Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study

Ulla Uusitalo, Xiang Liu, Jimin Yang, Carin Andrén Aronsson, Sandra Hummel, Martha Butterworth, Åke Lernmark, Marian Rewers, William Hagopian, Jin Xiong She, Olli Simell, Jorma Toppari, Anette G. Ziegler, Beena Akolkar, Jeffrey Krischer, Jill M. Norris, Suvi M. Virtanen, Kimberly Bautista, Judith Baxter, Ruth BedoyDaniel Felipe-Morales, Brigitte Frohnert, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Edwin Liu, Adela Samper-Imaz, Andrea Steck, Kathleen Waugh, Hali Wright, Desmond Schatz, Diane Hopkins, Leigh Steed, Jamie Thomas, Katherine Silvis, Michael Haller, Meena Shankar, Eleni Sheehan, Melissa Gardiner, Richard McIndoe, Ashok Sharma, Joshua Williams, Gabriela Foghis, Stephen W. Anderson, Richard Robinson, Andreas Beyerlein, Ezio Bonifacio, Michael Hummel, Kristina Foterek, Mathilde Kersting, Annette Knopff, Sibylle Koletzko, Claudia Peplow, Roswith Roth, Joanna Stock, Elisabeth Strauss, Katharina Warncke, Christiane Winkler, Olli G. Simell, Annika Adamsson, Heikki Hyöty, Jorma Ilonen, Sanna Jokipuu, Tiina Kallio, Miia Kähönen, Mikael Knip, Annika Koivu, Mirva Koreasalo, Kalle Kurppa, Maria Lönnrot, Elina Mäntymäki, Katja Multasuo, Juha Mykkänen, Tiina Niininen, Mia Nyblom, Petra Rajala, Jenna Rautanen, Anne Riikonen, Minna Romo, Satu Simell, Tuula Simell, Ville Simell, Maija Sjöberg, Aino Stenius, Maria Särmä, Sini Vainionpää, Eeva Varjonen, Riitta Veijola, Mari Vähä-Mäkilä, Mari Åkerlund, Daniel Agardh, Maria Ask, Jenny Bremer, Ulla Marie Carlsson, Corrado Cilio, Emelie Ericson-Hallström, Lina Fransson, Thomas Gard, Joanna Gerardsson, Rasmus Bennet, Monica Hansen, Gertie Hansson, Susanne Hyberg, Fredrik Johansen, Berglind Jonasdottir, Linda Jonsson, Helena Elding Larsson, Sigrid Lenrick Forss, Maria Månsson-Martinez, Maria Markan, Jessica Melin, Zeliha Mestan, Kobra Rahmati, Anita Ramelius, Anna Rosenquist, Falastin Salami, Sara Sibthorpe, Birgitta Sjöberg, Ulrica Swartling, Evelyn Tekum Amboh, Erika Trulsson, Carina Törn, Anne Wallin, Åsa Wimar, Sofie Åberg, William A. Hagopian, Xiang Yan, Michael Killian, Claire Cowen Crouch, Jennifer Skidmore, Stephen Ayres, Kayleen Dunson, Diana Heaney, Rachel Hervey, Corbin Johnson, Rachel Lyons, Arlene Meyer, Denise Mulenga, Emma Schulte, Elizabeth Scott, Joshua Stabbert, John Willis, Dorothy Becker, Margaret Franciscus, Maryellen Dalmagro Elias Smith, Ashi Daftary, Mary Beth Klein, Chrystal Yates, Jeffrey P. Krischer, Michael Abbondondolo, Sarah Austin-Gonzalez, Sandra Baethke, Rasheedah Brown, Brant Burkhardt, Joanna Clasen, David Cuthbertson, Christopher Eberhard, Steven Fiske, Dena Garcia, Jennifer Garmeson, Veena Gowda, David Hadley, Kathleen Heyman, Hye Seung Lee, Shu Liu, Kristian Lynch, Jamie Malloy, Cristina McCarthy, Wendy McLeod, Steven Meulemans, Chris Shaffer, Laura Smith, Susan Smith, Roy Tamura, Kendra Vehik, Ponni Vijayakandipan, Keith Wood, Kasia Bourcier, Thomas Briese, Suzanne Bennett Johnson, Steve Oberste, Eric Triplett, Liping Yu, Dongmei Miao, Polly Bingley, Alistair Williams, Kyla Chandler, Saba Rokni, Claire Caygill, Nicholas Lovis, Claire Williams, Rebecca Wyatt, Elisabeth Aardal Eriksson, Ing Marie Lundgren, Ewa Lönn Karlsson, Dzeneta Nezirevic Dernroth, Iris Erlund, Irma Salminen, Jouko Sundvall, Jaana Leiviskä, Nina Kangas, Randie R. Little, Alethea L. Tennill, Henry Erlich, Steven J. Mack, Anna Lisa Fear, Oliver Fiehn, Bill Wikoff, Brian Defelice, Dmitry Grapov, Tobias Kind, Mine Palazoglu, Luis Valdiviez, Benjamin Wancewicz, Gert Wohlgemuth, Joyce Wong, Joseph F. Petrosino, Santica M. Marcovina, Vinod P. Gaur, Richard D. Smith, Thomas O. Metz, Charles Ansong, Bobbie Jo Webb-Robertson, Hugh D. Mitchell, Heather Higgins, Sandra Ke, Haitao Liu, John Nechtman, Yansheng Zhao, Na Jiang, Yanna Tian, Guangkuo Dong, Stephen S. Rich, Wei Min Chen, Suna Onengut-Gumuscu, Emily Farber, Rebecca Roche Pickin, Jordan Davis, Dan Gallo, Jessica Bonnie, Paul Campolieto

