Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans
Open accessAbstract
According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but are less prevalent in Russia. We found that Bacteroides species are lowly abundant in Russians but dominate in Finnish and Estonian infants. Therefore, their lipopolysaccharide (LPS) exposures arose primarily from Bacteroides rather than from Escherichia coli, which is a potent innate immune activator. We show that Bacteroides LPS is structurally distinct from E. coli LPS and inhibits innate immune signaling and endotoxin tolerance; furthermore, unlike LPS from E. coli, B. dorei LPS does not decrease incidence of autoimmune diabetes in non-obese diabetic mice. Early colonization by immunologically silencing microbiota may thus preclude aspects of immune education.
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In humans, hexa-acylated LPS potently activates TLR4 and host immunity, whereas hypo-acylated penta- and tetra-acylated LPS poorly activate TLR4 and can antagonize immune activation by hexa-acylated LPS.
“In humans, hexa-acylated LPS potently activates TLR4 and host immunity, whereas hypo-acylated penta- and tetra-acylated LPS poorly activate TLR4 and can antagonize immune activation by hexa-acylated LPS6–9.”
From Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses (2025) · cites this paper as [6]
LPS-TLR4 signalling modulates systemic autoimmune activity.
“and modulate systemic autoimmune activity6.”
From Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses (2025) · cites this paper as [6]
The acylation state of LPS lipid A directly impacts immune signalling through TLR4.
“Given that the acylation state of LPS lipid A has been shown to directly impact immune signalling through TLR46,21”
From Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses (2025) · cites this paper as [6]
Intestinal microbiota composition varies by geography and has been linked to autoimmunity.
“Moreover, geographic variations in the composition of intestinal microbiota have been described and implicated in the development of autoimmunity.28,29”
From Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation (2020) · cites this paper as [29]
Every strain in the artificial communities came from a human subject originally, and HMP reference genomes were added when available.
“All strains were originally isolated from human subjects, and HMP genome reference strains were included where available5.”
From Assessment of variation in microbial community amplicon sequencing by the Microbiome Quality Control (MBQC) project consortium (2017) · cites this paper as [5]
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Sokol, H., Pigneur, B., Watterlot, L., Lakhdari, O., Bermúdez-Humarán, L. G., Gratadoux, J.-J., Blugeon, S., Bridonneau, C., Furet, J.-P., Corthier, G., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804812105 · Cited by 4,413 · see citing works
Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life
Bäckhed, F., Roswall, J., Peng, Y., Feng, Q., Jia, H., Kovatcheva-Datchary, P., Li, Y., Xia, Y., Xie, H., Zhong, H., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.004 · Cited by 3,315 · see citing works
The effect of infections on susceptibility to autoimmune and allergic diseases.
Bach, J. (2002) · New England Journal of Medicine · doi:10.1056/nejmra020100 · Cited by 2,714 · see citing works
Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment
Morgan, X. C., Tickle, T. L., Sokol, H., Gevers, D., Devaney, K. L., Ward, D. V., Reyes, J. A., Shah, S. A., LeLeiko, N., Snapper, S. B., et al. (2012) · Genome Biology · doi:10.1186/gb-2012-13-9-r79 · Cited by 2,713 · see citing works
Self-citationSuccession of microbial consortia in the developing infant gut microbiome
Koenig, J. E., Spor, A., Scalfone, N., Fricker, A. D., Stombaugh, J., Knight, R., Angenent, L. T., & Ley, R. E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000081107 · Cited by 2,540 · see citing works
