Lack of effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomised controlled trial

Lidia Groele, Hania Szajewska, Mieczysław Szalecki, Jolanta Świderska, Marta Wysocka-Mincewicz, Agnieszka Ochocińska, Anna Stelmaszczyk-Emmel, Urszula Demkow, Agnieszka Szypowska, Lidia Groele, Hania Szajewska, Mieczysław Szalecki, Jolanta Świderska, Marta Wysocka-Mincewicz, Agnieszka Ochocińska, Anna Stelmaszczyk-Emmel, Urszula Demkow, Agnieszka Szypowska

Abstract

Introduction: The gut microbiota may be relevant in the development of type 1 diabetes (T1D). We examined the effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed T1D.

Research design and methods: Children aged 8-17 years with newly (within 60 days) diagnosed T1D were enrolled in a double-blind, randomised controlled trial in which they received L. rhamnosus GG and B. lactis Bb12 at a dose of 109 colony-forming units or placebo, orally, once daily, for 6 months. The follow-up was for 12 months. The primary outcome measure was the area under the curve (AUC) of the C-peptide level during 2-hour responses to a mixed meal.

Results: Ninety-six children were randomised (probiotics, n=48; placebo n=48; median age 12.3 years). Eighty-eight (92%) completed the 6-month intervention, and 87 (91%) completed the follow-up at 12 months. There was no significant difference between the study groups for the AUC of the C-peptide level. For the secondary outcomes at 6 months, there were no differences between the study groups. At 12 months, with one exception, there also were no significant differences between the groups. Compared with the placebo group, there was a significantly increased number of subjects with thyroid autoimmunity in the probiotic group. However, at baseline, there was also a higher frequency of thyroid autoimmunity in the probiotic group. There were no cases of severe hypoglycemia or ketoacidosis in any of the groups. No adverse events related to the study products were reported.

Conclusions: L. rhamnosus GG and B. lactis Bb12, as administered in this study, had no significant effect in maintaining the residual pancreatic beta-cell function in children with newly diagnosed T1D. It remains unclear which probiotics, if any, alone or in combination, are potentially the most useful for management of T1D.

Trial registration number: NCT03032354.

Keywords: cytokines; diabetes mellitus; inflammation; type 1.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flow chart of subject participating in the study.

References

    1. Szalecki M, Wysocka-Mincewicz M, Ramotowska A, et al. . Epidemiology of type 1 diabetes in Polish children: a multicentre cohort study. Diabetes Metab Res Rev 2018;34:dmrr.2962. 10.1002/dmrr.2962
    1. Krischer JP, Lynch KF, Schatz DA, et al. . The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia 2015;58:980–7. 10.1007/s00125-015-3514-y
    1. Knip M, Honkanen J. Modulation of type 1 diabetes risk by the intestinal microbiome. Curr Diab Rep 2017;17:105. 10.1007/s11892-017-0933-9
    1. Siljander H, Honkanen J, Knip M. Microbiome and type 1 diabetes. EBioMedicine 2019;46:512–21. 10.1016/j.ebiom.2019.06.031
    1. de Oliveira GLV, Leite AZ, Higuchi BS, et al. . Intestinal dysbiosis and probiotic applications in autoimmune diseases. Immunology 2017;152:1–12. 10.1111/imm.12765
    1. de Goffau MC, Luopajärvi K, Knip M, et al. . Fecal microbiota composition differs between children with β-cell autoimmunity and those without. Diabetes 2013;62:1238–44. 10.2337/db12-0526
    1. de Goffau MC, Fuentes S, van den Bogert B, et al. . Aberrant gut microbiota composition at the onset of type 1 diabetes in young children. Diabetologia 2014;57:1569–77. 10.1007/s00125-014-3274-0
    1. Murri M, Leiva I, Gomez-Zumaquero JM, et al. . Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Med 2013;11:46. 10.1186/1741-7015-11-46
    1. Sales-Campos H, Soares SC, Oliveira CJF. An introduction of the role of probiotics in human infections and autoimmune diseases. Crit Rev Microbiol 2019;45:413–32. 10.1080/1040841X.2019.1621261
    1. Jamshidi P, Hasanzadeh S, Tahvildari A, et al. . Is there any association between gut microbiota and type 1 diabetes? A systematic review. Gut Pathog 2019;11:49. 10.1186/s13099-019-0332-7
    1. Mishra SP, Wang S, Nagpal R, et al. . Probiotics and prebiotics for the amelioration of type 1 diabetes: present and future perspectives. Microorganisms 2019;7:67. 10.3390/microorganisms7030067
    1. Valladares R, Sankar D, Li N, et al. . Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats. PLoS One 2010;5:e10507. 10.1371/journal.pone.0010507
    1. Lau K, Benitez P, Ardissone A, et al. . Inhibition of type 1 diabetes correlated to a Lactobacillus johnsonii N6.2-mediated Th17 bias. J Immunol 2011;186:3538–46. 10.4049/jimmunol.1001864
    1. Uusitalo U, Liu X, Yang J, et al. . Association of early exposure of probiotics and islet autoimmunity in the TEDDY study. JAMA Pediatr 2016;170:20–8. 10.1001/jamapediatrics.2015.2757
    1. Zheng J, Wittouck S, Salvetti E, et al. . A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int J Syst Evol Microbiol 2020;70:2782–858. 10.1099/ijsem.0.004107
    1. Liu Y, Alookaran JJ, Rhoads JM. Probiotics in Autoimmune and Inflammatory Disorders. Nutrients. 2018 Oct 18;10:1537.
    1. Groele L, Szajewska H, Szypowska A. Effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: protocol of a randomised controlled trial. BMJ Open 2017;7:e017178. 10.1136/bmjopen-2017-017178
    1. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 2001;357:1191–4. 10.1016/S0140-6736(00)04337-3
    1. Greenbaum CJ, Mandrup-Poulsen T, McGee PF, et al. . Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes. Diabetes Care 2008;31:1966–71. 10.2337/dc07-2451
    1. Lachin JM, McGee PL, Greenbaum CJ, et al. . Sample size requirements for studies of treatment effects on beta-cell function in newly diagnosed type 1 diabetes. PLoS One 2011;6:e26471. 10.1371/journal.pone.0026471
    1. Guidelines on the management of diabetic patients. A position of diabetes Poland. Clinical Diabetology 2019.
    1. Yamamura S, Fukui T, Mori Y, et al. . Circulating anti-glutamic acid decarboxylase-65 antibody titers are positively associated with the capacity of insulin secretion in acute-onset type 1 diabetes with short duration in a Japanese population. J Diabetes Investig 2019;10:1480–9. 10.1111/jdi.13052
    1. Zare Javid A, Aminzadeh M, Haghighi-Zadeh MH, et al. . The effects of synbiotic supplementation on glycemic status, lipid profile, and biomarkers of oxidative stress in type 1 diabetic patients. A placebo-controlled, double-blind, randomized clinical trial. Diabetes Metab Syndr Obes 2020;13:607–17. 10.2147/DMSO.S238867
    1. Szajewska H, Hojsak I. Health benefits of Lactobacillus rhamnosus GG and Bifidobacterium animalis subspecies lactis BB-12 in children. Postgrad Med 2020;132:441–51. 10.1080/00325481.2020.1731214

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