Objectives: Pediatric-onset T2D is twice as common in girls vs. boys and is tightly linked with puberty and obesity. Alterations in gut microbiota, specifically the Firmicutes:Bacteroidetes ratio (F:B), may be associated with insulin sensitivity (Si) and may play a role in the pathophysiology of T2D. We aimed to evaluate associations between gut microbiome composition and Si and insulin secretion in obese prepubertal (PP) vs. late-pubertal (LP) girls.
Methods: Obese PP (N=9, age 8.5 ±0.8 year, BMIz 2.0±0.5) and LP (Tanner 4-5, N=9, age 13.0±2.0 year, BMIz 2.0±0.5) obese girls underwent stool collection and intravenous glucose tolerance testing after an overnight fast. High-throughput sequencing of the bacterial 16S rRNA gene V3-V4 region was used to profile fecal bacterial communities. Bergman's minimal model was used to estimate Si and insulin secretion (acute insulin response to glucose, AIRg) and disposition index (DI). T-tests assessed group differences in Si, AIRg and DI. Spearman’s correlation examined relationships between microbiota relative abundance (%RA) and Si, AIRg and DI.
Results: PP vs. LP girls had significantly higher Si (8.0±1.0 vs. 2.0±0.5 x10-4/min-1/μIU/ml, p<0.001) and DI (3,525 ± 636 vs. 1,687 ± 385 x10-4/min-1, p=0.03). AIRg was not different between PP and LP girls (568 ± 132 vs. 840 ± 174 μIU/ml, p=0.23). F:B ratio related to insulin secretion and DI, (r=-0.32, p=0.20; r=-0.39, p=0.11) but not Si. At the genus level, Si was correlated to Ruminococus and Lachnospira %RA (r=0.53, p=0.02; r=0.50, p=0.036). AIRg was correlated to Peptostreptococcaceae %RA (r=-0.48, p=0.045). DI was correlated with Prevotella and Bifidobacterium %RA (r=0.57, p=0.01; R=- 0.54, p=0.02).
Conclusion: These pilot study results suggest possible relationships among the gut microbiome, glucose metabolism, and puberty in girls at risk for T2D that merit further exploration.
B. Jobira: None. D.N. Frank: None. L. Pyle: None. S. Gross: None. D. Ir: None. W. Pendleton: None. C.E. Robertson: None. K.J. Nadeau: None. M.M. Kelsey: None.
University of Colorado Center for Women’s Health; National Institutes of Health/Colorado Clinical Translational Science Award (UL1TR002535)