Abstract
Elevated postprandial plasma glucose is a risk factor for development of type 2 diabetes and cardiovascular disease. We hypothesized that the inter-individual postprandial plasma glucose response varies partly depending on the intestinal microbiome composition and function. We analyzed data from Danish adults (n = 106), who were self-reported healthy and attended the baseline visit of two previously reported randomized controlled cross-over trials within the Gut, Grain and Greens project. Plasma glucose concentrations at five time points were measured before and during three hours after a standardized breakfast. Based on these data, we devised machine learning algorithms integrating bio-clinical, as well as shotgun-sequencing-derived taxa and functional potentials of the intestinal microbiome to predict individual postprandial glucose excursions. In this post hoc study, we found microbial and clinical features, which predicted up to 48% of the inter-individual variance of postprandial plasma glucose responses (Pearson correlation coefficient of measured vs. predicted values, R = 0.69, 95% CI: 0.45 to 0.84, p<0.001). The features were age, fasting serum triglycerides, systolic blood pressure, BMI, fasting total serum cholesterol, abundance of Bifidobacterium genus, richness of metagenomics species and abundance of a metagenomic species annotated to Clostridiales at order level. A model based only on microbial features predicted up to 14% of the variance in postprandial plasma glucose excursions (R = 0.37, 95% CI: 0.02 to 0.64, p = 0.04). Adding fasting glycaemic measures to the model including microbial and bio-clinical features increased the predictive power to R = 0.78 (95% CI: 0.59 to 0.89, p<0.001), explaining more than 60% of the inter-individual variance of postprandial plasma glucose concentrations. The outcome of the study points to a potential role of the taxa and functional potentials of the intestinal microbiome. If validated in larger studies our findings may be included in future algorithms attempting to develop personalized nutrition, especially for prediction of individual blood glucose excursions in dys-glycaemic individuals.
Highlights
More than 451 million people suffer from diabetes worldwide and the number is expected to increase to 693 million by 2045 [1]
The intestinal microbiome is a co-determinant of the postprandial plasma glucose response written informed consent
The intestinal microbiome is a co-determinant of the postprandial plasma glucose response eight features included in the hypothesis model were age, metagenomic species (MGS) richness, systolic blood pressure, BMI, abundance of the Bifidobacterium genus, abundance of KEGG module glutamate transport system (M00233), intestinal transit time and sagittal abdominal diameter (S3 Table, S2 Fig)
Summary
More than 451 million people suffer from diabetes worldwide and the number is expected to increase to 693 million by 2045 [1]. Postprandial hyperglycaemia is a risk factor for the development of type 2 diabetes and cardiovascular disease [2]. A landmark study in the field involved about 800 healthy and pre-diabetic Israeli individuals, who consumed identical standardized meals [3]. The investigators demonstrated that PPGRs vary considerably among and within study participants, and constructed an algorithm that accurately predicted PPGRs to a variety of meals with the gut microbiota composition and functional potential contributing to the model [3]. The developed computational frameworks outperformed models considering solely the calorie or carbohydrate content of the meals consumed; traditional approaches, which are commonly used for prediction of blood glucose responses [4]. Only relatively few details on the microbiome contributions to the predictive value of the models were reported
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