Jessica E Harbison1,2, Alexandra J Roth-Schulze3, Lynne C Giles2, Cuong D Tran4, Katrina M Ngui3, Megan A Penno2, Rebecca L Thomson2, John M Wentworth3,5, Peter G Colman6, Maria E Craig7, Grant Morahan8, Anthony T Papenfuss3, Simon C Barry1,2, Leonard C Harrison3, Jennifer J Couper1,2. 1. Department of Diabetes and Endocrinology, Women's and Children's Hospital, North Adelaide, South Australia, Australia. 2. Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia. 3. Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. 4. CSIRO, Health and Biosecurity, North Adelaide, South Australia, Australia. 5. Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia. 6. Royal Melbourne Hospital, Melbourne, Victoria, Australia. 7. The Children's Hospital at Westmead and University of Sydney, Sydney, New South Wales, Australia. 8. Harry Perkins Institute of Medical Research, Nedlands, Western Australia, Australia.
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.
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 microbiomedysbiosis. 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 microbiomedysbiosis 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: Naiara G Bediaga; Alexandra L Garnham; Gaetano Naselli; Esther Bandala-Sanchez; Natalie L Stone; Joanna Cobb; Jessica E Harbison; John M Wentworth; Annette-G Ziegler; Jennifer J Couper; Gordon K Smyth; Leonard C Harrison Journal: Diabetes Date: 2022-03-01 Impact factor: 9.461
Authors: Marie-Christine Simon; Anna Lena Reinbeck; Corinna Wessel; Julia Heindirk; Tomas Jelenik; Kirti Kaul; Juan Arreguin-Cano; Alexander Strom; Michael Blaut; Fredrik Bäckhed; Volker Burkart; Michael Roden Journal: J Biol Chem Date: 2019-12-10 Impact factor: 5.157