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

85 Citations (Scopus)

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

Fingerprint

Probiotics
Autoimmunity
Type 1 Diabetes Mellitus
Genotype
Autoantibodies
Parturition
HLA-DQ Antigens
Infant Formula
Birth Order
Environmental Exposure
Maternal Age
HLA-DR Antigens
Finland
Breast Feeding
Sweden
Germany
Cohort Studies
Smoking
History
Prospective Studies

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Uusitalo, U., Liu, X., Yang, J., Aronsson, C. A., Hummel, S., Butterworth, M., ... 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

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

In: JAMA Pediatrics, Vol. 170, No. 1, 01.01.2016, p. 20-28.

Research output: Contribution to journalArticle

Uusitalo, U, Liu, X, Yang, J, Aronsson, CA, Hummel, S, Butterworth, M, Lernmark, Å, Rewers, M, Hagopian, W, She, JX, Simell, O, Toppari, J, Ziegler, AG, Akolkar, B, Krischer, J, Norris, JM, Virtanen, SM, Bautista, K, Baxter, J, Bedoy, R, Felipe-Morales, D, Frohnert, B, Gesualdo, P, Hoffman, M, Karban, R, Liu, E, Samper-Imaz, A, Steck, A, Waugh, K, Wright, H, Schatz, D, Hopkins, D, Steed, L, Thomas, J, Silvis, K, Haller, M, Shankar, M, Sheehan, E, Gardiner, M, McIndoe, R, Sharma, A, Williams, J, Foghis, G, Anderson, SW, Robinson, R, Beyerlein, A, Bonifacio, E, Hummel, M, Foterek, K, Kersting, M, Knopff, A, Koletzko, S, Peplow, C, Roth, R, Stock, J, Strauss, E, Warncke, K, Winkler, C, Simell, OG, Adamsson, A, Hyöty, H, Ilonen, J, Jokipuu, S, Kallio, T, Kähönen, M, Knip, M, Koivu, A, Koreasalo, M, Kurppa, K, Lönnrot, M, Mäntymäki, E, Multasuo, K, Mykkänen, J, Niininen, T, Nyblom, M, Rajala, P, Rautanen, J, Riikonen, A, Romo, M, Simell, S, Simell, T, Simell, V, Sjöberg, M, Stenius, A, Särmä, M, Vainionpää, S, Varjonen, E, Veijola, R, Vähä-Mäkilä, M, Åkerlund, M, Agardh, D, Ask, M, Bremer, J, Carlsson, UM, Cilio, C, Ericson-Hallström, E, Fransson, L, Gard, T, Gerardsson, J, Bennet, R, Hansen, M, Hansson, G, Hyberg, S, Johansen, F, Jonasdottir, B, Jonsson, L, Larsson, HE, Forss, SL, Månsson-Martinez, M, Markan, M, Melin, J, Mestan, Z, Rahmati, K, Ramelius, A, Rosenquist, A, Salami, F, Sibthorpe, S, Sjöberg, B, Swartling, U, Amboh, ET, Trulsson, E, Törn, C, Wallin, A, Wimar, Å, Åberg, S, Hagopian, WA, Yan, X, Killian, M, Crouch, CC, Skidmore, J, Ayres, S, Dunson, K, Heaney, D, Hervey, R, Johnson, C, Lyons, R, Meyer, A, Mulenga, D, Schulte, E, Scott, E, Stabbert, J, Willis, J, Becker, D, Franciscus, M, Smith, MDE, Daftary, A, Klein, MB, Yates, C, Krischer, JP, Abbondondolo, M, Austin-Gonzalez, S, Baethke, S, Brown, R, Burkhardt, B, Clasen, J, Cuthbertson, D, Eberhard, C, Fiske, S, Garcia, D, Garmeson, J, Gowda, V, Hadley, D, Heyman, K, Lee, HS, Liu, S, Lynch, K, Malloy, J, McCarthy, C, McLeod, W, Meulemans, S, Shaffer, C, Smith, L, Smith, S, Tamura, R, Vehik, K, Vijayakandipan, P, Wood, K, Bourcier, K, Briese, T, Johnson, SB, Oberste, S, Triplett, E, Yu, L, Miao, D, Bingley, P, Williams, A, Chandler, K, Rokni, S, Caygill, C, Lovis, N, Williams, C, Wyatt, R, Eriksson, EA, Lundgren, IM, Karlsson, EL, Dernroth, DN, Erlund, I, Salminen, I, Sundvall, J, Leiviskä, J, Kangas, N, Little, RR, Tennill, AL, Erlich, H, Mack, SJ, Fear, AL, Fiehn, O, Wikoff, B, Defelice, B, Grapov, D, Kind, T, Palazoglu, M, Valdiviez, L, Wancewicz, B, Wohlgemuth, G, Wong, J, Petrosino, JF, Marcovina, SM, Gaur, VP, Smith, RD, Metz, TO, Ansong, C, Webb-Robertson, BJ, Mitchell, HD, Higgins, H, Ke, S, Liu, H, Nechtman, J, Zhao, Y, Jiang, N, Tian, Y, Dong, G, Rich, SS, Chen, WM, Onengut-Gumuscu, S, Farber, E, Pickin, RR, Davis, J, Gallo, D, Bonnie, J & Campolieto, P 2016, 'Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study', JAMA Pediatrics, vol. 170, no. 1, pp. 20-28. https://doi.org/10.1001/jamapediatrics.2015.2757
Uusitalo U, Liu X, Yang J, Aronsson CA, Hummel S, Butterworth M et al. Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study. JAMA Pediatrics. 2016 Jan 1;170(1):20-28. https://doi.org/10.1001/jamapediatrics.2015.2757
Uusitalo, Ulla ; Liu, Xiang ; Yang, Jimin ; Aronsson, Carin Andrén ; Hummel, Sandra ; Butterworth, Martha ; Lernmark, Åke ; Rewers, Marian ; Hagopian, William ; She, Jin Xiong ; Simell, Olli ; Toppari, Jorma ; Ziegler, Anette G. ; Akolkar, Beena ; Krischer, Jeffrey ; Norris, Jill M. ; Virtanen, Suvi M. ; Bautista, Kimberly ; Baxter, Judith ; Bedoy, Ruth ; Felipe-Morales, Daniel ; Frohnert, Brigitte ; Gesualdo, Patricia ; Hoffman, Michelle ; Karban, Rachel ; Liu, Edwin ; Samper-Imaz, Adela ; Steck, Andrea ; Waugh, Kathleen ; Wright, Hali ; Schatz, Desmond ; Hopkins, Diane ; Steed, Leigh ; Thomas, Jamie ; Silvis, Katherine ; Haller, Michael ; Shankar, Meena ; Sheehan, Eleni ; Gardiner, Melissa ; McIndoe, Richard ; Sharma, Ashok ; Williams, Joshua ; Foghis, Gabriela ; Anderson, Stephen W. ; Robinson, Richard ; Beyerlein, Andreas ; Bonifacio, Ezio ; Hummel, Michael ; Foterek, Kristina ; Kersting, Mathilde ; Knopff, Annette ; Koletzko, Sibylle ; Peplow, Claudia ; Roth, Roswith ; Stock, Joanna ; Strauss, Elisabeth ; Warncke, Katharina ; Winkler, Christiane ; Simell, Olli G. ; Adamsson, Annika ; Hyöty, Heikki ; Ilonen, Jorma ; Jokipuu, Sanna ; Kallio, Tiina ; Kähönen, Miia ; Knip, Mikael ; Koivu, Annika ; Koreasalo, Mirva ; Kurppa, Kalle ; Lönnrot, Maria ; Mäntymäki, Elina ; Multasuo, Katja ; Mykkänen, Juha ; Niininen, Tiina ; Nyblom, Mia ; Rajala, Petra ; Rautanen, Jenna ; Riikonen, Anne ; Romo, Minna ; Simell, Satu ; Simell, Tuula ; Simell, Ville ; Sjöberg, Maija ; Stenius, Aino ; Särmä, Maria ; Vainionpää, Sini ; Varjonen, Eeva ; Veijola, Riitta ; Vähä-Mäkilä, Mari ; Åkerlund, Mari ; Agardh, Daniel ; Ask, Maria ; Bremer, Jenny ; Carlsson, Ulla Marie ; Cilio, Corrado ; Ericson-Hallström, Emelie ; Fransson, Lina ; Gard, Thomas ; Gerardsson, Joanna ; Bennet, Rasmus ; Hansen, Monica ; Hansson, Gertie ; Hyberg, Susanne ; Johansen, Fredrik ; Jonasdottir, Berglind ; Jonsson, Linda ; Larsson, Helena Elding ; Forss, Sigrid Lenrick ; Månsson-Martinez, Maria ; Markan, Maria ; Melin, Jessica ; Mestan, Zeliha ; Rahmati, Kobra ; Ramelius, Anita ; Rosenquist, Anna ; Salami, Falastin ; Sibthorpe, Sara ; Sjöberg, Birgitta ; Swartling, Ulrica ; Amboh, Evelyn Tekum ; Trulsson, Erika ; Törn, Carina ; Wallin, Anne ; Wimar, Åsa ; Åberg, Sofie ; Hagopian, William A. ; Yan, Xiang ; Killian, Michael ; Crouch, Claire Cowen ; Skidmore, Jennifer ; Ayres, Stephen ; Dunson, Kayleen ; Heaney, Diana ; Hervey, Rachel ; Johnson, Corbin ; Lyons, Rachel ; Meyer, Arlene ; Mulenga, Denise ; Schulte, Emma ; Scott, Elizabeth ; Stabbert, Joshua ; Willis, John ; Becker, Dorothy ; Franciscus, Margaret ; Smith, Maryellen Dalmagro Elias ; Daftary, Ashi ; Klein, Mary Beth ; Yates, Chrystal ; Krischer, Jeffrey P. ; Abbondondolo, Michael ; Austin-Gonzalez, Sarah ; Baethke, Sandra ; Brown, Rasheedah ; Burkhardt, Brant ; Clasen, Joanna ; Cuthbertson, David ; Eberhard, Christopher ; Fiske, Steven ; Garcia, Dena ; Garmeson, Jennifer ; Gowda, Veena ; Hadley, David ; Heyman, Kathleen ; Lee, Hye Seung ; Liu, Shu ; Lynch, Kristian ; Malloy, Jamie ; McCarthy, Cristina ; McLeod, Wendy ; Meulemans, Steven ; Shaffer, Chris ; Smith, Laura ; Smith, Susan ; Tamura, Roy ; Vehik, Kendra ; Vijayakandipan, Ponni ; Wood, Keith ; Bourcier, Kasia ; Briese, Thomas ; Johnson, Suzanne Bennett ; Oberste, Steve ; Triplett, Eric ; Yu, Liping ; Miao, Dongmei ; Bingley, Polly ; Williams, Alistair ; Chandler, Kyla ; Rokni, Saba ; Caygill, Claire ; Lovis, Nicholas ; Williams, Claire ; Wyatt, Rebecca ; Eriksson, Elisabeth Aardal ; Lundgren, Ing Marie ; Karlsson, Ewa Lönn ; Dernroth, Dzeneta Nezirevic ; Erlund, Iris ; Salminen, Irma ; Sundvall, Jouko ; Leiviskä, Jaana ; Kangas, Nina ; Little, Randie R. ; Tennill, Alethea L. ; Erlich, Henry ; Mack, Steven J. ; Fear, Anna Lisa ; Fiehn, Oliver ; Wikoff, Bill ; Defelice, Brian ; Grapov, Dmitry ; Kind, Tobias ; Palazoglu, Mine ; Valdiviez, Luis ; Wancewicz, Benjamin ; Wohlgemuth, Gert ; Wong, Joyce ; Petrosino, Joseph F. ; Marcovina, Santica M. ; Gaur, Vinod P. ; Smith, Richard D. ; Metz, Thomas O. ; Ansong, Charles ; Webb-Robertson, Bobbie Jo ; Mitchell, Hugh D. ; Higgins, Heather ; Ke, Sandra ; Liu, Haitao ; Nechtman, John ; Zhao, Yansheng ; Jiang, Na ; Tian, Yanna ; Dong, Guangkuo ; Rich, Stephen S. ; Chen, Wei Min ; Onengut-Gumuscu, Suna ; Farber, Emily ; Pickin, Rebecca Roche ; Davis, Jordan ; Gallo, Dan ; Bonnie, Jessica ; Campolieto, Paul. / Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study. In: JAMA Pediatrics. 2016 ; Vol. 170, No. 1. pp. 20-28.
