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      Metagenomic analysis of microbe-mediated vitamin metabolism in the human gut microbiome

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          Abstract

          Background

          Human gut microbial communities have been known to produce vitamins, which are subsequently absorbed by the host in the large intestine. However, the relationship between species with vitamin pathway associated functional features or their gene abundance in different states of health and disease is lacking. Here, we analyzed shotgun fecal metagenomes of individuals from four different countries for genes that are involved in vitamin biosynthetic pathways and transport mechanisms and corresponding species’ abundance.

          Results

          We found that the prevalence of these genes were found to be distributed across the dominant phyla of gut species. The number of positive correlations were high between species harboring genes related to vitamin biosynthetic pathways and transporter mechanisms than that with either alone. Although, the range of total gene abundances remained constant across healthy populations at the global level, species composition and their presence for metabolic pathway related genes determine the abundance and functional genetic content of vitamin metabolism. Based on metatranscriptomics data, the equation between abundance of vitamin-biosynthetic enzymes and vitamin-dependent enzymes suggests that the production and utilization potential of these enzymes seems way more complex usage allocations than just mere direct linear associations.

          Conclusions

          Our findings provide a rationale to examine and disentangle the interrelationship between B-vitamin dosage (dietary or microbe-mediated) on gut microbial members and the host, in the gut microbiota of individuals with under- or overnutrition.

          Electronic supplementary material

          The online version of this article (10.1186/s12864-019-5591-7) contains supplementary material, which is available to authorized users.

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          Most cited references42

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          Fast and sensitive protein alignment using DIAMOND.

          The alignment of sequencing reads against a protein reference database is a major computational bottleneck in metagenomics and data-intensive evolutionary projects. Although recent tools offer improved performance over the gold standard BLASTX, they exhibit only a modest speedup or low sensitivity. We introduce DIAMOND, an open-source algorithm based on double indexing that is 20,000 times faster than BLASTX on short reads and has a similar degree of sensitivity.
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            A human gut microbial gene catalogue established by metagenomic sequencing.

            To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, approximately 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.
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              A metagenome-wide association study of gut microbiota in type 2 diabetes.

              Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.
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                Author and article information

                Contributors
                promi@chalmers.se
                parizad@chalmers.se
                +46 (0)31 772 3804 , nielsenj@chalmers.se
                Journal
                BMC Genomics
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                12 March 2019
                12 March 2019
                2019
                : 20
                : 208
                Affiliations
                [1 ]ISNI 0000 0001 0775 6028, GRID grid.5371.0, Department of Biology and Biological Engineering, , Chalmers University of Technology, ; 41296 Gothenburg, Sweden
                [2 ]ISNI 0000 0001 2181 8870, GRID grid.5170.3, Novo Nordisk Foundation Center for Biosustainability, , Technical University of Denmark, ; 2800 Lyngby, Denmark
                Article
                5591
                10.1186/s12864-019-5591-7
                6417177
                30866812
                9b850ba2-2c5a-47bf-a83b-5f21e3633619
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 9 January 2019
                : 6 March 2019
                Funding
                Funded by: METACARDIS
                Award ID: HEALTH-F4-2012-305312
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Genetics
                b-vitamins,gut metabolism,metagenomics,metatranscriptomics,vitamin prototrophs,vitamin consumers

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