NEW YORK – By profiling changes in blood metabolites and the gut microbial community in individuals with impaired blood glucose control, an international team has identified potential treatment targets and lifestyle changes to dial down type 2 diabetes (T2D) risk.
"Understanding the connections between diet, gut microbiota, and clinical factors provides valuable insights into T2D and highlights the need for diverse intervention strategies," senior and co-corresponding author Fredrik Bäckhed, a researcher affiliated with the University of Gothenburg and Sahlgrenska University Hospital, and his colleagues wrote in a paper published in Nature Medicine on Tuesday.
For their study, researchers from Fudan University, the University of Gothenburg, and other international centers profiled 978 metabolites to search for glucose control-associated markers in blood plasma samples from 697 participants between 50 and 64 years old who were enrolled in a Swedish Impaired Glucose Tolerance (IGT) study.
The group included 220 individuals with normal glucose tolerance, 185 with impaired fasting glucose, 173 with impaired glucose tolerance, 74 with combined glucose intolerance, and 45 with T2D.
The team's analyses highlighted 502 blood metabolites linked to impaired glucose control, including 143 produced by microbes — results they verified using data for another 470 Swedish Cardiopulmonary Bioimage Study (SCAPIS) participants with normal glucose tolerance, impaired glucose tolerance, combined glucose intolerance, or T2D.
By bringing in metagenomic, clinical, and dietary data from a study that members of the same team published on IGT and SCAPIS project participants in Cell Metabolism in 2020, the researchers went on to find ties between specific gut microbes and blood plasma metabolites associated with glucose control.
Based on the dynamic interactions between hundreds of plasma metabolites and microbial species, the investigators flagged a handful of blood metabolites, including hippurate, that were linked to decreasing levels of Lachnospiraceae family microbes such as Hominifimenecus microfluidus and Blautia wexlerae that appeared to be associated with T2D and prediabetic changes in glucose tolerance.
"Our findings identified metabolic disruptions in microbiome-metabolome dynamics as potential mediators of compromised glucose homeostasis," the authors reported, suggesting that "microbiome-associated metabolites, alone or with host-specific ones, have greater potential as biomarkers for prediabetes and T2D."
Because longitudinal and questionnaire data from published diet and exercise studies revealed shifts in certain blood metabolites in relation to physical activity or dietary changes, the investigators further speculated that blood metabolites involved in impaired glucose tolerance and T2D may be modifiable through lifestyle interventions.
Together, the authors wrote, the latest results suggest that "the microbiome-metabolome axis is a modifiable target for T2D management, with optimal health benefits achievable through a combination of lifestyle modifications."