The dynamics of the gut microbiota in prediabetes during a four-year follow-up among European patients-an IMI-DIRECT prospective study
Author(s)
Type
Journal Article
Abstract
Background
Previous case–control studies have reported aberrations of the gut microbiota in individuals with prediabetes. The primary objective of the present study was to explore the dynamics of the gut microbiota of individuals with prediabetes over 4 years with a secondary aim of relating microbiota dynamics to temporal changes of metabolic phenotypes.
Methods
The study included 486 European patients with prediabetes. Gut microbiota profiling was conducted using shotgun metagenomic sequencing and the same bioinformatics pipelines at study baseline and after 4 years. The same phenotyping protocols and core laboratory analyses were applied at the two timepoints. Phenotyping included anthropometrics and measurement of fasting plasma glucose and insulin levels, mean plasma glucose and insulin under an oral glucose tolerance test (OGTT), 2-h plasma glucose after an OGTT, oral glucose insulin sensitivity index, Matsuda insulin sensitivity index, body mass index, waist circumference, and systolic and diastolic blood pressure. Measures of the dynamics of bacterial microbiota were related to concomitant changes in markers of host metabolism.
Results
Over 4 years, significant declines in richness were observed in gut bacterial and viral species and microbial pathways accompanied by significant changes in the relative abundance and the genetic composition of multiple bacterial species. Additionally, bacterial-viral interactions diminished over time. Despite the overall reduction in bacterial richness and microbial pathway richness, 80 dominant core bacterial species and 78 core microbial pathways were identified at both timepoints in 99% of the individuals, representing a resilient component of the gut microbiota. Over the same period, individuals with prediabetes exhibited a significant increase in glycemia and insulinemia alongside a significant decline in insulin sensitivity. Estimates of the gut bacterial microbiota dynamics were significantly correlated with temporal impairments in host metabolic health.
Conclusions
In this 4-year prospective study of European patients with prediabetes, the gut microbiota exhibited major changes in taxonomic composition, bacterial species genetics, and microbial functional potentials, many of which paralleled an aggravation of host metabolism. Whether the temporal gut microbiota changes represent an adaptation to the progression of metabolic abnormalities or actively contribute to these in prediabetes cases remains unsettled.
Previous case–control studies have reported aberrations of the gut microbiota in individuals with prediabetes. The primary objective of the present study was to explore the dynamics of the gut microbiota of individuals with prediabetes over 4 years with a secondary aim of relating microbiota dynamics to temporal changes of metabolic phenotypes.
Methods
The study included 486 European patients with prediabetes. Gut microbiota profiling was conducted using shotgun metagenomic sequencing and the same bioinformatics pipelines at study baseline and after 4 years. The same phenotyping protocols and core laboratory analyses were applied at the two timepoints. Phenotyping included anthropometrics and measurement of fasting plasma glucose and insulin levels, mean plasma glucose and insulin under an oral glucose tolerance test (OGTT), 2-h plasma glucose after an OGTT, oral glucose insulin sensitivity index, Matsuda insulin sensitivity index, body mass index, waist circumference, and systolic and diastolic blood pressure. Measures of the dynamics of bacterial microbiota were related to concomitant changes in markers of host metabolism.
Results
Over 4 years, significant declines in richness were observed in gut bacterial and viral species and microbial pathways accompanied by significant changes in the relative abundance and the genetic composition of multiple bacterial species. Additionally, bacterial-viral interactions diminished over time. Despite the overall reduction in bacterial richness and microbial pathway richness, 80 dominant core bacterial species and 78 core microbial pathways were identified at both timepoints in 99% of the individuals, representing a resilient component of the gut microbiota. Over the same period, individuals with prediabetes exhibited a significant increase in glycemia and insulinemia alongside a significant decline in insulin sensitivity. Estimates of the gut bacterial microbiota dynamics were significantly correlated with temporal impairments in host metabolic health.
Conclusions
In this 4-year prospective study of European patients with prediabetes, the gut microbiota exhibited major changes in taxonomic composition, bacterial species genetics, and microbial functional potentials, many of which paralleled an aggravation of host metabolism. Whether the temporal gut microbiota changes represent an adaptation to the progression of metabolic abnormalities or actively contribute to these in prediabetes cases remains unsettled.
Date Issued
2025-07-15
Date Acceptance
2025-06-30
Citation
Genome Medicine, 2025, 17
ISSN
1756-994X
Publisher
BMC
Journal / Book Title
Genome Medicine
Volume
17
Copyright Statement
© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40665409
PII: 10.1186/s13073-025-01508-7
Subjects
CHILDREN
COHORT PROFILE
DANISH
Genetics & Heredity
GLUCOSE-TOLERANCE
Gut bacterial genetics
Gut bacterial microbiota
Gut viral microbiota
INSIGHT
Insulin sensitivity
INSULIN SENSITIVITY
Life Sciences & Biomedicine
Long-term dynamics
MECHANISMS
Metabolism
Microbial functional pathways
Prediabetes
PREVENTION
RISK
Science & Technology
STABILITY
Publication Status
Published
Coverage Spatial
England
Article Number
78
Date Publish Online
2025-07-15