@article{aa2d94dea75040a2bbf88eb45f30b9eb,
title = "Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study",
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.",
author = "Ulla Uusitalo and Xiang Liu and Jimin Yang and Aronsson, {Carin Andr{\'e}n} and Sandra Hummel and Martha Butterworth and {\AA}ke Lernmark and Marian Rewers and William Hagopian and She, {Jin Xiong} and Olli Simell and Jorma Toppari and Ziegler, {Anette G.} and Beena Akolkar and Jeffrey Krischer and Norris, {Jill M.} and Virtanen, {Suvi M.} and Kimberly Bautista and Judith Baxter and Ruth Bedoy and Daniel Felipe-Morales and Brigitte Frohnert and Patricia Gesualdo and Michelle Hoffman and Rachel Karban and Edwin Liu and Adela Samper-Imaz and Andrea Steck and Kathleen Waugh and Hali Wright and Desmond Schatz and Diane Hopkins and Leigh Steed and Jamie Thomas and Katherine Silvis and Michael Haller and Meena Shankar and Eleni Sheehan and Melissa Gardiner and Richard McIndoe and Ashok Sharma and Joshua Williams and Gabriela Foghis and Anderson, {Stephen W.} and Richard Robinson and Andreas Beyerlein and Ezio Bonifacio and Michael Hummel and Kristina Foterek and Mathilde Kersting and Annette Knopff and Sibylle Koletzko and Claudia Peplow and Roswith Roth and Joanna Stock and Elisabeth Strauss and Katharina Warncke and Christiane Winkler and Simell, {Olli G.} and Annika Adamsson and Heikki Hy{\"o}ty and Jorma Ilonen and Sanna Jokipuu and Tiina Kallio and Miia K{\"a}h{\"o}nen and Mikael Knip and Annika Koivu and Mirva Koreasalo and Kalle Kurppa and Maria L{\"o}nnrot and Elina M{\"a}ntym{\"a}ki and Katja Multasuo and Juha Mykk{\"a}nen and Tiina Niininen and Mia Nyblom and Petra Rajala and Jenna Rautanen and Anne Riikonen and Minna Romo and Satu Simell and Tuula Simell and Ville Simell and Maija Sj{\"o}berg and Aino Stenius and Maria S{\"a}rm{\"a} and Sini Vainionp{\"a}{\"a} and Eeva Varjonen and Riitta Veijola and Mari V{\"a}h{\"a}-M{\"a}kil{\"a} and Mari {\AA}kerlund and Daniel Agardh and Maria Ask and Jenny Bremer and Carlsson, {Ulla Marie} and Corrado Cilio and Emelie Ericson-Hallstr{\"o}m and Lina Fransson and Thomas Gard and Joanna Gerardsson and Rasmus Bennet and Monica Hansen and Gertie Hansson and Susanne Hyberg and Fredrik Johansen and Berglind Jonasdottir and Linda Jonsson and Larsson, {Helena Elding} and Forss, {Sigrid Lenrick} and Maria M{\aa}nsson-Martinez and Maria Markan and Jessica Melin and Zeliha Mestan and Kobra Rahmati and Anita Ramelius and Anna Rosenquist and Falastin Salami and Sara Sibthorpe and Birgitta Sj{\"o}berg and Ulrica Swartling and Amboh, {Evelyn Tekum} and Erika Trulsson and Carina T{\"o}rn and Anne Wallin and {\AA}sa Wimar and Sofie {\AA}berg and Hagopian, {William A.