The gut microbiota and mucosal homeostasis: Colonized at birth or at adulthood, does it matter?
Open accessAbstract
The intimate interplay between the gut microbiota and the host may contribute to health and disease in the host. Experiments using conventionalized and conventionally raised animal models have illustrated the role of the intestinal microbiota in shaping and maintaining the host immune system. However, it is still unclear whether colonization at birth or at adulthood induces different host responses. Here, we perform comparative transcriptome analyses to elucidate the impact of the gut microbiota on the development and maintenance of the immune system in adult conventionalized (after 16 and 30 days of colonization) and conventionally raised mice, which were obtained in two independent laboratories. Transcriptional profiles of jejunum, ileum and colon were compared between germfree, conventionally raised mice and conventionalized mice. Germfree mice from the two different facilities clustered together, establishing the validity of the comparative analysis. Nevertheless, significant spatial differences were detected along the gut; the jejunum and colon exhibited a transient response (conventionalized mice) that eventually returned to a homeostatic level (conventionally raised). In contrast, the ileal response to microbiota was similar in conventionalized and conventionally raised mice. Overall, this comparative analysis supports the hypothesis that co-development of the gut microbiota and its host initiates at early stage of development and indicates that despite the achieved homeostasis, immune development is substantially different in mice conventionalized in adulthood. These findings imply that colonization during development is required to meet the window of opportunity where the gut microbiota can imprint the host's mucosal immune-homeostasis in a way that cannot be achieved at later stages in life.
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Deficits in germ-free mice can be corrected by colonization with diverse commensal bacteria, but this is age-dependent, suggesting composition and timing of colonization are critical for immune education.
“These deficits can be corrected by colonization with diverse commensal bacteria; however, this has been shown to be age-dependent, suggesting that both composition and timing of colonization are critical for the education of the immune system [16–18].”
From The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders (2018) · cites this paper as [17]
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Cites
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
Bioconductor: open software development for computational biology and bioinformatics
Gentleman, R., Carey, V., Bates, D., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., et al. (2004) · Genome Biology · doi:10.1186/gb-2004-5-10-r80 · Cited by 13,133 · see citing works
Adjusting batch effects in microarray expression data using empirical Bayes methods
Johnson, W. E., Li, C., & Rabinovic, A. (2007) · Biostatistics · doi:10.1093/biostatistics/kxj037 · Cited by 8,658 · see citing works
Host-gut microbiota metabolic interactions
Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., & Pettersson, S. (2012) · Science · doi:10.1126/science.1223813 · Cited by 4,760 · see citing works
Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Cryan, J. F., & Dinan, T. G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3346 · Cited by 4,572 · see citing works
Normal gut microbiota modulates brain development and behavior
Heijtz, R. D., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., Hibberd, M. L., Forssberg, H., & Pettersson, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010529108 · Cited by 3,228 · see citing works
Development of the Human Infant Intestinal Microbiota
Palmer, C., Bik, E. M., DiGiulio, D. B., Relman, D. A., & Brown, P. O. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050177 · Cited by 2,877 · see citing works
Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X., Kubo, C., & Koga, Y. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.063388 · Cited by 2,735 · see citing works
Commensal Host-Bacterial Relationships in the Gut
Hooper, L. V., & Gordon, J. I. (2001) · Science · doi:10.1126/science.1058709 · Cited by 2,362 · see citing works
[9] TM4 Microarray Software Suite
Saeed, A. I., BHAGABATI, N. K., Braisted, J. C., Liang, W. P., Sharov, V., Howe, E., Li, J., Thiagarajan, M., White, J., & Quackenbush, J. F. (2006) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(06)11009-5 · Cited by 1,982 · see citing works
STEM: a tool for the analysis of short time series gene expression data
Ernst, J., & Bar-Joseph, Z. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-191 · Cited by 1,703 · see citing works
Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function
Olszak, T., An, D., Zeissig, S., Vera, M. P., Richter, J., Franke, A., Glickman, J. N., Siebert, R., Baron, R. M., Kasper, D. L., et al. (2012) · Science · doi:10.1126/science.1219328 · Cited by 1,661 · see citing works
Gene-specific control of inflammation by TLR-induced chromatin modifications
Foster, S. L., Hargreaves, D. C., & Medzhitov, R. (2007) · Nature · doi:10.1038/nature05836 · Cited by 1,344 · see citing works
Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System?
Lee, Y. K., & Mazmanian, S. K. (2010) · Science · doi:10.1126/science.1195568 · Cited by 1,115 · see citing works
Is meconium from healthy newborns actually sterile?
