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      Maternal diet and gut microbiome composition modulate early‐life immune development

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          Abstract

          In early life, the intestinal mucosa and immune system undergo a critical developmental process to contain the expanding gut microbiome while promoting tolerance toward commensals, yet the influence of maternal diet and microbial composition on offspring immune maturation remains poorly understood. We colonized germ‐free mice with a consortium of 14 strains, fed them a standard fiber‐rich chow or a fiber‐free diet, and then longitudinally assessed offspring development during the weaning period. Unlike pups born to dams fed the fiber‐rich diet, pups of fiber‐deprived dams demonstrated delayed colonization with Akkermansia muciniphila, a mucin‐foraging bacterium that can also use milk oligosaccharides. The pups of fiber‐deprived dams exhibited an enrichment of colonic transcripts corresponding to defense response pathways and a peak in Il22 expression at weaning. Removal of A.  muciniphila from the community, but maintenance on the fiber‐rich diet, was associated with reduced proportions of RORγt‐positive innate and adaptive immune cell subsets. Our results highlight the potent influence of maternal dietary fiber intake and discrete changes in microbial composition on the postnatal microbiome assemblage and early immune development.

          Abstract

          A fiber‐free (FF) maternal diet alters microbiome establishment in pups, with diminished pre‐weaning levels of Akkermansia muciniphila (AM). These results underscore the important influence of maternal diet and microbiome on immune maturation in offspring during a critical developmental period.

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          Most cited references60

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          Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

          In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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            STAR: ultrafast universal RNA-seq aligner.

            Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases. To align our large (>80 billon reads) ENCODE Transcriptome RNA-seq dataset, we developed the Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. STAR outperforms other aligners by a factor of >50 in mapping speed, aligning to the human genome 550 million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions, STAR can discover non-canonical splices and chimeric (fusion) transcripts, and is also capable of mapping full-length RNA sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons, we experimentally validated 1960 novel intergenic splice junctions with an 80-90% success rate, corroborating the high precision of the STAR mapping strategy. STAR is implemented as a standalone C++ code. STAR is free open source software distributed under GPLv3 license and can be downloaded from http://code.google.com/p/rna-star/.
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              clusterProfiler: an R package for comparing biological themes among gene clusters.

              Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
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                Author and article information

                Contributors
                mahesh.desai@lih.lu
                Journal
                EMBO Mol Med
                EMBO Mol Med
                10.1002/(ISSN)1757-4684
                EMMM
                embomm
                EMBO Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1757-4676
                1757-4684
                06 June 2023
                August 2023
                : 15
                : 8 ( doiID: 10.1002/emmm.v15.8 )
                : e17241
                Affiliations
                [ 1 ] Department of Infection and Immunity Luxembourg Institute of Health Esch‐sur‐Alzette Luxembourg
                [ 2 ] Faculty of Science, Technology and Medicine University of Luxembourg Esch‐sur‐Alzette Luxembourg
                [ 3 ] Bioinformatics Platform, Data Integration and Analysis Luxembourg Institute of Health Strassen Luxembourg
                [ 4 ] LuxGen, Translational Medicine Operation Hub Luxembourg Institute of Health Dudelange Luxembourg
                [ 5 ] Department of Visceral Surgery and Medicine Bern University Hospital, University of Bern Bern Switzerland
                Author notes
                [*] [* ]Corresponding author. Tel: +352 26970 389; E‐mail: mahesh.desai@ 123456lih.lu
                Author information
                https://orcid.org/0000-0002-7632-4939
                https://orcid.org/0000-0003-4775-0514
                https://orcid.org/0000-0001-5722-8282
                https://orcid.org/0000-0002-7192-0184
                https://orcid.org/0000-0002-9223-2209
                Article
                EMMM202217241
                10.15252/emmm.202217241
                10405054
                37278126
                aee19cf9-ce98-4aea-abd8-1718dbd8c609
                © 2023 The Authors. Published under the terms of the CC BY 4.0 license

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 May 2023
                : 29 November 2022
                : 16 May 2023
                Page count
                Figures: 10, Tables: 1, Pages: 19, Words: 12381
                Funding
                Funded by: European Commission (EC) , doi 10.13039/501100000780;
                Award ID: 897408
                Funded by: Fonds National de la Recherche Luxembourg (FNR) , doi 10.13039/100007869;
                Award ID: CORE C15/BM/10318186
                Award ID: C18/BM/12585940
                Award ID: PRIDE (17/11823097)
                Categories
                Article
                Articles
                Custom metadata
                2.0
                07 August 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.2 mode:remove_FC converted:07.08.2023

                Molecular medicine
                akkermansia,dietary fiber,early life,immune development,microbiome,evolution & ecology,microbiology, virology & host pathogen interaction

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