MetaPhlAn2 for enhanced metagenomic taxonomic profiling
Truong, D. T., Franzosa, E. A., Tickle, T. L., Scholz, M., Weingart, G., Pasolli, E., Tett, A., Huttenhower, C., & Segata, N. (2015) · Nature Methods · doi:10.1038/nmeth.3589 · Cited by 2,185 · see citing works
Self-citationSex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity
Markle, J. G. M., Frank, D. N., Mortin-Toth, S., Robertson, C. E., Feazel, L. M., Rolle-Kampczyk, U., von Bergen, M., McCoy, K. D., Macpherson, A. J., & Danska, J. S. (2013) · Science · doi:10.1126/science.1233521 · Cited by 2,025 · see citing works
Innate immunity and intestinal microbiota in the development of Type 1 diabetes
Wen, L., Ley, R. E., Volchkov, P. Y., Stranges, P. B., Avanesyan, L., Stonebraker, A. C., Hu, C., Wong, F. S., Szot, G. L., Bluestone, J. A., et al. (2008) · Nature · doi:10.1038/nature07336 · Cited by 1,921 · see citing works
Endotoxin tolerance: new mechanisms, molecules and clinical significance
Biswas, S. K., & Lopez-Collazo, E. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.07.009 · Cited by 1,318 · see citing works
Crystal Structure of the TLR4-MD-2 Complex with Bound Endotoxin Antagonist Eritoran
Kim, H. M., Park, B. S., Kim, J.-I., Kim, S. E., Lee, J., Oh, S. C., Enkhbayar, P., Matsushima, N., Lee, H., Yoo, O. J., et al. (2007) · Cell · doi:10.1016/j.cell.2007.08.002 · Cited by 1,180 · see citing works
Kostic, A. D., Gevers, D., Siljander, H., Vatanen, T., Hyötyläinen, T., Hämäläinen, A., Peet, A., Tillmann, V., Pöhö, P., Mattila, I. M., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.01.001 · Cited by 1,165 · see citing works
Self-citationHirschfeld, M. J., Ma, Y., Weis, J. H., Vogel, S. N., & Weis, J. J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.2.618 · Cited by 1,155 · see citing works
Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome
Abubucker, S., Segata, N., Goll, J. B., Schubert, A. M., Izard, J., Cantarel, B. L., Rodriguez-Mueller, B., Zucker, J., Thiagarajan, M., Henrissat, B., et al. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002358 · Cited by 1,050 · see citing works
Self-citationSela, D. A., Chapman, J., Adeuya, A., Kim, J., Chen, F., Whitehead, T. R., Lapidus, A. L., Rokhsar, D. S., Lebrilla, C. B., German, J. B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809584105 · Cited by 884 · see citing works
Commensal 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
Characterization of the Diversity and Temporal Stability of Bacterial Communities in Human Milk
Hunt, K. M., Foster, J. A., Forney, L. J., Schütte, U. M. E., Beck, D. L., Abdo, Z., Fox, L. K., Williams, J. E., McGuire, M. K., & McGuire, M. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021313 · Cited by 765 · see citing works
Biosynthesis and Export of Bacterial Lipopolysaccharides
Whitfield, C., & Trent, M. S. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060713-035600 · Cited by 716 · see citing works
Farm living: effects on childhood asthma and allergy
von Mutius, E., & Vercelli, D. (2010) · Nature reviews. Immunology · doi:10.1038/nri2871 · Cited by 697 · see citing works
HLA susceptibility genes in celiac disease: Genetic mapping and role in pathogenesis
Sollid, L. M., & Thorsby, E. (1993) · Gastroenterology · doi:10.1016/0016-5085(93)90912-v · Cited by 604 · see citing works
Human Toll-like receptor 4 recognizes host-specific LPS modifications
Hajjar, A. M., Ernst, R. K., Tsai, J. H., Wilson, C. B., & Miller, S. I. (2002) · Nature Immunology · doi:10.1038/ni777 · Cited by 579 · see citing works
Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways
Marcobal, A., Barboza, M., Sonnenburg, E. D., Pudlo, N., Martens, E. C., Desai, P., Lebrilla, C. B., Weimer, B. C., Mills, D. A., German, J. B., et al. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.10.007 · Cited by 574 · see citing works
Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides
Sela, D. A., & Mills, D. A. (2010) · Trends in Microbiology · doi:10.1016/j.tim.2010.03.008 · Cited by 468 · see citing works
Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation
Cullen, T. W., Schofield, W. B., Barry, N. A., Putnam, E. E., Rundell, E. A., Trent, M. S., Degnan, P. H., Booth, C. J., Yu, H., & Goodman, A. L. (2015) · Science · doi:10.1126/science.1260580 · Cited by 395 · see citing works
Davis‐Richardson, A. G., Ardissone, A. N., Dias, R., Simell, V., Leonard, M. T., Kemppainen, K. M., Drew, J. C., Schatz, D., Atkinson, M. A., Kolaczkowski, B. D., et al. (2014) · Frontiers in Microbiology · doi:10.3389/fmicb.2014.00678 · Cited by 313 · see citing works
Self-citationConStrains identifies microbial strains in metagenomic datasets
Luo, C., Knight, R. D., Siljander, H., Knip, M., Xavier, R. J., & Gevers, D. (2015) · Nature Biotechnology · doi:10.1038/nbt.3319 · Cited by 267 · see citing works
Self-citationModulating the innate immune response by combinatorial engineering of endotoxin
Needham, B. D., Carroll, S. M., Giles, D. K., Georgiou, G., Whiteley, M., & Trent, M. S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218080110 · Cited by 232 · see citing works
Lower economic status and inferior hygienic environment may protect against celiac disease
Kondrashova, A., Mustalahti, K., Kaukinen, K., Viskari, H., Volodicheva, V., Haapala, A., Ilonen, J., Knip, M., Mäki, M., Hyöty, H., et al. (2008) · Annals of Medicine · doi:10.1080/07853890701678689 · Cited by 147 · see citing works
Self-citationLoCascio, R. G., Niñonuevo, M. R., Kronewitter, S. R., Freeman, S. L., German, J. B., Lebrilla, C. B., & Mills, D. A. (2008) · Microbial Biotechnology · doi:10.1111/j.1751-7915.2008.00072.x · Cited by 140 · see citing works
Breast-fed and bottle-fed infant rhesus macaques develop distinct gut microbiotas and immune systems
Ardeshir, A., Narayan, N. R., Méndez-Lagares, G., Lu, D., Rauch, M., Huang, Y., Van Rompay, K. K. A., Lynch, S. V., & Hartigan-O’Connor, D. J. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008791 · Cited by 134 · see citing works
Aumeunier, A., Grela, F., Ramadan, A. M., Pham, L., Bardel, É., Alcala, A. G., Jeannin, P., Akira, S., Bach, J., & Thiéblemont, N. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011484 · Cited by 132 · see citing works
The Hygiene Hypothesis: An Explanation for the Increased Frequency of Insulin-Dependent DiabetesPreprint
Bach, J., & Chatenoud, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a007799 · Cited by 129 · see citing works
Allergic sensitization and microbial load – a comparison between Finland and Russian Karelia
The EPIVIR study group, Seiskari, T., Kondrashova, A., Viskari, H., Kaila, M., Haapala, A., Aittoniemi, J., Virta, M., Hurme, M., Uibo, R., et al. (2007) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2007.03333.x · Cited by 125 · see citing works
Self-citationMODIFICATION OF HOST RESPONSES TO BACTERIAL ENDOTOXINS
Watson, D. W., & Kim, Y. B. (1963) · The Journal of Experimental Medicine · doi:10.1084/jem.118.3.425 · Cited by 124 · see citing works
Herath, T. D. K., Wang, Y., Seneviratne, C., Lu, Q., Darveau, R., Wang, C.-Y., & Jin, L. (2011) · Journal of Clinical Periodontology · doi:10.1111/j.1600-051x.2011.01741.x · Cited by 89 · see citing works
Kondrashova, A., Viskari, H., Haapala, A., Seiskari, T., Kulmala, P., Ilonen, J., Knip, M., & Hyöty, H. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1644 · Cited by 68 · see citing works
Self-citationGülden, E., Ihira, M., Ohashi, A., Reinbeck, A. L., Freudenberg, M. A., Kolb, H., & Burkart, V. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075385 · Cited by 66 · see citing works
Saï, P., & As, R. (1996) · PubMed · Cited by 55 · see citing works