} and Xiang Yan and Michael Killian and Crouch, {Claire Cowen} and Jennifer Skidmore and Stephen Ayres and Kayleen Dunson and Diana Heaney and Rachel Hervey and Corbin Johnson and Rachel Lyons and Arlene Meyer and Denise Mulenga and Emma Schulte and Elizabeth Scott and Joshua Stabbert and John Willis and Dorothy Becker and Margaret Franciscus and Smith, {Maryellen Dalmagro Elias} and Ashi Daftary and Klein, {Mary Beth} and Chrystal Yates and Krischer, {Jeffrey P.} and Michael Abbondondolo and Sarah Austin-Gonzalez and Sandra Baethke and Rasheedah Brown and Brant Burkhardt and Joanna Clasen and David Cuthbertson and Christopher Eberhard and Steven Fiske and Dena Garcia and Jennifer Garmeson and Veena Gowda and David Hadley and Kathleen Heyman and Lee, {Hye Seung} and Shu Liu and Kristian Lynch and Jamie Malloy and Cristina McCarthy and Wendy McLeod and Steven Meulemans and Chris Shaffer and Laura Smith and Susan Smith and Roy Tamura and Kendra Vehik and Ponni Vijayakandipan and Keith Wood and Kasia Bourcier and Thomas Briese and Johnson, {Suzanne Bennett} and Steve Oberste and Eric Triplett and Liping Yu and Dongmei Miao and Polly Bingley and Alistair Williams and Kyla Chandler and Saba Rokni and Claire Caygill and Nicholas Lovis and Claire Williams and Rebecca Wyatt and Eriksson, {Elisabeth Aardal} and Lundgren, {Ing Marie} and Karlsson, {Ewa L{\"o}nn} and Dernroth, {Dzeneta Nezirevic} and Iris Erlund and Irma Salminen and Jouko Sundvall and Jaana Leivisk{\"a} and Nina Kangas and Little, {Randie R.} and Tennill, {Alethea L.} and Henry Erlich and Mack, {Steven J.} and Fear, {Anna Lisa} and Oliver Fiehn and Bill Wikoff and Brian Defelice and Dmitry Grapov and Tobias Kind and Mine Palazoglu and Luis Valdiviez and Benjamin Wancewicz and Gert Wohlgemuth and Joyce Wong and Petrosino, {Joseph F.} and Marcovina, {Santica M.} and Gaur, {Vinod P.} and Smith, {Richard D.} and Metz, {Thomas O.} and Charles Ansong and Webb-Robertson, {Bobbie Jo} and Mitchell, {Hugh D.} and Heather Higgins and Sandra Ke and Haitao Liu and John Nechtman and Yansheng Zhao and Na Jiang and Yanna Tian and Guangkuo Dong and Rich, {Stephen S.} and Chen, {Wei Min} and Suna Onengut-Gumuscu and Emily Farber and Pickin, {Rebecca Roche} and Jordan Davis and Dan Gallo and Jessica Bonnie and Paul Campolieto",
year = "2016",
month = "1",
day = "1",
doi = "10.1001/jamapediatrics.2015.2757",
language = "English (US)",
volume = "170",
pages = "20--28",
journal = "JAMA Pediatrics",
issn = "2168-6203",
publisher = "American Medical Association",
number = "1",

