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      Intestinal Microbiota in Patients with Spinal Cord Injury

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          Abstract

          Human intestinal flora comprises thousands of bacterial species. Growth and composition of intestinal microbiota is dependent on various parameters, including immune mechanisms, dietary factors and intestinal motility. Patients with spinal cord injury (SCI) frequently display neurogenic bowel dysfunction due to the absence of central nervous system control over the gastrointestinal system. Considering the bowel dysfunction and altered colonic transit time in patients with SCI, we hypothesized the presence of a significant change in the composition of their gut microbiome. The objective of this study was to characterize the gut microbiota in adult SCI patients with different types of bowel dysfunction. We tested our hypothesis on 30 SCI patients (15 upper motor neuron [UMN] bowel syndrome, 15 lower motor neuron [LMN] bowel syndrome) and 10 healthy controls using the 16S rRNA sequencing. Gut microbial patterns were sampled from feces. Independent of study groups, gut microbiota of the participants were dominated by Blautia, Bifidobacterium, Faecalibacterium and Ruminococcus. When we compared all study groups, Roseburia, Pseudobutyrivibrio, Dialister, Marvinbryantia and Megamonas appeared as the genera that were statistically different between groups. In comparison to the healthy group, total bacterial counts of Pseudobutyrivibrio, Dialister and Megamonas genera were significantly lower in UMN bowel dysfunction group. The total bacterial count of Marvinbryantia genus was significantly lower in UMN bowel dysfunction group when compared to the LMN group. Total bacterial counts of Roseburia, Pseudobutyrivibrio and Megamonas genera were significantly lower in LMN bowel dysfunction group when compared to healthy groups. Our results demonstrate for the first time that butyrate-producing members are specifically reduced in SCI patients when compared to healthy subjects. The results of this study would be of interest since to our knowledge, microbiome-associated studies targeting SCI patients are non-existent and the results might help explain possible implications of gut microbiome in SCI.

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          Most cited references18

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          Towards the human intestinal microbiota phylogenetic core.

          The paradox of a host specificity of the human faecal microbiota otherwise acknowledged as characterized by global functionalities conserved between humans led us to explore the existence of a phylogenetic core. We investigated the presence of a set of bacterial molecular species that would be altogether dominant and prevalent within the faecal microbiota of healthy humans. A total of 10 456 non-chimeric bacterial 16S rRNA sequences were obtained after cloning of PCR-amplified rDNA from 17 human faecal DNA samples. Using alignment or tetranucleotide frequency-based methods, 3180 operational taxonomic units (OTUs) were detected. The 16S rRNA sequences mainly belonged to the phyla Firmicutes (79.4%), Bacteroidetes (16.9%), Actinobacteria (2.5%), Proteobacteria (1%) and Verrumicrobia (0.1%). Interestingly, while most of OTUs appeared individual-specific, 2.1% were present in more than 50% of the samples and accounted for 35.8% of the total sequences. These 66 dominant and prevalent OTUs included members of the genera Faecalibacterium, Ruminococcus, Eubacterium, Dorea, Bacteroides, Alistipes and Bifidobacterium. Furthermore, 24 OTUs had cultured type strains representatives which should be subjected to genome sequence with a high degree of priority. Strikingly, 52 of these 66 OTUs were detected in at least three out of four recently published human faecal microbiota data sets, obtained with very different experimental procedures. A statistical model confirmed these OTUs prevalence. Despite the species richness and a high individual specificity, a limited number of OTUs is shared among individuals and might represent the phylogenetic core of the human intestinal microbiota. Its role in human health deserves further study.
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            Glial activation: a driving force for pathological pain.

            Pain is classically viewed as being mediated solely by neurons, as are other sensory phenomena. The discovery that spinal cord glia (microglia and astrocytes) amplify pain requires a change in this view. These glia express characteristics in common with immune cells in that they respond to viruses and bacteria, releasing proinflammatory cytokines, which create pathological pain. These spinal cord glia also become activated by certain sensory signals arriving from the periphery. Similar to spinal infection, these signals cause release of proinflammatory cytokines, thus creating pathological pain. Taken together, these findings suggest a new, dramatically different approach to pain control, as all clinical therapies are focused exclusively on altering neuronal, rather than glial, function.
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              Intestinal crosstalk: a new paradigm for understanding the gut as the "motor" of critical illness.

              For more than 20 years, the gut has been hypothesized to be the "motor" of multiple organ dysfunction syndrome. As critical care research has evolved, there have been multiple mechanisms by which the gastrointestinal tract has been proposed to drive systemic inflammation. Many of these disparate mechanisms have proved to be important in the origin and propagation of critical illness. However, this has led to an unusual situation where investigators describing the gut as a "motor" revving the systemic inflammatory response syndrome are frequently describing wholly different processes to support their claim (i.e., increased apoptosis, altered tight junctions, translocation, cytokine production, crosstalk with commensal bacteria, etc). The purpose of this review is to present a unifying theory as to how the gut drives critical illness. Although the gastrointestinal tract is frequently described simply as "the gut," it is actually made up of (1) an epithelium; (2) a diverse and robust immune arm, which contains most of the immune cells in the body; and (3) the commensal bacteria, which contain more cells than are present in the entire host organism. We propose that the intestinal epithelium, the intestinal immune system, and the intestine's endogenous bacteria all play vital roles driving multiple organ dysfunction syndrome, and the complex crosstalk between these three interrelated portions of the gastrointestinal tract is what cumulatively makes the gut a "motor" of critical illness.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                11 January 2016
                2016
                : 11
                : 1
                : e0145878
                Affiliations
                [1 ]Department of Molecular Biology and Genetics, Middle East Technical University, Ankara, Turkey
                [2 ]Department of PMR, Gulhane Military Medical Academy, Turkish Armed Forces Rehabilitation Center, Ankara,Turkey
                [3 ]THORLAB, Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey
                University of Illinois at Chicago, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MG BY IG. Performed the experiments: BG EA. Analyzed the data: MG BY IG. Contributed reagents/materials/analysis tools: MG BY IG. Wrote the paper: MG BY BG EA IG.

                Article
                PONE-D-15-20238
                10.1371/journal.pone.0145878
                4709077
                26752409
                60abece7-d7ea-4101-a86f-e88fc8452649
                © 2016 Gungor et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 May 2015
                : 9 December 2015
                Page count
                Figures: 3, Tables: 1, Pages: 10
                Funding
                This project was supported by a METU-GATA collaborative grant to MG and BY (BAP-08-11-2013-005). Supporting Agencies, Middle East Technical University, and Gulhane Askeri Tip Akademisi.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information file.

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