Gut Microbiota Differs in Composition and Functionality Between Children With Type 1 Diabetes and MODY2 and Healthy Control Subjects: A Case-Control Study Original paper

What was studied?

This case-control study tested whether type-1-diabetes-gut-microbiota patterns in children differ not only from healthy peers but also from a nonautoimmune diabetes model (MODY2), helping separate effects of autoimmunity from hyperglycemia alone. Investigators profiled fecal microbiota using 16S rRNA sequencing and inferred functional capacity with PICRUSt, while also measuring systemic inflammation (cytokines), endotoxemia (LPS), and gut permeability via zonulin.

Who was studied?

Participants were 43 Caucasian children (<18 years) from the same geographic region: 15 with type 1 diabetes, genetically confirmed mody2 (gck mutation; autoantibody-negative), and 13 healthy controls matched for age, sex, bmi, delivery mode, breastfeeding duration. design attempted to reduce common microbiome confounders: recent antibiotics prebiotics probiotics were excluded, diets activity patterns similar, glycemic control was comparable between two diabetes groups (with on insulin drug-naïve).< p>

Most important findings

Type 1 diabetes showed a distinct clustering of microbial communities versus both MODY2 and healthy controls, alongside reduced diversity compared with healthy children, supporting a disease-specific dysbiosis rather than a pure “high glucose” effect. Taxonomically, type 1 diabetes was characterized by higher relative abundance of proinflammatory/Gram-negative and lactate-utilizing taxa (notably Bacteroides, Veillonella, plus increases in Ruminococcus, Blautia, Streptococcus, and Enterobacter) and depletion of taxa commonly linked to gut barrier support and short-chain fatty acid production (Bifidobacterium, Roseburia, Faecalibacterium, Lachnospira). MODY2, in contrast, showed a prominent Prevotella signal with lower Ruminococcus and Bacteroides than type 1 diabetes, suggesting a different ecological “solution” to dysglycemia. Mechanistically aligned host markers strengthened clinical relevance: proinflammatory cytokines and LPS were higher in type 1 diabetes, while zonulin (permeability marker) was elevated in both diabetes groups—highest in MODY2—linking altered microbes to barrier dysfunction. Regression/correlation analyses tied higher Bacteroides and Veillonella (and lower Faecalibacterium/Roseburia) to higher zonulin in type 1 diabetes, and higher Prevotella to higher zonulin in MODY2. Functionally, inferred metagenomes in type 1 diabetes were enriched for pathways plausibly relevant to immune activation and inflammation (LPS biosynthesis, antigen processing/presentation, chemokine signaling, ABC transporters) and shifted toward lipid/amino-acid metabolism, with relative depletion of carbohydrate/energy metabolism functions compared with MODY2/healthy controls.

Key implications

Clinically, these data suggest a taxonomic-and-functional type-1-diabetes-gut-microbiota signature in children that tracks with inflammatory tone and gut barrier disruption, and that differs fundamentally from MODY2 despite similar hyperglycemia—supporting the idea that microbial ecology may interact with (or reflect) autoimmunity rather than glucose exposure alone. For microbiome-signature databases, the most exportable features are the “proinflammatory/Gram-negative + lactate-utilizer” enrichment (Bacteroides, Veillonella, Enterobacteriaceae-related signals) paired with depletion of butyrate-associated genera (Faecalibacterium, Roseburia, Lachnospira) and the distinct MODY2 Prevotella pattern, plus functional enrichments around LPS biosynthesis and immune pathways. Because this is cross-sectional and 16S+PICRUSt (not shotgun), it supports association and hypothesis generation, not causality; nonetheless, it sharpens targets for longitudinal risk studies and microbiome-modulation trials in children at risk for type 1 diabetes.

Citation

Leiva-Gea I, Sanchez-Alcoholado L, Martín-Tejedor B, et al. Gut microbiota differs in composition and functionality between children with type 1 diabetes, MODY2, and healthy control subjects: a case-control study. Diabetes Care. 2018;Publish Ahead of Print. doi:10.2337/dc18-0253