Reciprocal interactions of the intestinal microbiota and immune system
Open accessAbstract
The emergence of the adaptive immune system in vertebrates set the stage for evolution of an advanced symbiotic relationship with the intestinal microbiota. The defining features of specificity and memory that characterize adaptive immunity have afforded vertebrates the mechanisms for efficiently tailoring immune responses to diverse types of microbes, whether to promote mutualism or host defence. These same attributes can put the host at risk of immune-mediated diseases that are increasingly linked to the intestinal microbiota. Understanding how the adaptive immune system copes with the remarkable number and diversity of microbes that colonize the digestive tract, and how the system integrates with more primitive innate immune mechanisms to maintain immune homeostasis, holds considerable promise for new approaches to modulate immune networks to treat and prevent disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Intestinal tissues are enriched in both Th17 and Treg cells and are subject to ongoing antigenic stimulation from the intestinal microbiome.
“This is of particular importance in intestinal tissues, which are enriched in both Th17 and Treg cells and are subject to ongoing antigenic stimulation from the intestinal microbiome (70).”
From T <sub>H</sub> 17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity (2020) · cites this paper as [70]
Ecological conditions vary immensely along both the length of the GI tract as well as in cross-section from lumen to the mucosal brush-border.
“Ecological conditions vary immensely along both the length of the GI tract as well as in cross-section from lumen to the mucosal brush-border[173,267,308,309].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [308]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A human gut microbial gene catalogue established by metagenomic sequencing
MetaHIT Consortium, Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., et al. (2010) · Nature · doi:10.1038/nature08821 · Cited by 11,624 · see citing works
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
Hugot, J.-P., Chamaillard, M., Zouali, H., Lesage, S., Cézard, J.-P., Belaiche, J., Almer, S., Tysk, C., O'Morain, C. A., Gassull, M., et al. (2001) · Nature · doi:10.1038/35079107 · Cited by 5,591 · see citing works
A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
Ogura, Y., Bonen, D. K., Inohara, N., Nicolae, D. L., Chen, F. F., Ramos, R., Britton, H., Moran, T., Karaliuskas, R., Duerr, R. H., et al. (2001) · Nature · doi:10.1038/35079114 · Cited by 5,030 · see citing works
Dominguez-Bello, M. G., Costello, E. K., Contreras, M., Magris, M., Hidalgo, G., Fierer, N., & Knight, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002601107 · Cited by 4,774 · see citing works
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554 · see citing works
Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis
Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., & Medzhitov, R. (2004) · Cell · doi:10.1016/j.cell.2004.07.002 · Cited by 4,251 · see citing works
Interleukin-10-deficient mice develop chronic enterocolitis
Kühn, R., Löhler, J., Rennick, D. M., Rajewsky, K., & Müller, W. (1993) · Cell · doi:10.1016/0092-8674(93)80068-p · Cited by 4,248 · see citing works
Induction of Colonic Regulatory T Cells by Indigenous <i>Clostridium</i> Species
Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., et al. (2011) · Science · doi:10.1126/science.1198469 · Cited by 3,752 · see citing works
Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine
Ley, R. E., Peterson, D. A., & Gordon, J. I. (2006) · Cell · doi:10.1016/j.cell.2006.02.017 · Cited by 3,358 · see citing works
Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43
Maslowski, K. M., Vieira, A. T., Ng, A., Kranich, J., Sierro, F., Yu, D., Schilter, H. C., Rolph, M. S., Mackay, F., Artis, D., et al. (2009) · Nature · doi:10.1038/nature08530 · Cited by 3,241 · 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
Coombes, J. L., Siddiqui, K. R. R., Arancibia-Cárcamo, C. V., Hall, J. A., Sun, C., Belkaid, Y., & Powrie, F. M. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070590 · Cited by 2,708 · see citing works
Genetics and pathogenesis of inflammatory bowel disease
Khor, B., Gardet, A., & Xavier, R. J. (2011) · Nature · doi:10.1038/nature10209 · Cited by 2,629 · see citing works
Bifidobacteria can protect from enteropathogenic infection through production of acetate
Fukuda, S., Toh, H., Hase, K., Oshima, K., Nakanishi, Y., Yoshimura, K., Tobe, T., Clarke, J. M., Topping, D. L., Suzuki, T., et al. (2011) · Nature · doi:10.1038/nature09646 · Cited by 2,387 · see citing works
NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis
Elinav, E., Strowig, T., Kau, A. L., Henao-Mejia, J., Thaiss, C. A., Booth, C. J., Peaper, D. R., Bertin, J., Eisenbarth, S. C., Gordon, J. I., et al. (2011) · Cell · doi:10.1016/j.cell.2011.04.022 · Cited by 2,024 · see citing works
Reciprocal T <sub>H</sub> 17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid
Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M., & Cheroutre, H. (2007) · Science · doi:10.1126/science.1145697 · Cited by 1,982 · see citing works
Sun, C., Hall, J. A., Blank, R. B., Bouladoux, N. J., Oukka, M., Mora, J. R., & Belkaid, Y. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070602 · Cited by 1,880 · see citing works
Phenotypic and functional features of human Th17 cells
Annunziato, F., Cosmi, L., Santarlasci, V., Maggi, L., Liotta, F., Mazzinghi, B., Parente, E., Filì, L., Ferri, S., Frosali, F., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070663 · Cited by 1,861 · see citing works
Ivanov, I. I., Frutos, R. D. L., Manel, N., Yoshinaga, K., Rifkin, D. B., Sartor, R. B., Finlay, B. B., & Littman, D. R. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.09.009 · Cited by 1,770 · see citing works
Van der Sluis, M., De Koning, B. A. E., De Bruijn, A. C. J. M., Velcich, A., Meijerink, J. P. P., Van Goudoever, J. B., Büller, H. A., Dekker, J., Van Seuningen, I., Renes, I. B., et al. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.04.020 · Cited by 1,684 · 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
The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota
Round, J. L., Lee, S. M., Li, J., Tran, G., Jabri, B., Chatila, T. A., & Mazmanian, S. K. (2011) · Science · doi:10.1126/science.1206095 · Cited by 1,604 · see citing works
Induction of Protective IgA by Intestinal Dendritic Cells Carrying Commensal Bacteria
Macpherson, A. J., & Uhr, T. (2004) · Science · doi:10.1126/science.1091334 · Cited by 1,584 · see citing works
Gut-Residing Segmented Filamentous Bacteria Drive Autoimmune Arthritis via T Helper 17 Cells
Wu, H.-J., Ivanov, I. I., Darce, J., Hattori, K., Shima, T., Umesaki, Y., Littman, D. R., Benoist, C., & Mathis, D. (2010) · Immunity · doi:10.1016/j.immuni.2010.06.001 · Cited by 1,577 · see citing works
IL-23 is essential for T cell–mediated colitis and promotes inflammation via IL-17 and IL-6
