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Original article
Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial
  1. Yi Wan1,
  2. Fenglei Wang1,2,
  3. Jihong Yuan3,
  4. Jie Li3,
  5. Dandan Jiang3,
  6. Jingjing Zhang4,
  7. Hao Li1,
  8. Ruoyi Wang1,2,
  9. Jun Tang1,
  10. Tao Huang5,
  11. Jusheng Zheng6,
  12. Andrew J Sinclair7,
  13. Jim Mann8,
  14. Duo Li1,9
  1. 1 Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China
  2. 2 Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, USA
  3. 3 No. 1 Department of Nutrition, Chinese People’s Liberation Army General Hospital, Beijing, China
  4. 4 Department of Gastroenterology, School of Medicine, Zhejiang University, Hangzhou, China
  5. 5 Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
  6. 6 Institute of Basic Medical Science, Westlake University, Hangzhou, China
  7. 7 Department of Nutrition, Dietetics and Food, Monash University, Melbourne, Australia
  8. 8 Department of Human Nutrition and Medicine, University of Otago, Otago, New Zealand
  9. 9 Institute of Nutrition and Health, Qingdao University, Qingdao, China
  1. Correspondence to Professor Duo Li, Institute of Nutrition and Health, Qingdao University, Qingdao 266071, China; duoli{at}


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/m2; 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 proinflammatory factors, which might confer adverse consequences for long-term health outcomes.

Trial registration number NCT02355795; Results.

  • diet
  • nutrition
  • intestinal microbiology
  • gut inflammation
  • clinical trials

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Supplementary materials


  • YW and FW contributed equally.

  • Contributors Conception and design of the study: DL, YW, and FW. Collection of data: JL, DJ, JY, JiZ, HL and RW. Analysis and interpretation of data: YW, FW, JT, TH and JuZ. Drafting of the manuscript: YW and FW. Critical revision of the manuscript for important intellectual content: AJS, JM, and DL. Administrative support and study supervision: DL and JY. All authors read, revised and approved the final draft.

  • Funding This study was funded by the National Basic Research Program of China (2015CB553604) and China Postdoctoral Science Foundation (2018M642466). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Institutional review board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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