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

Abstract

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.

Keywords: colonic microflora; diet; immune response; inflammation; obesity.

Figure 1

Change in body composition was associated with change in energy intake. The difference in total energy intake between the two interventions (ΔEnergy) was associated with changes in (A) ΔBody weight, (B) ΔFat-free mass and (C) ΔSagittal abdominal diameter, where Δ refers to change of the given measure during the whole grain period minus the change of the given measure during the refined grain period. Correlations were calculated using Spearman’s rank or Pearson’s correlation depending on whether the data were normally distributed (n=50).

Figure 2

Change in fasting serum concentrations of IL-6 was associated with whole grain intake. (A) ΔIL-6, designating change in serum concentrations during the whole grain period minus the change during the refined grain, was negatively associated with ΔWhole grain intake, designating difference in whole grain intake between the two periods, as calculated by Spearman’s rank correlation (n=47). (B) Serum concentrations of IL-6 were negatively associated with plasma AR homologues (biomarkers of whole grain intake) and in particular with the C17:0 homologue (p=0.0003) and the ratio of C17:0-to-C21:0 (p=0.024), indicating a specific association with intake of whole grain rye, as calculated by linear regression analyses adjusted for age and gender (n=50) (see also online supplementary table S6). AR, alkylresorcinol; IL-6, interleukin 6.

Figure 3

Faecal microbiome composition did not differ between the two diets. (A) The subjects’ faecal microbial species diversity assessed by Shannon Index and (B) richness did not significantly differ between the two diets. Shown is the species diversity at baselines (white boxes) and at the end of the refined grain diet (orange boxes) and whole grain diet (green boxes). (C) Heatmap of the median fold changes in relative abundance of the individual MGSs during refined grain and whole grain diet, respectively. No MGSs changed significantly comparing the two periods. Of note, five species differed between diets with a FDR-P below 0.2 (red dotted line). (D) Gene diversity assessed by Shannon Index and (E) richness did not differ significantly between diets. Shown is the gene diversity at baselines (white boxes) and at the end of the refined grain diet (orange boxes) and whole grain diet (green boxes). (F) Heatmap of the median fold changes in relative abundance of the individual gene functions (KOs) during refined grain and whole grain diet, respectively. Two KOs differed significantly between diets with a FDR-P below 0.05 (red dotted line). Changes in microbiome composition were assessed by linear mixed model adjusted for age and gender followed by correction for multiple testing by the Benjamini-Hochberg approach (n=48) (see also online supplementary table S7 and S8). Among the bacterial species responding most to the intervention, several species were associated with (G) whole grain intake and (H) fibre intake, whereas only Erysipelatoclostridium ramosum was associated with (I) serum IL-6 concentrations and no species were associated with (J) serum CRP concentrations as assessed by the linear mixed model adjusted for age and gender followed by correction for multiple testing by the Benjamini-Hochberg approach (n=48) (see also online supplementary table S11). CRP, C-reactive protein; FDR-P, false discovery rate corrected p value; KEGG, Kyoto Encyclopaedia of Genes and Genomes; KO, KEGG orthologies; MGS, metagenomic species.