Atopic sensitization and atopic dermatitis in Estonian and Swedish infants
Voor, T., Julge, K., Böttcher, M. F., et al. (2005) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2005.02157.x · Cited by 54 · see citing works
Standard of hygiene and immune adaptation in newborn infants
Kallionpää, H., Laajala, E., Öling, V., Härkönen, T., Tillmann, V., Доршакова, Н. В., Ilonen, J., Lähdesmäki, H. J., Knip, M., Lahesmaa, R., et al. (2014) · Clinical Immunology · doi:10.1016/j.clim.2014.09.009 · Cited by 39 · see citing works
Self-citationTeeäär, T., Liivak, N., Heilman, K., Kool, P., Šor, R., Paal, M., Einberg, Ü., & Tillmann, V. (2009) · Pediatric Diabetes · doi:10.1111/j.1399-5448.2009.00535.x · Cited by 39 · see citing works
Self-citationLarizza, D., Calcaterra, V., Klersy, C., et al. (2012) · Autoimmunity · doi:10.3109/08916934.2012.697594 · Cited by 34 · see citing works
Hofstad, T., Svéen, K., & Dahlén, G. (1977) · Acta Pathologica Microbiologica Scandinavica Section B Microbiology · doi:10.1111/j.1699-0463.1977.tb01972.x · Cited by 31 · see citing works
Peet, A., Kool, P., Ilonen, J., Knip, M., Tillmann, V., & for the DIABIMMUNE Study Group (2012) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2303 · Cited by 27 · see citing works
Self-citation
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Current 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
Large-scale association analyses identify host factors influencing human gut microbiome composition
Kurilshikov, A., Medina-Gomez, C., Bacigalupe, R., Radjabzadeh, D., Wang, J., Demirkan, A., Le Roy, C. I., Raygoza Garay, J. A., Finnicum, C. T., Liu, X., et al. (2021) · Nature Genetics · doi:10.1038/s41588-020-00763-1 · Cited by 1,786 · see citing works
Dysbiosis and the immune system
Levy, M., Kolodziejczyk, A. A., Thaiss, C. A., & Elinav, E. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.7 · Cited by 1,769 · see citing works
Emerging Pathogenic Links Between Microbiota and the Gut-Lung Axis
Budden, K. F., Gellatly, S. L., Wood, D. L. A., Cooper, M. A., Morrison, M., Hugenholtz, P., & Hansbro, P. M. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.142 · Cited by 1,606 · see citing works
Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization
Zuo, T., Zhang, F., Lui, G. C. Y., Yeoh, Y. K., Li, A. Y. L., Zhan, H., Wan, Y., Chung, A. C. K., Cheung, C. P., Chen, N., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.05.048 · Cited by 1,537 · see citing works
Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases
Sanna, S., van Zuydam, N. R., Mahajan, A., Kurilshikov, A., Vich Vila, A., Võsa, U., Mujagic, Z., Masclee, A. A. M., Jonkers, D. M. A. E., Oosting, M., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0350-x · Cited by 1,539 · see citing works
Ferretti, P., Pasolli, E., Tett, A., Asnicar, F., Gorfer, V., Fedi, S., Armanini, F., Truong, D. T., Manara, S., Zolfo, M., et al. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.06.005 · Cited by 1,292 · see citing works
Self-citationThe microbiome in early life: Implications for health outcomes
Tamburini, S., Shen, N., Wu, H. C., & Clemente, J. C. (2016) · Nature Medicine · doi:10.1038/nm.4142 · Cited by 1,213 · see citing works
Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth
Shao, Y., Forster, S. C., Tsaliki, E., Vervier, K., Strang, A., Simpson, N., Kumar, N., Stares, M. D., Rodger, A., Brocklehurst, P., et al. (2019) · Nature · doi:10.1038/s41586-019-1560-1 · Cited by 1,088 · see citing works
The intestinal microbiota fuelling metabolic inflammation
Tilg, H., Zmora, N., Adolph, T. E., & Elinav, E. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0198-4 · Cited by 1,089 · see citing works
Chu, D. M., Ma, J., Prince, A. L., Antony, K. M., Seferovic, M. D., & Aagaard, K. M. (2017) · Nature Medicine · doi:10.1038/nm.4272 · Cited by 1,063 · see citing works
Gut microbiota and cardiovascular disease.
Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020) · Circulation Research · doi:10.1161/circresaha.120.316242 · Cited by 1,051 · see citing works
Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration
Leeming, E. R., Johnson, A. J., Spector, T. D., & Le Roy, C. I. (2019) · Nutrients · doi:10.3390/nu11122862 · Cited by 817 · see citing works
The effect of host genetics on the gut microbiome
Bonder, M. J., Kurilshikov, A., Tigchelaar, E. F., Mujagic, Z., Imhann, F., Vila, A. V., Deelen, P., Vatanen, T., Schirmer, M., Smeekens, S. P., et al. (2016) · Nature Genetics · doi:10.1038/ng.3663 · Cited by 819 · see citing works
Self-citationMicrobiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation
Peled, J. U., Gomes, A. L. C., Devlin, S. M., Littmann, E. R., Taur, Y., Sung, A. D., Weber, D., Hashimoto, D., Slingerland, A. E., Slingerland, J. B., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1900623 · Cited by 765 · see citing works
New insights from uncultivated genomes of the global human gut microbiome
Nayfach, S., Shi, Z. J., Seshadri, R., Pollard, K. S., & Kyrpides, N. C. (2019) · Nature · doi:10.1038/s41586-019-1058-x · Cited by 737 · see citing works
Brodin, P., & Davis, M. M. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2016.125 · Cited by 730 · see citing works
Mariño, E., Richards, J. L., McLeod, K. H., Stanley, D., Yap, Y. A., Knight, J., McKenzie, C., Kranich, J., Oliveira, A. C., Rossello, F. J., et al. (2017) · Nature Immunology · doi:10.1038/ni.3713 · Cited by 686 · see citing works
Maturation of the gut microbiome and risk of asthma in childhood
Stokholm, J., Blaser, M. J., Thorsen, J., Rasmussen, M. A., Waage, J., Vinding, R. K., Schoos, A.-M. M., Kunøe, A., Fink, N. R., Chawes, B. L., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02573-2 · Cited by 614 · see citing works
Development of the gut microbiota in infancy and its impact on health in later life
Tanaka, M., & Nakayama, J. (2017) · Allergology International · doi:10.1016/j.alit.2017.07.010 · Cited by 639 · see citing works
The Microbiome Quality Control Project Consortium, Sinha, R., Abu-Ali, G., Vogtmann, E., Fodor, A. A., Ren, B., Amir, A., Schwager, E., Crabtree, J., Ma, S., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.3981 · Cited by 587 · see citing works
Self-citationYoshida, N., Emoto, T., Yamashita, T., Watanabe, H., Hayashi, T., Tabata, T., Hoshi, N., Hatano, N., Ozawa, G., Sasaki, N., et al. (2018) · Circulation · doi:10.1161/circulationaha.118.033714 · Cited by 619 · see citing works
The multiple pathways to autoimmunity
Theofilopoulos, A. N., Kono, D. H., & Baccala, R. (2017) · Nature Immunology · doi:10.1038/ni.3731 · Cited by 590 · see citing works
Accessible, curated metagenomic data through ExperimentHub
Pasolli, E., Schiffer, L., Manghi, P., Renson, A., Obenchain, V., Truong, D. T., Beghini, F., Malik, F., Ramos, M., Dowd, J. B., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4468 · Cited by 514 · see citing works
Self-citationThe endotoxin hypothesis of neurodegeneration
Brown, G. C. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1564-7 · Cited by 457 · see citing works
Role of priority effects in the early-life assembly of the gut microbiota
Sprockett, D., Fukami, T., & Relman, D. A. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.173 · Cited by 419 · see citing works
Kim, C. H. (2023) · Cellular & Molecular Immunology · doi:10.1038/s41423-023-00987-1 · Cited by 420 · see citing works
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Tsai, Y.-L., Lin, T.-L., Chang, C.-J., Wu, T.-R., Lai, W.-F., Lu, C.-C., & Lai, H.-C. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-018-0493-6 · Cited by 388 · see citing works
Large-scale genome-wide analysis links lactic acid bacteria from food with the gut microbiome
Pasolli, E., De Filippis, F., Mauriello, I. E., Cumbo, F., Walsh, A. M., Leech, J., Cotter, P. D., Segata, N., & Ercolini, D. (2020) · Nature Communications · doi:10.1038/s41467-020-16438-8 · Cited by 367 · see citing works
Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling
d’Hennezel, E., Abubucker, S., Murphy, L. O., & Cullen, T. W. (2017) · mSystems · doi:10.1128/msystems.00046-17 · Cited by 324 · see citing works
Self-citationConnecting the immune system, systemic chronic inflammation and the gut microbiome: the role of sex
Rizzetto, L., Fava, F., Tuohy, K. M., & Selmi, C. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.05.008 · Cited by 331 · see citing works
Mucosal Prevalence and Interactions with the Epithelium Indicate Commensalism of Sutterella spp.