}

TY - JOUR

T1 - Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study

AU - Uusitalo, Ulla

AU - Liu, Xiang

AU - Yang, Jimin

AU - Aronsson, Carin Andrén

AU - Hummel, Sandra

AU - Butterworth, Martha

AU - Lernmark, Åke

AU - Rewers, Marian

AU - Hagopian, William

AU - She, Jin Xiong

AU - Simell, Olli

AU - Toppari, Jorma

AU - Ziegler, Anette G.

AU - Akolkar, Beena

AU - Krischer, Jeffrey

AU - Norris, Jill M.

AU - Virtanen, Suvi M.

AU - Bautista, Kimberly

AU - Baxter, Judith

AU - Bedoy, Ruth

AU - Felipe-Morales, Daniel

AU - Frohnert, Brigitte

AU - Gesualdo, Patricia

AU - Hoffman, Michelle

AU - Karban, Rachel

AU - Liu, Edwin

AU - Samper-Imaz, Adela

AU - Steck, Andrea

AU - Waugh, Kathleen

AU - Wright, Hali

AU - Schatz, Desmond

AU - Hopkins, Diane

AU - Steed, Leigh

AU - Thomas, Jamie

AU - Silvis, Katherine

AU - Haller, Michael

AU - Shankar, Meena

AU - Sheehan, Eleni

AU - Gardiner, Melissa

AU - McIndoe, Richard

AU - Sharma, Ashok

AU - Williams, Joshua

AU - Foghis, Gabriela

AU - Anderson, Stephen W.

AU - Robinson, Richard

AU - Beyerlein, Andreas

AU - Bonifacio, Ezio

AU - Hummel, Michael

AU - Foterek, Kristina

AU - Kersting, Mathilde

AU - Knopff, Annette

AU - Koletzko, Sibylle

AU - Peplow, Claudia

AU - Roth, Roswith

AU - Stock, Joanna

AU - Strauss, Elisabeth

AU - Warncke, Katharina

AU - Winkler, Christiane

AU - Simell, Olli G.

AU - Adamsson, Annika

AU - Hyöty, Heikki

AU - Ilonen, Jorma

AU - Jokipuu, Sanna

AU - Kallio, Tiina

AU - Kähönen, Miia

AU - Knip, Mikael

AU - Koivu, Annika

AU - Koreasalo, Mirva

AU - Kurppa, Kalle

AU - Lönnrot, Maria

AU - Mäntymäki, Elina

AU - Multasuo, Katja

AU - Mykkänen, Juha

AU - Niininen, Tiina

AU - Nyblom, Mia

AU - Rajala, Petra

AU - Rautanen, Jenna

AU - Riikonen, Anne

AU - Romo, Minna

AU - Simell, Satu

AU - Simell, Tuula

AU - Simell, Ville

AU - Sjöberg, Maija

AU - Stenius, Aino

AU - Särmä, Maria

AU - Vainionpää, Sini

AU - Varjonen, Eeva

AU - Veijola, Riitta

AU - Vähä-Mäkilä, Mari

AU - Åkerlund, Mari

AU - Agardh, Daniel

AU - Ask, Maria

AU - Bremer, Jenny

AU - Carlsson, Ulla Marie

AU - Cilio, Corrado

AU - Ericson-Hallström, Emelie

AU - Fransson, Lina

AU - Gard, Thomas

AU - Gerardsson, Joanna

AU - Bennet, Rasmus

AU - Hansen, Monica

AU - Hansson, Gertie

AU - Hyberg, Susanne

AU - Johansen, Fredrik

AU - Jonasdottir, Berglind

AU - Jonsson, Linda

AU - Larsson, Helena Elding

AU - Forss, Sigrid Lenrick

AU - Månsson-Martinez, Maria

AU - Markan, Maria

AU - Melin, Jessica

AU - Mestan, Zeliha

AU - Rahmati, Kobra

AU - Ramelius, Anita

AU - Rosenquist, Anna

AU - Salami, Falastin

AU - Sibthorpe, Sara

AU - Sjöberg, Birgitta

AU - Swartling, Ulrica

AU - Amboh, Evelyn Tekum

AU - Trulsson, Erika

AU - Törn, Carina

AU - Wallin, Anne

AU - Wimar, Åsa

AU - Åberg, Sofie

AU - Hagopian, William A.

