An Okinawan-based Nordic diet leads to profound effects on gut microbiota and plasma metabolites linked to glucose and lipid metabolism

Background: Dietary interventions modify gut microbiota and clinical outcomes. Weight reduction and improved glucose- and lipid homeostasis have been observed after Okinawan-based Nordic diet (O-BN) in type 2 diabetes. Objectives: To explore changes in metabolomics and gut microbiota during O-BN and correlate changes with clinical outcomes. Methods: 30 patients (17 women), aged 57.5±8.2 years, diabetes duration 10.4±7.6 years, 90% over-weight, were included. Participants were provided O-BN for 12 weeks. Before and after intervention, and 16 weeks afterwards, anthropometry and clinical data were estimated, and blood and stool samples along with questionnaires were collected. Plasma metabolomics was determined by gas (GC-MS) or liquid (LC-MS) chromatography-based mass spectrometry and fecal microbiota were obtained based on 16S rRNA amplicons from regions V1–V2. Results: During the intervention, weight (6.8%) and waist circumference (6.1%), and fasting levels of glucose, HbA1c, insulin, triglycerides, and cholesterol, were decreased. 323 of 602 metabolites were changed, reflecting dietary changes. 199 (101 lipids) metabolites showed decreased levels, while 58 (43 lipids) metabolites showed increases. Changes in glucose homeostasis were linked to changes of e.g., 1,5-anhydroglucitol, thyroxine, and chiro-inositol. Changes of microbe beta-diversity correlated positively with food components and negatively with IL-18 (p=0.045). Abundance differences at phylum and genus levels were found. Abundances of Actinobacteria, Bacteroidetes, Firmicutes, and Verrucomicrobia correlated with anthropometry, HbA1c, lipids, inflammation, and food. Changes in metabolites and microbiota were reversed after the intervention. Conclusion: The O-BN-induced changes in metabolomics and gut microbiota correspond to clinical outcomes of weight reduction, improved glucose and lipid metabolism, and inflammation.