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      Heterochronic faecal transplantation boosts gut germinal centres in aged mice

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          Abstract

          Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system; however, it is not clear whether there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer’s patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli.

          Abstract

          Microbiota impacts all major aspects of physiology, but little is known about its effects on age-related changes in immune responses. Here the authors show that gut microbiota transfer between adult and old mice increases local but not systemic germinal centre responses regardless of age directionality.

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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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            Calypso: a user-friendly web-server for mining and visualizing microbiome–environment interactions

            Abstract Calypso is an easy-to-use online software suite that allows non-expert users to mine, interpret and compare taxonomic information from metagenomic or 16S rDNA datasets. Calypso has a focus on multivariate statistical approaches that can identify complex environment-microbiome associations. The software enables quantitative visualizations, statistical testing, multivariate analysis, supervised learning, factor analysis, multivariable regression, network analysis and diversity estimates. Comprehensive help pages, tutorials and videos are provided via a wiki page. Availability and Implementation: The web-interface is accessible via http://cgenome.net/calypso/. The software is programmed in Java, PERL and R and the source code is available from Zenodo (https://zenodo.org/record/50931). The software is freely available for non-commercial users. Contact: l.krause@uq.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.
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              Inflammation-associated enterotypes, host genotype, cage and inter-individual effects drive gut microbiota variation in common laboratory mice

              Background Murine models are a crucial component of gut microbiome research. Unfortunately, a multitude of genetic backgrounds and experimental setups, together with inter-individual variation, complicates cross-study comparisons and a global understanding of the mouse microbiota landscape. Here, we investigate the variability of the healthy mouse microbiota of five common lab mouse strains using 16S rDNA pyrosequencing. Results We find initial evidence for richness-driven, strain-independent murine enterotypes that show a striking resemblance to those in human, and which associate with calprotectin levels, a marker for intestinal inflammation. After enterotype stratification, we find that genetic, caging and inter-individual variation contribute on average 19%, 31.7% and 45.5%, respectively, to the variance in the murine gut microbiota composition. Genetic distance correlates positively to microbiota distance, so that genetically similar strains have more similar microbiota than genetically distant ones. Specific mouse strains are enriched for specific operational taxonomic units and taxonomic groups, while the 'cage effect' can occur across mouse strain boundaries and is mainly driven by Helicobacter infections. Conclusions The detection of enterotypes suggests a common ecological cause, possibly low-grade inflammation that might drive differences among gut microbiota composition in mammals. Furthermore, the observed environmental and genetic effects have important consequences for experimental design in mouse microbiome research.
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                Author and article information

                Contributors
                michelle.linterman@babraham.ac.uk
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                4 June 2019
                4 June 2019
                2019
                : 10
                : 2443
                Affiliations
                [1 ]ISNI 0000 0001 0694 2777, GRID grid.418195.0, Laboratory of Lymphocyte Signalling and Development, , Babraham Institute, ; Babraham Research Campus, Cambridge, CB22 3AT UK
                [2 ]Department of Veterinary Medicine, Madingley Road, Cambridge, CB3 0ES UK
                [3 ]ISNI 0000 0001 0694 2777, GRID grid.418195.0, Biological Services Unit, , Babraham Institute, ; Babraham Research Campus, Cambridge, CB22 3AT UK
                Author information
                http://orcid.org/0000-0001-8434-8271
                http://orcid.org/0000-0003-0533-1629
                http://orcid.org/0000-0001-6863-2950
                http://orcid.org/0000-0003-2126-5828
                http://orcid.org/0000-0001-6047-1996
                Article
                10430
                10.1038/s41467-019-10430-7
                6547660
                31164642
                dc1817cc-b643-4ce6-a5fc-3197415a2735
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 13 November 2018
                : 10 May 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100000268, RCUK | Biotechnology and Biological Sciences Research Council (BBSRC);
                Award ID: BBS/E/B/000C0407
                Award ID: BBS/E/B/000C0427
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100010663, EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council);
                Award ID: 637801
                Award ID: 675395
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                follicular b cells,mucosal immunology,microbiome,ageing
                Uncategorized
                follicular b cells, mucosal immunology, microbiome, ageing

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