AU - Yan, Xiang

AU - Killian, Michael

AU - Crouch, Claire Cowen

AU - Skidmore, Jennifer

AU - Ayres, Stephen

AU - Dunson, Kayleen

AU - Heaney, Diana

AU - Hervey, Rachel

AU - Johnson, Corbin

AU - Lyons, Rachel

AU - Meyer, Arlene

AU - Mulenga, Denise

AU - Schulte, Emma

AU - Scott, Elizabeth

AU - Stabbert, Joshua

AU - Willis, John

AU - Becker, Dorothy

AU - Franciscus, Margaret

AU - Smith, Maryellen Dalmagro Elias

AU - Daftary, Ashi

AU - Klein, Mary Beth

AU - Yates, Chrystal

AU - Krischer, Jeffrey P.

AU - Abbondondolo, Michael

AU - Austin-Gonzalez, Sarah

AU - Baethke, Sandra

AU - Brown, Rasheedah

AU - Burkhardt, Brant

AU - Clasen, Joanna

AU - Cuthbertson, David

AU - Eberhard, Christopher

AU - Fiske, Steven

AU - Garcia, Dena

AU - Garmeson, Jennifer

AU - Gowda, Veena

AU - Hadley, David

AU - Heyman, Kathleen

AU - Lee, Hye Seung

AU - Liu, Shu

AU - Lynch, Kristian

AU - Malloy, Jamie

AU - McCarthy, Cristina

AU - McLeod, Wendy

AU - Meulemans, Steven

AU - Shaffer, Chris

AU - Smith, Laura

AU - Smith, Susan

AU - Tamura, Roy

AU - Vehik, Kendra

AU - Vijayakandipan, Ponni

AU - Wood, Keith

AU - Bourcier, Kasia

AU - Briese, Thomas

AU - Johnson, Suzanne Bennett

AU - Oberste, Steve

AU - Triplett, Eric

AU - Yu, Liping

AU - Miao, Dongmei

AU - Bingley, Polly

AU - Williams, Alistair

AU - Chandler, Kyla

AU - Rokni, Saba

AU - Caygill, Claire

AU - Lovis, Nicholas

AU - Williams, Claire

AU - Wyatt, Rebecca

AU - Eriksson, Elisabeth Aardal

AU - Lundgren, Ing Marie

AU - Karlsson, Ewa Lönn

AU - Dernroth, Dzeneta Nezirevic

AU - Erlund, Iris

AU - Salminen, Irma

AU - Sundvall, Jouko

AU - Leiviskä, Jaana

AU - Kangas, Nina

AU - Little, Randie R.

AU - Tennill, Alethea L.

AU - Erlich, Henry

AU - Mack, Steven J.

AU - Fear, Anna Lisa

AU - Fiehn, Oliver

AU - Wikoff, Bill

AU - Defelice, Brian

AU - Grapov, Dmitry

AU - Kind, Tobias

AU - Palazoglu, Mine

AU - Valdiviez, Luis

AU - Wancewicz, Benjamin

AU - Wohlgemuth, Gert

AU - Wong, Joyce

AU - Petrosino, Joseph F.

AU - Marcovina, Santica M.

AU - Gaur, Vinod P.

AU - Smith, Richard D.

AU - Metz, Thomas O.

AU - Ansong, Charles

AU - Webb-Robertson, Bobbie Jo

AU - Mitchell, Hugh D.

AU - Higgins, Heather

AU - Ke, Sandra

AU - Liu, Haitao

AU - Nechtman, John

AU - Zhao, Yansheng

AU - Jiang, Na

AU - Tian, Yanna

AU - Dong, Guangkuo

AU - Rich, Stephen S.

AU - Chen, Wei Min

AU - Onengut-Gumuscu, Suna

AU - Farber, Emily

AU - Pickin, Rebecca Roche

AU - Davis, Jordan

AU - Gallo, Dan

AU - Bonnie, Jessica

AU - Campolieto, Paul

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84954121518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84954121518&partnerID=8YFLogxK

U2 - 10.1001/jamapediatrics.2015.2757

DO - 10.1001/jamapediatrics.2015.2757

M3 - Article

C2 - 26552054

AN - SCOPUS:84954121518

VL - 170

SP - 20

EP - 28

JO - JAMA Pediatrics

JF - JAMA Pediatrics

SN - 2168-6203

IS - 1

ER -