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      Diet rapidly and reproducibly alters the human gut microbiome

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          Abstract

          Long-term diet influences the structure and activity of the trillions of microorganisms residing in the human gut 15 , but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here, we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms ( Alistipes, Bilophila, and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides ( Roseburia, Eubacterium rectale , and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals 2 , reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi, and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids, and the outgrowth of microorganisms capable of triggering inflammatory bowel disease 6 . In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

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          Most cited references25

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          Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample.

          The ongoing revolution in high-throughput sequencing continues to democratize the ability of small groups of investigators to map the microbial component of the biosphere. In particular, the coevolution of new sequencing platforms and new software tools allows data acquisition and analysis on an unprecedented scale. Here we report the next stage in this coevolutionary arms race, using the Illumina GAIIx platform to sequence a diverse array of 25 environmental samples and three known "mock communities" at a depth averaging 3.1 million reads per sample. We demonstrate excellent consistency in taxonomic recovery and recapture diversity patterns that were previously reported on the basis of metaanalysis of many studies from the literature (notably, the saline/nonsaline split in environmental samples and the split between host-associated and free-living communities). We also demonstrate that 2,000 Illumina single-end reads are sufficient to recapture the same relationships among samples that we observe with the full dataset. The results thus open up the possibility of conducting large-scale studies analyzing thousands of samples simultaneously to survey microbial communities at an unprecedented spatial and temporal resolution.
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            SSAHA: a fast search method for large DNA databases.

            We describe an algorithm, SSAHA (Sequence Search and Alignment by Hashing Algorithm), for performing fast searches on databases containing multiple gigabases of DNA. Sequences in the database are preprocessed by breaking them into consecutive k-tuples of k contiguous bases and then using a hash table to store the position of each occurrence of each k-tuple. Searching for a query sequence in the database is done by obtaining from the hash table the "hits" for each k-tuple in the query sequence and then performing a sort on the results. We discuss the effect of the tuple length k on the search speed, memory usage, and sensitivity of the algorithm and present the results of computational experiments which show that SSAHA can be three to four orders of magnitude faster than BLAST or FASTA, while requiring less memory than suffix tree methods. The SSAHA algorithm is used for high-throughput single nucleotide polymorphism (SNP) detection and very large scale sequence assembly. Also, it provides Web-based sequence search facilities for Ensembl projects.
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              Xenobiotics shape the physiology and gene expression of the active human gut microbiome.

              The human gut contains trillions of microorganisms that influence our health by metabolizing xenobiotics, including host-targeted drugs and antibiotics. Recent efforts have characterized the diversity of this host-associated community, but it remains unclear which microorganisms are active and what perturbations influence this activity. Here, we combine flow cytometry, 16S rRNA gene sequencing, and metatranscriptomics to demonstrate that the gut contains a distinctive set of active microorganisms, primarily Firmicutes. Short-term exposure to a panel of xenobiotics significantly affected the physiology, structure, and gene expression of this active gut microbiome. Xenobiotic-responsive genes were found across multiple bacterial phyla, encoding antibiotic resistance, drug metabolism, and stress response pathways. These results demonstrate the power of moving beyond surveys of microbial diversity to better understand metabolic activity, highlight the unintended consequences of xenobiotics, and suggest that attempts at personalized medicine should consider interindividual variations in the active human gut microbiome. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                16 December 2013
                11 December 2013
                23 January 2014
                23 July 2014
                : 505
                : 7484
                : 559-563
                Affiliations
                [1 ]FAS Center for Systems Biology, Harvard University, Cambridge, MA, 02138, USA.
                [2 ]Society of Fellows, Harvard University, Cambridge, MA, 02138, USA.
                [3 ]Division of Endocrinology, Children’s Hospital Boston, Harvard Medical School, Boston, MA, 02115, USA.
                [4 ]Department of Bioengineering & Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, 94158, USA.
                Author notes
                [* ]To whom correspondence should be addressed. pturnbaugh@ 123456fas.harvard.edu
                [#]

                Present address: Mocular Genetics & Microbiology and Institute for Genome Sciences & Policy, Duke University, Durham, NC, 27708.

                Article
                NIHMS536070
                10.1038/nature12820
                3957428
                24336217
                255723c6-4850-4e3e-8f28-fb8ef9f5ee99

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