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JAMA Pediatr. 2016 Jan;170(1):20-8. doi: 10.1001/jamapediatrics.2015.2757.

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

Collaborators (241)

Rewers M, Bautista K, Baxter J, Bedoy R, Felipe-Morales D, Frohnert B, Gesualdo P, Hoffman M, Karban R, Liu E, Norris J, Samper-Imaz A, Steck A, Waugh K, Wright H, She JX, 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, Ziegler AG, Beyerlein A, Bonifacio E, Hummel M, Hummel S, Foterek K, Kersting M, Knopff A, Koletzko S, Peplow C, Roth R, Stock J, Strauss E, Warncke K, Winkler C, Toppari J, 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, Virtanen SM, Vähä-Mäkilä M, Åkerlund M, Lernmark Å, Agardh D, Aronsson CA, 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 MD, Daftary A, Klein MB, Yates C, Krischer JP, Abbondondolo M, Austin-Gonzalez S, Baethke S, Brown R, Burkhardt B, Butterworth M, Clasen J, Cuthbertson D, Eberhard C, Fiske S, Garcia D, Garmeson J, Gowda V, Hadley D, Heyman K, Lee HS, Liu S, Liu X, Lynch K, Malloy J, McCarthy C, McLeod W, Meulemans S, Shaffer C, Smith L, Smith S, Tamura R, Uusitalo U, Vehik K, Vijayakandipan P, Wood K, Yang J, Akolkar B, 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, Davis B, 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, She JX, McIndoe R, 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.

Author information

1
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa.
2
Department of Clinical Sciences, Lund University, Malmö, Sweden.
3
Institute of Diabetes Research, Helmholtz Zentrum München and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München and Forschergruppe Diabetes e.V., Munich, Germany.
4
Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora.
5
Pacific Northwest Diabetes Research Institute, Seattle, Washington.
6
Medical College of Georgia, Georgia Regents University, Augusta.
7
Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.
8
Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland8Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
9
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
10
Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora.
11
National Institute for Health and Welfare, Nutrition Unit, Helsinki, Finland12School of Health Sciences and Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland 13The Science Center of Pirkanmaa Hospita.

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.

PMID:
26552054
PMCID:
PMC4803028
DOI:
10.1001/jamapediatrics.2015.2757
[Indexed for MEDLINE]
Free PMC Article

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