Hiippala, K., Kainulainen, V., Kalliomäki, M., Arkkila, P., & Satokari, R. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01706 · Cited by 351 · see citing works
Host Genetics and Gut Microbiome: Challenges and Perspectives
Kurilshikov, A., Wijmenga, C., Fu, J., & Zhernakova, A. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.06.003 · Cited by 309 · see citing works
Wampach, L., Heintz-Buschart, A., Fritz, J. V., Ramiro-Garcia, J., Habier, J., Herold, M., Narayanasamy, S., Kaysen, A., Hogan, A. H., Bindl, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07631-x · Cited by 292 · see citing works
Harris, V. C., Armah, G., Fuentes, S., Korpela, K. E., Parashar, U., Victor, J. C., Tate, J., de Weerth, C., Giaquinto, C., Wiersinga, W. J., et al. (2017) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiw518 · Cited by 299 · see citing works
Microbiota succession throughout life from the cradle to the grave
Martino, C., Dilmore, A. H., Burcham, Z. M., Metcalf, J. L., Jeste, D., & Knight, R. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00768-z · Cited by 275 · see citing works
Luo, Y., Zeng, B., Zeng, L., Du, X., Li, B., Huo, R., Liu, L., Wang, H., Dong, M., Pan, J., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0240-5 · Cited by 245 · see citing works
An exposome perspective: Early-life events and immune development in a changing world
Renz, H., Holt, P. G., Inouye, M., Logan, A. C., Prescott, S. L., & Sly, P. D. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.05.015 · Cited by 226 · see citing works
Frese, S. A., Hutton, A. A., Contreras, L. N., Shaw, C. A., Palumbo, M. C., Casaburi, G., Xu, G., Davis, J. C. C., Lebrilla, C. B., Henrick, B. M., et al. (2017) · mSphere · doi:10.1128/msphere.00501-17 · Cited by 231 · see citing works
Leveraging diet to engineer the gut microbiome
Wolter, M., Grant, E. T., Boudaud, M., Steimle, A., Pereira, G. V., Martens, E. C., & Desai, M. S. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00512-7 · Cited by 211 · see citing works
Endotoxemia—menace, marker, or mistake?