Yen, D., Cheung, J., Scheerens, H., Poulet, F. M., McClanahan, T. K., McKenzie, B. S., Kleinschek, M. A., Owyang, A. M., Mattson, J. D., Blumenschein, W. M., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci21404 · Cited by 1,532 · see citing works
Sellon, R. K., Tonkonogy, S., Schultz, M., Dieleman, L. A., Grenther, W., Balish, E., Rennick, D. M., & Sartor, R. B. (1998) · Infection and Immunity · doi:10.1128/iai.66.11.5224-5231.1998 · Cited by 1,483 · see citing works
Inflammatory Bowel Disease and Mutations Affecting the Interleukin-10 Receptor
Glocker, E., Kotlarz, D., Boztuǧ, K., Gertz, E. M., Schäffer, A. A., Noyan, F., Perro, M., Diestelhorst, J., Saborowski, A. L., Murugan, D., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0907206 · Cited by 1,464 · see citing works
Johansson, M., Larsson, J. M. H., & Hansson, G. C. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006451107 · Cited by 1,459 · see citing works
Gaboriau-Routhiau, V., Rakotobe, S., Lécuyer, E., Mulder, I., Lan, A., Bridonneau, C., Rochet, V., Pisi, A., De Paepe, M., Brandi, G., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.020 · Cited by 1,452 · see citing works
Symbiotic bacteria direct expression of an intestinal bactericidal lectin
Cash, H. L., Whitham, C. V., Behrendt, C. L., & Hooper, L. V. (2006) · Science · doi:10.1126/science.1127119 · Cited by 1,432 · see citing works
Vaishnava, S., Yamamoto, M., Severson, K. M., Ruhn, K. A., Yu, X., Koren, O., Ley, R., Wakeland, E. K., & Hooper, L. V. (2011) · Science · doi:10.1126/science.1209791 · Cited by 1,412 · see citing works
Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis
Lee, Y. K., Menezes, J. S., Umesaki, Y., & Mazmanian, S. K. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000082107 · Cited by 1,323 · see citing works
Lupp, C., Robertson, M. L., Wickham, M. E., Sekirov, I., Champion, O. L., Gaynor, E. C., & Finlay, B. B. (2007) · Cell Host & Microbe · doi:10.1016/j.chom.2007.06.010 · Cited by 1,310 · see citing works
A human NK cell subset provides an innate source of IL-22 for mucosal immunity
Cella, M., Fuchs, A., Vermi, W., Facchetti, F., Otero, K., Lennerz, J., Doherty, J., Mills, J., & Colonna, M. (2008) · Nature · doi:10.1038/nature07537 · Cited by 1,230 · see citing works
Takeda, K., Clausen, B. E., Kaisho, T., Tsujimura, T., Terada, N., Förster, I., & Akira, S. (1999) · Immunity · doi:10.1016/s1074-7613(00)80005-9 · Cited by 1,220 · see citing works
Enteric defensins are essential regulators of intestinal microbial ecology
Salzman, N. H., Hung, K., Haribhai, D., Chu, H., Karlsson-Sjöberg, J., Amir, E., Teggatz, P., Barman, M., Hayward, M., Eastwood, D., et al. (2010) · Nature Immunology · doi:10.1038/ni.1825 · Cited by 1,156 · see citing works
Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis
Bouskra, D., Brézillon, C., Bérard, M., Werts, C., Varona, R., Boneca, I. G., & Eberl, G. (2008) · Nature · doi:10.1038/nature07450 · Cited by 1,107 · see citing works
ATP drives lamina propria TH17 cell differentiation
Atarashi, K., Nishimura, J., Shima, T., Umesaki, Y., Yamamoto, M., Onoue, M., Yagita, H., Ishii, N., Evans, R., Honda, K., et al. (2008) · Nature · doi:10.1038/nature07240 · Cited by 1,089 · see citing works
Sonnenberg, G. F., Fouser, L., & Artis, D. (2011) · Nature Immunology · doi:10.1038/ni.2025 · Cited by 1,067 · see citing works
Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology
Buonocore, S. M., Ahern, P. P., Uhlig, H. H., Ivanov, I. I., Littman, D. R., Maloy, K. J., & Powrie, F. M. (2010) · Nature · doi:10.1038/nature08949 · Cited by 1,066 · see citing works
Late Developmental Plasticity in the T Helper 17 Lineage
Lee, Y. K., Turner, H., Maynard, C. L., Oliver, J. R., Chen, D., Elson, C. O., & Weaver, C. T. (2009) · Immunity · doi:10.1016/j.immuni.2008.11.005 · Cited by 1,053 · see citing works
Self-citationPeripheral education of the immune system by colonic commensal microbiota
Lathrop, S. K., Bloom, S. M., Rao, S. M., Nutsch, K., Lio, C.-W., Santacruz, N., Peterson, D. A., Stappenbeck, T. S., & Hsieh, C.-S. (2011) · Nature · doi:10.1038/nature10434 · Cited by 1,034 · see citing works
Kelly, D., Campbell, J. I., King, T. P., Grant, G., Jansson, E. Å., Coutts, A., Pettersson, S., & Conway, S. (2003) · Nature Immunology · doi:10.1038/ni1018 · Cited by 997 · see citing works
Chaudhry, A., Samstein, R. M., Treuting, P., Liang, Y., Pils, M. C., Heinrich, J.-M., Jack, R. S., Wunderlich, F. T., Brüning, J. C., Müller, W., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.03.018 · Cited by 980 · see citing works
Smythies, L. E., Sellers, M. T., Clements, R. H., Mosteller‐Barnum, M., Meng, G., Benjamin, W. H., Orenstein, J. M., & Smith, P. D. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200519229 · Cited by 924 · see citing works
IgT, a primitive immunoglobulin class specialized in mucosal immunity
Zhang, Y., Salinas, I., Li, J., Parra, D., Bjork, S. J., Xu, Z., LaPatra, S. E., Bartholomew, J. L., & Sunyer, J. O. (2010) · Nature Immunology · doi:10.1038/ni.1913 · Cited by 904 · see citing works
The Aryl Hydrocarbon Receptor Regulates Gut Immunity through Modulation of Innate Lymphoid Cells
Qiu, J., Heller, J. J., Guo, X.-H., Chen, Z.-M. E., Fish, K., Fu, Y.-X., & Zhou, L. (2011) · Immunity · doi:10.1016/j.immuni.2011.11.011 · Cited by 850 · see citing works
Prokaryotic Regulation of Epithelial Responses by Inhibition of IκB-α Ubiquitination
Neish, A. S., Gewirtz, A. T., Zeng, H., Young, A. N., Hobert, M. E., Karmali, V., Rao, A. S., & Madara, J. (2000) · Science · doi:10.1126/science.289.5484.1560 · Cited by 843 · see citing works
Spits, H., & Santo, J. P. D. (2010) · Nature Immunology · doi:10.1038/ni.1962 · Cited by 842 · see citing works
Intestinal Bacterial Colonization Induces Mutualistic Regulatory T Cell Responses
Geuking, M. B., Cahenzli, J., Lawson, M. A. E., Ng, D. C. K., Slack, E., Hapfelmeier, S., McCoy, K. D., & Macpherson, A. J. (2011) · Immunity · doi:10.1016/j.immuni.2011.03.021 · Cited by 840 · see citing works
Extrathymically generated regulatory T cells control mucosal TH2 inflammation
Josefowicz, S. Z., Niec, R. E., Kim, H. Y., Treuting, P. M., Chinen, T., Zheng, Y., Umetsu, D. T., & Rudensky, A. Y. (2012) · Nature · doi:10.1038/nature10772 · Cited by 823 · see citing works
Bacterial flagellin is a dominant antigen in Crohn disease
Lodes, M. J., Cong, Y., Elson, C. O., Mohamath, R., Landers, C. J., Targan, S. R., Fort, M., & Hershberg, R. M. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420295 · Cited by 802 · see citing works
Garrett, W. S., Gallini, C. A., Yatsunenko, T., Michaud, M., DuBois, A., Delaney, M. L., Punit, S., Karlsson, M., Bry, L., Glickman, J. N., et al. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.08.004 · Cited by 788 · see citing works
Kastelein, R. A., Hunter, C. A., & Cua, D. J. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104758 · Cited by 758 · see citing works
He, B., Xu, W., Santini, P. A., Polydorides, A. D., Chiu, A., Estrella, J. S., Shan, M., Chadburn, A., Villanacci, V., Plebani, A., et al. (2007) · Immunity · doi:10.1016/j.immuni.2007.04.014 · Cited by 748 · see citing works
Lymphoid tissue inducer–like cells are an innate source of IL-17 and IL-22
