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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial
  1. Henrik Munch Roager1,
  2. Josef K Vogt2,
  3. Mette Kristensen3,
  4. Lea Benedicte S Hansen2,
  5. Sabine Ibrügger3,
  6. Rasmus B Mærkedahl3,4,
  7. Martin Iain Bahl1,
  8. Mads Vendelbo Lind3,5,
  9. Rikke L Nielsen2,
  10. Hanne Frøkiær4,
  11. Rikke Juul Gøbel6,
  12. Rikard Landberg5,
  13. Alastair B Ross5,
  14. Susanne Brix7,
  15. Jesper Holck8,
  16. Anne S Meyer8,
  17. Morten H Sparholt9,
  18. Anders F Christensen9,
  19. Vera Carvalho1,
  20. Bolette Hartmann6,
  21. Jens Juul Holst6,10,
  22. Jüri Johannes Rumessen11,
  23. Allan Linneberg12,13,14,
  24. Thomas Sicheritz-Pontén2,
  25. Marlene D Dalgaard7,
  26. Andreas Blennow15,
  27. Henrik Lauritz Frandsen1,
  28. Silas Villas-Bôas16,
  29. Karsten Kristiansen17,
  30. Henrik Vestergaard6,18,
  31. Torben Hansen6,
  32. Claus T Ekstrøm19,
  33. Christian Ritz3,
  34. Henrik Bjørn Nielsen2,20,
  35. Oluf Borbye Pedersen6,
  36. Ramneek Gupta2,
  37. Lotte Lauritzen3,
  38. Tine Rask Licht1
  1. 1 National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark
  2. 2 Department of Bio and Heath Informatics, Technical University of Denmark, Kongens Lyngby, Denmark
  3. 3 Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Frederiksberg, Denmark
  4. 4 Department of Veterinary Disease Biology, Faculty of Science, University of Copenhagen, Copenhagen, Frederiksberg, Denmark
  5. 5 Department of Biology and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden
  6. 6 The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
  7. 7 Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
  8. 8 Department of Chemical and Biochemical Engineering, Technical University of Denmark, Kongens Lyngby, Denmark
  9. 9 Department of Radiology, Bispebjerg Hospital, Copenhagen, Denmark
  10. 10 Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
  11. 11 Research Unit and Department of Gastroenterology, Herlev and Gentofte Hospital, Copenhagen, Denmark
  12. 12 Research Centre for Prevention and Health, Copenhagen, Denmark
  13. 13 Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark
  14. 14 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  15. 15 Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark
  16. 16 School of Biological Sciences, The University of Auckland, Auckland, New Zealand
  17. 17 Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
  18. 18 Steno Diabetes Center Copenhagen, Gentofte, Denmark
  19. 19 Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
  20. 20 Clinical-Microbiomics A/S, Copenhagen, Denmark
  1. Correspondence to Associate Professor Ramneek Gupta, Department of Bio and Heath Informatics, Technical University of Denmark, 2800 Kgs Lyngby, Denmark; ramneek{at}, Associate Professor Lotte Lauritzen, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, 1958 Frederiksberg, Denmark; ll{at} and Professor Tine Rask Licht, National Food Institute, Technical University of Denmark, 2800 Kgs Lyngby, Denmark; trli{at}


Objective To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality.

Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed.

Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye.

Conclusion Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation.

Trial registration number NCT01731366; Results.

  • colonic microflora
  • diet
  • immune response
  • inflammation
  • obesity

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  • HMR and JKV contributed equally.

  • Contributors Conception and design of the study: MK, LL, MIB, HF, RG, KK,HV, TH, OP, TRL; collection of data and biological samples: MK, SI, RG, MVL,RBM, LL; analysis of markers of host physiology: RBM, HF, LL, MVL, SB, JJH; faecal microbiota: JKV, LBSH, RLN, MIB, MDD, VC, HBN, RG; plasma short-chainfatty acids: RL; plasma alkylresorcinols: MVL, ABR; urine metabolome: HMR, HLF,SVB; intestinal transit time: MHS, AFC; lactulose-mannitol excretion: ABR; study products: MK, SI, MVL, JH, ASM, AB; data analysis and interpretation: HMR, JKV,MK, LBSH, MVL, RBM, MIB, RLN, HF, CTE, CR, HBN, RG, LL, TLR; manuscript drafting: HMR, JKV, MK, MIB, LL and TLR. All authors read, revised and approved the final manuscript.

  • Funding This study was supported by the Innovation Fund Denmark (grant no. 11-116163/0603-00487B; Center for Gut, Grain and Greens (3G Center)). RLN was supported by a grant from DTU and the Sino-Danish Center for Education and Research.

  • Competing interests MV Lind was partly supported by an unrestricted grant from Cereal Partners Worldwide, a joint venture between Nestlé SA and General Mills Ltd. There were no conflict of interest to declare for the other authors. Intervention products were sponsored by Kohberg, Lantmännen, AXA, Wasa, Urtekram, Finax and Doves Farm. Sponsors of grants and products played no role in the design, methods, data management and analysis nor in the decision to publish.

  • Ethics approval Municipal Ethical Committee of the Capital Region of Denmark.

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

  • Correction notice This article has been corrected since it published Online First. An additional author has been added.

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