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PMID: 15070763 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 13 ·2004-03-30 ·Pages 4596-601

Rawls JF, Samuel BS, Gordon JI

Abstract

Animals have developed the means for supporting complex and dynamic consortia of microorganisms during their life cycle. A transcendent view of vertebrate biology therefore requires an understanding of the contributions of these indigenous microbial communities to host development and adult physiology. These contributions are most obvious in the gut, where studies of gnotobiotic mice have disclosed that the microbiota affects a wide range of biological processes, including nutrient processing and absorption, development of the mucosal immune system, angiogenesis, and epithelial renewal. The zebrafish (Danio rerio) provides an opportunity to investigate the molecular mechanisms underlying these interactions through genetic and chemical screens that take advantage of its transparency during larval and juvenile stages. Therefore, we developed methods for producing and rearing germ-free zebrafish through late juvenile stages. DNA microarray comparisons of gene expression in the digestive tracts of 6 days post fertilization germ-free, conventionalized, and conventionally raised zebrafish revealed 212 genes regulated by the microbiota, and 59 responses that are conserved in the mouse intestine, including those involved in stimulation of epithelial proliferation, promotion of nutrient metabolism, and innate immune responses. The microbial ecology of the digestive tracts of conventionally raised and conventionalized zebrafish was characterized by sequencing libraries of bacterial 16S rDNA amplicons. Colonization of germ-free zebrafish with individual members of its microbiota revealed the bacterial species specificity of selected host responses. Together, these studies establish gnotobiotic zebrafish as a useful model for dissecting the molecular foundations of host-microbial interactions in the vertebrate digestive tract.

MeSH Terms
Air Sacs/microbiology Animals Biological Evolution Digestive System/microbiology Epithelial Cells/cytology,immunology Fisheries Germ-Free Life Intestinal Mucosa/microbiology Intestines/microbiology Mammals/microbiology Molecular Sequence Data Transcription, Genetic Zebrafish/microbiology
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Rawls John F
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63108, USA.
Samuel Buck S
Gordon Jeffrey I
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0400706101
Published
2004-03-30
Epub
2004-00-19
Pages
4596-601
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC384792
Subset
IM
Grants
NIDDK NIH HHS · DK62675 · United States
NIDDK NIH HHS · R01 DK030292 · United States
NIDDK NIH HHS · DK30292 · United States
NIDDK NIH HHS · F32 DK062675 · United States
NIDDK NIH HHS · R37 DK030292 · United States
Databases
GENBANK
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AY537721, AY537722, AY537723, AY537724, AY537725, AY537726, AY537727, AY537728, AY537729, AY537730, AY537731, AY537732, AY537733, AY537734, AY537735, AY537736, AY537737, AY537738, AY537739, AY537740, AY537741, AY537742, AY537743, AY537744, AY537745, AY537746, AY537747, AY537748, AY537749, AY537750, AY537751, AY537752, AY537753, AY537754, AY537755, AY537756, AY537757, AY537758, AY537759, AY537760, AY537761, AY537762, AY537763, AY537764, AY537765, AY537766, AY537767, AY537768, AY537769, AY537770, AY537771, AY537772, AY537773, AY537774, AY537775, AY537776, AY537777, AY537778, AY537779, AY537780, AY537781, AY537782, AY537783, AY537784, AY537785, AY537786, AY537787, AY537788, AY537789, AY537790, AY537791, AY537792, AY537793, AY537794, AY537795, AY537796, AY537797, AY537798, AY537799, AY537800, AY537801, AY537802, AY537803, AY537804, AY537805, AY537806, AY537807, AY537808, AY537809, AY537810, AY537811, AY537812, AY537813, AY537814, AY537815, AY537816, AY537817, AY537818, AY537819, AY537820, AY537821, AY537822, AY537823, AY537824, AY537825, AY537826, AY537827, AY537828, AY537829, AY537830, AY537831, AY537832, AY537833, AY537834, AY537835, AY537836, AY537837, AY537838, AY537839, AY537840, AY537841, AY537842, AY537843, AY537844, AY537845, AY537846, AY537847, AY537848, AY537849, AY537850, AY537851, AY537852, AY537853, AY537854, AY537855, AY537856, AY537857, AY537858, AY537859, AY537860, AY537861, AY537862, AY537863, AY537864, AY537865, AY537866, AY537867, AY537868, AY537869, AY537870, AY537871, AY537872, AY537873, AY537874, AY537875, AY537876, AY537877, AY537878, AY537879, AY537880, AY537881, AY537882, AY537883, AY537884, AY537885, AY537886, AY537887, AY537888, AY537889, AY537890, AY537891, AY537892, AY537893, AY537894, AY537895, AY537896, AY537897, AY537898, AY537899, AY537900, AY537901, AY537902, AY537903, AY537904, AY537905, AY537906, AY537907, AY537908, AY537909, AY537910, AY537911, AY537912, AY537913, AY537914, AY537915, AY537916, AY537917, AY537918, AY537919, AY537920
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PubMed source DOI: 10.1073/pnas.0400706101 PMC Full Text View journal details
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