Takatori, H., Kanno, Y., Watford, W. T., Tato, C. M., Weiss, G. E., Ivanov, I. I., Littman, D. R., & O’Shea, J. J. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20072713 · Cited by 737 · see citing works
Bergstrom, K. S. B., Kissoon-Singh, V., Gibson, D. L., Ma, C., Montero, M., Sham, H. P., Ryz, N., Huang, T., Velcich, A., Finlay, B. B., et al. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000902 · Cited by 625 · see citing works
Maynard, C. L., Harrington, L. E., Janowski, K. M., Oliver, J. R., Zindl, C. L., Rudensky, A. Y., & Weaver, C. T. (2007) · Nature Immunology · doi:10.1038/ni1504 · Cited by 599 · see citing works
New insights into the development of lymphoid tissues
van de Pavert, S. A., & Mebius, R. E. (2010) · Nature reviews. Immunology · doi:10.1038/nri2832 · Cited by 597 · see citing works
Preferential Generation of Follicular B Helper T Cells from Foxp3 + T Cells in Gut Peyer's Patches
Tsuji, M., Komatsu, N., Kawamoto, S., Suzuki, K., Kanagawa, O., Honjo, T., Hori, S., & Fagarasan, S. (2009) · Science · doi:10.1126/science.1169152 · Cited by 592 · see citing works
the IBSEN study group, Franke, A., Balschun, T. C., Karlsen, T. H., Skiecevičienė, J., Nikolaus, S., Gabriele Mayr, B., Domingues, F. S., Albrecht, M., Nothnagel, M., et al. (2008) · Nature Genetics · doi:10.1038/ng.221 · Cited by 590 · see citing works
Intestinal Bacteria and the Regulation of Immune Cell Homeostasis
Hill, D. A., & Artis, D. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101330 · Cited by 586 · see citing works
Huber, S., Gagliani, N., Esplugues, E., O'Connor, W., Huber, F. J., Chaudhry, A., Kamanaka, M., Kobayashi, Y., Booth, C. J., Rudensky, A. Y., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.01.020 · Cited by 581 · see citing works
CD4+ Lymphoid Tissue-Inducer Cells Promote Innate Immunity in the Gut
Sonnenberg, G. F., Monticelli, L. A., Elloso, M. M., Fouser, L. A., & Artis, D. (2010) · Immunity · doi:10.1016/j.immuni.2010.12.009 · Cited by 573 · see citing works
Sawa, S., Lochner, M., Satoh‐Takayama, N., Dulauroy, S., Berard, M., Kleinschek, M. A., Cua, D., Santo, J. P. D., & Eberl, G. (2011) · Nature Immunology · doi:10.1038/ni.2002 · Cited by 568 · see citing works
Regulatory Lymphocytes and Intestinal Inflammation
Ízcue, A., Coombes, J. L., & Powrie, F. M. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132657 · Cited by 505 · see citing works
Caesarean delivery and risk of atopy and allergic disesase: meta‐analyses
Bager, P., Wohlfahrt, J., & Westergaard, T. (2008) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2008.02939.x · Cited by 503 · see citing works
Hall, J. A., Bouladoux, N. J., Sun, C., Wohlfert, E. A., Blank, R. B., Zhu, Q., Grigg, M. E., Berzofsky, J. A., & Belkaid, Y. (2008) · Immunity · doi:10.1016/j.immuni.2008.08.009 · Cited by 490 · see citing works
Targan, S. R., Landers, C. J., Yang, H., Lodes, M. J., Cong, Y., Papadakis, K. A., Vasiliauskas, E., Elson, C. O., & Hershberg, R. M. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.03.046 · Cited by 476 · see citing works
Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells
Lotz, M., Gütle, D., Walther, S., Ménard, S., Bogdan, C., & Hornef, M. W. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20050625 · Cited by 464 · see citing works
Tsuji, M., Suzuki, K., Kitamura, H., Maruya, M., Kinoshita, K., Ivanov, I. I., Itoh, K., Littman, D. R., & Fagarasan, S. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.014 · Cited by 441 · see citing works
A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota
Cong, Y., Feng, T., Fujihashi, K., Schoeb, T. R., & Elson, C. O. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812681106 · Cited by 430 · see citing works
Developmental plasticity of Th17 and Treg cells
Lee, Y. K., Mukasa, R., Hatton, R. D., & Weaver, C. T. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.05.021 · Cited by 423 · see citing works
Talham, G. L., Jiang, H.-Q., Bos, N. A., & Cebra, J. J. (1999) · Infection and Immunity · doi:10.1128/iai.67.4.1992-2000.1999 · Cited by 408 · see citing works
Kanamori, Y., Ishimaru, K., Nanno, M., Maki, K., Ikuta, K., Nariuchi, H., & Ishikawa, H. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.4.1449 · Cited by 402 · see citing works
Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective
Weaver, C. T., & Hatton, R. D. (2009) · Nature reviews. Immunology · doi:10.1038/nri2660 · Cited by 396 · see citing works
Franchi, L., Kamada, N., Nakamura, Y., Burberry, A., Kuffa, P., Suzuki, S., Shaw, M. H., Kim, Y., & Núñez, G. (2012) · Nature Immunology · doi:10.1038/ni.2263 · Cited by 394 · see citing works
Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens
DePaolo, R. W., Abadie, V., Tang, F., Fehlner-Peach, H., Hall, J. A., Wang, W., Marietta, E. V., Kasarda, D. D., Waldmann, T. A., Murray, J. A., et al. (2011) · Nature · doi:10.1038/nature09849 · Cited by 389 · see citing works
Importance and regulation of the colonic mucus barrier in a mouse model of colitis
Petersson, J., Schreiber, O., Hansson, G. C., Gendler, S. J., Velcich, A., Lundberg, J. O., Roos, S., Holm, L., & Phillipson, M. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00422.2010 · Cited by 384 · see citing works
Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease
McGovern, D. P. B., Jones, M. R., Taylor, K. D., Marciante, K. D., Yan, X., Dubinsky, M. C., Ippoliti, A., Vasiliauskas, E. A., Berel, D., Derkowski, C. A., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq248 · Cited by 379 · see citing works
McFall‐Ngai, M. (2007) · Nature · doi:10.1038/445153a · Cited by 345 · see citing works
Role of Toll-like Receptors in Spontaneous Commensal-Dependent Colitis
Rakoff-Nahoum, S., Hao, L., & Medzhitov, R. M. (2006) · Immunity · doi:10.1016/j.immuni.2006.06.010 · Cited by 343 · see citing works
Shaw, M. H., Kamada, N., Yun-Gi, K., & Núñez, G. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20111703 · Cited by 331 · see citing works
Dendritic cells in intestinal homeostasis and disease
Rescigno, M., & Sabatino, A. D. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39134 · Cited by 327 · see citing works
Patterns 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
Roers, A., Siewe, L., Strittmatter, E., Deckert, M., Schlüter, D., Stenzel, W., Gruber, A. D., Krieg, T. M., Rajewsky, K., & Müller, W. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20041789 · Cited by 309 · see citing works
Colonna, M. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.008 · Cited by 305 · see citing works
Ismail, A. S., Severson, K. M., Vaishnava, S., Behrendt, C. L., Yu, X., Benjamin, J. L., Ruhn, K. A., Hou, B., DeFranco, A. L., Yarovinsky, F., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019574108 · Cited by 302 · see citing works
Commensal-dependent expression of IL-25 regulates the IL-23–IL-17 axis in the intestine
Zaph, C., Du, Y., Saenz, S. A., Nair, M. G., Perrigoue, J., Taylor, B. C., Troy, A. E., Kobuley, D. E., Kastelein, R. A., Cua, D. J., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080720 · Cited by 292 · see citing works
Wacklin, P., Mäkivuokko, H., Alakulppi, N. S., Nikkilä, J., Tenkanen, H., Räbinä, J., Partanen, J., Aranko, K., & Mättö, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020113 · Cited by 283 · see citing works
