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      The Intestinal Microbiota in Acute Anorexia Nervosa and During Renourishment: Relationship to Depression, Anxiety, and Eating Disorder Psychopathology

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          Abstract

          Objective

          The relevance of the microbe-gut-brain axis to psychopathology is of interest in anorexia nervosa (AN), as the intestinal microbiota plays a critical role in metabolic function and weight regulation.

          Methods

          We characterized the composition and diversity of the intestinal microbiota in AN, using stool samples collected at inpatient admission (T1) (n=16) and discharge (T2) (n=10). At T1, participants completed the Beck Depression and Anxiety Inventories and the Eating Disorder Examination-Questionnaire. Patients with AN were compared to healthy individuals who participated in a previous study (healthy comparison group; HCG). Genomic DNA was isolated from stool samples, and bacterial composition was characterized by 454 pyrosequencing of the 16S rRNA gene. Sequencing results were processed by the Quantitative Insights Into Microbial Ecology pipeline. We compared T1 vs. T2 samples, samples from both points were compared to HCG (n=12), and associations between psychopathology and T1 samples were explored.

          Results

          In patients with AN, significant changes emerged between T1 and T2 in taxa abundance and beta (between-sample) diversity. Patients with AN had significantly lower alpha (within-sample) diversity than HCG at both T1 (p=0.0001) and T2 (p=0.016), and differences in taxa abundance were found between AN patients and HCG. Levels of depression, anxiety, and eating disorder psychopathology at T1 were associated with composition and diversity of the intestinal microbiota.

          Conclusions

          We provide evidence of intestinal dysbiosis in AN and an association between mood and the enteric microbiota in this patient population. Future directions include mechanistic investigations of the microbe-gut-brain axis in animal models and association of microbial measures with metabolic changes and recovery indices.

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          Most cited references39

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          Error-correcting barcoded primers for pyrosequencing hundreds of samples in multiplex.

          We constructed error-correcting DNA barcodes that allow one run of a massively parallel pyrosequencer to process up to 1,544 samples simultaneously. Using these barcodes we processed bacterial 16S rRNA gene sequences representing microbial communities in 286 environmental samples, corrected 92% of sample assignment errors, and thus characterized nearly as many 16S rRNA genes as have been sequenced to date by Sanger sequencing.
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            Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression.

            The concept that intestinal microbial composition not only affects the health of the gut, but also influences centrally-mediated systems involved in mood, is supported by a growing body of literature. Despite the emergent interest in brain-gut communication and its possible role in the pathogenesis of psychiatric disorders such as depression, particularly subtypes with accompanying gastrointestinal (GI) symptoms, there are few studies dedicated to the search for therapeutic solutions that address both central and peripheral facets of these illnesses. This study aims to assess the potential benefits of the probiotic Bifidobacterium infantis in the rat maternal separation (MS) model, a paradigm that has proven to be of value in the study of stress-related GI and mood disorders. MS adult rat offsprings were chronically treated with bifidobacteria or citalopram and subjected to the forced swim test (FST) to assess motivational state. Cytokine concentrations in stimulated whole blood samples, monoamine levels in the brain, and central and peripheral hypothalamic-pituitary-adrenal (HPA) axis measures were also analysed. MS reduced swim behavior and increased immobility in the FST, decreased noradrenaline (NA) content in the brain, and enhanced peripheral interleukin (IL)-6 release and amygdala corticotrophin-releasing factor mRNA levels. Probiotic treatment resulted in normalization of the immune response, reversal of behavioral deficits, and restoration of basal NA concentrations in the brainstem. These findings point to a more influential role for bifidobacteria in neural function, and suggest that probiotics may have broader therapeutic applications than previously considered. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
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              The core gut microbiome, energy balance and obesity.

              Metagenomics is an emerging field focused on characterizing the structures, functions and dynamic operations of microbial communities sampled in their native habitats without the need for culture. Here, we present findings from a 16S rRNA gene sequence- and whole community DNA shotgun sequencing-based analysis of the adult human gut microbiomes of lean and obese mono- and dizygotic twins. Our findings indicate that a core microbiome can be found at the gene level, despite large variation in community membership, and that variations from the core are associated with obesity. These findings have implications for ongoing Human Microbiome Project(s), and highlight important challenges to the field of metagenomics.
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                Author and article information

                Journal
                0376505
                6793
                Psychosom Med
                Psychosom Med
                Psychosomatic medicine
                0033-3174
                1534-7796
                23 August 2015
                Nov-Dec 2015
                01 November 2016
                : 77
                : 9
                : 969-981
                Affiliations
                [1 ]Department of Nutrition, the University of North Carolina at Chapel Hill, United States
                [2 ]Department of Psychiatry, the University of North Carolina at Chapel Hill, United States
                [3 ]Eating Disorders Program, Child and Adolescent Health Service, Department of Health in Western Australia, Australia
                [4 ]School of Psychology and Speech Pathology, Curtin University, Australia
                [5 ]School of Paediatrics and Child Health, The University of Western Australia, Australia
                [6 ]Kenyon College, United States
                [7 ]Department of Medicine, the University of North Carolina at Chapel Hill, United States
                [8 ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
                Author notes
                Corresponding author: Dr. Ian M. Carroll, University of North Carolina at Chapel Hill, 111 Mason Farm Road, CB #7032, 7340 MBRB Building, Chapel Hill, NC 27599-7032, Voice: (919) 843-4893, Fax: (919) 843-8000, ian_carroll@ 123456med.unc.edu
                Article
                PMC4643361 PMC4643361 4643361 nihpa717099
                10.1097/PSY.0000000000000247
                4643361
                26428446
                71f42b3e-3e33-4d20-b7e5-61e5725c850d
                History
                Categories
                Article

                anxiety,eating disorders,anorexia nervosa,intestinal microbiota,gut-brain axis,depression

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