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Abstract
Epidemiological studies have shown associations between whole-grain intake and lowered disease risk. A sufficient level of whole-grain intake to reach the health benefits has not been established, and there is limited knowledge about the impact of whole-grain intake on metabolite levels. In this clinical intervention study, we aimed to identify plasma and urine metabolites associated with two different intake levels of whole-grain wheat and rye and to correlate them with clinical plasma biomarkers. Healthy volunteers (N = 68) were divided into two groups receiving either whole-grain wheat or whole-grain rye in two four-week interventions with 48 and 96 g/d of whole grains consumed. The metabolomics of the plasma samples was performed with UPLC–QTOF-MS. Plasma alkylresorcinols were quantified with GC-MS and plasma and urinary mammalian lignans with HPLC-ECD. The high-dose intervention impacted the metabolite profile, including microbial metabolites, more in the rye-enriched diet compared with wheat. Among the increased metabolites were alkylresorcinol glucuronides, sinapyl alcohol, and pipecolic acid betaine, while the decreased metabolites included acylcarnitines and ether lipids. Plasma alkylresorcinols, urinary enterolactone, and total mammalian lignans reflected the study diets in a dose-dependent manner. Several key metabolites linked with whole-grain consumption and gut microbial metabolism increased in a linear manner between the two interventions. The results reveal that an increase in whole-grain intake, particularly rye, is strongly reflected in the metabolite profile, is correlated with clinical variables, and suggests that a diet rich in whole grains promotes the growth and/or metabolism of microbes producing potentially beneficial microbial metabolites.
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1 University of Turku, Food Sciences Unit, Department of Life Technologies, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371); University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, Finland (GRID:grid.9668.1) (ISNI:0000 0001 0726 2490)
2 Yong Loo Lin School of Medicine, Clinical Nutrition Research Centre, Singapore Institute of Food and Biotechnology Innovations (SIFBI), Singapore, Singapore (GRID:grid.490025.a)
3 University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, Finland (GRID:grid.9668.1) (ISNI:0000 0001 0726 2490)
4 University of Eastern Finland, School of Pharmacy, Kuopio, Finland (GRID:grid.9668.1) (ISNI:0000 0001 0726 2490)
5 Aberystwyth University, Department of Biological, Environmental and Rural Sciences, Wales, UK (GRID:grid.8186.7) (ISNI:0000 0001 2168 2483)
6 Newcastle University, Human Nutrition and Exercise Research Centre, Population Health Sciences Institute, Newcastle upon Tyne, UK (GRID:grid.1006.7) (ISNI:0000 0001 0462 7212)
7 AgResearch, Lincoln, New Zealand (GRID:grid.417738.e) (ISNI:0000 0001 2110 5328)
8 Newcastle University, School of Mathematics, Statistics and Physics, Newcastle upon Tyne, UK (GRID:grid.1006.7) (ISNI:0000 0001 0462 7212)
9 University of Turku, Food Sciences Unit, Department of Life Technologies, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371); University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, Finland (GRID:grid.9668.1) (ISNI:0000 0001 0726 2490); Food and Nutrition Science Division, Chalmers University of Technology, Gothenburg, Sweden (GRID:grid.5371.0) (ISNI:0000 0001 0775 6028)