From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling

Designing Simulation-Based Training for Prehospital Emergency Care : Participation from a Participants Perspective

Simulation-based training for prehospital emergency care is characterized by high degrees of complexity. Thorough knowledge of both the work and the setting is crucial and it is therefore important to involve both end-users and other stakeholders during the whole design process. This paper investigates a design process by focusing on how project participants experience the work process and participation of a multi-disciplinary, research-practitioner design team. This case study focuses on the work within a development project of a new prehospital emergency training facility. Open-ended interviews were conducted with the project participants halfway through the project. Strikingly, the results show that while there are problems and tensions that potentially could overturn the project, all participants express strong satisfaction with their participation in the project. This implies that the accumulated positive experiences are so strong that they overshadow tensions and problems that under other circumstances could have caused a project breakdown.Simulation, Ambulance, Research, Education, Kinship (SAREK

Fecal microbiota profiles in treatment-naïve pediatric inflammatory bowel disease – associations with disease phenotype, treatment, and outcome

Purpose: Imbalance in the microbiota, dysbiosis, has been identified in inflammatory bowel disease (IBD). We explored the fecal microbiota in pediatric patients with treatment-naïve IBD, non-IBD patients with gastrointestinal symptoms and healthy children, its relation to IBD subgroups, and treatment outcomes. Patients and methods: Fecal samples were collected from 235 children below 18 years of age. Eighty children had Crohn’s disease (CD), 27 ulcerative colitis (UC), 3 IBD unclassified, 50 were non-IBD symptomatic patients, and 75 were healthy. The bacterial abundance of 54 predefined DNA markers was measured with a 16S rRNA DNA-based test using GA-Map ™ technology at diagnosis and after therapy in IBD patients. Results: Bacterial abundance was similarly reduced in IBD and non-IBD patients in 51 of 54 markers compared to healthy patients (P&lt;0.001). Only Prevotella was more abundant in patients (P&lt;0.01). IBD patients with ileocolitis or total colitis had more Ruminococcus gnavus (P=0.02) than patients with colonic CD or left-sided UC. CD patients with upper gastrointestinal manifestations had higher Veillonella abundance (P&lt;0.01). IBD patients (58%) who received biologic therapy had lower baseline Firmicutes and Mycoplasma hominis abundance (P&lt;0.01) than conventionally treated. High Proteobacteria abundance was associated with stricturing/penetrating CD, surgery (P&lt;0.01), and nonmucosal healing (P&lt;0.03). Low Faecalibacterium prausnitzii abundance was associated with prior antibiotic therapy (P=0.001), surgery (P=0.02), and nonmucosal healing (P&lt;0.03). After therapy, IBD patients had unchanged dysbiosis. Conclusion: Fecal microbiota profiles differentiated IBD and non-IBD symptomatic children from healthy children, but displayed similar dysbiosis in IBD and non-IBD symptomatic patients. Pretreatment fecal microbiota profiles may be of prognostic value and aid in treatment individu-alization in pediatric IBD as severe dysbiosis was associated with an extensive, complicated phenotype, biologic therapy, and nonmucosal healing. The dysbiosis persisted after therapy, regardless of treatments and mucosal healing.</p

Fecal microbiota profiles in treatment-na&iuml;ve pediatric inflammatory bowel disease &ndash; associations with disease phenotype, treatment, and outcome

Christine Olbj&oslash;rn,1,2 Milada Cvancarova Sm&aring;stuen,3 Espen Thiis-Evensen,4 Britt Nakstad,1,2 Morten Harald Vatn,5 J&oslash;rgen Jahnsen,2,6 Petr Ricanek,2,6 Simen Vatn,2,6 Aina EF Moen,5 Tone M Tann&aelig;s,5 Jonas C Lindstr&oslash;m,7 Johan D S&ouml;derholm,8 Jonas Halfvarson,9 Fernando Gomoll&oacute;n,10 Christina Cas&eacute;n,11 Magdalena K Karlsson,11 Rahul Kalla,12 Alex T Adams,12,13 Jack Satsangi,12,13 G&oslash;ri Perminow14 1Department of Pediatric and Adolescent Medicine, Akershus University Hospital, L&oslash;renskog, Norway; 2Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway; 3Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway; 4Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; 5Department of Clinical Molecular Biology (EpiGen), Division of Medicine, Akershus University Hospital, L&oslash;renskog, and University of Oslo, Oslo, Norway; 6Department of Gastroenterology, Akerhus University Hospital, L&oslash;renskog, Norway; 7Institute of Clinical Medicine, University of Oslo, Health Services Research Unit, Akershus University Hospital, L&oslash;renskog, Norway; 8Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Link&ouml;ping University, Link&ouml;ping, Sweden; 9Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Link&ouml;ping University, Link&ouml;ping, Sweden; 10Digestive Diseases Unit, IIS Arag&oacute;n, Zaragoza, Spain; 11Genetic-Analysis AS, Oslo, Norway; 12Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK; 13Translational Gastroenterology Unit, Experimental Medicine Division, University of Oxford, Oxford, UK; 14Department of Pediatrics, Oslo University Hospital, Ullev&aring;l, Oslo, Norway Purpose: Imbalance in the microbiota, dysbiosis, has been identified in inflammatory bowel disease (IBD). We explored the fecal microbiota in pediatric patients with treatment-na&iuml;ve IBD, non-IBD patients with gastrointestinal symptoms and healthy children, its relation to IBD subgroups, and treatment outcomes.Patients and methods: Fecal samples were collected from 235 children below 18 years of age. Eighty children had Crohn&rsquo;s disease (CD), 27 ulcerative colitis (UC), 3 IBD unclassified, 50 were non-IBD symptomatic patients, and 75 were healthy. The bacterial abundance of 54 predefined DNA markers was measured with a 16S rRNA DNA-based test using GA-Map&trade; technology at diagnosis and after therapy in IBD patients.Results: Bacterial abundance was similarly reduced in IBD and non-IBD patients in 51 of 54 markers compared to healthy patients (P&lt;0.001). Only Prevotella was more abundant in patients (P&lt;0.01). IBD patients with ileocolitis or total colitis had more Ruminococcus gnavus (P=0.02) than patients with colonic CD or left-sided UC. CD patients with upper gastrointestinal manifestations had higher Veillonella abundance (P&lt;0.01). IBD patients (58%) who received biologic therapy had lower baseline Firmicutes and Mycoplasma hominis abundance (P&lt;0.01) than conventionally treated. High Proteobacteria abundance was associated with stricturing/penetrating CD, surgery (P&lt;0.01), and nonmucosal healing (P&lt;0.03). Low Faecalibacterium prausnitzii abundance was associated with prior antibiotic therapy (P=0.001), surgery (P=0.02), and nonmucosal healing (P&lt;0.03). After therapy, IBD patients had unchanged dysbiosis.Conclusion: Fecal microbiota profiles differentiated IBD and non-IBD symptomatic children from healthy children, but displayed similar dysbiosis in IBD and non-IBD symptomatic patients. Pretreatment fecal microbiota profiles may be of prognostic value and aid in treatment individualization in pediatric IBD as severe dysbiosis was associated with an extensive, complicated phenotype, biologic therapy, and nonmucosal healing. The dysbiosis persisted after therapy, regardless of treatments and mucosal healing. Keywords: dysbiosis, Crohn&rsquo;s disease, ulcerative colitis, Proteobacteria, biologic therapy, Faecalibacterium prausnitzi