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, TEDDY Study Group, Marian Rewers, Kimberly Bautista, Judith Baxter, Ruth Bedoy, Daniel Felipe-Morales, Brigitte Frohnert, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Edwin Liu, Jill Norris, Adela Samper-Imaz, Andrea Steck, Kathleen Waugh, Hali Wright, Jin-Xiong She, 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, Anette G Ziegler, Andreas Beyerlein, Ezio Bonifacio, Michael Hummel, Sandra Hummel, Kristina Foterek, Mathilde Kersting, Annette Knopff, Sibylle Koletzko, Claudia Peplow, Roswith Roth, Joanna Stock, Elisabeth Strauss, Katharina Warncke, Christiane Winkler, Jorma Toppari, 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, Suvi M Virtanen, Mari Vähä-Mäkilä, Mari Åkerlund, Åke Lernmark, Daniel Agardh, Carin Andrén Aronsson, 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, Martha Butterworth, Joanna Clasen, David Cuthbertson, Christopher Eberhard, Steven Fiske, Dena Garcia, Jennifer Garmeson, Veena Gowda, David Hadley, Kathleen Heyman, Hye-Seung Lee, Shu Liu, Xiang Liu, Kristian Lynch, Jamie Malloy, Cristina McCarthy, Wendy McLeod, Steven Meulemans, Chris Shaffer, Laura Smith, Susan Smith, Roy Tamura, Ulla Uusitalo, Kendra Vehik, Ponni Vijayakandipan, Keith Wood, Jimin Yang, Beena Akolkar, 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, Barbara Davis, 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, Jin-Xiong She, Richard McIndoe, 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, 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, TEDDY Study Group, Marian Rewers, Kimberly Bautista, Judith Baxter, Ruth Bedoy, Daniel Felipe-Morales, Brigitte Frohnert, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Edwin Liu, Jill Norris, Adela Samper-Imaz, Andrea Steck, Kathleen Waugh, Hali Wright, Jin-Xiong She, 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, Anette G Ziegler, Andreas Beyerlein, Ezio Bonifacio, Michael Hummel, Sandra Hummel, Kristina Foterek, Mathilde Kersting, Annette Knopff, Sibylle Koletzko, Claudia Peplow, Roswith Roth, Joanna Stock, Elisabeth Strauss, Katharina Warncke, Christiane Winkler, Jorma Toppari, 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, Suvi M Virtanen, Mari Vähä-Mäkilä, Mari Åkerlund, Åke Lernmark, Daniel Agardh, Carin Andrén Aronsson, 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, Martha Butterworth, Joanna Clasen, David Cuthbertson, Christopher Eberhard, Steven Fiske, Dena Garcia, Jennifer Garmeson, Veena Gowda, David Hadley, Kathleen Heyman, Hye-Seung Lee, Shu Liu, Xiang Liu, Kristian Lynch, Jamie Malloy, Cristina McCarthy, Wendy McLeod, Steven Meulemans, Chris Shaffer, Laura Smith, Susan Smith, Roy Tamura, Ulla Uusitalo, Kendra Vehik, Ponni Vijayakandipan, Keith Wood, Jimin Yang, Beena Akolkar, 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, Barbara Davis, 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, Jin-Xiong She, Richard McIndoe, 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
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, and Washington) 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.
Figures
Source: PubMed