index and the relative abundance of specific bacterial taxa were compared using a linear mixed model. RESULTS: The clustering of microbiota was the highest between patients who achieved remission compared to patients still showing active disease (p = 0.029); this effect was independent of the diagnosis or treatment type. All patients showed a significant increase in Shannon diversity over the 8 weeks of treatment. By week 2, a significant difference was seen in Shannon diversity between patients who would go on to achieve remission and those who would not. CONCLUSION: The gut microbiota of pediatric UC and CD patients was most influenced by patients' success or failure to achieve remission and was largely independent of the choice of treatment or disease type. Significant differences in Shannon diversity indices occurred as early as week 2 between patients who went on to achieve remission and those who continued to have active disease.