{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:32:39Z","timestamp":1791952359707,"version":"4.3.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,9,18]],"date-time":"2015-09-18T00:00:00Z","timestamp":1442534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,9,18]],"date-time":"2015-09-18T00:00:00Z","timestamp":1442534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The intestinal microbiota plays a critical role in the development of the immune system. Recent investigations have highlighted the potential of helminth therapy for treating a range of inflammatory disorders, including celiac disease (CeD); however, the mechanisms by which helminths modulate the immune response of the human host and ameliorate CeD pathology are unknown. In this study, we investigated the potential role of alterations in the human gut microbiota in helminth-mediated suppression of an inflammatory disease. We assessed the qualitative and quantitative changes in the microbiota of human volunteers with CeD prior to and following infection with human hookworms and following challenge with escalating doses of dietary gluten. Experimental hookworm infection of the trial subjects resulted in maintenance of the composition of the intestinal flora, even after a moderate gluten challenge. Notably, we observed a significant increase in microbial species richness over the course of the trial, which could represent a potential mechanism by which hookworms can regulate gluten-induced inflammation and maintain intestinal immune homeostasis.<\/jats:p>","DOI":"10.1038\/srep13797","type":"journal-article","created":{"date-parts":[[2015,9,18]],"date-time":"2015-09-18T08:52:39Z","timestamp":1442566359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Experimental hookworm infection and escalating gluten challenges are associated with increased microbial richness in celiac subjects"],"prefix":"10.1038","volume":"5","author":[{"given":"Paul","family":"Giacomin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Zakrzewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Croese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopei","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Sotillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leisa","family":"McCann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severine","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makedonka","family":"Mitreva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Krause","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Loukas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Cantacessi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,9,18]]},"reference":[{"key":"BFsrep13797_CR1","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1126\/science.1223490","volume":"336","author":"LV Hooper","year":"2012","unstructured":"Hooper, L. V., Littman, D. R. & Macpherson, A. J. Interactions between the microbiota and the immune system. Science 336, 1268\u20131273 (2012).","journal-title":"Science"},{"key":"BFsrep13797_CR2","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/ni.2611","volume":"14","author":"EM Brown","year":"2013","unstructured":"Brown, E. M., Sadarangani, M. & Finlay, B. B. The role of the immune system in governing host-microbe interactions in the intestine. Nat Immunol. 14, 660\u2013667 (2013).","journal-title":"Nat Immunol."},{"key":"BFsrep13797_CR3","doi-asserted-by":"publisher","first-page":"3866","DOI":"10.1016\/j.jmb.2014.05.029","volume":"426","author":"MK Gibson","year":"2014","unstructured":"Gibson, M. K., Peseky, M. W. & Dantas, D. The Yin and Yang of bacterial resilience in the human gut microbiota. J Mol Biol. 426, 3866\u20133876 (2014).","journal-title":"J Mol Biol."