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      Intestinal Dysbiosis Associated with Systemic Lupus Erythematosus

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          ABSTRACT

          Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease in humans and is characterized by the presence of hyperactive immune cells and aberrant antibody responses to nuclear and cytoplasmic antigens, including characteristic anti–double-stranded DNA antibodies. We performed a cross-sectional study in order to determine if an SLE-associated gut dysbiosis exists in patients without active disease. A group of 20 SLE patients in remission, for which there was strict inclusion and exclusion criteria, was recruited, and we used an optimized Ion Torrent 16S rRNA gene-based analysis protocol to decipher the fecal microbial profiles of these patients and compare them with those of 20 age- and sex-matched healthy control subjects. We found diversity to be comparable based on Shannon’s index. However, we saw a significantly lower Firmicutes/ Bacteroidetes ratio in SLE individuals (median ratio, 1.97) than in healthy subjects (median ratio, 4.86; P < 0.002). A lower Firmicutes/ Bacteroidetes ratio in SLE individuals was corroborated by quantitative PCR analysis. Notably, a decrease of some Firmicutes families was also detected. This dysbiosis is reflected, based on in silico functional inference, in an overrepresentation of oxidative phosphorylation and glycan utilization pathways in SLE patient microbiota.

          IMPORTANCE

          Growing evidence suggests that the gut microbiota might impact symptoms and progression of some autoimmune diseases. However, how and why this microbial community influences SLE remains to be elucidated. This is the first report describing an SLE-associated intestinal dysbiosis, and it contributes to the understanding of the interplay between the intestinal microbiota and the host in autoimmune disorders.

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          Most cited references27

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          Obesity and the human microbiome.

          Ruth E Ley (2010)
          Obesity was once rare, but the last few decades have seen a rapid expansion of the proportion of obese individuals worldwide. Recent work has shown obesity to be associated with a shift in the representation of the dominant phyla of bacteria in the gut, both in humans and animal models. This review summarizes the latest research into the association between microbial ecology and host adiposity, and the mechanisms by which microbes in the gut may mediate host metabolism in the context of obesity. Studies of the effect of excess body fat on the abundances of different bacteria taxa in the gut generally show alterations in the gastrointestinal microbiota, and changes during weight loss. The gastrointestinal microbiota have been shown to impact insulin resistance, inflammation, and adiposity via interactions with epithelial and endocrine cells. Large-scale alterations of the gut microbiota and its microbiome (gene content) are associated with obesity and are responsive to weight loss. Gut microbes can impact host metabolism via signaling pathways in the gut, with effects on inflammation, insulin resistance, and deposition of energy in fat stores. Restoration of the gut microbiota to a healthy state may ameliorate the conditions associated with obesity and help maintain a healthy weight.
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            Diversity of Bifidobacteria within the Infant Gut Microbiota

            Background The human gastrointestinal tract (GIT) represents one of the most densely populated microbial ecosystems studied to date. Although this microbial consortium has been recognized to have a crucial impact on human health, its precise composition is still subject to intense investigation. Among the GIT microbiota, bifidobacteria represent an important commensal group, being among the first microbial colonizers of the gut. However, the prevalence and diversity of members of the genus Bifidobacterium in the infant intestinal microbiota has not yet been fully characterized, while some inconsistencies exist in literature regarding the abundance of this genus. Methods/Principal Findings In the current report, we assessed the complexity of the infant intestinal bifidobacterial population by analysis of pyrosequencing data of PCR amplicons derived from two hypervariable regions of the 16 S rRNA gene. Eleven faecal samples were collected from healthy infants of different geographical origins (Italy, Spain or Ireland), feeding type (breast milk or formula) and mode of delivery (vaginal or caesarean delivery), while in four cases, faecal samples of corresponding mothers were also analyzed. Conclusions In contrast to several previously published culture-independent studies, our analysis revealed a predominance of bifidobacteria in the infant gut as well as a profile of co-occurrence of bifidobacterial species in the infant’s intestine.
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              Gut microbiome composition is linked to whole grain-induced immunological improvements.

              The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on fecal microbial ecology and blood markers of inflammation, glucose and lipid metabolism. All treatments increased microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of the genus Blautia in fecal samples. The inclusion of WGB enriched the genera Roseburia, Bifidobacterium and Dialister, and the species Eubacterium rectale, Roseburia faecis and Roseburia intestinalis. Whole grains, and especially the BR+WGB treatment, reduced plasma interleukin-6 (IL-6) and peak postprandial glucose. Shifts in the abundance of Eubacterium rectale were associated with changes in the glucose and insulin postprandial response. Interestingly, subjects with greater improvements in IL-6 levels harbored significantly higher proportions of Dialister and lower abundance of Coriobacteriaceae. In conclusion, this study revealed that a short-term intake of whole grains induced compositional alterations of the gut microbiota that coincided with improvements in host physiological measures related to metabolic dysfunctions in humans.
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                Author and article information

                Journal
                mBio
                MBio
                mbio
                mbio
                mBio
                mBio
                American Society of Microbiology (1752 N St., N.W., Washington, DC )
                2150-7511
                30 September 2014
                Sep-Oct 2014
                : 5
                : 5
                : e01548-14
                Affiliations
                [ a ]Instituto de Productos Lácteos de Asturias, Consejo Superior de Investigaciones Científicas, Villaviciosa, Asturias, Spain
                [ b ]Laboratory of Probiogenomics, Department of Life Sciences, University of Parma, Parma, Italy
                [ c ]Immunology Area, Department of Functional Biology, University of Oviedo, Asturias, Spain
                [ d ]Physiology Area, Department of Functional Biology, University of Oviedo, Asturias, Spain
                Author notes
                Address correspondence to Borja Sánchez, borja.sanchez@ 123456uvigo.es , or Abelardo Margolles, amargolles@ 123456ipla.csic.es .
                [*]

                Present address: Francesca Turroni, Alimentary Pharmabiotic Centre and Department of Microbiology, Bioscience Institute, National University of Ireland, Cork, Ireland; Borja Sánchez, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain.

                Invited Editor Nicola Segata, University of Trento Editor Maria Gloria Dominguez Bello, New York University School of Medicine

                Article
                mBio01548-14
                10.1128/mBio.01548-14
                4196225
                25271284
                48257a0a-0e64-416c-ac1d-183b71e12a64
                Copyright © 2014 Hevia et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 June 2014
                : 29 August 2014
                Page count
                Pages: 10
                Categories
                Research Article
                Custom metadata
                September/October 2014

                Life sciences
                Life sciences

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