Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors:A 6-month randomised controlled-feeding trial

Objective: To investigate whether diets differing in fat content alter the gut microbiota and faecal metabolomic profiles, and to determine their relationship with cardiometabolic risk factors in healthy adults whose diet is in a transition from a traditional low-fat diet to a diet high in fat and reduced in carbohydrate. Methods: In a 6-month randomised controlled-feeding trial, 217 healthy young adults (aged 18-35 years; body mass index <28 kg/m 2 ; 52% women) who completed the whole trial were included. All the foods were provided during the intervention period. The three isocaloric diets were: A lower-fat diet (fat 20% energy), a moderate-fat diet (fat 30% energy) and a higher-fat diet (fat 40% energy). The effects of the dietary interventions on the gut microbiota, faecal metabolomics and plasma inflammatory factors were investigated. Results: The lower-fat diet was associated with increased α-diversity assessed by the Shannon index (p=0.03), increased abundance of Blautia (p=0.007) and Faecalibacterium (p=0.04), whereas the higher-fat diet was associated with increased Alistipes (p=0.04), Bacteroides (p<0.001) and decreased Faecalibacterium (p=0.04). The concentration of total short-chain fatty acids was significantly decreased in the higher-fat diet group in comparison with the other groups (p<0.001). The cometabolites p-cresol and indole, known to be associated with host metabolic disorders, were decreased in the lower-fat diet group. In addition, the higher-fat diet was associated with faecal enrichment in arachidonic acid and the lipopolysaccharide biosynthesis pathway as well as elevated plasma proinflammatory factors after the intervention. Conclusion: Higher-fat consumption by healthy young adults whose diet is in a state of nutrition transition appeared to be associated with unfavourable changes in gut microbiota, faecal metabolomic profiles and plasma proinï ammatory factors, which might confer adverse consequences for long-term health outcomes. Trial registration number: NCT02355795; Results.