and PV Desmond have no conflicts of interest to declare. P De Cruz has received travel grant support from Abbott and Schering-Plough. MA Kamm has acted as an advisor to Abbott and Janssen, has received research support from Abbott, and has acted as a speaker at symposiums sponsored by Abbott and Janssen. A Hamilton has received an educational grant from Abbott. D Liew has served on advisory boards and received research grants from Abbott. IC Lawrance has been on an advisory board for Abbott and Janssen, a speaker for Abbott and Janssen, and has held research and travel grants from Abbott and Janssen. JM Andrews has been an advisory board member for both Janssen and Abbott, spoken for both Abbott and Janssen, received research funds from both Abbott and Janssen, and received travel grants from both Abbott and Janssen. PA Bampton has been on advisory boards for Janssen and Abbott, has received research funding from Abbott, and travel sponsorship from both Abbott and Janssen. PR Gibson has received consulting fees from Abbott, Janssen, and Schering-Plough; research support from Abbott; and payments for lectures from Abbott and Janssen. FA Macrae has been on an advisory board to Janssen, has received travel grants from Abbott, and has received clinical research support from Janssen, Abbott and MSD. W Selby has been on an advisory board for Abbott. SJ Bell has received travel assistance from Abbott. SJ Brown has received travel support and speaker fees from both Abbott and Janssen. WR Connell has been on advisory board for Janssen and a speaker for Abbott and Janssen. AS Day has been an M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT advisor to Janssen. RB Gearry has been on an advisory board for Abbott and Janssen, a speaker for Abbott and Janssen, and held research, educational and travel grants from Abbott and Janssen.
Cystic fibrosis (CF) is a genetic disorder that leads to formation of thick epithelial secretions in affected organs. Chronic microbial infections associated with thick mucus secretions are the hallmarks of lung disease in CF. Despite similar conditions existing in the gastrointestinal tract, it is much less studied. We therefore examined the microbial communities within the gastrointestinal tract of children with and without CF (either pancreatic sufficient or insufficient) across a range of childhood ages (0.87–17 years). We observed a substantial reduction in the richness and diversity of gut bacteria associated with CF from early childhood (2 years) until late adolescence (17 years). A number of bacteria that establish themselves in the gut of healthy children were unable to do so in children with CF. In contrast, a few bacteria dominated the gut microbiota in children with CF and are unlikely to be beneficial for the metabolic function of the gut. A functioning pancreas (pancreatic sufficient) under a CF lifestyle showed little effect on microbial communities. Our results argue that any attempts to rectify the loss of bacterial diversity and provide normal bacterial function in the gut of CF patients should be conducted no later than early childhood.
Objectives:Exclusive enteral nutrition (EEN) is commonly used to treat pediatric Crohn's disease (CD). Meta-analysis of pediatric studies that have compared the effect of EEN with other treatments have shown that EEN induces remission in up to 80–85% of patients. We aimed to gain a comprehensive understanding of the effect of EEN on the microbiota of CD patients.Methods:We used 16S rRNA gene and whole-genome high throughout sequencing to determine changes in the fecal microbiota of five CD children, before, during, and after EEN therapy and compared this with five healthy controls.Results:The microbial diversity observed in CD patients tended to be lower than that in controls (CD: 2.25±0.24, controls: 2.75±0.14, P=0.11). In all CD patients, dysbiosis was observed prior to therapy. EEN therapy had a positive effect in all patients, with 80% going into remission. In some patients, the positive effect diminished following the conclusion of EEN therapy. Significantly, the number of operational taxonomic units (OTU) decreased dramatically upon starting EEN and this corresponded with CD remission. Recurrence of CD corresponded with an increase in OTUs. Six families within the Firmicutes were found to correlate with disease activity during and following EEN therapy, a finding that was confirmed by whole-genome high throughput sequencing.Conclusions:Our results demonstrate that EEN leads to common and patient-specific alterations in the microbiota of CD patients, a number of which correlate with disease activity.
The pattern of intestinal inflammation in CF is unique and distinct from inflammatory bowel disease, with elevated faecal calprotectin but normal faecal S100A12 and osteoprotegerin concentrations. The severity of intestinal inflammation, based on faecal calprotectin, significantly correlates with poor growth.
Immune cells not only affect tissue homeostasis at the site of inflammation but also exert systemic effects contributing to multiple chronic conditions. Recent evidence clearly supports an altered T helper 17/regulatory T cell (Th17/Treg) balance leading to the development and progression of inflammatory diseases that not only affect the gastrointestinal tract but also have whole-body manifestations, including insulin resistance. Epigenetic mechanisms are amenable to both environmental and circulating factors and contribute to determining the T cell landscape. The recently identified participation of the gut microbiota in the remodeling of the epigenome of immune cells has triggered a paradigm shift in our understanding of the etiology of various inflammatory diseases and opened new paths toward therapeutic strategies. In this review, we provide an overview of the contribution of the Th17/Treg balance in the development and progression of inflammatory bowel diseases and metabolic diseases. We discuss the involvement of epigenetic mechanisms in the regulation of T cell function in the particular context of dysbiosis. Finally, we examine the potential for nutritional interventions affecting the gut microbiota to reshape the T cell epigenome and address the inflammatory component of various diseases.
Poor growth and inability to manage age-appropriate textures are often present in children with EA, particularly in the younger years. This highlights the need for early intervention in a specialist multidisciplinary EA clinic in which dietetics and speech pathology are available.
Over the last two decades, knowledge on fecal biomarkers has substantially increased. Nowadays, these non-invasive markers of inflammation have significant clinical utility in the management of inflammatory bowel disease. Their use informs the decision to perform endoscopy before diagnosis is made right through to influencing therapeutic choices and the need for interval endoscopic assessment. In this review, the roles of two S100 proteins, calprotectin, and S100A12 are described along with that of lactoferrin, in the context of inflammatory bowel disease.
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