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      The influence of a short-term gluten-free diet on the human gut microbiome

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          Abstract

          Background

          A gluten-free diet (GFD) is the most commonly adopted special diet worldwide. It is an effective treatment for coeliac disease and is also often followed by individuals to alleviate gastrointestinal complaints. It is known there is an important link between diet and the gut microbiome, but it is largely unknown how a switch to a GFD affects the human gut microbiome.

          Methods

          We studied changes in the gut microbiomes of 21 healthy volunteers who followed a GFD for four weeks. We collected nine stool samples from each participant: one at baseline, four during the GFD period, and four when they returned to their habitual diet (HD), making a total of 189 samples. We determined microbiome profiles using 16S rRNA sequencing and then processed the samples for taxonomic and imputed functional composition. Additionally, in all 189 samples, six gut health-related biomarkers were measured.

          Results

          Inter-individual variation in the gut microbiota remained stable during this short-term GFD intervention. A number of taxon-specific differences were seen during the GFD: the most striking shift was seen for the family Veillonellaceae (class Clostridia), which was significantly reduced during the intervention ( p = 2.81 × 10 −05). Seven other taxa also showed significant changes; the majority of them are known to play a role in starch metabolism. We saw stronger differences in pathway activities: 21 predicted pathway activity scores showed significant association to the change in diet. We observed strong relations between the predicted activity of pathways and biomarker measurements.

          Conclusions

          A GFD changes the gut microbiome composition and alters the activity of microbial pathways.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13073-016-0295-y) contains supplementary material, which is available to authorized users.

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          Most cited references24

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          Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature.

          Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches.
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            A peptide antibiotic from human skin.

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              Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders

              Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a “re-discovered” disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS.
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                Author and article information

                Contributors
                bonder.m.j@gmail.com
                e.f.feenstra@gmail.com
                cxh.bupt@gmail.com
                gosia.trynka@gmail.com
                mccenit81@gmail.com
                barbarahrdlickova@gmail.com
                zhonghuanzi@genomics.cn
                vatanen@broadinstitute.org
                dirk.gevers@gmail.com
                cisca.wijmenga@gmail.com
                yangwang.bgi@gmail.com
                +31-50-3617100 , sashazhernakova@gmail.com
                Journal
                Genome Med
                Genome Med
                Genome Medicine
                BioMed Central (London )
                1756-994X
                21 April 2016
                21 April 2016
                2016
                : 8
                : 45
                Affiliations
                [ ]Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
                [ ]Top Institute Food and Nutrition, Wageningen, The Netherlands
                [ ]BGI, Shenzhen, 518083 China
                [ ]Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA UK
                [ ]Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA
                [ ]Department of Computer Science, Aalto University School of Science, Espoo, 02150 Finland
                Article
                295
                10.1186/s13073-016-0295-y
                4841035
                27102333
                0a0165a5-4b6e-4b3c-9035-db1fdbd0d895
                © Bonder et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 29 October 2015
                : 5 April 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000781, European Research Council;
                Award ID: FP/2007–2013/ERC grant 2012-322698
                Award Recipient :
                Funded by: Top Institute Food and Nutrition Wageningen
                Award ID: GH001
                Award Recipient :
                Funded by: Rosalind Franklin Fellowship from the University of Groningen
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Molecular medicine
                microbiome,gluten-free diet,biomarker,observation study
                Molecular medicine
                microbiome, gluten-free diet, biomarker, observation study

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