Munford, R. S. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ru0316-151r · Cited by 219 · see citing works
Martínez, I., Maldonado-Gomez, M. X., Gomes-Neto, J. C., Kittana, H., Ding, H., Schmaltz, R., Joglekar, P., Cardona, R. J., Marsteller, N. L., Kembel, S. W., et al. (2018) · eLife · doi:10.7554/elife.36521 · Cited by 199 · see citing works
Kurilshikov, A., van den Munckhof, I. C. L., Chen, L., Bonder, M. J., Schraa, K., Rutten, J. H. W., Riksen, N. P., de Graaf, J., Oosting, M., Sanna, S., et al. (2019) · Circulation Research · doi:10.1161/circresaha.118.314642 · Cited by 178 · see citing works
Self-citationHost genotype and gut microbiome modulate insulin secretion and diet-induced metabolic phenotypes
Kreznar, J. H., Keller, M. P., Traeger, L. L., Rabaglia, M. E., Schueler, K. L., Stapleton, D. S., Zhao, W., Vivas, E. I., Yandell, B. S., Broman, A. T., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.01.062 · Cited by 177 · see citing works
Hughes, J. W., Riddlesworth, T. D., DiMeglio, L. A., Miller, K. M., Rickels, M. R., McGill, J. B., & for the T1D Exchange Clinic Network (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2478 · Cited by 173 · see citing works
Leonard, M. M., Valitutti, F., Karathia, H., Pujolassos, M., Kenyon, V., Fanelli, B., Troisi, J., Subramanian, P., Camhi, S., Colucci, A., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2020322118 · Cited by 162 · see citing works
Liao, J.-F., Cheng, Y.-F., You, S.-T., Kuo, W.-C., Huang, C.-W., Chiou, J.-J., Hsu, C.-C., Hsieh-Li, H.-M., Wang, S., & Tsai, Y.-C. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.07.036 · Cited by 159 · see citing works
Lin, T.-L., Shu, C.-C., Chen, Y.-M., Lu, J.-J., Wu, T.-S., Lai, W.-F., Tzeng, C.-M., Lai, H.-C., & Lu, C.-C. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00554 · Cited by 143 · see citing works
Symbionts exploit complex signaling to educate the immune system
Erturk-Hasdemir, D., Oh, S. F., Okan, N. A., Stefanetti, G., Gazzaniga, F. S., Seeberger, P. H., Plevy, S. E., & Kasper, D. L. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1915978116 · Cited by 129 · see citing works
Early-life gut microbiome modulation reduces the abundance of antibiotic-resistant bacteria
Casaburi, G., Duar, R. M., Vance, D. P., Mitchell, R., Contreras, L., Frese, S. A., Smilowitz, J. T., & Underwood, M. A. (2019) · Antimicrobial Resistance & Infection Control · doi:10.1186/s13756-019-0583-6 · Cited by 101 · see citing works
Maternal modifiers of the infant gut microbiota: Metabolic consequences
Mulligan, C. M., & Friedman, J. E. (2017) · Journal of Endocrinology · doi:10.1530/joe-17-0303 · Cited by 101 · see citing works
Gut microbiome-mediated metabolism effects on immunity in rural and urban African populations
Stražar, M., Temba, G. S., Vlamakis, H., Kullaya, V. I., Lyamuya, F., Mmbaga, B. T., Joosten, L. A. B., van der Ven, A. J. A. M., Netea, M. G., de Mast, Q., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25213-2 · Cited by 91 · see citing works
Self-citationGarcia-Vello, P., Tytgat, H. L. P., Elzinga, J., Van Hul, M., Plovier, H., Tiemblo-Martin, M., Cani, P. D., Nicolardi, S., Fragai, M., De Castro, C., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52683-x · Cited by 74 · see citing works
Duar, R. M., Kyle, D., & Casaburi, G. (2020) · High-Throughput · doi:10.3390/ht9020007 · Cited by 70 · see citing works
Composition and diversity of gut microbiota in diabetic retinopathy
Bai, J., Wan, Z., Zhang, Y., Wang, T., Xue, Y., & Peng, Q. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.926926 · Cited by 70 · see citing works
Paun, A., & Danska, J. S. (2016) · Pediatric Diabetes · doi:10.1111/pedi.12424 · Cited by 67 · see citing works
Brown, D. G., Soto, R., Yandamuri, S., Stone, C., Dickey, L., Gomes-Neto, J. C., Pastuzyn, E. D., Bell, R., Petersen, C., Buhrke, K., et al. (2019) · eLife · doi:10.7554/elife.47117 · Cited by 60 · see citing works
Revisiting the intestinal microbiome and its role in Diarrhea and constipation
Iancu, M. A., Profir, M., Roşu, O. A., Ionescu, R. F., Cretoiu, S. M., & Gaspar, B. S. (2023) · Microorganisms · doi:10.3390/microorganisms11092177 · Cited by 53 · see citing works
“…short-or long-term dietary interventions, preserving the core microbial profile and increasing the number of beneficial bacteria might influence the overall improvement of intestinal health by re-establishing the integrity of the intestinal barrier and the immune response homeostasis [220–222].”
