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DNA Research Advance Access first published online on October 3, 2007
This version published online on October 16, 2007
DNA Research, doi:10.1093/dnares/dsm018
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© The Author 2007. Kazusa DNA Research Institute
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Comparative Metagenomics Revealed Commonly Enriched Gene Sets in Human Gut Microbiomes

Ken Kurokawa1 {dagger}, Takehiko Itoh2 {dagger}, Tomomi Kuwahara3 {dagger}, Kenshiro Oshima4, Hidehiro Toh4,5, Atsushi Toyoda6, Hideto Takami7, Hidetoshi Morita8, Vineet K. Sharma6, Tulika P. Srivastava6, Todd D. Taylor6, Hideki Noguchi9, Hiroshi Mori1, Yoshitoshi Ogura10, Dusko S. Ehrlich11, Kikuji Itoh12, Toshihisa Takagi9, Yoshiyuki Sakaki6, Tetsuya Hayashi10,* and Masahira Hattori4,6,9,*

1 Laboratory of Comparative Genomics, Graduate School of Information Science, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, Japan
2 Life Science Research Group, Research Center for Advanced Science and Technology, Mitsubishi Research Institute, 3-6 Otemachi 2-chome Chiyoda-ku, Tokyo 100-8141, Japan
3 Department of Molecular Bacteriology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-5 Kuramoto-cho, Tokushima 770-8503, Japan
4 Kitasato Institute for Life Science, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan
5 Center for Basic Research, Kitasato Institute, 5-9-1 Shirokane, Minato-ku, Tokyo 108- 8641, Japan
6 RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
7 Extremophiles Research Program, Extremobiosphere Research Center, Japan Agency for Marine-Earth Science and Technology, 2-15 Natsushima, Yokosuka, Kanagawa 237-0061, Japan
8 School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501, Japan
9 Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan
10 Frontier Science Research Center, University of Miyazaki, 5200 Kiyotake, Miyazaki 889-1692, Japan
11 Institut National de la Recherche Agronomique, Domaine de Vilvet, 8352 Jouy en Josas, France
12 Department of Veterinary Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

Received 22 June 2007 ; accepted 30 July 2007.

Numerous microbes inhabit the human intestine, many of which are uncharacterized or uncultivable. They form a complex microbial community that deeply affects human physiology. To identify the genomic features common to all human gut microbiomes as well as those variable among them, we performed a large-scale comparative metagenomic analysis of fecal samples from 13 healthy individuals of various ages, including unweaned infants. We found that, while the gut microbiota from unweaned infants were simple and showed a high inter-individual variation in taxonomic and gene composition, those from adults and weaned children were more complex but showed a high functional uniformity regardless of age or sex. In searching for the genes over-represented in gut microbiomes, we identified 237 gene families commonly enriched in adult-type and 136 families in infant-type microbiomes, with a small overlap. An analysis of their predicted functions revealed various strategies employed by each type of microbiota to adapt to its intestinal environment, suggesting that these gene sets encode the core functions of adult and infant-type gut microbiota. By analysing the orphan genes, 647 new gene families were identified to be exclusively present in human intestinal microbiomes. In addition, we discovered a conjugative transposon family explosively amplified in human gut microbiomes, which strongly suggests that the intestine is a ‘hot spot’ for horizontal gene transfer between microbes.

Key words: metagenomics; human gut microbiota; gene family; conjugative transposon

* To whom correspondence should be addressed. Masahira Hattori. Tel. +81-7136-4070. Fax. +81-4-7136-4084. E-mail: hattori{at}k.u-tokyo.ac.jp; or Tetsuya Hayashi. Tel. +81-985-85-0871. Fax. +81-985-85-6475.

Edited by Osamu Ohara

{dagger} These authors contributed equally to this work.


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