Tags

Type your tag names separated by a space and hit enter

Type 1 diabetes susceptibility alleles are associated with distinct alterations in the gut microbiota.
Microbiome 2018; 6(1):35M

Abstract

BACKGROUND

Dysbiosis of the gut microbiota has been implicated in the pathogenesis of many autoimmune conditions including type 1 diabetes (T1D). It is unknown whether changes in the gut microbiota observed in T1D are due to environmental drivers, genetic risk factors, or both. Here, we have performed an analysis of associations between the gut microbiota and T1D genetic risk using the non-obese diabetic (NOD) mouse model of T1D and the TwinsUK cohort.

RESULTS

Through the analysis of five separate colonies of T1D susceptible NOD mice, we identified similarities in NOD microbiome that were independent of animal facility. Introduction of disease protective alleles at the Idd3 and Idd5 loci (IL2, Ctla4, Slc11a1, and Acadl) resulted in significant alterations in the NOD microbiome. Disease-protected strains exhibited a restoration of immune regulatory pathways within the gut which could also be reestablished using IL-2 therapy. Increased T1D disease risk from IL-2 pathway loci in the TwinsUK cohort of human subjects resulted in some similar microbiota changes to those observed in the NOD mouse.

CONCLUSIONS

These findings demonstrate for the first time that type 1 diabetes-associated genetic variants that restore immune tolerance to islet antigens also result in functional changes in the gut immune system and resultant changes in the microbiota.

Authors+Show Affiliations

Translational Research Institute, The University of Queensland Diamantina Institute, University of Queensland, Brisbane, QLD, Australia. AgResearch Limited, Grasslands Research Centre, Palmerston North, New Zealand.Translational Research Institute, The University of Queensland Diamantina Institute, University of Queensland, Brisbane, QLD, Australia.Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, QLD, Australia.Translational Research Institute, The University of Queensland Diamantina Institute, University of Queensland, Brisbane, QLD, Australia.Translational Research Institute, The University of Queensland Diamantina Institute, University of Queensland, Brisbane, QLD, Australia.Translational Research Institute, The University of Queensland Diamantina Institute, University of Queensland, Brisbane, QLD, Australia.Translational Research Institute, The University of Queensland Diamantina Institute, University of Queensland, Brisbane, QLD, Australia.Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK.Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, QLD, Australia.Translational Research Institute, The University of Queensland Diamantina Institute, University of Queensland, Brisbane, QLD, Australia. e.hamiltonwilliams@uq.edu.au. Translational Research Institute, The University of Queensland Diamantina Institute, 37 Kent St, Woolloongabba, QLD, 4102, Australia. e.hamiltonwilliams@uq.edu.au.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29454391

Citation

Mullaney, Jane A., et al. "Type 1 Diabetes Susceptibility Alleles Are Associated With Distinct Alterations in the Gut Microbiota." Microbiome, vol. 6, no. 1, 2018, p. 35.
Mullaney JA, Stephens JE, Costello ME, et al. Type 1 diabetes susceptibility alleles are associated with distinct alterations in the gut microbiota. Microbiome. 2018;6(1):35.
Mullaney, J. A., Stephens, J. E., Costello, M. E., Fong, C., Geeling, B. E., Gavin, P. G., ... Hamilton-Williams, E. E. (2018). Type 1 diabetes susceptibility alleles are associated with distinct alterations in the gut microbiota. Microbiome, 6(1), p. 35. doi:10.1186/s40168-018-0417-4.
Mullaney JA, et al. Type 1 Diabetes Susceptibility Alleles Are Associated With Distinct Alterations in the Gut Microbiota. Microbiome. 2018 02 17;6(1):35. PubMed PMID: 29454391.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Type 1 diabetes susceptibility alleles are associated with distinct alterations in the gut microbiota. AU - Mullaney,Jane A, AU - Stephens,Juliette E, AU - Costello,Mary-Ellen, AU - Fong,Cai, AU - Geeling,Brooke E, AU - Gavin,Patrick G, AU - Wright,Casey M, AU - Spector,Timothy D, AU - Brown,Matthew A, AU - Hamilton-Williams,Emma E, Y1 - 2018/02/17/ PY - 2017/07/26/received PY - 2018/01/26/accepted PY - 2018/2/19/entrez PY - 2018/2/20/pubmed PY - 2019/1/15/medline KW - Autoimmunity KW - Genetic susceptibility KW - Gut microbiota KW - Interleukin-2 pathway KW - Type 1 diabetes SP - 35 EP - 35 JF - Microbiome JO - Microbiome VL - 6 IS - 1 N2 - BACKGROUND: Dysbiosis of the gut microbiota has been implicated in the pathogenesis of many autoimmune conditions including type 1 diabetes (T1D). It is unknown whether changes in the gut microbiota observed in T1D are due to environmental drivers, genetic risk factors, or both. Here, we have performed an analysis of associations between the gut microbiota and T1D genetic risk using the non-obese diabetic (NOD) mouse model of T1D and the TwinsUK cohort. RESULTS: Through the analysis of five separate colonies of T1D susceptible NOD mice, we identified similarities in NOD microbiome that were independent of animal facility. Introduction of disease protective alleles at the Idd3 and Idd5 loci (IL2, Ctla4, Slc11a1, and Acadl) resulted in significant alterations in the NOD microbiome. Disease-protected strains exhibited a restoration of immune regulatory pathways within the gut which could also be reestablished using IL-2 therapy. Increased T1D disease risk from IL-2 pathway loci in the TwinsUK cohort of human subjects resulted in some similar microbiota changes to those observed in the NOD mouse. CONCLUSIONS: These findings demonstrate for the first time that type 1 diabetes-associated genetic variants that restore immune tolerance to islet antigens also result in functional changes in the gut immune system and resultant changes in the microbiota. SN - 2049-2618 UR - https://www.unboundmedicine.com/medline/citation/29454391/Type_1_diabetes_susceptibility_alleles_are_associated_with_distinct_alterations_in_the_gut_microbiota_ L2 - https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-018-0417-4 DB - PRIME DP - Unbound Medicine ER -