Machine Learning Reveals Time-Varying Microbial Predictors with Complex Effects on Glucose Regulation
Year: 2021
Type: article
Study design: Observational Study
Abstract: The incidence of type 2 diabetes (T2D) has been increasing globally and a growing body of evidence links type 2 diabetes with altered microbiota composition. Type 2 diabetes is preceded by a long pre-diabetic state characterized by changes in various metabolic parameters. We tested whether the gut microbiome could have predictive potential for T2D development during the healthy and pre-diabetic disease stages. We used prospective data of 608 well-phenotyped Finnish men collected from the population-based Metabolic Syndrome In Men (METSIM) study to build machine learning models for predicting continuous glucose and insulin measures in a shorter (1.5 year) and longer (4.5 year) period. Our results show that the inclusion of gut microbiome improves prediction accuracy for modelling T2D associated parameters such as glycosylated hemoglobin and insulin measures. We identified novel microbial biomarkers and described their effects on the predictions using interpretable machine learning techniques, which revealed complex linear and non-linear associations. Additionally, the modelling strategy carried out allowed us to compare the stability of model performances and biomarker selection, also revealing differences in short-term and long-term predictions. The identified microbiome biomarkers provide a predictive measure for various metabolic traits related to T2D, thus providing an additional parameter for personal risk assessment. Our work also highlights the need for robust modelling strategies and the value of interpretable machine learning. Importance Recent studies have shown a clear link between gut microbiota and type 2 diabetes. However, current results are based on cross-sectional studies that aim to determine the microbial dysbiosis when the disease is already prevalent. In order to consider microbiome as a factor in disease risk assessment, prospective studies are needed. Our study is the first study that assesses the gut microbiome as a predictive measure for several type 2 diabetes associated parameters in a longitudinal study setting. Our results revealed a number of novel microbial biomarkers that can improve the prediction accuracy for continuous insulin measures and glycosylated hemoglobin levels. These results make the prospect of using microbiome in personalized medicine promising.
Source: mSystems
Authors: Oliver Aasmets, Kreete Lüll, Jennifer M. Lang, Calvin Pan, Johanna Kuusisto, Krista Fischer, Markku Laakso, Aldons J. Lusis, Elin Org
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,500
Funders: European Molecular Biology Organization, Foundation for Cardiovascular Research, European Commission, Eesti Teadusagentuur, Academy of Finland, Kuopion Yliopistollinen Sairaala, Sydäntutkimussäätiö, National Institutes of Health, European Regional Development Fund, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G2970981986, G3863117035, G4579096045, Gut microbiota and metabolite interactions in atherosclerosis, G6318795230, Genetic and epidemiological predictors for all-cause and cause-specific mortality in the Estonian population., G7543358569, G7892971461, G8120543758, The interplay between gut microbiota and metformin treatment in type 2 diabetes through bile acid metabolism, G8568466929, Molecular Genetic Approaches in Atherosclerosis Research, G9000061537, Systems Genetics Dissection of Non-alcoholic Steatohepatitis
OpenAlex ID: W3132721801
