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      The dormant blood microbiome in chronic, inflammatory diseases

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          Abstract

          Blood in healthy organisms is seen as a ‘sterile’ environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. ‘Non-culturability’, reflected by discrepancies between plate counts and total counts, is commonplace in environmental microbiology. It is overcome by improved culturing methods, and we asked how common this would be in blood. A number of recent, sequence-based and ultramicroscopic studies have uncovered an authentic blood microbiome in a number of non-communicable diseases. The chief origin of these microbes is the gut microbiome (especially when it shifts composition to a pathogenic state, known as ‘dysbiosis’). Another source is microbes translocated from the oral cavity. ‘Dysbiosis’ is also used to describe translocation of cells into blood or other tissues. To avoid ambiguity, we here use the term ‘atopobiosis’ for microbes that appear in places other than their normal location. Atopobiosis may contribute to the dynamics of a variety of inflammatory diseases. Overall, it seems that many more chronic, non-communicable, inflammatory diseases may have a microbial component than are presently considered, and may be treatable using bactericidal antibiotics or vaccines.

          Abstract

          Atopobiosis of microbes (the term describing microbes that appear in places other than where they should be), as well as the products of their metabolism, seems to correlate with, and may contribute to, the dynamics of a variety of inflammatory diseases.

          Abstract

          Graphical Abstract Figure.

          Atopobiosis of microbes (the term describing microbes that appear in places other than where they should be), as well as the products of their metabolism, seems to correlate with, and may contribute to, the dynamics of a variety of inflammatory diseases.

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          Bacterial persistence as a phenotypic switch.

          A fraction of a genetically homogeneous microbial population may survive exposure to stress such as antibiotic treatment. Unlike resistant mutants, cells regrown from such persistent bacteria remain sensitive to the antibiotic. We investigated the persistence of single cells of Escherichia coli with the use of microfluidic devices. Persistence was linked to preexisting heterogeneity in bacterial populations because phenotypic switching occurred between normally growing cells and persister cells having reduced growth rates. Quantitative measurements led to a simple mathematical description of the persistence switch. Inherent heterogeneity of bacterial populations may be important in adaptation to fluctuating environments and in the persistence of bacterial infections.
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            The microbiome in inflammatory bowel disease: current status and the future ahead.

            Studies of the roles of microbial communities in the development of inflammatory bowel disease (IBD) have reached an important milestone. A decade of genome-wide association studies and other genetic analyses have linked IBD with loci that implicate an aberrant immune response to the intestinal microbiota. More recently, profiling studies of the intestinal microbiome have associated the pathogenesis of IBD with characteristic shifts in the composition of the intestinal microbiota, reinforcing the view that IBD results from altered interactions between intestinal microbes and the mucosal immune system. Enhanced technologies can increase our understanding of the interactions between the host and its resident microbiota and their respective roles in IBD from both a large-scale pathway view and at the metabolic level. We review important microbiome studies of patients with IBD and describe what we have learned about the mechanisms of intestinal microbiota dysfunction. We describe the recent progress in microbiome research from exploratory 16S-based studies, reporting associations of specific organisms with a disease, to more recent studies that have taken a more nuanced view, addressing the function of the microbiota by metagenomic and metabolomic methods. Finally, we propose study designs and methodologies for future investigations of the microbiome in patients with inflammatory gut and autoimmune diseases in general. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
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              Energy contributions of volatile fatty acids from the gastrointestinal tract in various species.

              E BERGMAN (1990)
              The VFA, also known as short-chain fatty acids, are produced in the gastrointestinal tract by microbial fermentation of carbohydrates and endogenous substrates, such as mucus. This can be of great advantage to the animal, since no digestive enzymes exist for breaking down cellulose or other complex carbohydrates. The VFA are produced in the largest amounts in herbivorous animal species and especially in the forestomach of ruminants. The VFA, however, also are produced in the lower digestive tract of humans and all animal species, and intestinal fermentation resembles that occurring in the rumen. The principal VFA in either the rumen or large intestine are acetate, propionate, and butyrate and are produced in a ratio varying from approximately 75:15:10 to 40:40:20. Absorption of VFA at their site of production is rapid, and large quantities are metabolized by the ruminal or large intestinal epithelium before reaching the portal blood. Most of the butyrate is converted to ketone bodies or CO2 by the epithelial cells, and nearly all of the remainder is removed by the liver. Propionate is similarly removed by the liver but is largely converted to glucose. Although species differences exist, acetate is used principally by peripheral tissues, especially fat and muscle. Considerable energy is obtained from VFA in herbivorous species, and far more research has been conducted on ruminants than on other species. Significant VFA, however, are now known to be produced in omnivorous species, such as pigs and humans. Current estimates are that VFA contribute approximately 70% to the caloric requirements of ruminants, such as sheep and cattle, approximately 10% for humans, and approximately 20-30% for several other omnivorous or herbivorous animals. The amount of fiber in the diet undoubtedly affects the amount of VFA produced, and thus the contribution of VFA to the energy needs of the body could become considerably greater as the dietary fiber increases. Pigs and some species of monkey most closely resemble humans, and current research should be directed toward examining the fermentation processes and VFA metabolism in those species. In addition to the energetic or nutritional contributions of VFA to the body, the VFA may indirectly influence cholesterol synthesis and even help regulate insulin or glucagon secretion. In addition, VFA production and absorption have a very significant effect on epithelial cell growth, blood flow, and the normal secretory and absorptive functions of the large intestine, cecum, and rumen. The absorption of VFA and sodium, for example, seem to be interdependent, and release of bicarbonate usually occurs during VFA absorption.(ABSTRACT TRUNCATED AT 400 WORDS)
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                Author and article information

                Journal
                FEMS Microbiol Rev
                FEMS Microbiol. Rev
                femsre
                femsre
                FEMS Microbiology Reviews
                Oxford University Press
                0168-6445
                1574-6976
                04 May 2015
                July 2015
                04 May 2015
                : 39
                : 4
                : 567-591
                Affiliations
                [1 ]Department of Physiology, Faculty of Health Sciences, University of Pretoria, Arcadia 0007, South Africa
                [2 ]School of Chemistry and The Manchester Institute of Biotechnology, The University of Manchester, 131, Princess St, Manchester M1 7DN, Lancs, UK
                Author notes
                [* ] Corresponding author: School of Chemistry and The Manchester Institute of Biotechnology, The University of Manchester, 131, Princess St, Manchester M1 7DN, Lancs, UK. Tel: (+44)161 306 4492; E-mail: dbk@ 123456manchester.ac.uk
                Article
                10.1093/femsre/fuv013
                4487407
                25940667
                c5c1c312-43d1-4a49-802a-f4ce3c31bbcd
                © FEMS 2015.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 March 2015
                : 26 January 2015
                Page count
                Pages: 25
                Categories
                Review Article
                Custom metadata
                July 2015

                Microbiology & Virology
                ‘sterile’ blood microbiome,culturability,dormancy,dysbiosis,atopobiosis,parkinson's disease,alzheimer disease

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