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Gut microbiome dysbiosis and increased intestinal permeability in children with islet autoimmunity and type 1 diabetes: A prospective cohort study.
Pediatr Diabetes. 2019 08; 20(5):574-583.PD

Abstract

AIMS/HYPOTHESIS

To investigate the longitudinal relationship between the gut microbiome, circulating short chain fatty acids (SCFAs) and intestinal permeability in children with islet autoimmunity or type 1 diabetes and controls.

METHODS

We analyzed the gut bacterial microbiome, plasma SCFAs, small intestinal permeability and dietary intake in 47 children with islet autoimmunity or recent-onset type 1 diabetes and in 41 unrelated or sibling controls over a median (range) of 13 (2-34) months follow-up.

RESULTS

Children with multiple islet autoantibodies (≥2 IA) or type 1 diabetes had gut microbiome dysbiosis. Anti-inflammatory Prevotella and Butyricimonas genera were less abundant and these changes were not explained by differences in diet. Small intestinal permeability measured by blood lactulose:rhamnose ratio was higher in type 1 diabetes. Children with ≥2 IA who progressed to type 1 diabetes (progressors), compared to those who did not progress, had higher intestinal permeability (mean [SE] difference +5.14 [2.0], 95% confidence interval [CI] 1.21, 9.07, P = .006), lower within-sample (alpha) microbial diversity (31.3 [11.2], 95% CI 9.3, 53.3, P = .005), and lower abundance of SCFA-producing bacteria. Alpha diversity (observed richness) correlated with plasma acetate levels in all groups combined (regression coefficient [SE] 0.57 [0.21], 95% CI 0.15, 0.99 P = .008).

CONCLUSIONS/INTERPRETATION

Children with ≥2 IA who progress to diabetes, like those with recent-onset diabetes, have gut microbiome dysbiosis associated with increased intestinal permeability. Interventions that expand gut microbial diversity, in particular SCFA-producing bacteria, may have a role to decrease progression to diabetes in children at-risk.

Authors+Show Affiliations

Department of Diabetes and Endocrinology, Women's and Children's Hospital, North Adelaide, South Australia, Australia. Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.CSIRO, Health and Biosecurity, North Adelaide, South Australia, Australia.Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.Royal Melbourne Hospital, Melbourne, Victoria, Australia.The Children's Hospital at Westmead and University of Sydney, Sydney, New South Wales, Australia.Harry Perkins Institute of Medical Research, Nedlands, Western Australia, Australia.Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.Department of Diabetes and Endocrinology, Women's and Children's Hospital, North Adelaide, South Australia, Australia. Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.Department of Diabetes and Endocrinology, Women's and Children's Hospital, North Adelaide, South Australia, Australia. Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.

Pub Type(s)

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

Language

eng

PubMed ID

31081243

Citation

Harbison, Jessica E., et al. "Gut Microbiome Dysbiosis and Increased Intestinal Permeability in Children With Islet Autoimmunity and Type 1 Diabetes: a Prospective Cohort Study." Pediatric Diabetes, vol. 20, no. 5, 2019, pp. 574-583.
Harbison JE, Roth-Schulze AJ, Giles LC, et al. Gut microbiome dysbiosis and increased intestinal permeability in children with islet autoimmunity and type 1 diabetes: A prospective cohort study. Pediatr Diabetes. 2019;20(5):574-583.
Harbison, J. E., Roth-Schulze, A. J., Giles, L. C., Tran, C. D., Ngui, K. M., Penno, M. A., Thomson, R. L., Wentworth, J. M., Colman, P. G., Craig, M. E., Morahan, G., Papenfuss, A. T., Barry, S. C., Harrison, L. C., & Couper, J. J. (2019). Gut microbiome dysbiosis and increased intestinal permeability in children with islet autoimmunity and type 1 diabetes: A prospective cohort study. Pediatric Diabetes, 20(5), 574-583. https://doi.org/10.1111/pedi.12865
Harbison JE, et al. Gut Microbiome Dysbiosis and Increased Intestinal Permeability in Children With Islet Autoimmunity and Type 1 Diabetes: a Prospective Cohort Study. Pediatr Diabetes. 2019;20(5):574-583. PubMed PMID: 31081243.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gut microbiome dysbiosis and increased intestinal permeability in children with islet autoimmunity and type 1 diabetes: A prospective cohort study. AU - Harbison,Jessica E, AU - Roth-Schulze,Alexandra J, AU - Giles,Lynne C, AU - Tran,Cuong D, AU - Ngui,Katrina M, AU - Penno,Megan A, AU - Thomson,Rebecca L, AU - Wentworth,John M, AU - Colman,Peter G, AU - Craig,Maria E, AU - Morahan,Grant, AU - Papenfuss,Anthony T, AU - Barry,Simon C, AU - Harrison,Leonard C, AU - Couper,Jennifer J, Y1 - 2019/05/20/ PY - 2019/01/31/received PY - 2019/04/26/revised PY - 2019/05/02/accepted PY - 2019/5/14/pubmed PY - 2020/3/12/medline PY - 2019/5/14/entrez KW - gut microbiome KW - intestinal permeability KW - islet autoimmunity KW - short chain fatty acids KW - type 1 diabetes SP - 574 EP - 583 JF - Pediatric diabetes JO - Pediatr Diabetes VL - 20 IS - 5 N2 - AIMS/HYPOTHESIS: To investigate the longitudinal relationship between the gut microbiome, circulating short chain fatty acids (SCFAs) and intestinal permeability in children with islet autoimmunity or type 1 diabetes and controls. METHODS: We analyzed the gut bacterial microbiome, plasma SCFAs, small intestinal permeability and dietary intake in 47 children with islet autoimmunity or recent-onset type 1 diabetes and in 41 unrelated or sibling controls over a median (range) of 13 (2-34) months follow-up. RESULTS: Children with multiple islet autoantibodies (≥2 IA) or type 1 diabetes had gut microbiome dysbiosis. Anti-inflammatory Prevotella and Butyricimonas genera were less abundant and these changes were not explained by differences in diet. Small intestinal permeability measured by blood lactulose:rhamnose ratio was higher in type 1 diabetes. Children with ≥2 IA who progressed to type 1 diabetes (progressors), compared to those who did not progress, had higher intestinal permeability (mean [SE] difference +5.14 [2.0], 95% confidence interval [CI] 1.21, 9.07, P = .006), lower within-sample (alpha) microbial diversity (31.3 [11.2], 95% CI 9.3, 53.3, P = .005), and lower abundance of SCFA-producing bacteria. Alpha diversity (observed richness) correlated with plasma acetate levels in all groups combined (regression coefficient [SE] 0.57 [0.21], 95% CI 0.15, 0.99 P = .008). CONCLUSIONS/INTERPRETATION: Children with ≥2 IA who progress to diabetes, like those with recent-onset diabetes, have gut microbiome dysbiosis associated with increased intestinal permeability. Interventions that expand gut microbial diversity, in particular SCFA-producing bacteria, may have a role to decrease progression to diabetes in children at-risk. SN - 1399-5448 UR - https://www.unboundmedicine.com/medline/citation/31081243/Gut_microbiome_dysbiosis_and_increased_intestinal_permeability_in_children_with_islet_autoimmunity_and_type_1_diabetes:_A_prospective_cohort_study_ L2 - https://doi.org/10.1111/pedi.12865 DB - PRIME DP - Unbound Medicine ER -