Connection between diet, the gut microbiota and polygenic risk of unfavorable body fat accumulation in relation to liver fat and type 2 diabetes

Project: Research

Project Details

Description

BACKGROUND
Common genetic risk factors for overall adiposity (BMI), abdominal obesity, fatty liver, type 2 diabetes (T2D) and cardiovascular disease (CVD) are numerous but largely distinct between diseases. Similarly, we have observed distinct association patterns in our large gut microbiota (GM) studies. In order to understand the potential of GM in prevention and treatment of cardiometabolic diseases large longitudinal population studies with repeated measurements, in combination with targeted intervention studies, are needed.
RESEARCH QUESTIONS AND WORK PLAN
1) Animal studies propose a causal role of GM in fatty liver disease but human evidence is scarce and based on small studies. What is the connection between GM and liver fat content in large population?
In SCAPIS Malmö/Uppsala (N~10 000) we examine cross-sectional connection between GM and liver fat content in relation to plasma metabolome and polygenic risk of unfavorable fat distribution.
2) Is (the expected) decrease in liver fat content during long-term dietary management of T2D mediated by changes in GM?
In a randomized 3-arm diet intervention (anti-lipogenic/healthy Nordic/control) with proven 12-month compliance we investigate changes in GM in relation to (primarily) liver fat content.
3) For development of novel precision nutrition strategies/GT-based interventions, understanding of longitudinal connections is needed. Can changes in diet, medication and glycemic status be monitored by changes in GM after up to 10-years follow-up?
By re-investigation of 240 participants (with/without prediabetes at baseline, 54 with incident T2D) of the Malmö Offspring Study after a mean follow-up of 7.3y we monitor changes in GM in relation to changes in diet and glycemic status.
4) Metformin (Met) affects GM. Are glycemic treatment targets of Met vs SGLT2i mediated by GM. We investigate changes in GM and plasma metabolome in a sub-study of the national (Swe) RCT, SMARTEST, comparing Met to SGLT2i, in early T2D.
StatusActive
Effective start/end date2024/01/012025/12/31

Funding

  • Novo Nordisk Foundation