Gut microbiome shifts in people with type 1 diabetes are associated with glycaemic control: an INNODIA study

Abstract

Aims/hypothesis The gut microbiome is implicated in the disease process leading to clinical type 1 diabetes, but less is known about potential changes in the gut microbiome after the diagnosis of type 1 diabetes and implications in glucose homeostasis. We aimed to analyse potential associations between the gut microbiome composition and clinical and laboratory data during a 2 year follow-up of people with newly diagnosed type 1 diabetes, recruited to the Innovative approaches to understanding and arresting type 1 diabetes (INNODIA) study. In addition, we analysed the microbiome composition in initially unaffected family members, who progressed to clinical type 1 diabetes during or after their follow-up for 4 years. Methods We characterised the gut microbiome composition of 98 individuals with newly diagnosed type 1 diabetes (ND cohort) and 194 autoantibody-positive unaffected family members (UFM cohort), representing a subgroup of the INNODIA Natural History Study, using metagenomic sequencing. Participants from the ND cohort attended study visits within 6 weeks from the diagnosis and 3, 6, 12 and 24 months later for stool sample collection and laboratory tests (HbA1c, C-peptide, diabetes-associated autoantibodies). Participants from the UFM cohort were assessed at baseline and 6, 12, 18, 24 and 36 months later. Results We observed a longitudinal increase in 21 bacterial species in the ND cohort but not in the UFM cohort. The relative abundance of Faecalibacterium prausnitzii was inversely associated with the HbA1c levels at diagnosis (p=0.0019). The rate of the subsequent disease progression in the ND cohort, as assessed by change in HbA1c, C-peptide levels and insulin dose, was associated with the abundance of several bacterial species. Individuals with rapid decrease in C-peptide levels in the ND cohort had the lowest gut microbiome diversity. Nineteen individuals who were diagnosed with type 1 diabetes in the UFM cohort had increased abundance of Sutterella sp. KLE1602 compared with the undiagnosed UFM individuals (p=1.2 × 10−4). Conclusions/interpretation Our data revealed associations between the gut microbiome composition and the disease progression in individuals with recent-onset type 1 diabetes. Future mechanistic studies as well as animal studies and human trials are needed to further validate the significance and causality of these associations. Graphical Abstract

The Impact of Parabacteroides distasonis Colonization on Hosts' Microbiome, Metabolome, Immune Responses, and Diabetes Onset

“…The Environmental Determinants of Diabetes in the Young (TEDDY) study, another key longitudinal cohort, used samples from 903 high-risk infants reported, Parabacteroides as the only genus significantly associated with the T1D onset 15 . Similarly, the Innovative Approaches to Understanding and Arresting Type 1 Diabetes (INNODIA) study identified Parabacteroides distasonis as one of the 30 most abundant species in newly diagnosed individuals 16 . These longitudinal studies offer valuable insights into gut microbiome changes, identifying specific alterations for specific gut commensals, including a significant association between Parabacteroides and T1D before disease onset.…”

“…The copyright holder for this preprint this version posted June 17, 2024. ; https://doi.org/10.1101/2024.06. 13.598927 doi: bioRxiv preprint Understanding and Arresting Type 1 Diabetes (INNODIA) study identified Parabacteroides distasonis as one of the 30 most abundant species in newly diagnosed individuals 16 . These longitudinal studies offer valuable insights into gut microbiome changes, identifying specific alterations for specific gut commensals, including a significant association between Parabacteroides and T1D before disease onset.…”

“…Recent studies suggest that alterations in the gut microbes and T1D could be linked to several factors, such as increased gut permeability 34 and microbial metabolites, including SCFAs 16 35 and other proinflammatory metabolites. Here, we further investigated the impact of P. distasonis on the host.…”