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      Limited prolonged effects of rifaximin treatment on irritable bowel syndrome-related differences in the fecal microbiome and metabolome

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          ABSTRACT

          Irritable bowel syndrome (IBS) is a chronic functional disorder and its development may be linked, directly and indirectly, to intestinal dysbiosis. Here we investigated the interactions between IBS symptoms and the gut microbiome, including the relation to rifaximin (1200 mg daily; 11.2 g per a treatment). We recruited 72 patients, including 31 with IBS-D (diarrhea), 11 with IBS-C (constipation), and 30 with IBS-M (mixed constipation and diarrhea) and 30 healthy controls (HCs). Of them, 68%, 64%, and 53% patients with IBS-D, IBS-C, and IBS-M, respectively, achieved 10–12 week-term improvement after the rifaximin treatment. Stool samples were collected before and after the treatment, and fecal microbiotic profiles were analyzed by deep sequencing of 16S rRNA, while stool metabolic profiles were studied by hydrogen 1-nuclear magnetic resonance ( 1H-NMR) and gas chromatography–mass spectrometry (GC-MS). Of 26 identified phyla, only Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria were consistently found in all samples. Bacteroidetes was predominant in fecal samples from HCs and IBS-D and IBS-M subjects, whereas Firmicutes was predominant in samples from IBS-C subjects. Species richness, but not community diversity, differentiated all IBS patients from HCs. Metabolic fingerprinting, using NMR spectra, distinguished HCs from all IBS patients. Thirteen metabolites identified by GC-MS differed HCs and IBS patients. However, neither metagenomics nor metabolomics analyses identified significant differences between patients with and without improvement after treatment.

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            Modulation of the fecal bile acid profile by gut microbiota in cirrhosis.

            The 7α-dehydroxylation of primary bile acids (BAs), chenodeoxycholic (CDCA) and cholic acid (CA) into the secondary BAs, lithocholic (LCA) and deoxycholic acid (DCA), is a key function of the gut microbiota. We aimed at studying the linkage between fecal BAs and gut microbiota in cirrhosis since this could help understand cirrhosis progression. Fecal microbiota were analyzed by culture-independent multitagged-pyrosequencing, fecal BAs using HPLC and serum BAs using LC-MS in controls, early (Child A) and advanced cirrhotics (Child B/C). A subgroup of early cirrhotics underwent BA and microbiota analysis before/after eight weeks of rifaximin. Cross-sectional: 47 cirrhotics (24 advanced) and 14 controls were included. In feces, advanced cirrhotics had the lowest total, secondary, secondary/primary BA ratios, and the highest primary BAs compared to early cirrhotics and controls. Secondary fecal BAs were detectable in all controls but in a significantly lower proportion of cirrhotics (p<0.002). Serum primary BAs were higher in advanced cirrhotics compared to the rest. Cirrhotics, compared to controls, had a higher Enterobacteriaceae (potentially pathogenic) but lower Lachonospiraceae, Ruminococcaceae and Blautia (7α-dehydroxylating bacteria) abundance. CDCA was positively correlated with Enterobacteriaceae (r=0.57, p<0.008) while Ruminococcaceae were positively correlated with DCA (r=0.4, p<0.05). A positive correlation between Ruminococcaceae and DCA/CA (r=0.82, p<0.012) and Blautia with LCA/CDCA (r=0.61, p<0.03) was also seen. Prospective study: post-rifaximin, six early cirrhotics had reduction in Veillonellaceae and in secondary/primary BA ratios. Cirrhosis, especially advanced disease, is associated with a decreased conversion of primary to secondary fecal BAs, which is linked to abundance of key gut microbiome taxa. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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              AGA technical review on irritable bowel syndrome.

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                Author and article information

                Journal
                Gut Microbes
                Gut Microbes
                KGMI
                kgmi20
                Gut Microbes
                Taylor & Francis
                1949-0976
                1949-0984
                2016
                26 July 2016
                26 July 2016
                : 7
                : 5
                : 397-413
                Affiliations
                [a ]Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education , Warsaw, Poland
                [b ]Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology , Warsaw, Poland
                [c ]Institute of Radioelectronics, Warsaw University of Technology , Warsaw, Poland
                [d ]Department of Bioorganic Chemistry Wroclaw University of Technology , Wroclaw, Poland
                [e ]Institute of Bioorganic Chemistry Polish Academy of Sciences , Poznań, Poland
                Author notes
                CONTACT Jerzy Ostrowski, MD, PhD jostrow@ 123456warman.com.pl Cancer Center-Institute , Roentgena 5, 02-781 Warsaw, Poland

                Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/kgmi.

                Supplemental data for this article can be accessed on the publisher's website.

                [†]

                equal contribution

                Article
                1215805
                10.1080/19490976.2016.1215805
                5046165
                27662586
                6f076b6e-b034-41dd-a18e-78d756cd8d72
                © 2016 The Author(s). Published with license by Taylor & Francis

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                : 11 March 2016
                : 18 June 2016
                : 18 July 2016
                Page count
                Figures: 6, Tables: 2, References: 88, Pages: 17
                Categories
                Research Paper/Report

                Microbiology & Virology
                16s rrna sequencing,irritable bowel syndrome,metagenomics,metabolomics,rifaximin

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