The environmental microbiome, allergic disease, and asthma
Kelly, M. S., Bunyavanich, S., Phipatanakul, W., & Lai, P. S. (2022) · The Journal of Allergy and Clinical Immunology: In Practice · doi:10.1016/j.jaip.2022.06.006 · Cited by 47 · see citing works
Gut microbiota in ALS: possible role in pathogenesis?
McCombe, P. A., Henderson, R. D., Lee, A., Lee, J. D., Woodruff, T. M., Restuadi, R., McRae, A., Wray, N. R., Ngo, S., & Steyn, F. J. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2019.1623026 · Cited by 46 · see citing works
Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses
Sardar, P., Beresford-Jones, B. S., Xia, W., Shabana, O., Suyama, S., Ramos, R. J. F., Soderholm, A. T., Tourlomousis, P., Kuo, P., Evans, A. C., et al. (2025) · Nature Microbiology · doi:10.1038/s41564-025-01930-y · Cited by 49 · see citing works
Breastfeeding and early Bifidobacterium-driven microbial colonization shape the infant gut resistome
Samarra, A., Alcañiz, A. J., Martínez-Costa, C., Marina, A., Comas, I., Segata, N., Quijada, N. M., & Collado, M. C. (2025) · Nature Communications · doi:10.1038/s41467-025-61154-w · Cited by 32 · see citing works
Maternal and food microbial sources shape the infant microbiome of a rural Ethiopian population
Manara, S., Selma-Royo, M., Huang, K. D., Asnicar, F., Armanini, F., Blanco-Miguez, A., Cumbo, F., Golzato, D., Manghi, P., Pinto, F., et al. (2023) · Current Biology · doi:10.1016/j.cub.2023.04.011 · Cited by 30 · see citing works
Mizobuchi, H. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1110583 · Cited by 11 · see citing works
- Authors
- Vatanen, T., Kostic, A. D., d’Hennezel, E., Siljander, H., Franzosa, E. A., Yassour, M., Kolde, R., Vlamakis, H., Arthur, T. D., Hämäläinen, A.-M., Peet, A., Tillmann, V., Uibo, R., Mokurov, S., Dorshakova, N., Ilonen, J., Virtanen, S. M., Szabo, S. J., Porter, J. A., Lähdesmäki, H., Huttenhower, C., Gevers, D., Cullen, T. W., Knip, M., & Xavier, R. J.
- Affiliations
- Broad Institute (US)
- University of Helsinki (FI)
- Harvard University (US)
- Helsinki University Hospital (FI)
- Tartu University Hospital (EE)
- University of Tartu (EE)
- University of Turku (FI)
- Tampere University (FI)
- Aalto University (FI)
- Corresponding author
- Xavier, Ramnik J.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 165
- Issue
- 4
- Pages
- 842-853
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4950857
- OpenAlex
- W2343597029
- Cited by
- 1,289
- References
- 43
- Citations by year
- 2026: 70 · 2025: 107 · 2024: 122 · 2023: 127 · 2022: 160 · 2021: 162 · 2020: 123 · 2019: 147 · 2018: 115 · 2017: 114 · 2016: 40 · 2015: 1
- FWCI
- 72.09
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-06-02)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- Novo Nordisk Fonden (NNF11OC1014751)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK092405, U54DK102557, P30DK043351)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- gut microbiota, lipopolysaccharide, Bacteroides, Bacteroides dorei, Escherichia coli, endotoxin tolerance, innate immune signaling, autoimmunity, autoimmune diabetes, NOD mice, infant microbiome, hygiene hypothesis, microbial colonization, Finland, Estonia, Russia
- MeSH terms
- Gastrointestinal Microbiome, Animals, Bacteroides, Diabetes Mellitus, Type 1, Estonia, Feces, Finland, Food Microbiology, Humans, Infant, Lipopolysaccharides, Milk, Human, Russia, Mice, Inbred NOD, Mice
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