Jiménez, E., Marín, M. L., Martı́n, R., Odriozola, J. M., Olivares, M. M., Xaus, J., Fernández, L., & Rodríguez, J. M. (2008) · Research in Microbiology · doi:10.1016/j.resmic.2007.12.007 · Cited by 944 · see citing works
Falk, P. G., Hooper, L. V., Midtvedt, T., & Gordon, J. I. (1998) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.62.4.1157-1170.1998 · Cited by 643 · see citing works
SECKL, J. R., & MEANEY, M. J. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1314.006 · Cited by 556 · see citing works
The ‘microflora hypothesis’ of allergic diseases
Noverr, M. C., & Huffnagle, G. B. (2005) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2005.02379.x · Cited by 394 · see citing works
Larsson, E., Tremaroli, V., Lee, Y. S., Koren, O., Nookaew, I., Fricker, A. D., Nielsen, J., Ley, R. E., & Bäckhed, F. (2011) · Gut · doi:10.1136/gutjnl-2011-301104 · Cited by 386 · see citing works
Self-citationPatterns of Early Gut Colonization Shape Future Immune Responses of the Host
Hansen, C. H. F., Nielsen, D. S., Kverka, M., Zakostelska, Z. J., Kostovcikova, K., Hudcovic, T., Tlaskalová‐Hogenová, H., & Hansen, A. K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034043 · Cited by 310 · see citing works
Aidy, S. E., van Baarlen, P., Derrien, M., Lindenbergh-Kortleve, D. J., Hooiveld, G. J. E. J., Levenez, F., Dore, J. M., Dekker, J. P., Samsom, J. N., Nieuwenhuis, E. E. S., et al. (2012) · Mucosal Immunology · doi:10.1038/mi.2012.32 · Cited by 247 · see citing works
Self-citationGalindo‐Villegas, J., García‐Moreno, D., de Oliveira, S., Meseguer, J., & Mulero, V. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209920109 · Cited by 228 · see citing works
Mulder, I. E., Schmidt, B., Lewis, M. C., Delday, M. I., Stokes, C., Bailey, M., Aminov, R. I., Gill, B. P., Pluske, J. R., Mayer, C., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028279 · Cited by 179 · see citing works
MADMAX – Management and analysis database for multiple ~omics experiments
Lin, K., Kools, H. J., de Groot, P. J., Gavai, A., Basnet, R. K., Cheng, F., Wu, J., Wang, X., Lommen, A., Hooiveld, G. J. E. J., et al. (2011) · Berichte aus der medizinischen Informatik und Bioinformatik/Journal of integrative bioinformatics · doi:10.1515/jib-2011-160 · Cited by 170 · see citing works
Self-citationLundin, A., Bok, C. M., Aronsson, L., Björkholm, B., Gustafsson, J.-Å., Pott, S., Arulampalam, V., Hibberd, M. L., Rafter, J. J., & Pettersson, S. (2008) · Cellular Microbiology · doi:10.1111/j.1462-5822.2007.01108.x · Cited by 153 · see citing works
Experimental Design and Low-Level Analysis of Microarray Data
Bolstad, B. M., Collin, F., Simpson, K., Irizarry, R. A., & Speed, T. P. (2004) · International review of neurobiology · doi:10.1016/s0074-7742(04)60002-x · Cited by 125 · see citing works
Quality Assessment of Affymetrix GeneChip Data
Heber, S., & Sick, B. (2006) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2006.10.358 · Cited by 118 · see citing works
The “Microflora Hypothesis” of Allergic Disease
Shreiner, A. B., Huffnagle, G. B., & Noverr, M. C. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-09550-9_10 · Cited by 112 · see citing works
MADMAX - Management and analysis database for multiple ~omics experiments
Lin, K., Kools, H. J., de Groot, P. J., et al. (2011) · PubMed · doi:10.2390/biecoll-jib-2011-160 · Cited by 77 · see citing works
Mittal, P., Romero, R. J., Kusanovic, J. P., Edwin, S. S., Gotsch, F., Mazaki‐Tovi, S., Espinoza, J., Erez, O., Nhan‐Chang, C., Than, N. G., et al. (2008) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2008.00620.x · Cited by 71 · see citing works
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Gensollen, T., Iyer, S. S., Kasper, D. L., & Blumberg, R. S. (2016) · Science · doi:10.1126/science.aad9378 · Cited by 2,044 · see citing works
The gut microbiota at the intersection of diet and human health
Gentile, C. L., & Weir, T. L. (2018) · Science · doi:10.1126/science.aau5812 · Cited by 1,049 · see citing works
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Hughes, H. K., Rose, D., & Ashwood, P. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0887-6 · Cited by 225 · see citing works
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O’Mahony, S. M., Clarke, G., Dinan, T. G., & Cryan, J. F. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2015.09.068 · Cited by 203 · see citing works
- Authors
- El Aidy, S., Hooiveld, G., Tremaroli, V., Bäckhed, F., & Kleerebezem, M.
- Affiliations
- Wageningen University & Research (NL)
- Nederlands Instituut Voor Zuivel Oonderzoek (NL)
- Corresponding author
- Kleerebezem, Michiel
- Venue
- Gut Microbes
- Publisher
- Informa UK Limited
- Published
- 2013-01
- Volume
- 4
- Issue
- 2
- Pages
- 118-124
- ISSN
- 1949-0976 (ISSN-L)
- 1949-0984
- PMC
- PMC3595071
- OpenAlex
- W1933219276
- Cited by
- 131
- References
- 30
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 11 · 2023: 14 · 2022: 20 · 2021: 11 · 2020: 10 · 2019: 9 · 2018: 7 · 2017: 10 · 2016: 4 · 2015: 6 · 2014: 9 · 2013: 2
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut Microbes (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- gut microbiota, mucosal immunity, immune homeostasis, germ-free mice, conventionalization, host-microbe interactions, intestinal transcriptome, jejunum, ileum, colon, immune system development
- MeSH terms
- Age Factors, Animals, Animals, Newborn, Homeostasis, Mice, Inbred C57BL, Gene Expression Profiling, Gastrointestinal Tract, Mice, Metagenome
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