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      The function of our microbiota: who is out there and what do they do?

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          Abstract

          Current meta-omics developments provide a portal into the functional potential and activity of the intestinal microbiota. The comparative and functional meta-omics approaches have made it possible to get a molecular snap shot of microbial function at a certain time and place. To this end, metagenomics is a DNA-based approach, metatranscriptomics studies the total transcribed RNA, metaproteomics focuses on protein levels and metabolomics describes metabolic profiles. Notably, the metagenomic toolbox is rapidly expanding and has been instrumental in the generation of draft genome sequences of over 1000 human associated microorganisms as well as an astonishing 3.3 million unique microbial genes derived from the intestinal tract of over 100 European adults. Remarkably, it appeared that there are at least 3 clusters of co-occurring microbial species, termed enterotypes, that characterize the intestinal microbiota throughout various continents. The human intestinal microbial metagenome further revealed unique functions carried out in the intestinal environment and provided the basis for newly discovered mechanisms for signaling, vitamin production and glycan, amino-acid and xenobiotic metabolism. The activity and composition of the microbiota is affected by genetic background, age, diet, and health status of the host. In its turn the microbiota composition and activity influence host metabolism and disease development. Exemplified by the differences in microbiota composition and activity between breast- as compared to formula-fed babies, healthy and malnourished infants, elderly and centenarians as compared to youngsters, humans that are either lean or obese and healthy or suffering of inflammatory bowel diseases (IBD). In this review we will focus on our current understanding of the functionality of the human intestinal microbiota based on all available metagenome, metatranscriptome, and metaproteome results

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          Most cited references39

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          Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians

          Background Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections. Methodology/Principal Findings By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians. Conclusions/Significance We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.
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            The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome.

            Following birth, the breast-fed infant gastrointestinal tract is rapidly colonized by a microbial consortium often dominated by bifidobacteria. Accordingly, the complete genome sequence of Bifidobacterium longum subsp. infantis ATCC15697 reflects a competitive nutrient-utilization strategy targeting milk-borne molecules which lack a nutritive value to the neonate. Several chromosomal loci reflect potential adaptation to the infant host including a 43 kbp cluster encoding catabolic genes, extracellular solute binding proteins and permeases predicted to be active on milk oligosaccharides. An examination of in vivo metabolism has detected the hallmarks of milk oligosaccharide utilization via the central fermentative pathway using metabolomic and proteomic approaches. Finally, conservation of gene clusters in multiple isolates corroborates the genomic mechanism underlying milk utilization for this infant-associated phylotype.
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              Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease.

              To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. The effect of SCFAs on cytokine release from human neutrophils was studied with ELISA. SCFA-dependent modulation of NF-kappaB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFalpha release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-kappaB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-kappaB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.
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                Author and article information

                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Inf. Microbio.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                09 August 2012
                2012
                : 2
                : 104
                Affiliations
                [1] 1simpleLaboratory of Microbiology, Wageningen University Wageningen, Netherlands
                [2] 2simpleDepartment of Basic Veterinary Medicine and Department of Bacteriology and Immunology, University of Helsinki Helsinki, Finland
                Author notes

                Edited by: Lorenza Putignani, Children's ‘Hospital and Research Institute Bambino Gesù, Italy

                Reviewed by: Lorenza Putignani, Children's ‘Hospital and Research Institute Bambino Gesù, Italy; Andrea Petrucca, Azienda Ospedaliera Sant'Andrea, Italy

                *Correspondence: Clara Belzer, Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB, Wageningen, Netherlands. e-mail: clara.belzer@ 123456wur.nl
                Article
                10.3389/fcimb.2012.00104
                3417542
                22919693
                539d2760-cc00-4667-ac14-3564b5748f25
                Copyright © 2012 Ottman, Smidt, de Vos and Belzer.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 17 June 2012
                : 15 July 2012
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 85, Pages: 11, Words: 10729
                Categories
                Microbiology
                Review Article

                Infectious disease & Microbiology
                metatranscriptomics,human intestinal microbiota,metaproteomics,functional metagenomics

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