Enteric Virome and Bacterial Microbiota in Children With Ulcerative Colitis and Crohn Disease.

OBJECTIVES: We examined the fecal virome and bacterial community composition of children with Crohn disease (CD), ulcerative colitis (UC), and healthy controls to test the hypothesis that unique patterns of viral organisms and/or presence of bacterial pathogens may be identified that could contribute to the pathogenesis of pediatric inflammatory bowel disease (IBD). METHODS: Fecal samples from 24 children (mean 12.2 years) with CD (n = 7) or UC (n = 5) and similar aged controls (n = 12) were processed to determine individual viromes. Viral sequences were identified through translated protein sequence similarity search. Bacterial microbiota were determined by sequencing of the V4 region of the 16S rRNA gene. RESULTS: Only a few human viruses were detected, so virome analyses focused on bacterial viruses. The relative abundance of Caudovirales was greater than that of Microviridae phages in both IBD and healthy controls. Caudovirales phages were more abundant in CD (mean 80.8%) than UC (48.8%) (P = 0.05) but not controls. The richness of viral strains in Microviridae but not Caudovirales was higher in controls than CD (P = 0.05) but not UC cases. No other measure of phage abundance, richness, or Shannon diversity showed significant difference between the 2 IBD and control groups. Bacterial microbiota analysis revealed that IBD diagnosis, albumin, hemoglobin, erythrocyte sedimentation rate, and probiotic supplementation correlated to the composition of gut bacterial microbiota. CONCLUSIONS: Minor patterns in gut virome and bacterial community composition distinguish pediatric IBD patients from healthy controls. Probiotics are associated with bacterial microbiota composition. These exploratory results need confirmation in larger studies.

De novo inflammatory bowel disease after pediatric kidney or liver transplant.

A subset of children who receive a liver and/or kidney transplant develop de novo inflammatory bowel disease-like chronic intestinal inflammation, not explained by infection or medications, following transplant. We have conducted a single-center, retrospective case series describing the unique clinical and histologic features of this IBD-like chronic intestinal inflammation following solid organ transplant. At our center, nine of 327 kidney or liver recipients developed de novo IBD following transplant (six liver, two kidney, one liver-kidney). Most children presented with prolonged hematochezia and diarrhea and were treated with aminosalicylates. At time of diagnosis, five were not currently using mycophenolate mofetil for transplant immunosuppression. Histologic and endoscopic findings at IBD diagnosis included inflammation, ulcerations, granulomas, and chronic colitis. Since diagnosis, no patients have required surgical intervention, or escalation to biologic therapy, nor developed stricturing or perianal disease. In this case series, de novo post-transplant IBD developed in 4% of pediatric liver and/or kidney recipients; however, it often does not fit the classic patterns of Crohn's disease or ulcerative colitis.

Addition of Histology to the Paris Classification of Pediatric Crohn Disease Alters Classification of Disease Location.

OBJECTIVES: The aim of the study was to investigate the value of microscopic findings in the classification of pediatric Crohn disease (CD) by determining whether classification of disease changes significantly with inclusion of histologic findings. METHODS: Sixty patients were randomly selected from a cohort of patients studied at the Pediatric Inflammatory Bowel Disease Clinic at the University of California, San Francisco Benioff Children's Hospital. Two physicians independently reviewed the electronic health records of the included patients to determine the Paris classification for each patient by adhering to present guidelines and then by including microscopic findings. RESULTS: Macroscopic and combined disease location classifications were discordant in 34 (56.6%), with no statistically significant differences between groups. Interobserver agreement was higher in the combined classification (κ = 0.73, 95% confidence interval 0.65-0.82) as opposed to when classification was limited to macroscopic findings (κ = 0.53, 95% confidence interval 0.40-0.58). When evaluating the proximal upper gastrointestinal tract (Paris L4a), the interobserver agreement was better in macroscopic compared with the combined classification. CONCLUSIONS: Disease extent classifications differed significantly when comparing isolated macroscopic findings (Paris classification) with the combined scheme that included microscopy. Further studies are needed to determine which scheme provides more accurate representation of disease extent.

Improved enteral tolerance following step procedure: systematic literature review and meta-analysis.

Surgical management of children with short bowel syndrome (SBS) changed with the introduction of the serial transverse enteroplasty procedure (STEP). We conducted a systematic review and meta-analysis using MEDLINE and SCOPUS to determine if children with SBS had improved enteral tolerance following STEP. Studies were included if information about a child's pre- and post-STEP enteral tolerance was provided. A random effects meta-analysis provided a summary estimate of the proportion of children with enteral tolerance increase following STEP. From 766 abstracts, seven case series involving 86 children were included. Mean percent tolerance of enteral nutrition improved from 35.1 to 69.5. Sixteen children had no enteral improvement following STEP. A summary estimate showed that 87 % (95 % CI 77-95 %) of children who underwent STEP had an increase in enteral tolerance. Compilation of the literature supports the belief that SBS subjects' enteral tolerance improves following STEP. Enteral nutritional tolerance is a measure of efficacy of STEP and should be presented as a primary or secondary outcome. By standardizing data collection on children undergoing STEP procedure, better determination of nutritional benefit from STEP can be ascertained.

Reanalysis of clinical exome identifies the second variant in two individuals with recessive disorders.

Clinical exome/genome sequencing is increasingly being utilized by clinicians to diagnose various likely genetic conditions, but many cases remain undiagnosed. In a subset of those undiagnosed cases, a single heterozygous variant in an autosomal recessive (AR) condition with consistent phenotype may be identified, raising the question if a second variant is missing. Here, we report two cases of recessive conditions in which only one heterozygous variant was initially reported by clinical exome sequencing, and on research reanalysis a second heterozygous variant in trans was identified. We performed a review of the existing exome reanalysis literature and found that this aspect is often not emphasized. These findings highlight the importance of data reanalysis in undiagnosed cases where only a single disease-associated variant is identified in an AR condition with a strong link to presenting phenotype.