A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2
Wang, Q., McLoughlin, R. M., Cobb, B. A., Charrel-Dennis, M., Zaleski, K. J., Golenbock, D. T., Tzianabos, A. O., & Kasper, D. L. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20062008 · Cited by 277 · see citing works
Mebius, R. E., Streeter, P. R., Michie, S. A., Butcher, E. C., & Weissman, I. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.20.11019 · Cited by 250 · see citing works
Tumanov, A. V., Koroleva, E. P., Guo, X., Wang, Y., Kruglov, A., Nedospasov, S. A., & Fu, Y. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.06.002 · Cited by 199 · see citing works
Ota, N., Wong, K., Valdez, P. A., Zheng, Y., Crellin, N. K., Diehl, L. J., & Ouyang, W. (2011) · Nature Immunology · doi:10.1038/ni.2089 · Cited by 160 · see citing works
Morrow, A. L., Meinzen‐Derr, J. K., Huang, P., Schibler, K. R., Cahill, T. E., Keddache, M. A., Kallapur, S. G., Newburg, D. S., Tabangin, M. E., Warner, B. B., et al. (2011) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2010.10.043 · Cited by 120 · see citing works
Maynard, C. L., Hatton, R. D., Helms, W. S., Oliver, J. R., Stephensen, C. B., & Weaver, C. T. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20080950 · Cited by 106 · see citing works
Toll like receptor-5: protecting the gut from enteric microbes
Vijay–Kumar, M., Aitken, J. D., & Gewirtz, A. T. (2007) · Seminars in Immunopathology · doi:10.1007/s00281-007-0100-5 · Cited by 75 · see citing works
Cherrier, M., & Eberl, G. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.02.003 · Cited by 61 · see citing works
Susceptibility to winter vomiting disease: a sweet matter
Rydell, G. E., Kindberg, E., Larson, G., & Svensson, L. (2011) · Reviews in Medical Virology · doi:10.1002/rmv.704 · Cited by 60 · see citing works
Lane, P. J. L., McConnell, F. M., Withers, D. R., Gaspal, F., Saini, M. K., & Anderson, G. (2009) · Mucosal Immunology · doi:10.1038/mi.2009.111 · Cited by 44 · see citing works
Plasticity of Treg at infected sites
Wohlfert, E. A., & Belkaid, Y. (2010) · Mucosal Immunology · doi:10.1038/mi.2010.11 · Cited by 37 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Interaction between microbiota and immunity in health and disease
Zheng, D., Liwinski, T., & Elinav, E. (2020) · Cell Research · doi:10.1038/s41422-020-0332-7 · Cited by 3,947 · see citing works
Intestinal epithelial cells: regulators of barrier function and immune homeostasis
Peterson, L. W., & Artis, D. (2014) · Nature reviews. Immunology · doi:10.1038/nri3608 · Cited by 3,191 · see citing works
Microbiota in health and diseases
Hou, K., Wu, Z.-X., Chen, X.-Y., Wang, J.-Q., Zhang, D., Xiao, C., Zhu, D., Koya, J. B., Wei, L., Li, J., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00974-4 · Cited by 3,171 · see citing works
“Moreover, before the solidification of infant immune system, the sIgA significantly protects the newborn against pathogens.(99) To summarize, the maternal-neonatal microbial bond supports the close relationship between microbiota and the immune system.”
BackgroundAnimals in a bacterial world, a new imperative for the life sciences
McFall‐Ngai, M., Hadfield, M. G. ., Bosch, T. C. G., Carey, H. V., Domazet‐Lošo, T., Douglas, A. E., Dubilier, N., Eberl, G., Fukami, T., Gilbert, S. F., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218525110 · Cited by 2,741 · see citing works
“Finally, immunologists are beginning to examine the possibility that, in addition to a role in pathogenesis, a principal selection pressure acting on the form and function of the adaptive immune system is the need to maintain balance among the complex, coevolved consortia that form persistent symbioses with the mucosa…”
BackgroundCurrent understanding of the human microbiome
Gilbert, J. A., Blaser, M. J., Caporaso, J. G., Jansson, J. K., Lynch, S. V., & Knight, R. (2018) · Nature Medicine · doi:10.1038/nm.4517 · Cited by 2,609 · see citing works
Milani, C., Duranti, S., Bottacini, F., Casey, E., Turroni, F., Mahony, J., Belzer, C., Delgado Palacio, S., Arboleya Montes, S., Mancabelli, L., et al. (2017) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00036-17 · Cited by 1,950 · see citing works
“” IgAs obtained from breast milk promote a regulatory and more “tolerogenic” immune system (105).”
BackgroundIntestinal permeability – a new target for disease prevention and therapy
Bischoff, S. C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J.-D., Serino, M., Tilg, H., Watson, A., & Wells, J. M. (2014) · BMC Gastroenterology · doi:10.1186/s12876-014-0189-7 · Cited by 1,755 · see citing works
“of the mammalian intestinal mucosa fulfill two seemingly opposing functions: firstly to allow a peaceful co-existence with intestinal symbionts without eliciting chronic inflammation and secondly to provide a measured inflammatory and defensive response according to the threat from pathogens [2,3].”
BackgroundImmunopathogenesis of IBD: current state of the art
de Souza, H. S. P., & Fiocchi, C. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.186 · Cited by 1,551 · see citing works
Chaput, N., Lepage, P., Coutzac, C., Soularue, E., Le Roux, K., Monot, C., Boselli, L., Routier, E., Cassard, L., Collins, M., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx108 · Cited by 1,310 · see citing works
“several butyrate-producing bacteria promote the development of tolerogenic macrophages and dendritic cells, as well as induced and thymic Treg accumulation, and thereby contribute to the anti-inflammatory balance of the intestines [32, 33].”
BackgroundThe composition of the gut microbiota throughout life, with an emphasis on early life
Rodríguez, J. M., Murphy, K., Stanton, C., Ross, R. P., Kober, O. I., Juge, N., Avershina, E., Rudi, K., Narbad, A., Jenmalm, M. C., et al. (2015) · Microbial Ecology in Health and Disease · doi:10.3402/mehd.v26.26050 · Cited by 1,320 · see citing works
“It is also important to bear in mind that assessments of stool samples reflect luminal colonic microbiota and not necessarily the colonization of the small intestine, where the major part of the gut immune system is situated (162, 163).”
BackgroundFlavonoids as Anticancer Agents
Kopustinskienė, D. M., Jakštas, V., Savickas, A., & Bernatonienė, J. (2020) · Nutrients · doi:10.3390/nu12020457 · Cited by 1,313 · see citing works
“These studies show that flavonoids can affect microbial populations by changing endotoxin production, converting primary into secondary bile acids [220], sustaining immune homeostasis [221] and participating in bioactive and nutrient absorption and metabolism, thereby regulating short-chain fatty acid formation [222].”
BackgroundProbiotics, gut microbiota, and their influence on host health and disease
Sánchez, B., Delgado, S., Blanco‐Míguez, A., Lourenço, A., Gueimonde, M., & Margolles, A. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600240 · Cited by 1,104 · see citing works
“Contrary to this, there is an inner, dense, and compact mucin sublayer immediately adjacent to the epithelial cells, restricting access to the bacteria, and where few, or no, microorganisms are observed [55, 56].”