},{"key":"BFsrep13797_CR4","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/nature11550","volume":"489","author":"CA Lozupone","year":"2012","unstructured":"Lozupone, C. A., Stombaugh J. I., Gordon, J. I., Jansson, J. K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220\u2013230 (2012).","journal-title":"Nature"},{"key":"BFsrep13797_CR5","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.2174\/138161209788168146","volume":"15","author":"GT Macfarlane","year":"2009","unstructured":"Macfarlane, G. T., Blackett, K. L., Nakayama, T., Steed, H. & Macfarlane, S. The gut microbiota in inflammatory bowel disease. Curr Pharm Des. 15, 1528\u20131536 (2009).","journal-title":"Curr Pharm Des"},{"key":"BFsrep13797_CR6","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1002\/ibd.21830","volume":"18","author":"E Nistal","year":"2012","unstructured":"Nistal, E. et al. Differences of small intestinal bacteria populations in adults and children with\/without celiac disease: effect of age, gluten diet and disease. Inflamm Bowel Dis. 18, 649\u2013656 (2012).","journal-title":"Inflamm Bowel Dis."},{"key":"BFsrep13797_CR7","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.3748\/wjg.v19.i10.1541","volume":"19","author":"ZK Wang","year":"2013","unstructured":"Wang, Z. K. & Yang, Y. S. Upper gastrointestinal microbiota and digestive diseases. World J Gastroenterol. 19, 1541\u20131550 (2013).","journal-title":"World J Gastroenterol."},{"key":"BFsrep13797_CR8","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1053\/gast.2002.30294","volume":"122","author":"A Swidsinski","year":"2002","unstructured":"Swidsinski, A. et al. Mucosal flora in inflammatory bowel disease. Gastroenterology 122, 44\u201354 (2002).","journal-title":"Gastroenterology"},{"key":"BFsrep13797_CR9","doi-asserted-by":"publisher","first-page":"13780","DOI":"10.1073\/pnas.0706625104","volume":"104","author":"DN Frank","year":"2007","unstructured":"Frank, D. N. et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 104, 13780\u201313785 (2007).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep13797_CR10","doi-asserted-by":"publisher","first-page":"S76","DOI":"10.1017\/S0007114512005521","volume":"109","author":"M Olivares","year":"2013","unstructured":"Olivares, M., Laparra, J. M. & Sanz, Y. Host genotype, intestinal microbiota and inflammatory disorders. Br J Nutr. 109, S76\u2013S80 (2013).","journal-title":"Br J Nutr."},{"key":"BFsrep13797_CR11","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1586\/eci.09.70","volume":"6","author":"S Guandalini","year":"2010","unstructured":"Guandalini, S. Update on the role of probiotics in the therapy of pediatric inflammatory bowel disease. Expert Rev Clin Immunol. 6, 47\u201354 (2010).","journal-title":"Expert Rev Clin Immunol."},{"key":"BFsrep13797_CR12","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.jaci.2013.06.025","volume":"132","author":"RL Greer","year":"2013","unstructured":"Greer, R. L., Morgun, A. & Shulzhenko, N. Bridging immunity and lipid metabolism by gut microbiota. J Allergy Clin Immunol. 132, 253\u2013262 (2013).","journal-title":"J Allergy Clin Immunol."},{"key":"BFsrep13797_CR13","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1128\/CMR.00106-13","volume":"27","author":"LF de Sousa Moraes","year":"2014","unstructured":"de Sousa Moraes, L. F., Grzeskowiak, L. M., de Sales-Texeira, T. F. & do Carmo Gouveia Peluzio, M. Intestinal microbiota and probiotics in celiac disease. Clin Microbiol Rev. 27, 482\u2013489 (2014).","journal-title":"Clin Microbiol Rev."},{"key":"BFsrep13797_CR14","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1126\/science.296.5567.490","volume":"296","author":"M Yazdanbakhsh","year":"2002","unstructured":"Yazdanbakhsh, M., Kremsner, P. G. & van Ree, R. Allergy, parasites and the hygiene hypothesis. Science 296, 490\u2013494 (2002).","journal-title":"Science"},{"key":"BFsrep13797_CR15","doi-asserted-by":"publisher","first-page":"2034","DOI":"10.1111\/j.1572-0241.2003.07660.x","volume":"98","author":"RW Summers","year":"2003","unstructured":"Summers, R. W. et al. Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am J Gastroenterol. 98, 2034\u20132041 (2003).","journal-title":"Am J Gastroenterol."},{"key":"BFsrep13797_CR16","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1053\/j.gastro.2005.01.005","volume":"128","author":"RW Summers","year":"2005","unstructured":"Summers, R. W., Elliott, D. E., Urban, J. F. Jr, Thompson, R. A. & Weinstock, J. V. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128, 825\u2013832 (2005).","journal-title":"Gastroenterology"},{"key":"BFsrep13797_CR17","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1136\/gut.2005.079129","volume":"55","author":"J Croese","year":"2006","unstructured":"Croese, J. et al. A proof of concept study establishing Necator americanus in Crohn\u2019s patients and reservoir donors. Gut 55, 136\u2013137 (2006).","journal-title":"Gut"},{"key":"BFsrep13797_CR18","doi-asserted-by":"publisher","first-page":"e17366","DOI":"10.1371\/journal.pone.0017366","volume":"6","author":"AJ Daveson","year":"2011","unstructured":"Daveson, A. J. et al. Effect of hookworm infection on wheat challenge in celiac disease \u2013 a randomised double-blinded placebo controlled trial. PLoS One 6, e17366 (2011).","journal-title":"PLoS One"},{"key":"BFsrep13797_CR19","doi-asserted-by":"publisher","first-page":"e24092","DOI":"10.1371\/journal.pone.0024092","volume":"6","author":"HJ McSorley","year":"2011","unstructured":"McSorley, H. J. et al. Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection. PLoS One 6, e24092 (2011).","journal-title":"PLoS One"},{"key":"BFsrep13797_CR20","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.ijpara.2012.12.005","volume":"43","author":"J Croese","year":"2013","unstructured":"Croese, J., Gaze, S. T. & Loukas, A. Changed gluten immunity in celiac disease by Necator americanus provides new insights into autoimmunity. Int J Parasitol. 43, 275\u2013282 (2013).","journal-title":"Int J Parasitol."},{"key":"BFsrep13797_CR21","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.ijpara.2012.10.016","volume":"43","author":"JV Weinstock","year":"2013","unstructured":"Weinstock, J. V. & Elliott, D. E. Translatability of helminth therapy in inflammatory bowel disease. Int J Parasitol. 43, 245\u2013251 (2013).","journal-title":"Int J Parasitol."},{"key":"BFsrep13797_CR22","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.jaci.2014.07.022","volume":"135","author":"J Croese","year":"2015","unstructured":"Croese, J. et al. Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease. J Allergy Clin Immunol. 135, 508\u2013516 (2015).","journal-title":"J Allergy Clin Immunol."},{"key":"BFsrep13797_CR23","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1002\/ibd.21299","volume":"16","author":"ST Walk","year":"2010","unstructured":"Walk, S. T., Blum, A. M., Ewing, S. A., Weinstock, J. V. & Young, V. B. Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrus. Inflamm Bowel Dis. 16, 1841\u20131849 (2010).","journal-title":"Inflamm Bowel Dis."},{"key":"BFsrep13797_CR24","doi-asserted-by":"publisher","first-page":"e1003000","DOI":"10.1371\/journal.ppat.1003000","volume":"8","author":"MJ Broadhurst","year":"2012","unstructured":"Broadhurst, M. J. et al. Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon. PLoS Pathog. 8, e1003000 (2012).","journal-title":"PLoS Pathog."},{"key":"BFsrep13797_CR25","doi-asserted-by":"publisher","first-page":"e35470","DOI":"10.1371\/journal.pone.0035470","volume":"7","author":"RW Li","year":"2012","unstructured":"Li, R. W. et al. Worm-burden dependent disruption of the porcine colon microbiota by Trichuris suis infection. PLoS One 7, e35470 (2012).","journal-title":"PLoS One"},{"key":"BFsrep13797_CR26","doi-asserted-by":"publisher","first-page":"e1002520","DOI":"10.1371\/journal.ppat.1002520","volume":"8","author":"S Gaze","year":"2012","unstructured":"Gaze, S. et al. Characterising the mucosal and systemic immune responses to experimental human hookworm infection. PLoS Pathog. 8, e1002520 (2012).","journal-title":"PLoS Pathog."},{"key":"BFsrep13797_CR27","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1136\/gutjnl-2014-306931","volume":"14","author":"M Olivares","year":"2015","unstructured":"Olivares, M. et al. The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease. Gut. 14, 406\u2013417 (2015).","journal-title":"Gut."},{"key":"BFsrep13797_CR28","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1093\/infdis\/jiu256","volume":"210","author":"C Cantacessi","year":"2014","unstructured":"Cantacessi, C. et al. Impact of experimental hookworm infection on the human gut microbiota. J Infect Dis. 210, 1431\u20131434 (2014).","journal-title":"J Infect Dis."