Minor Changes in the Composition and Function of the Gut Microbiota During a 12-Week Whole Grain Wheat or Refined Wheat Intervention Correlate with Liver Fat in Overweight and Obese Adults

Mara P H van Trijp, Sophie Schutte, Diederik Esser, Suzan Wopereis, Femke P M Hoevenaars, Guido J E J Hooiveld, Lydia A Afman, Mara P H van Trijp, Sophie Schutte, Diederik Esser, Suzan Wopereis, Femke P M Hoevenaars, Guido J E J Hooiveld, Lydia A Afman

Abstract

Background: Whole grain wheat (WGW) products are advocated as a healthy choice when compared with refined wheat (RW). One proposed mechanism for these health benefits is via the microbiota, because WGW contains multiple fibers. WGW consumption has been proposed to ameliorate nonalcoholic fatty liver disease, in which microbiota might play a role.

Objectives: We investigated the effect of WGW compared with RW intervention on the fecal microbiota composition and functionality, and correlated intervention-induced changes in bacteria with changes in liver health parameters in adults with overweight or obesity.

Methods: We used data of a 12-wk double-blind, randomized, controlled, parallel trial to examine the effects of a WGW (98 g/d) or RW (98 g/d) intervention on the secondary outcomes fecal microbiota composition, predicted microbiota functionality, and stool consistency in 37 women and men (aged 45-70 y, BMI 25-35 kg/m2). The changes in microbiota composition, measured using 16S ribosomal RNA gene sequencing, after a 12-wk intervention were analyzed with nonparametric tests, and correlated with changes in liver fat and circulating concentrations of liver enzymes including alanine transaminase, aspartate transaminase, γ-glutamyltransferase, and serum amyloid A.

Results: The WGW intervention increased the mean (± SD) relative abundances of Ruminococcaceae_UCG-014 (baseline: 2.2 ± 4.6%, differential change over time (Δ) 0.51 ± 4.2%), Ruminiclostridium_9 (baseline: 0.065 ± 0.11%, Δ 0.054 ± 0.14%), and Ruminococcaceae_NK4A214_group (baseline: 0.37 ± 0.56%, Δ 0.17 ± 0.83%), and also the predicted pathway acetyl-CoA fermentation to butyrate II (baseline: 0.23 ± 0.062%, Δ 0.035 ± 0.059%), compared with the RW intervention (P values <0.05). A change in Ruminococcaceae_NK4A214_group was positively correlated with the change in liver fat, in both the WGW (ρ = 0.54; P = 0.026) and RW (ρ = 0.67; P = 0.024) groups.

Conclusions: In middle-aged overweight and obese adults, a 12-wk WGW intervention increased the relative abundance of a number of bacterial taxa from the family Ruminococcaceae and increased predicted fermentation pathways when compared with an RW intervention. Potential protective health effects of replacement of RW by WGW on metabolic organs, such as the liver, via modulation of the microbiota, deserve further investigation.This trial was registered at clinicaltrials.gov as NCT02385149.

Keywords: fatty liver; fermentation; gut microbiota; human; overweight/obesity; refined wheat; whole grain wheat.

© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Significantly different fecal bacterial taxa and bacterial pathways at baseline and after 12-wk of an RW or WGW intervention in middle-aged overweight and obese adults. The flow diagram shows the number of bacterial taxa at the genus level and the predicted pathways for which the change in relative abundance was significantly different among interventions. RW, refined wheat; WGW, whole grain wheat.
FIGURE 2
FIGURE 2
The effect of 12 wk of an RW or WGW intervention on the fecal microbiota diversity in middle-aged overweight and obese adults. (A) PCoA plot using weighted UniFrac dissimilarity to visualize the overall microbiota community variation. Color and shape highlight the intervention groups before or after the intervention. The lines connect the within-person samples over time; 95% CIs are plotted. (B) Microbial diversity as assessed using Faith phylogenetic diversity at baseline and after the 12-wk intervention (end). Individual paired samples are connected by a line. The width of the colored shapes indicates the sample density, the squared shape inside indicates the group mean. PCoA, principal coordinate analysis; RW, refined wheat; WGW, whole grain wheat.
FIGURE 3
FIGURE 3
Fecal bacterial taxa at the genus level at baseline and after the 12-wk RW or WGW intervention (end) that were found to be significantly different between the groups in middle-aged overweight and obese adults. The relative abundances of (A) Ruminococcaceae_NK4A214_group; (B) Ruminococcaceae_UCG-014; (C) Lachnospiraceae_UCG-008; and (D) Ruminiclostridium_9 are shown. Data are presented as group mean (the squared shape), n = 16 (RW) or n = 21 (WGW), and the width of the colored shapes indicates the sample density. Individual paired samples are connected by a line. RW, refined wheat; WGW, whole grain wheat.
FIGURE 4
FIGURE 4
Fecal bacterial taxa at the genus level that were found to be significantly correlated with IHTGs at baseline in middle-aged overweight and obese adults. The relative abundances of (A) Roseburia; (B) Ruminococcus_2; (C) Faecalibacterium; (D) Ruminococcaceae_UCG-010; (E) Ruminococcaceae_UCG-005; and (F) Akkermansia are shown, fitted with a linear regression model with a 95% CI. Noncorrected P values are shown. Data of n = 35 participants are shown, who had both microbiota and IHTG data at baseline available. IHTG, intrahepatic triglyceride.
FIGURE 5
FIGURE 5
Predicted fecal microbial pathway relative abundance at baseline and after 12 wk of RW or WGW intervention that were found to be significantly different between the groups in middle-aged overweight and obese adults. The relative abundances of the predicted pathways (A) superpathway of hexitol degradation; (B) pantothenate and coenzyme A biosynthesis; (C) acetyl-CoA fermentation to butyrate II; (D) pyruvate fermentation to acetone; (E) aromatic biogenic amine degradation; and (F) l-alanine biosynthesis are shown. Data are presented as group mean (the squared shape), n = 16 (RW) or n = 21 (WGW), and the width of the colored shapes indicates the sample density. Individual paired samples are connected by a line. RW, refined wheat; WGW, whole grain wheat.

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