BackgroundMicrobiota and neurodevelopmental windows: implications for brain disorders
Borre, Y. E., O’Keeffe, G. W., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.05.002 · Cited by 1,089 · see citing works
Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months
Azad, M. B., Konya, T., Maughan, H., Guttman, D. S., Field, C. J., Chari, R. S., Sears, M. R., Becker, A. B., Scott, J. A., & Kozyrskyj, A. L. (2013) · Canadian Medical Association Journal · doi:10.1503/cmaj.121189 · Cited by 953 · see citing works
“Gut bacteria play a fundamental role in human health by promoting intestinal homeostasis, stimulating development of the immune system, providing protection against pathogens, and contributing to the processing of nutrients and harvesting of energy.(1,2) The disruption of the gut microbiota has been linked to an incre…”
BackgroundHuman memory T cells: generation, compartmentalization and homeostasis
Farber, D. L., Yudanin, N. A., & Restifo, N. P. (2014) · Nature Reviews Immunology · doi:10.1038/nri3567 · Cited by 897 · see citing works
Kim, H. J., Li, H., Collins, J. J., & Ingber, D. E. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1522193112 · Cited by 926 · see citing works
Taur, Y., Jenq, R. R., Perales, M.-A., Littmann, E. R., Morjaria, S., Ling, L., No, D., Gobourne, A., Viale, A., Dahi, P. B., et al. (2014) · Blood · doi:10.1182/blood-2014-02-554725 · Cited by 885 · see citing works
“including stimulation of gut immune systemdevelopment, inhibition of potentially pathogenic microbes, and breakdown of otherwise unabsorbable nutrients.(14,15) Prior studies have shown that the intestinal microbiota of patients undergoing allo-HSCT often loses diversity, resulting in domination by a range of microbes…”
BackgroundThe Balance of Th17 versus Treg Cells in Autoimmunity
Lee, G. R. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030730 · Cited by 868 · see citing works
“The effect of IL-6 is bolstered by other proinflammatory cytokines, including IL-1β, IL-21, IL-23, and TNF-α [3,53,58].”
BackgroundInfluentialRomero, R., Hassan, S. S., Gajer, P., Tarca, A. L., Fadrosh, D. W., Nikita, L., Galuppi, M., Lamont, R. F., Chaemsaithong, P., Miranda, J., et al. (2014) · Microbiome · doi:10.1186/2049-2618-2-4 · Cited by 852 · see citing works
“Stability and resilience of ecosystems are now recognized to be important in understanding the fitness of the community, as well as the response to perturbations [56,214-220].”
BackgroundActinobacteria: A relevant minority for the maintenance of gut homeostasis
Binda, C., Lopetuso, L. R., Rizzatti, G., Gibiino, G., Cennamo, V., & Gasbarrini, A. (2018) · Digestive and Liver Disease · doi:10.1016/j.dld.2018.02.012 · Cited by 814 · see citing works
Mom Knows Best: The Universality of Maternal Microbial Transmission
Funkhouser-Jones, L. J., & Bordenstein, S. R. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001631 · Cited by 795 · see citing works
“components by pattern-recognition receptors on intestinal epithelial cells (reviewed in [71,72]).”
BackgroundThe mucosal immune system of fish: The evolution of tolerating commensals while fighting pathogens
Gómez, D., Sunyer, J. O., & Salinas, I. (2013) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2013.09.032 · Cited by 800 · see citing works
“Some specific examples include harvesting of nutrients from food, providing essential vitamins and producing biofilms that block pathogen entrance [4].”
InfluentialCommensal bacteria protect against food allergen sensitization
Stefka, A. T., Feehley, T., Tripathi, P., Qiu, J., McCoy, K. D., Mazmanian, S. K., Tjota, M. Y., Seo, G., Cao, S. Z., Theriault, B. R., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1412008111 · Cited by 795 · see citing works
“Mucosal IgA and regulatory T-cell (Treg) responses induced by commensal bacteria are critical for sustaining the homeostatic host– microbe relationship and preventing intestinal inflammation (10).”
BackgroundLi, J., Lin, S., Vanhoutte, P. M., Woo, C. W., & Xu, A. (2016) · Circulation · doi:10.1161/circulationaha.115.019645 · Cited by 775 · see citing works
“2434 The gut microbiota, a complex community of >100 trillion microbes, plays an important physiological role in modulating host nutrition, metabolism, and immunity.(1,2)”
BackgroundInteraction Between the Microbiota, Epithelia, and Immune Cells in the Intestine
Kayama, H., Okumura, R., & Takeda, K. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-070119-115104 · Cited by 765 · see citing works
Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis
Ma, Q., Xing, C., Long, W., Wang, H. Y., Liu, Q., & Wang, R. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1434-3 · Cited by 752 · see citing works
“Accumulating evidence suggests that microbiota are involved in the physiology and pathology of cellular organisms, and hence has implications in both health and disease [3].”
BackgroundMichielan, A., & D’Incà, R. (2015) · Mediators of Inflammation · doi:10.1155/2015/628157 · Cited by 709 · see citing works
“[9] “permeability” is defined as a functional feature of this barrier that on one hand allows the coexistence with bacterial symbionts necessary for our organism and on the other hand prevents luminal penetration of macromolecules and pathogens [10, 11].”
BackgroundRole of intestinal microbiota and metabolites on gut homeostasis and human diseases
Lin, L., & Zhang, J. (2017) · BMC Immunology · doi:10.1186/s12865-016-0187-3 · Cited by 731 · see citing works
“Microbiota, by establishing inter-connected metabolic/ nutritional networks and developing biofilms among their components, are able to confine the resources to potential pathogens that out-compete well-adapted indigenous microbes for ecological niches [124].”
BackgroundThe Gut Microbiota in the First Decade of Life
Derrien, M., Alvarez, A., & de Vos, W. M. (2019) · Trends in Microbiology · doi:10.1016/j.tim.2019.08.001 · Cited by 648 · see citing works
“From birth onwards, the gut microbiota coevolves with the host and the host’s metabolic and neurological programming; the development of this microbial community is thus of crucial importance for health in later life [4,5].”
Jaeggi, T., Kortman, G. A. M., Moretti, D., Chassard, C., Holding, P., Dostal, A., Boekhorst, J., Timmerman, H. M., Swinkels, D. W., Tjalsma, H., et al. (2015) · Gut · doi:10.1136/gutjnl-2014-307720 · Cited by 622 · see citing works
Shono, Y., Docampo, M. D., Peled, J. U., Perobelli, S. M., Velardi, E., Tsai, J. J., Slingerland, A. E., Smith, O. M., Young, L. F., Gupta, J., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf2311 · Cited by 592 · see citing works
“The intestinal microbiota consists of diverse bacterial taxa that contribute to host health through a variety of functions (6, 7).”
BackgroundEvolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort
Hill, C. J., Lynch, D. B., Murphy, K., Ulaszewska, M., Jeffery, I. B., O’Shea, C. A., Watkins, C., Dempsey, E., Mattivi, F., Tuohy, K., et al. (2017) · Microbiome · doi:10.1186/s40168-016-0213-y · Cited by 573 · see citing works
“This dynamic microbial population develops rapidly from birth until 2 to 3 years of age, when adult-like composition and stability is established [1, 2].”
BackgroundMucins: A biologically relevant glycan barrier in mucosal protection
Corfield, A. P. (2014) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2014.05.003 · Cited by 567 · see citing works
“In addition, there are many indications for significant roles of the enteric microflora in the innate and adaptive immune systems [132,231–237], but this is a large topic and is beyond the scope of this review.”
Background(2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.08.014 · Cited by 536 · see citing works
“…and the intestinal epithelium, host cells isolated from primary biopsy samples will be cultured and perturbed in vitro (Gallo and Hooper, 2012; Maynard et al., 2012; Stappenbeck et al., 1998) to determine the relative contribution of metabolites and host epithelial cells in this…”
BackgroundMukherji, A., Kobiita, A., Ye, T., & Chambon, P. (2013) · Cell · doi:10.1016/j.cell.2013.04.020 · Cited by 560 · see citing works
Kawamoto, S., Maruya, M., Kato, L. M., Suda, W., Atarashi, K., Doi, Y., Tsutsui, Y., Qin, H., Honda, K., Okada, T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.05.016 · Cited by 531 · see citing works
Antibiotics, Pediatric Dysbiosis, and Disease
Vangay, P., Ward, T., Gerber, J. S., & Knights, D. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.006 · Cited by 531 · see citing works
The Intestinal Microbiome and Estrogen Receptor–Positive Female Breast Cancer
Kwa, M. J., Plottel, C. S., Blaser, M. J., & Adams, S. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djw029 · Cited by 530 · see citing works
“tance effects involving hormonal intermediates, metabolites, and immunologic messengers (21,22).”
