Gut Microbial Changes Associated With Obesity in Youth With Type 1 Diabetes

Abstract

Context: Obesity is prevalent in type 1 diabetes (T1D) and is problematic with higher risk for diabetes complications. It is unknown to what extent gut microbiome changes are associated with obesity and T1D.

Objective: This work aimed to describe the gut microbiome and microbial metabolite changes associated with obesity in T1D. We hypothesized statistically significant gut microbial and metabolite differences in lean T1D youth (body mass index [BMI]: 5%-<85%) vs those with obesity (BMI: ≥95%).

Methods: We analyzed stool samples for gut microbial (using metagenomic shotgun sequencing) and short-chain fatty acid (SCFA) differences in lean (n = 27) and obese (n = 21) T1D youth in a pilot study. The mean ± SD age was 15.3 ± 2.2 years, glycated hemoglobin A1c 7.8 ± 1.3%, diabetes duration 5.1 ± 4.4 years, 42.0% female, and 94.0% were White.

Results: Bacterial community composition showed between sample diversity differences (β-diversity) by BMI group (P = .013). There was a higher ratio of Prevotella to Bacteroides in the obese group (P = .0058). There was a differential distribution of significantly abundant taxa in either the lean or obese groups, including increased relative abundance of Prevotella copri, among other taxa in the obese group. Functional profiling showed an upregulation of branched-chain amino acid (BCAA) biosynthesis in the obese group and upregulation of BCAA degradation, tyrosine metabolism, and secondary bile acid biosynthesis in the lean group. Stool SCFAs were higher in the obese vs the lean group (P < .05 for all).

Conclusion: Our findings identify a gut microbiome and microbial metabolite signature associated with obesity in T1D. These findings could help identify gut microbiome-targeted therapies to manage obesity in T1D.

Keywords: Prevotella; microbiome; obesity; secondary bile acids; short chain fatty acids; type 1 diabetes.

Figure 1.

Measures of α- and β-diversity in youth with type 1 diabetes. A, Observed operational taxonomic units (OTUs), Shannon diversity, and Simpson index were not significantly different between lean and obese body mass index (BMI) group samples. B, Bray-Curtis principal coordinate analysis ordination of stool samples from lean and obese BMI group showed a significant difference between the groups (P = .013). Overlaid bacterial taxonomy biplot shows the differences driven by Prevotellaceae and Bacteroidaceae.

Figure 2.

Comparison of the ratio between taxa commonly associated with type 1 diabetes (T1D) and obesity studies. A, Firmicutes to Bacteroidetes ratio (F/B)—no significant difference between body mass index groups. B, Prevotella to Bacteroides ratio (P/B)—significantly higher in the obese T1D group (P = .0058).

Figure 3.

Linear discriminant analysis (LDA) effect size of differentially abundant bacterial species and KEGG pathways in youth with type 1 diabetes. Horizontal bars represent the effect size for each pathway: orange enrichment in obese group, and blue enrichment in lean group. An LDA score cutoff of 2 was used. A and B, Differential abundance of bacterial species in A, total 48 sample set and B, matched 32 sample set. No per-sample normalization done. C and D, Differential abundance of KEGG pathways in C, total 48 sample set and D, matched 32 sample set. Per-sample normalization used and unmapped or unintegrated pathways removed.

Figure 4.

Differences in short-chain fatty acid (SCFA) levels in youth with type 1 diabetes. Differences in levels of the 3 main SCFAs, acetate, butyrate, and propionate, between lean and obese body mass index groups are seen.