Vasoactive intestinal peptide promotes host defense against enteric pathogens by modulating the recruitment of group 3 innate lymphoid cells.

Group 3 innate lymphoid cells (ILC3s) control the formation of intestinal lymphoid tissues and play key roles in intestinal defense. They express neuropeptide vasoactive intestinal peptide (VIP) receptor 2 (VPAC2), through which VIP modulates their function, but whether VIP exerts other effects on ILC3 remains unclear. We show that VIP promotes ILC3 recruitment to the intestine through VPAC1 independent of the microbiota or adaptive immunity. VIP is also required for postnatal formation of lymphoid tissues as well as the maintenance of local populations of retinoic acid (RA)-producing dendritic cells, with RA up-regulating gut-homing receptor CCR9 expression by ILC3s. Correspondingly, mice deficient in VIP or VPAC1 suffer a paucity of intestinal ILC3s along with impaired production of the cytokine IL-22, rendering them highly susceptible to the enteric pathogen Citrobacter rodentium This heightened susceptibility to C. rodentium infection was ameliorated by RA supplementation, adoptive transfer of ILC3s, or by recombinant IL-22. Thus, VIP regulates the recruitment of intestinal ILC3s and formation of postnatal intestinal lymphoid tissues, offering protection against enteric pathogens.

Allied Health Professional Support in Pediatric Inflammatory Bowel Disease: A Survey from the Canadian Children Inflammatory Bowel Disease Network-A Joint Partnership of CIHR and the CH.I.L.D. Foundation.

OBJECTIVES: The current number of healthcare providers (HCP) caring for children with inflammatory bowel disease (IBD) across Canadian tertiary-care centres is underinvestigated. The aim of this survey was to assess the number of healthcare providers (HCP) in ambulatory pediatric IBD care across Canadian tertiary-care centres. METHODS: Using a self-administered questionnaire, we examined available resources in academic pediatric centres within the Canadian Children IBD Network. The survey evaluated the number of HCP providing ambulatory care for children with IBD. RESULTS: All 12 tertiary pediatric gastroenterology centres participating in the network responded. Median full-time equivalent (FTE) of allied health professionals providing IBD care at each site was 1.0 (interquartile range (IQR) 0.6-1.0) nurse, 0.5 (IQR 0.2-0.8) dietitian, 0.3 (IQR 0.2-0.8) social worker, and 0.1 (IQR 0.02-0.3) clinical psychologists. The ratio of IBD patients to IBD physicians was 114 : 1 (range 31 : 1-537 : 1), patients to nurses/physician assistants 324 : 1 (range 150 : 1-900 : 1), dieticians 670 : 1 (range 250 : 1-4500 : 1), social workers 1558 : 1 (range 250 : 1-16000 : 1), and clinical psychologists 2910 : 1 (range 626 : 1-3200 : 1). CONCLUSIONS: There was a wide variation in HCP support among Canadian centres. Future work will examine variation in care including patients' outcomes and satisfaction across Canadian centres.

Milk Fat Globule Membrane Supplementation in Formula Modulates the Neonatal Gut Microbiome and Normalizes Intestinal Development.

Breast milk has many beneficial properties and unusual characteristics including a unique fat component, termed milk fat globule membrane (MFGM). While breast milk yields important developmental benefits, there are situations where it is unavailable resulting in a need for formula feeding. Most formulas do not contain MFGM, but derive their lipids from vegetable sources, which differ greatly in size and composition. Here we tested the effects of MFGM supplementation on intestinal development and the microbiome as well as its potential to protect against Clostridium difficile induced colitis. The pup-in-a-cup model was used to deliver either control or MFGM supplemented formula to rats from 5 to 15 days of age; with mother's milk (MM) reared animals used as controls. While CTL formula yielded significant deficits in intestinal development as compared to MM littermates, addition of MFGM to formula restored intestinal growth, Paneth and goblet cell numbers, and tight junction protein patterns to that of MM pups. Moreover, the gut microbiota of MFGM and MM pups displayed greater similarities than CTL, and proved protective against C. difficile toxin induced inflammation. Our study thus demonstrates that addition of MFGM to formula promotes development of the intestinal epithelium and microbiome and protects against inflammation.

25-Hydroxyvitamin D concentrations in children with Crohn's disease supplemented with either 2000 or 400 IU daily for 6 months: a randomized controlled study.