BackgroundGut microbiota and dysbiosis in Alzheimer's disease: Implications for pathogenesis and treatment
Liu, S., Gao, J., Zhu, M., Liu, K., & Zhang, H.-L. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02073-3 · Cited by 516 · see citing works
Host and Environmental Factors Affecting the Intestinal Microbiota in Chickens
Kers, J. G., Velkers, F. C., Fischer, E. A. J., Hermes, G. D. A., Stegeman, A., & Smidt, H. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00235 · Cited by 522 · see citing works
“…in life, before, during and shortly after hatching, during transport or at the start of the rearing period (for layers) or production period (for broilers) has a potentially large impact on microbiota composition and immune development for both the short- and the long-term (Maynard et al., 2012).”
BackgroundFunctions of Gut Microbiota Metabolites, Current Status and Future Perspectives
Liu, J., Tan, Y., Cheng, H., Zhang, D., Feng, W., & Peng, C. (2022) · Aging and disease · doi:10.14336/ad.2022.0104 · Cited by 529 · see citing works
“pathogens by stimulating hosts to secrete compounds with antimicrobial effects, competitive consumption of nutrients, and occupation of attachment sites [72].”
BackgroundImmunomodulatory potential of gut microbiome-derived short-chain fatty acids (SCFAs)
Ratajczak, W., Rył, A., Mizerski, A., Walczakiewicz, K., Sipak‐Szmigiel, O., & Laszczyńska, M. (2019) · Acta Biochimica Polonica · doi:10.18388/abp.2018_2648 · Cited by 520 · see citing works
Hepworth, M. R., Fung, T. C., Masur, S. H., Kelsen, J. R., McConnell, F. M., Dubrot, J., Withers, D. R., Hugues, S., Farrar, M. A., Reith, W., et al. (2015) · Science · doi:10.1126/science.aaa4812 · Cited by 515 · see citing works
Exploring host–microbiota interactions in animal models and humansPreprint
Kostic, A. D., Howitt, M. R., & Garrett, W. S. (2013) · Genes & Development · doi:10.1101/gad.212522.112 · Cited by 491 · see citing works
“It has been proposed that the ability of the adaptive immune system to recognize and remember specific organisms has facilitated the expansion of the resident microbiota in vertebrates (McFall-Ngai 2007; Maynard et al. 2012).”
The Intestinal Immune System in Obesity and Insulin Resistance
Winer, D. A., Luck, H., Tsai, S. J., & Winer, S. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.01.003 · Cited by 476 · see citing works
Protecting the Newborn and Young Infant from Infectious Diseases: Lessons from Immune Ontogeny
Kollmann, T. R., Kampmann, B., Mazmanian, S. K., Marchant, A., & Levy, O. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.009 · Cited by 478 · see citing works
Cancer and the gut microbiota: An unexpected link
Zitvogel, L., Galluzzi, L., Viaud, S., Vétizou, M., Daillère, R., Merad, M., & Kroemer, G. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010473 · Cited by 465 · see citing works
“A detailed description of the intestinal immune system is beyond the scope of this article and can be found in (2).”
BackgroundThe Female Vaginal Microbiome in Health and Bacterial Vaginosis
Chen, X. F., Lu, Y., Chen, T., & Li, R. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.631972 · Cited by 485 · see citing works
“The human body is a holobiont consisting of the host and multispecies microbes, and the interdependency among them has been progressively enhanced in the approximately half a billion years of human–microbial coevolution (Maynard et al., 2012; Lynch and Pedersen, 2016).”
BackgroundThe microbiome: stress, health and disease
Moloney, R. D., Desbonnet, L., Clarke, G., Dinan, T. G., & Cryan, J. F. (2014) · Mammalian Genome · doi:10.1007/s00335-013-9488-5 · Cited by 430 · see citing works
“Although infants delivered by Caesarean-section exhibit a delayed acquisition of the members (Firmicutes and Bacteroidetes) which dominate the adult microbiome, their microbiome do eventually match that of their vaginally delivered counterparts (Maynard et al. 2012).”
BackgroundZhou, D., Pan, Q., Shen, F., Cao, H.-X., Ding, W.-J., Chen, Y.-W., & Fan, J.-G. (2017) · Scientific Reports · doi:10.1038/s41598-017-01751-y · Cited by 421 · see citing works
Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection
Elahi, S., Ertelt, J. M., Kinder, J. M., Jiang, T. T., Zhang, X., Xin, L., Chaturvedi, V., Strong, B., Qualls, J. E., Steinbrecher, K. A., et al. (2013) · Nature · doi:10.1038/nature12675 · Cited by 421 · see citing works
Inflammation, ageing and chronic disease
Pawelec, G., Goldeck, D., & Derhovanessian, E. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.03.007 · Cited by 420 · see citing works
Lewis, Z. T., Totten, S. M., Smilowitz, J. T., Popović, M., Parker, E. A., Lemay, D. G., Tassell, M. L. V., Miller, M. J., Jin, Y., German, J. B., et al. (2015) · Microbiome · doi:10.1186/s40168-015-0071-z · Cited by 412 · see citing works
“Other benefits include protection from pathogens and development of the neonatal immune system [3,5,84,85].”
BackgroundApplication of metagenomics in the human gut microbiome
Wang, W., Xu, S., Ren, Z., Tao, L., Jiang, J., & Zheng, S. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i3.803 · Cited by 400 · see citing works
Stool microbiota and vaccine responses of infants
Huda, M. N., Lewis, Z., Kalanetra, K. M., Rashid, M., Ahmad, S. M., Raqib, R., Qadri, F., Underwood, M. A., Mills, D. A., & Stephensen, C. B. (2014) · PEDIATRICS · doi:10.1542/peds.2013-3937 · Cited by 392 · see citing works
Intestinal flora and disease mutually shape the regional immune system in the intestinal tract
Zhou, B., Yuan, Y., Zhang, S., Guo, C., Li, X., Li, G., Xiong, W., & Zeng, Z. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00575 · Cited by 396 · see citing works
“In early life, appropriate intestinal colonization by specific microflora stimulates maturation of the intestinal mucosa-associated lymphoid tissue (6).”
BackgroundSaid, H. S., Suda, W., Nakagome, S., Chinen, H., Oshima, K., Kim, S., Kimura, R., Iraha, A., Ishida, H., Fujita, J., et al. (2013) · DNA Research · doi:10.1093/dnares/dst037 · Cited by 394 · see citing works
Hooks, K. B., & O’Malley, M. A. (2017) · mBio · doi:10.1128/mbio.01492-17 · Cited by 386 · see citing works
“Many more papers noted that dysbiosis, although perceived as a real phenomenon, is not clearly established as a cause or an effect (e.g., 2, 28, and 63 to 65).”
Immune modulation by curcumin: The role of interleukin-10
Mollazadeh, H., Cicero, A. F. G., Blesso, C. N., Pirro, M., Majeed, M. A., & Sahebkar, A. (2017) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2017.1358139 · Cited by 382 · see citing works
“In this state, IL-10 transcription was increased by curcumin (McCann et al. 2014).”
BackgroundTonucci, L. B., dos Santos, K. M. O., de Oliveira, L. L., Ribeiro, S. M. R., & Martino, H. S. D. (2015) · Clinical Nutrition · doi:10.1016/j.clnu.2015.11.011 · Cited by 389 · see citing works
“Multiple cytokines are involved in the development of T2D, and are fundamental signals in the intestinal immune system, able to subvert the physiological status of inflammation in the gut [13].”