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

IMPORTANCE Probiotics have been hypothesized to affect immunologic responses to environmental exposures by supporting healthy gut microbiota and could therefore theoretically be used to prevent the development of type 1 diabetes mellitus (T1DM)-associated islet autoimmunity. OBJECTIVE To examine the association between supplemental probiotic use during the first year of life and islet autoimmunity among children at increased genetic risk of T1DM. DESIGN, SETTING, AND PARTICIPANTS In this ongoing prospective cohort study that started September 1, 2004, children from 6 clinical centers, 3 in the United States (Colorado, Georgia/Florida, andWashington) and 3 in Europe (Finland, Germany, and Sweden), were followed up for T1DM-related autoantibodies. Blood samples were collected every 3 months between 3 and 48 months of age and every 6 months thereafter to determine persistent islet autoimmunity. Details of infant feeding, including probiotic supplementation and infant formula use, were monitored from birth using questionnaires and diaries.We applied time-to-event analysis to study the association between probiotic use and islet autoimmunity, stratifying by country and adjusting for family history of type 1 diabetes, HLA-DR-DQ genotypes, sex, birth order, mode of delivery, exclusive breastfeeding, birth year, child's antibiotic use, and diarrheal history, as well as maternal age, probiotic use, and smoking. Altogether 8676 infants with an eligible genotype were enrolled in the follow-up study before the age of 4 months. The final sample consisted of 7473 children with the age range of 4 to 10 years (as of October 31, 2014). EXPOSURES Early intake of probiotics. MAIN OUTCOMES AND MEASURES Islet autoimmunity revealed by specific islet autoantibodies. RESULTS Early probiotic supplementation (at the age of 0-27 days) was associated with a decreased risk of islet autoimmunity when compared with probiotic supplementation after 27 days or no probiotic supplementation (hazard ratio [HR], 0.66; 95%CI, 0.46-0.94). The association was accounted for by children with the DR3/4 genotype (HR, 0.40; 95%CI, 0.21-0.74) and was absent among other genotypes (HR, 0.97; 95%CI, 0.62-1.54). CONCLUSIONS AND RELEVANCE Early probiotic supplementation may reduce the risk of islet autoimmunity in children at the highest genetic risk of T1DM. The result needs to be confirmed in further studies before any recommendation of probiotics use is made.

Original languageEnglish (US)
Pages (from-to)20-28
Number of pages9
JournalJAMA Pediatrics
Volume170
Issue number1
DOIs
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Uusitalo, U., Liu, X., Yang, J., Aronsson, C. A., Hummel, S., Butterworth, M., Lernmark, Å., Rewers, M., Hagopian, W., She, J. X., Simell, O., Toppari, J., Ziegler, A. G., Akolkar, B., Krischer, J., Norris, J. M., Virtanen, S. M., Bautista, K., Baxter, J., ... Campolieto, P. (2016). Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study. JAMA Pediatrics, 170(1), 20-28. https://doi.org/10.1001/jamapediatrics.2015.2757