OBJECTIVES: To assess vitamin D status of pediatric patients with Crohn's disease (CD) and to compare their serum 25-hydroxyvitamin D (s-25OHD) with established cutoffs and assess whether 6 months of supplementation with 2000 IU/d, vs 400 IU/d, would reduce the group prevalence of vitamin D below these cutoffs. STUDY DESIGN: Subjects 8-18 years (n = 83) with quiescent CD were randomized to either 400 or 2000 IU vitamin D3/d for 6 months. RESULTS: Baseline mean ± SD s-25OHD was 24 ± 8 ng/mL; 13 subjects (16%) had an s-25OHD <16 ng/mL, 27 (33%) < 20 ng/mL, and 65 (79%) < 30 ng/mL. There was no significant difference between groups in achieving the cutoffs of 16 ng/mL or 20 ng/mL at 6 months; however, only 35% of the 400 IU group achieved the greater cutoff of 30 ng/mL compared with 74% in the 2000 IU group (P < .001). Baseline adjusted mean s-25OHD concentrations at 6 months were 9.6 ng/mL (95% CI 6.0-13.2, P < .001) greater in the 2000 IU than the 400 IU group. Disease activity was not affected by supplement dose. Few subjects exceeded safety marker cutoffs, and this did not differ by dose. CONCLUSIONS: At baseline, a high proportion of patients had a mean s-25OHD >20 ng/mL. 2000 IU vitamin D3/d is more effective in raising s-25OHD concentrations to > 30 ng/mL in children with CD than 400 IU/d, but both treatments were equally effective at achieving 16 or 20 ng/mL.

Dietary oils modify the host immune response and colonic tissue damage following Citrobacter rodentium infection in mice.

Inflammatory bowel disease is an intestinal inflammatory disorder of multifactorial origin, in which diets that favor high n-6 and low n-3 fatty acids have been implicated. The present study addressed whether dietary n-6 and n-3 fatty acids alter colonic mucosal response to Citrobacter rodentium (C. rodentium) infection. Mice were fed diets identical except for fatty acids, with an energy percentage of 15% 18:2n-6 and <0.06% 18:3n-3, 4.2% 18:2n-6 and 1.9% 18:3n-3, or 1.44% 20:5n-3, 4.9% 22:6n-3, 0.32% 18:2n-6, and 0.12% 18:3n-3 from safflower, canola, or fish oil, respectively for 3 wk before infection. Dietary oils had no effect on colonic C. rodentium growth but altered colon 20:4n-6/(20:5n-3+22:6n-3) with 9.40 ± 0.06, 1.94 ± 0.08, and 0.32 ± 0.03% in colon phosphatidylcholine and 3.82 ± 0.18, 1.14 ± 0.02, and 0.30 ± 0.02% in phosphatidylethanolamine of mice fed safflower, canola, or fish oil, respectively. At 10 days postinfection, histological damage, F4/80-positive macrophages, and myeloperoxidase-positive neutrophils in colonic mucosa were higher in infected mice fed safflower than fish oil. Colon gene transcripts for macrophage inflammatory protein 2, keratinocyte cytokine, and monocyte chemoattractant protein 1 expression were significantly higher in infected mice fed safflower than canola or fish oil; IFN-γ, IL-6, and IL-17A expression were significantly elevated in mice fed safflower rather than fish oil; and IL-10 was significantly higher in mice fed fish oil rather than canola or safflower oil. This study demonstrates that oils high in 18:2n-6 with minimal n-3 fatty acids exacerbate mucosal immune response, whereas oils high in n-3 fatty acids attenuate mucosal immune response to C. rodentium. These studies implicate dietary oils as environmental modifiers of intestinal inflammation in response to infection.

The effect of dietary oils on cecal microflora in experimental colitis in mice.

OBJECTIVES: In spite of growing evidence indicating the benefits of probiotics, the effects of different dietary oils on intestinal microflora and probiotics have not been elucidated. This study aimed to examine the effects of different dietary oils on intestinal microflora in an experimental model of colitis. METHODS: Eight-week mice were fed isocaloric diets varying only in fat composition for 4 weeks. The oils used were fish oil, canola oil, safflower oil, and chow diet containing beef tallow. Colitis was induced by intracolonic administration of acetic acid on day 21. The inflammation and fecal microflora and serum lipid profiles were evaluated 1 week after induction. RESULTS: Inflammation was highest in the chow diet group followed by safflower, canola, and fish oil fed groups, respectively. The number of fecal bacteroideceae was greater, whereas the number of fecal bifidobacteria was lower in mice fed beef tallow than the other ones. In addition, fish oil reduced the plasma level of triacylglycerole significantly. CONCLUSION: Polyunsaturated fatty acids (PUFAs) can affect intestinal microflora increasing the number of probiotics. PUFAs might be recommended in addition to probiotics for the prevention and/or maintenance treatment of colitis.