BackgroundGut microbiota, a new frontier to understand traditional Chinese medicines
Feng, W., Ao, H., Peng, C. Y., & Yan, D. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.02.024 · Cited by 379 · see citing works
Thorning, T. K., Bertram, H. C., Bonjour, J., de Groot, C. P. G. M., Dupont, D., Feeney, E. L., Ipsen, R., Lecerf, J. M., Mackie, A. R., McKinley, M. C., et al. (2017) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.116.151548 · Cited by 380 · see citing works
Breast cancer in postmenopausal women is associated with an altered gut metagenome
Zhu, J., Liao, M., Yao, Z., Liang, W., Li, Q., Liu, J., Yang, H., Ji, Y., Wei, W., Tan, A., et al. (2018) · Microbiome · doi:10.1186/s40168-018-0515-3 · Cited by 377 · see citing works
Regulation of intestinal homeostasis and immunity with probiotic lactobacilli
van Baarlen, P., Wells, J. M., & Kleerebezem, M. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.01.005 · Cited by 369 · see citing works
Thomas, S., Izard, J., Walsh, E. K., Batich, K. A., Chongsathidkiet, P., Clarke, G. A., Sela, D. A., Muller, A. J., Mullin, J. M., Albert, K., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2929 · Cited by 369 · see citing works
“The collective genome, or metagenome, of the enteric microbiota contains over 100 times the number of genes in the human genome, and there are approximately 10-fold more genes in each of our microbiomes than in each of us, encoding the greatest source of potential antigens with which the immune system must cope (6).”
BackgroundMaintenance of intestinal homeostasis by mucosal barriers
Okumura, R., & Takeda, K. (2018) · Inflammation and Regeneration · doi:10.1186/s41232-018-0063-z · Cited by 368 · see citing works
“Regarding the mechanism by which the inner mucus layer is free of gut bacteria, various antimicrobial molecules such as immunoglobulin A (IgA) and the defensin family of proteins transported or produced by IECs may be involved in protecting against bacterial invasion of the inner mucus layer [17].”
BackgroundOntogeny of early life immunity
Dowling, D. J., & Levy, O. (2014) · Trends in Immunology · doi:10.1016/j.it.2014.04.007 · Cited by 365 · see citing works
Korpela, K., Helve, O., Kolho, K.-L., Saisto, T., Skogberg, K., Dikareva, E., Stefanović, V., Salonen, A., Andersson, S., & de Vos, W. M. (2020) · Cell · doi:10.1016/j.cell.2020.08.047 · Cited by 358 · see citing works
“It is thus very likely that the human system has adapted to receiving specific microbial signals during certain time windows for reciprocal immune and metabolic programming during early life (Maynard et al., 2012; Gensollen et al., 2016; Olin et al., 2018).”
BackgroundGut Microbiome Dysbiosis and Immunometabolism: New Frontiers for Treatment of Metabolic Diseases
Belizário, J. E., Faintuch, J., & Garay-Malpartida, M. (2018) · Mediators of Inflammation · doi:10.1155/2018/2037838 · Cited by 341 · see citing works
“The components of inflammasomes such as MyD88, TLRs, NODs, NLrp3/6, ASC, and caspase 1 and caspase 11 are known to play a control of the intestinal dysbiosis [29, 38, 39, 45, 46].”
BackgroundThe first thousand days - intestinal microbiology of early life: Establishing a symbiosis
Wopereis, H., Oozeer, R., Knipping, K., Belzer, C., & Knol, J. (2014) · Pediatric Allergy and Immunology · doi:10.1111/pai.12232 · Cited by 352 · see citing works
“The mucosal immune system is providing protection from the external environment and directly interacts with the environmental antigens and commensal bacteria (13).”
BackgroundInfluentialGut microbiome and its role in obesity and insulin resistance
Lee, C. J., Sears, C. L., & Maruthur, N. M. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14107 · Cited by 352 · see citing works
Probiotics Protect Mice from Ovariectomy-Induced Cortical Bone Loss
Ohlsson, C., Engdahl, C., Fåk, F., Andersson, A., Windahl, S. H., Farman, H. H., Movérare-Skrtic, S., Islander, U., & Sjögren, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092368 · Cited by 339 · see citing works
“Perturbed microbial composition has been postulated to be involved in a range of inflammatory conditions, within and outside the gut including Crohn’s disease, ulcerative colitis, rheumatoid arthritis, multiple sclerosis, diabetes, food allergies, eczema and asthma as well as obesity and the metabolic syndrome [13,14].”
BackgroundThe advancement of probiotics research and its application in fish farming industries
Banerjee, G., & Ray, A. K. (2017) · Research in Veterinary Science · doi:10.1016/j.rvsc.2017.01.016 · Cited by 337 · see citing works
Triggers and drivers of autoimmunity: lessons from coeliac disease
Sollid, L. M., & Jabrì, B. (2013) · Nature reviews. Immunology · doi:10.1038/nri3407 · Cited by 343 · see citing works
Fungal Dysbiosis in Mucosa-associated Microbiota of Crohn’s Disease Patients
Liguori, G., Lamas, B., Richard, M. L., Brandi, G., Costa, G. D., Hoffmann, T. W., Simone, M. P. D., Calabrese, C., Poggioli, G., Langella, P., et al. (2015) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjv209 · Cited by 332 · see citing works
Lai, H., Lin, T., Chen, T.-W., Kuo, Y.-L., Chang, C., Wu, T.-R., Shu, C.-C., Tsai, Y.-H., Swift, S., & Lu, C. (2021) · Gut · doi:10.1136/gutjnl-2020-322599 · Cited by 333 · see citing works
“6 7 The roles of microbiota in development of host health are emphasised, 8–10 some supporting the role of respiratory tract microbes towards the onset, progression, promotion and severity of COPD chronicity.”
BackgroundThe Impact of Microbiota on Brain and Behavior: Mechanisms & Therapeutic Potential
Borre, Y. E., Moloney, R. D., Clarke, G., Dinan, T. G., & Cryan, J. F. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_17 · Cited by 329 · see citing works
Jin, U.-H., Lee, S., Sridharan, G. V., Lee, K., Davidson, L. A., Jayaraman, A., Chapkin, R. S., Alaniz, R. C., & Safe, S. H. (2014) · Molecular Pharmacology · doi:10.1124/mol.113.091165 · Cited by 330 · see citing works
“It has been well established that the gut microbiome and its metabolites have a direct effect on intestinal homeostasis (Villard et al., 2007; DiNatale et al., 2010; Maynard et al., 2012; Tremaroli and Backhed, 2012), and the AHR plays an important role in maintaining gut homeostasis (Kawajiri et al.”
Memory T cells: strategies for optimizing tumor immunotherapy
Liu, Q., Sun, Z., & Chen, L. (2020) · Protein & Cell · doi:10.1007/s13238-020-00707-9 · Cited by 332 · see citing works
“Studies in mouse models have shown that the presence and composition of the microbiome are crucial in promoting appropriate immune responses to pathogens and maintaining proper immune homeostasis (Maynard et al., 2012).”
BackgroundCrosstalk Between Gut Microbiota and Innate Immunity and Its Implication in Autoimmune Diseases
Jiao, Y., Wu, L., Huntington, N. D., & Zhang, X. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00282 · Cited by 321 · see citing works
“At the meantime, environment, diet, and host immune system can impact gut microbiota vice versa (2).”
