Gut microbiota modulates differential lipid metabolism outcomes associated with FTO gene polymorphisms in response to personalized nutrition intervention

Background: Interindividual differences in response to personalized nutrition (PN) intervention were affected by multiple factors, including genetic backgrounds and gut microbiota. The fat mass and obesity associated (FTO) gene is an important factor related to hyperlipidemia and occurrence of cardiovascular diseases. However, few studies have explored the differences in response to intervention among subjects with different genotypes of FTO, and the associations between gut microbiota and individual responses. Objective: To explore the differential lipid metabolism outcomes associated with FTO gene polymorphisms in response to PN intervention, the altered taxonomic features of gut microbiota caused by the intervention, and the associations between gut microbiota and lipid metabolism outcomes. Methods: A total of 400 overweight or obese adults were recruited in the study and randomly divided into the PN group and control group, of whom 318 completed the 12-week intervention. The single nucleotide polymorphism (SNP) of rs1121980 in FTO was genotyped. Gut microbiota and blood lipids were determined at baseline and week 12. Functional property of microbiota was predicted using Tax4Fun functional prediction analysis. Results: Subjects with the risk genotype of FTO had significantly higher weight and waist circumference (WC) at baseline. Generalized linear regression models showed that the reduction in weight, body mass index (BMI), WC, body fat percentage, total cholesterol (TCHO), and low-density lipoprotein (LDL) was greater in subjects with the risk genotype of FTO and in the PN group. Significant interaction effects between genotype and intervention on weight, BMI, WC, TCHO, and LDL were found after stratifying for specific genotype of FTO. All subjects showed significant increasement in alpha diversity of gut microbiota after intervention except for those with the non-risk genotype in the control group. Gut microbiota, including Blautia and Firmicutes, might be involved in lipid metabolism in response to interventions. The predicted functions of the microbiota in subjects with different genotypes were related to lipid metabolism-related pathways, including fatty acid biosynthesis and degradation. Conclusion: Subjects with the risk genotype of FTO had better response to nutrition intervention, and PN intervention showed better amelioration in anthropometric parameters and blood lipids than the control. Gut microbiota might be involved in modulating differential lipid metabolism responses to intervention in subjects with different genotypes.