Predictors of Carotenoid Concentrations in Human Serum: Role of the Intestinal Microbiome

Abstract

Carotenoids from fruits and vegetables are suggested to reduce the risks of several cancers. Inter‐individual variability in serum carotenoid concentrations is large, and is only modestly explained by dietary intakes. There is evidence that the colonic microbiota can maximize the bio‐accessibility of carotenoids by digestion of plant cell walls. Here we evaluated if differences in the relative abundance of bacterial taxa in the colon could contribute to the inter‐individual variability in serum concentrations of carotenoids. We utilized data and samples from a dietary intervention study that enrolled healthy individuals at increased risk of colon cancer. Colon mucosal biopsies were obtained without prior preparation of the bowels, and 93% of the biopsies were successfully amplified for the V4 region of the 16s rRNA gene. The relative abundance of bacterial phyla in the colonic mucosa of 89 individuals was: 6.7% Proteobacteria, 60% Firmicutes, 27% Bacteroidetes, 1.9% Actinobacteria and 2.8%Verrucomicrobia. At baseline, higher serum concentrations and higher dietary intakes of carotenoids were both associated with a lower abundance of Firmicutes taxa, unlike the direct association of higher body mass index (BMI) with increased abundance of Firmicutes. Higher serum carotenoids also were positively associated with measures of bacterial diversity in contrast to the negative association of diversity with BMI. Surprisingly, there was little change in bacterial taxa post‐intervention with either a Mediterranean diet or a Healthy Eating diet. Subsequent analyses evaluated the contributions of the microbiome, diet and demographic factors to the inter‐individual variation in serum carotenoid concentrations at baseline. Correlations of individual serum carotenoids with bacterial Operational Taxonomic Units indicated that oxygenated carotenoids, namely xanthophylls, segregated from other carotenoids. In linear regression models with serum xanthophyll concentrations as the outcome, bacterial taxa accounted for an additional 11% of the variance after controlling for BMI, smoking, and dietary xanthophyll intakes, and all these factors together accounted for 35% of the inter‐individual variability in serum xanthophylls. For serum beta‐carotene, bacterial taxa contributed an additional 4% of the variance after controlling for BMI, smoking, and dietary intakes. Regression models for alpha‐carotene and lycopene were not improved by including bacterial abundance. These results are consistent with a significant role for colonic microbiota in accessibility of specific carotenoids from fruits and vegetables in humans, and especially for xanthophylls which are high in fruits and green, leafy vegetables.Support or Funding InformationWe acknowledge support from NIH grants RO1 CA120381, T32 CA009676, P30 CA046592, P60 DK20572, P30 DK089503, UL1RR024986, and the Rose and Lawrence C. Page, Sr. Family Charitable Foundation.