Colonic Mucosal Bacteria Are Associated with Inter-Individual Variability in Serum Carotenoid Concentrations

Abstract

Background: Relatively high serum carotenoid levels are associated with reduced risks of chronic diseases, but inter-individual variability in serum carotenoid concentrations is modestly explained by diet. The bacterial community in the colon could contribute to the bioaccessibility of carotenoids by completing digestion of plant cells walls and by modulating intestinal permeability.

Objective: To evaluate whether colonic bacterial composition is associated with serum and colon carotenoid concentrations.

Design: The study was a randomized dietary intervention trial in healthy individuals who were at increased risk of colon cancer. Colon mucosal biopsy samples were obtained before and after 6 months of intervention without prior preparation of the bowels.

Participants/setting: Participants were recruited from Ann Arbor, MI, and nearby areas from July 2007 to November 2010. Biopsy data were available from 88 participants at baseline and 82 participants after 6 months.

Methods: Study participants were randomized to counseling for either a Mediterranean diet or a Healthy Eating diet for 6 months.

Results: At baseline, bacterial communities in biopsy samples from study participants in the highest vs the lowest tertile of total serum carotenoid levels differed by several parameters. Linear discriminant analysis effect size identified 11 operational taxonomic units that were significantly associated with higher serum carotenoid levels. In linear regression analyses, three of these accounted for an additional 12% of the variance in serum total carotenoid concentrations after including body mass index, smoking, and dietary intakes in the model. These factors together explained 36% of the inter-individual variance in serum total carotenoid concentrations. The bacterial community in the colonic mucosa, however, was resistant to change after dietary intervention with either a Mediterranean diet or Healthy Eating diet, each of which doubled fruit and vegetable intakes.

Conclusions: The colonic mucosal bacterial community was associated with serum carotenoid concentrations at baseline but was not appreciably changed by dietary intervention.

Trial registration: ClinicalTrials.gov NCT00475722.

Keywords: Cancer prevention; Colon cancer; Diet-microbiome interactions; High fruit-vegetable diets.

Conflict of interest statement

None of the authors have conflicts of interest with the work reported in the following submission:

“Colonic Mucosal Bacteria Contribute to Inter-Individual Variability in Serum Carotenoid Concentrations”

Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Principal Covariate Analysis (PCoA) of colonic mucosal bacterial community θYC distances and tertile of serum total carotenoids at baseline. PCoA is a multidimensional scaling metric that is constructed using the θYC distance matrix of the samples. The analysis produces a set of uncorrelated (orthogonal) axes that summarize the variability in the data. Axis 1 contributed to 18.9% of the variance, axis 2 contributed 11.5% and axis contributed 7.8%. Objects ordinated closer to one another are more similar than those ordinated further away. Samples from study participants in the lowest tertile of serum carotenoids (filled black squares) are shown to cluster in a different pattern than samples from participants in the 2nd and 3rd tertiles (open circles and triangles, respectively).

Figure 2

Graphical representation of the regression models for baseline serum carotenoids. Models were constructed including dietary intakes of respective carotenoids per 1000 kcal, variables known to affect carotenoid concentrations (body mass index denoted as “BMI”, smoking, gender, serum total cholesterol) and the relative abundance of 11 bacterial operational taxonomic units (OTUs) that were identified to be associated with serum carotenoids from linear discriminant analysis effect size (LEfSe) analysis. OTUs are constructed based on sequence similarity and represent bacteria at the genus level. Only the variables that remained significant after stepwise selection are shown, and the final model explained 36% of the variance in total serum carotenoids. For bacterial relative abundance, the retained OTUs were OTU1 (Bacteroides), OTU118 (an unclassified species of Lachnospiraceae) and OTU4 (Roseburia). The adjusted R2 was significant across models (R2 = 0.034 for model 1, R2 = 0.243 for model 2 and R2 = 0.360 for model 3, p<0.05 for the F change in each case).