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 language | English (US) |
|---|---|
| Pages (from-to) | 20-28 |
| Number of pages | 9 |
| Journal | JAMA Pediatrics |
| Volume | 170 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2016 |
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
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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 journal › Article › peer-review
}
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 -