Dietary lipids in early development and intestinal inflammatory disease.

Inflammatory bowel diseases are life-long reoccurring inflammatory disorders of the gastrointestinal tract and have been increasing in incidence in recent decades, notably in the pediatric population. Although genetic predisposition remains an important factor, this increased incidence most likely reflects an environmental change. One potential contributor to this is the change in dietary fat intake, with dietary intake of n-6 polyunsaturated fatty acids (PUFAs) following a similar temporal pattern to the change in inflammatory bowel disease incidence. Dietary n-6 PUFAs comprise a major, modifiable, environmental factor known to promote a heightened inflammatory response through a number of pathways, including their role as precursors for synthesis of eicosanoids and their inhibitory effect on the synthesis of the n-3 PUFAs eicosapentanoic acid and docosahexanoic acid. The increase in n-6 PUFA intake affects individuals of all ages, with fetal PUFA accretion and infant dietary PUFA intake from breast milk reflecting maternal dietary intake. A high level of n-6 PUFA in milk results in increased n-6 PUFA in colonic phospholipids and an exaggerated inflammatory response to chemically induced colitis. Conversely, during development, a diet low in n-6 PUFAs and high in n-3 PUFAs increases colonic n-3 fatty acids, attenuates the inflammatory response, and lowers colonic damage. High dietary n-6 PUFA intake may be an important environmental modifier that contributes to inflammatory bowel diseases.

A randomized trial of yoga for adolescents with irritable bowel syndrome.

BACKGROUND: Adolescents with irritable bowel syndrome (IBS) frequently experience interference with everyday activities. Mind-body approaches such as yoga have been recommended as interventions for patients with IBS. Despite promising results among adult samples, there have been limited studies exploring the efficacy of yoga with pediatric patients. OBJECTIVE: To conduct a preliminary randomized study of yoga as treatment for adolescents with IBS. METHODS: Twenty-five adolescents aged 11 to 18 years with IBS were randomly assigned to either a yoga or wait list control group. Before the intervention, both groups completed questionnaires assessing gastrointestinal symptoms, pain, functional disability, coping, anxiety and depression. The yoga intervention consisted of a 1 h instructional session, demonstration and practice, followed by four weeks of daily home practice guided by a video. After four weeks, adolescents repeated the baseline questionnaires. The wait list control group then received the yoga intervention and four weeks later completed an additional set of questionnaires. RESULTS: Adolescents in the yoga group reported lower levels of functional disability, less use of emotion-focused avoidance and lower anxiety following the intervention than adolescents in the control group. When the pre- and postintervention data for the two groups were combined, adolescents had significantly lower scores for gastrointestinal symptoms and emotion-focused avoidance following the yoga intervention. Adolescents found the yoga to be helpful and indicated they would continue to use it to manage their IBS. CONCLUSIONS: Yoga holds promise as an intervention for adolescents with IBS.

Comparison of multidetector CT and barium studies of the small bowel: inflammatory bowel disease in children.

OBJECTIVE: We compared barium studies of the small bowel with multidetector CT (MDCT) in the evaluation of the small bowel during the initial presentation of inflammatory bowel disease in a pediatric population. SUBJECTS AND METHODS: This was a prospective study. Eighteen children undergoing workup for inflammatory bowel disease underwent MDCT, colonoscopy, and barium studies of the small bowel before commencement of therapy. Examinations were independently reviewed. The patients and their guardians completed a questionnaire assessing the acceptability of each study. RESULTS: In 13 of 18 children, the findings of MDCT and barium studies of the small bowel concurred in the evaluation of terminal ileum disease. In three of these children, MDCT detected skip segments of small-bowel disease not detected on barium studies of the small bowel. In two of 18 children, the terminal ileum was not visualized on barium studies of the small bowel, whereas MDCT showed substantial terminal ileum disease in both children. In three of 18 children, there was discordance between the two tests regarding terminal ileum disease. However, these discordant imaging findings were all subtle. In addition, MDCT revealed extraenteric abnormalities, clinically relevant in two children (ureteric obstruction and perirectal abscess), and showed the colon in all children, seven of whom had incomplete colonoscopy. The questionnaire revealed that 16 of 18 patients preferred MDCT to small-bowel barium studies. The reasons given were poor tolerance of oral barium and the long duration of barium studies of the small bowel. CONCLUSION: MDCT can be an alternative to barium studies of the small bowel for evaluation of the small bowel in patients with inflammatory bowel disease. MDCT also offers additional, clinically relevant information not obtained by small-bowel barium studies.