title: Mining the Human Gut Microbiota for Immunomodulatory Organisms.
abstract: Within the human gut reside diverse microbes coexisting with the host in a mutually advantageous relationship. Evidence has revealed the pivotal role of the gut microbiota in shaping the immune system. To date, only a few of these microbes have been shown to modulate specific immune parameters. Herein, we broadly identify the immunomodulatory effects of phylogenetically diverse human gut microbes. We monocolonized mice with each of 53 individual bacterial species and systematically analyzed host immunologic adaptation to colonization. Most microbes exerted several specialized, complementary, and redundant transcriptional and immunomodulatory effects. Surprisingly, these were independent of microbial phylogeny. Microbial diversity in the gut ensures robustness of the microbiota's ability to generate a consistent immunomodulatory impact, serving as a highly important epigenetic system. This study provides a foundation for investigation of gut microbiota-host mutualism, highlighting key players that could identify important therapeutics.
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Naama
authors.initials: N
authors.lastname: Geva-Zatorsky
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Esen
authors.initials: E
authors.lastname: Sefik
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Kua
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lesley
authors.initials: L
authors.lastname: Pasman
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Tze Guan
authors.initials: TG
authors.lastname: Tan
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Ortiz-Lopez
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Tsering Bakto
authors.initials: TB
authors.lastname: Yanortsang
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.affiliation: UCB Pharma, Slough, Berkshire SL1 3WE, UK.
authors.forename: Ray
authors.initials: R
authors.lastname: Jupp
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: dennis_kasper@hms.harvard.edu.
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Kasper
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001419:Bacteria / Q000145:classification*; D018407:Bacterial Physiological Phenomena; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000166:cytology / Q000276:immunology* / Q000382:microbiology* / Q000502:physiology; D005856:Germ-Free Life; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D013559:Symbiosis
keywords: gnotobiotic; gut bacteria; immunomodulation; immunoprofiling; innate and adaptive immunity; microbiome