},{"key":"BFsrep13797_CR29","doi-asserted-by":"publisher","first-page":"e2880","DOI":"10.1371\/journal.pntd.0002880","volume":"8","author":"SC Lee","year":"2014","unstructured":"Lee, S. C. et al. Helminth colonization is associated with increased diversity of the gut microbiota. PLoS Negl Trop Dis. 8, e2880 (2014).","journal-title":"PLoS Negl Trop Dis."},{"key":"BFsrep13797_CR30","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1002\/ibd.20101","volume":"13","author":"S Sepehri","year":"2007","unstructured":"Sepehri, S., Kotlowski, R., Bernstein, C. N. & Krause, D. O. Microbial diversity of inflamed and noninflamed gut biopsy tissues in inflammatory bowel disease. Inflamm Bowel Dis. 13, 675\u2013683 (2007).","journal-title":"Inflamm Bowel Dis."},{"key":"BFsrep13797_CR31","doi-asserted-by":"publisher","first-page":"250","DOI":"10.3329\/jhpn.v30i3.12287","volume":"30","author":"S Monira","year":"2012","unstructured":"Monira, S. et al. 16S rRNA gene\u2013targeted TTGE in determining diversity of gut microbiota during acute diarrhoea and convalescence. J Health Popul Nutr. 30, 250\u2013256 (2012).","journal-title":"J Health Popul Nutr."},{"key":"BFsrep13797_CR32","doi-asserted-by":"publisher","first-page":"e53838","DOI":"10.1371\/journal.pone.0053838","volume":"8","author":"A Lin","year":"2013","unstructured":"Lin, A. et al. Distinct distal gut microbiome diversity and composition in healthy children from Bangladesh and the United States. PLoS One 8, e53838 (2013).","journal-title":"PLoS One"},{"key":"BFsrep13797_CR33","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/nature09944","volume":"473","author":"M Arumugam","year":"2011","unstructured":"Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473, 174\u2013180 (2011).","journal-title":"Nature"},{"key":"BFsrep13797_CR34","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1111\/1574-6941.12295","volume":"88","author":"A Caminero","year":"2014","unstructured":"Caminero, A. et al. Diversity of the cultivable gut microbiome involved in gluten metabolism: isolation of microorganisms with potential interest for coeliac disease. FEMS Microbiol Ecol. 88, 109\u2013119 (2014).","journal-title":"FEMS Microbiol Ecol."},{"key":"BFsrep13797_CR35","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1136\/jcp.2008.061366","volume":"62","author":"MC Collado","year":"2009","unstructured":"Collado, M. C. et al. Specific duodenal and fecal bacterial groups associated with paediatric coeliac disease. J Clin Pathol. 62, 264\u2013269 (2009).","journal-title":"J Clin Pathol."},{"key":"BFsrep13797_CR36","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.ijpara.2012.11.011","volume":"43","author":"HJ McSorley","year":"2013","unstructured":"McSorley, H. J., Hewitson, J. P. & Maizels, R. M. Immunomodulation by helminth parasites: defining mechanisms and mediators. Int J Parasitol. 43, 301\u2013310 (2013).","journal-title":"Int J Parasitol."},{"key":"BFsrep13797_CR37","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nmeth.f.303","volume":"7","author":"JG Caporaso","year":"2010","unstructured":"Caporaso, J. G. et al. QIIME allows integration and analysis of high-throughput community sequencing data. Nat Methods 7, 335\u2013336 (2010).","journal-title":"Nat Methods"},{"key":"BFsrep13797_CR38","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1038\/nbt.2676","volume":"31","author":"MG Langille","year":"2013","unstructured":"Langille, M. G. et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 31, 814\u2013821 (2013).","journal-title":"Nat Biotechnol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep13797","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep13797.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep13797.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T23:38:59Z","timestamp":1672961939000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep13797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,18]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,11,26]]}},"alternative-id":["BFsrep13797"],"URL":"https:\/\/doi.org\/10.1038\/srep13797","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,18]]},"assertion":[{"value":"15 April 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 September 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"13797"}}