BackgroundRohani, M. F., Islam, S. M., Hossain, M. K., Ferdous, Z., Siddik, M. A. B., Nuruzzaman, M., Padeniya, U. M., Brown, C. L., & Shahjahan, M. (2021) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2021.12.037 · Cited by 321 · see citing works
Role of Th17 Cells in the Pathogenesis of Human IBD
Gálvez, J. (2014) · ISRN Inflammation · doi:10.1155/2014/928461 · Cited by 320 · see citing works
“In addition, the presence of the proinflammatory cytokine IL-6 in the intestine facilitates TGFβ-inducedTh17 differentiation instead of iTreg, thus providing a mechanism to combine immune homeostasis and pathogen clearance to extracellular bacteria at mucosal barrier locations, where a permanent interplay with intesti…”
BackgroundMicrobial symbionts accelerate wound healing via the neuropeptide hormone oxytocin
Poutahidis, T., Kearney, S. M., Levkovich, T., Qi, P., Varian, B. J., Lakritz, J. R., Ibrahim, Y. M., Chatzigiagkos, A., Alm, E. J., & Erdman, S. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078898 · Cited by 310 · see citing works
The Human Neonatal Gut Microbiome: A Brief Review
Gritz, E. C., & Bhandari, V. (2015) · Frontiers in Pediatrics · doi:10.3389/fped.2015.00017 · Cited by 309 · see citing works
“This promotes formation of regulatory immune networks that further govern development and function of the gut microbiome (12).”
BackgroundInfluentialThe Role of the Microbiota in Inflammation, Carcinogenesis, and Cancer Therapy
Dzutsev, A., Goldszmid, R. S., Viaud, S., Zitvogel, L., & Trinchieri, G. (2015) · European Journal of Immunology · doi:10.1002/eji.201444972 · Cited by 300 · see citing works
ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut
Lyu, M., Suzuki, H., Kang, L., Gaspal, F., Zhou, W., Goc, J., Zhou, L., Zhou, J., Zhang, W., Bank, J. L. C., et al. (2022) · Nature · doi:10.1038/s41586-022-05141-x · Cited by 295 · see citing works
Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study
Uusitalo, U., Liu, X., Yang, J.-M., Aronsson, C., Hummel, S., Butterworth, M. D., Lernmark, Å., Rewers, M., Hagopian, W., She, J., et al. (2016) · JAMA pediatrics · doi:10.1001/jamapediatrics.2015.2757 · Cited by 253 · see citing works
“Infants who have an FDR with T1DM were eligible for enrollment if they had any of the following HLA genotypes: (1) DR4-DQA1*03- DQB1*03:02/DR3-DQA1*05:01-DQB1*02: 01, (2) DR4-DQA1*03- DQB1*03:02/DR4-DQA1*03-DQB1*03: 02, (3) DR4-DQA1*03- DQB1*03:02/DR8-DQA1*04:01-DQB1*04: 02, (4) DR3-DQA1*05:01-DQB1*02:01/DR3-DQA1*05:0…”
Mammalian Host-Versus-Phage immune response determines phage fate in vivo
Hodyra-Stefaniak, K., Miernikiewicz, P., Drapała, J., Drab, M., Jończyk-Matysiak, E., Lecion, D., Kaźmierczak, Z., Beta, W., Majewska, J., Harhala, M., et al. (2015) · Scientific Reports · doi:10.1038/srep14802 · Cited by 302 · see citing works
Immunoglobulins, Mucosal Immunity and Vaccination in Teleost Fish
Yu, Y., Wang, Q., Huang, Z., Ding, L., & Xu, Z. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.567941 · Cited by 289 · see citing works
“The targeting of skin microbes by mammalian sIgA plays a key role in immune exclusion (90); however, mucosal Ig can promote the colonization of certain bacteria on the skin surface (91).”
BackgroundThe gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD
Soderborg, T. K., Clark, S. E., Mulligan, C. E., Janssen, R. C., Babcock, L. R., Ir, D., Young, B. E., Krebs, N. F., Lemas, D. J., Johnson, L. K., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06929-0 · Cited by 291 · see citing works
Development of the preterm infant gut microbiome: a research priority
Groer, M. W., Luciano, A. A., Dishaw, L. J., Ashmeade, T. L., Miller, E. M., & Gilbert, J. A. (2014) · Microbiome · doi:10.1186/2049-2618-2-38 · Cited by 285 · see citing works
“established leading to a lifelong signature [29], a process that usually takes place by about 3 years of age [3].”
Flavonoids and the gastrointestinal tract: local and systemic effects
Oteiza, P. I., Fraga, C. G., Mills, D. A., & Taft, D. H. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.01.001 · Cited by 281 · see citing works
Pellegrini, C., Antonioli, L., Colucci, R., Blandizzi, C., & Fornai, M. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1856-5 · Cited by 270 · see citing works
“Conversely, upon pathogen invasion, dysbiosis or barrier break, MAMPs stimulate macrophages and dendritic cells to produce pro-inflammatory cytokines that, in turn, activate adaptive immune cells, thus contributing to the breakdown of immune homeostasis [58].”
BackgroundLowrey, L., Woodhams, D. C., Tacchi, L., & Salinas, I. (2015) · Applied and Environmental Microbiology · doi:10.1128/aem.01826-15 · Cited by 276 · see citing works
The Role of Probiotics and Prebiotics in Inducing Gut Immunity
Vieira, A. T., Teixeira, M. M., & Martins, F. S. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00445 · Cited by 275 · see citing works
“However, perturbations of PRR-microbiota interactions, in different cells type and gut mucosal compartment, are more likely to promote disease states associated with exacerbated inflammation (42, 43).”
BackgroundThe Role of Gut Microbiota on Insulin Resistance
Caricilli, A. M., & Saad, M. A. (2013) · Nutrients · doi:10.3390/nu5030829 · Cited by 273 · see citing works
“fatty acids, suggesting an important role of TLR4 in the interface of innate immune system and energetic metabolism [95–102] (Figure 2).”
BackgroundMcCabe, L. R., Irwin, R., Schaefer, L., & Britton, R. A. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24340 · Cited by 274 · see citing works
“This is in part due to the key role that intestinal bacteria play in shaping the immune system (Chung et al., 2012; Maynard et al., 2012).”
Pirbaglou, M., Katz, J., de Souza, R. J., Stearns, J. C., Motamed, M., & Ritvo, P. (2016) · Nutrition Research · doi:10.1016/j.nutres.2016.06.009 · Cited by 270 · see citing works
Adaptive immune education by gut microbiota antigens
Zhao, Q. S., & Elson, C. O. (2018) · Immunology · doi:10.1111/imm.12896 · Cited by 272 · see citing works
Exploring fish microbial communities to mitigate emerging diseases in aquaculture
de Bruijn, I., Liu, Y., Wiegertjes, G. F., & Raaijmakers, J. M. (2017) · FEMS Microbiology Ecology · doi:10.1093/femsec/fix161 · Cited by 269 · see citing works
“…larvae, commensal bacteria were shown to elicit a mild inflammatory reaction, induce genes involved in priming of the innate immunity (Galindo-Villegas et al. 2012; Chu andMazmanian 2013) and activate the innate immune response (Nayak 2010; Maynard et al. 2012; Montalban-Arques et al. 2015).”
Background
- Authors
- Maynard, C. L., Elson, C. O., Hatton, R. D., & Weaver, C. T.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Weaver, Casey T.
- Venue
- Nature
- Published
- 2012-09
- Volume
- 489
- Issue
- 7415
- Pages
- 231-241
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4492337
- OpenAlex
- W2083102356
- Cited by
- 1,598
- References
- 101
- Citations by year
- 2026: 50 · 2025: 81 · 2024: 122 · 2023: 136 · 2022: 126 · 2021: 143 · 2020: 148 · 2019: 122 · 2018: 120 · 2017: 100 · 2016: 118 · 2015: 120 · 2014: 110 · 2013: 96 · 2012: 4
- FWCI
- 9.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Crohn's and Colitis Foundation
- National Institute of Allergy and Infectious Diseases (R01AI057956, T32AI007051)
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK064400, P01DK071176, R01DK093015)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- gut microbiota, adaptive immunity, innate immunity, host-microbe symbiosis, immune homeostasis, immune-mediated diseases, immunological memory, gut microbiota modulation, host defense
- MeSH terms
- Blood Group Antigens, Cesarean Section, Epithelium, Female, Homeostasis, Humans, Infant, Infant, Newborn, Intestines, Pregnancy, T-Lymphocytes, Vagina, Metagenome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
